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Like most regional cities on the volcanic landmass of Java
It's the Asia of one's backpacking days — uneven payments and roadside food stalls
It is most famous for tobacco and the production of cigars.
In the late 1990s, Dynand Fariz set out to change that. Fariz (1963-2019) a Jember native, acquired scholarships to study fashion and design in both Jakarta and France. Then, he decided to use his skills to create a promotional event for his native city. Jember Fashion Carnaval (JFC) was the result.
During the first decade of the festival's existence from its initiation in 2002
The twenty-second edition of the carnival was held from August 2-4 2024
It included five thematic carnivals over three days: The World Kids Carnival
the Wonderful Archipelago Carnival Indonesia
and the Grand Carnival of Jember Fashion Carnaval.
Each carnival features costumes and performers on an expansive sound stage and "runway"
The runway is a 120-meter stretch of street that borders the city's central park.
At the conclusion of each thematic carnival, the performers parade through the main thoroughfare of Jember for up to an extraordinary 3.6 kilometers. The crowds are five or six deep, or in places, considerably more. It seems as if the whole city turns out. In terms of size and scale, JFC is second only to the Rio Carnival of Brazil.
The principal fashion component occurs during the Artwear carnival
About 500 participants model the creations of contemporary designers
including international beauty pageant contestants
There they are joined by the audience.
the inclusion of the word "fashion" in "Jember Fashion Carnaval" is somewhat misleading
The costumes for which the carnival is best known have no application as wearable clothing
They can weigh as much as 20 kilograms and demand considerable space
the logistical considerations of transport
and assembly are little less than those of actual construction.
will be remembered as one of the most significant
it received a boost of serious star power from Japan.
The impact of the Japanese artists also went beyond their actual performances
The costumes created for the festival are indeed stunning
the insertion of the Japanese performers into the program provided a refreshing variety that enhanced the perception of the costumes that followed.
hanabi were set off from adjacent rooftops
It was very much a new experience for the Indonesian crowd
and many were so overwhelmed as to be moved to tears
The driving force behind this Japanese influx is Sakura Ijuin
Ijuin began working for an NPO in 2011 that engaged in cultural exchange between Japanese and Indonesian children
In 2018 she accepted the offer to become a JFC ambassador. She resolved to become involved with the World Kids Carnival. In addition, she hoped to introduce some Japanese participation throughout the totality of the five carnivals. When the NPO for which she was working ceased operations, she began the Sakuranesia Society
She is supporting JFC under that banner.
around 30 Japanese performers and spectators attended
it was an extraordinary 136 — way beyond what the carnival leaders expected
"We couldn't believe it" stated Aristorama Cahyo Putro (Arist) Creative Director of the carnival
"Every few weeks there was more good news."
an emerging online food and lifestyle supplier.
The carnival has very much maintained its grassroots origins
Participants commit to a training program in makeup
"It takes around 100 hours for a seasoned veteran to put together a costume," states Kalifa Diyantama (Tama)
Costume construction often becomes a family or even village-wide project with associated social benefits
He often receives comments about how the time spent creating costumes has healed relationships and brought families
neighborhoods and communities closer together.
there is no cavernous warehouse full of stock from previous years
Certain costume themes reappear from year to year
but performers are strictly forbidden to buy or borrow from past participants
"That would seriously undercut the personal developmental aims of the carnival," states Iwan
The Jember Fashion Carnival is an excellent example of successful regional self-branding
Jember has become known as a "carnival city." The carnival is also on the way to becoming a cross-cultural success story between Indonesia and Japan
the cultural exchange is primarily in the direction of Japan to Indonesia
efforts are being made to bring Indonesian nationals into the Japanese performances.
On the final day, for example, Kadokawa Dreams accompanied popular Indonesian singer Raisa
Their lineup included three Indonesian guest dancers
the dance team is also looking to recruit international members from Asian nations
The organizers are most certainly grateful for the Japanese involvement, as are the local political elite. Bubah Alfian is a JFC art director and celebrity makeup artist with 1.1 million Instagram followers
he characterized Sakura Ijuin as a tribute to Indonesia
This was effusive but not outrageous praise.
When asked by JAPAN Forward about their hopes and plans for 2025 and beyond
both Ijuin and JFC president Iwan first mentioned honor to the legacy of founder Dynand Fariz
His tragic death from the preventable disease of tuberculosis at age 55 most certainly galvanized all who had known him to see his mission through
Ijuin spoke of aiming for eight Japanese performance acts and 500 total performers and guests from Japan
That is a significant increase from the 136 of 2024.
"But Sakura always seems to make it happen." He then spoke of the challenges with which opportunities are inevitably paired
"We feel very comfortable with the costuming and our community-based programs
Our challenge is internationalizing without losing our community focus
But everyone knows about the Rio carnival"
JFC CEO and the oldest brother of founder Dynand Fariz
"They just don't realize it." Photos of JFC sourced from international news agencies "have surpassed those of Rio" he announced
"We just need to make people realize what they are looking at."
There will surely be a great deal more to see in the coming years from the Jember Fashion Carnaval
both literally and in terms of enhanced relations between Japan and its Indonesian neighbor.
Author: Paul de VriesFind other reviews and articles by the author on Asia Pacific history on JAPAN Forward
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a government-designated site of scenic beauty that was once closed to the public
is now inviting visitors to wander its serene paths under the autumn leaves
The traditional garden opened to the public this fall for the first time since its current owner
Media representatives were invited to visit on Nov
Tairyu-Sanso Garden was designed by Ogawa Jihei VII
Its villa was built in 1896 by Ijuin Kanetsune
The site spans approximately 6,000 square meters
The garden overlooks the Higashiyama and Hieizan mountains
and is filled with the gentle sounds of a stream and waterfall fed from the Lake Biwa Canal
which has been designated as a national important cultural property
Admission to the garden is 2,000 yen ($13) and no reservation is required
Belgian Embassy villa in Nikko to be open to public in summer
Adachi museum garden ranked Japan's best for 18 years straight
Information on the latest cherry blossom conditions
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A series based on diplomatic documents declassified by Japan’s Foreign Ministry
Here is a collection of first-hand accounts by “hibakusha” atomic bomb survivors
chefs and others involved in the field of food introduce their special recipes intertwined with their paths in life
A series about Japanese-Americans and their memories of World War II
In-house News and Messages
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Methods: To clarify the role of mitochondrial function, we biopsied multiple parts of each human embryo and observed the remaining embryos under in vitro culture as a model of post-implantation development (n = 27 embryos). Karyotyping, whole mitochondrial DNA (mtDNA) sequencing, and mtDNA copy number assays were performed on all pre- and post-culture samples.
Results: The ratio of euploid embryos was significantly enhanced during in vitro culture, whereas the ratio of mosaic embryos was significantly reduced. Furthermore, post-culture euploid and culturable embryos had significantly few mtDNA mutations, although mtDNA copy numbers did not differ.
Discussion: Our results indicate that aneuploid cells decrease in human embryos post-implantation, and mtDNA mutations might induce low mitochondrial function and influence the development of post-implantation embryos with not only aneuploidy but also euploidy. Analyzing the whole mtDNA mutation number may be a novel method for selecting a better mosaic embryo for transfer.
Volume 11 - 2023 | https://doi.org/10.3389/fcell.2023.1215626
Introduction: Several healthy euploid births have been reported following the transfer of mosaic embryos
including both euploid and aneuploid blastomeres
This has been attributed to a reduced number of aneuploid cells
We hypothesized that mitochondrial function
one of the most critical factors for embryonic development
can influence human post-implantation embryonic development
including a decrease of aneuploid cells in mosaic embryos
Methods: To clarify the role of mitochondrial function
we biopsied multiple parts of each human embryo and observed the remaining embryos under in vitro culture as a model of post-implantation development (n = 27 embryos)
whole mitochondrial DNA (mtDNA) sequencing
and mtDNA copy number assays were performed on all pre- and post-culture samples
Results: The ratio of euploid embryos was significantly enhanced during in vitro culture
whereas the ratio of mosaic embryos was significantly reduced
post-culture euploid and culturable embryos had significantly few mtDNA mutations
although mtDNA copy numbers did not differ
Discussion: Our results indicate that aneuploid cells decrease in human embryos post-implantation
and mtDNA mutations might induce low mitochondrial function and influence the development of post-implantation embryos with not only aneuploidy but also euploidy
Analyzing the whole mtDNA mutation number may be a novel method for selecting a better mosaic embryo for transfer
The underlying factor responsible for this decrease in aneuploid cells is yet to be identified
and we hypothesized that certain factors are also critical for the development of human mosaic embryos
Each mtDNA molecule includes mutations that occasionally induce dysfunction owing to the location of the mutation and the percentage of mutated mtDNA
detailed mtDNA mutation analysis is used to determine mitochondrial function from mtDNA
as well as additional factors such as heteroplasmy and location
To reveal the correlation between mitochondrial function and post-implantation embryonic development, it is important to evaluate mtDNA copy number and mtDNA mutations, which can induce mitochondrial dysfunction (Cecchino and Garcia-Velasco, 2019)
we aimed to clarify the correlation between mitochondria and post-implantation embryonic development
including the development of mosaic embryos into euploids
and the difference between well-developed post-implantation embryos and other embryos
and mtDNA mutations in embryos from the blastocyst stage to the in vitro artificial post-implantation stage
In this study we aimed to evaluate the karyotype and mitochondria at peri-implantation stage
to collect samples at pre-implantation stage
we biopsied 1–3 parts of trophectoderm from each donated embryo
to obtain samples at post-implantation stage
we performed in vitro culture as model of implantation and collected some parts of proliferated cell mass
in order to evaluate the change of embryonic karyotype during post-implantation development
To clarify the role of mitochondrial quantity and quality during post-implantation development of human embryos
we analyzed mtDNA mutations and mtDNA copy number
Karyotyping and mtDNA mutation analysis was performed with next generation sequencing
and mtDNA analysis was performed with real time PCR
This study was approved under the ethics committee of Yokohama City University (approval number: A171130002)
and the Japan Society of Obstetrics and Gynecology (approval number: 192)
This study included not only morphologically high-grade surplus embryos but also degraded embryos to evaluate the culture process of mosaic embryos
All embryos were created initially for clinical use in ART at our institution
They were donated because the patients achieved live birth with another embryo
or because the embryos were not used clinically due to slow development or morphologically low grade
All patients provided a written informed consent before donation and research use
On 5–7 day post-fertilization (dpf), all blastocysts were biopsied one to three times from TE with laser pulse and quick flicking movement, avoiding ICM injury (Figures 1A–C)
These biopsied TE samples (pre-culture sample) contained 5–10 cells each
If the biopsied embryos did not shrink after TE biopsy
we did not perform additional biopsy to avoid too much embryo damage for subsequent culture
we mechanically removed zona pellucida from the remained embryo
and cells adhering to zona pellucida were collected as TE (pre-culture sample)
All pre-culture samples were washed and applied to the reagent for DNA extraction
To clarify the role of mitochondrial quantity and quality during the post-implantation stage of human embryos
we biopsied the trophectoderm from donated human embryos
performed in vitro culture for artificial implantation
and analyzed the karyotype and mitochondrial DNA sequence with NGS and mtDNA copy number using real-time PCR
(B) Morphological findings of experimental blastocysts before biopsy
(C) Morphological findings of blastocysts obtained during biopsy
(D) Morphological findings of experimental cell mass 4‒5 days post-biopsy culture
The scale bar indicates 100 μm
The remained embryo containing ICM were immediately plated and cultured individually per plate (Figure 1A). The in vitro culture modelling post-implantation development started with a medium including the following ingredients as previously described (Tachibana et al., 2013): Knockout DMEM/F12 (Gibco
1% Penicillin-Streptomycin-Glutamine (Fujifilm
0.1 mM β-Mercaptoethanol (Sigma-Aldrich
5 ng/mL basic Fibroblast Growth Factor (Fujifilm
and 10 μM Rock Inhibitor (Enzo Life Sciences
We removed the Rock Inhibitor and FBS and added knockout serum replacement to 20% after outgrowth occurred
Tachibana, who referred to the culture method used in this present study, described that the expression of Oct-4 and Sox-2 was confirmed in the proliferated cell mass by immunostaining, and the images were shown (Tachibana et al., 2013)
we thought the outgrowth of the embryos in this in vitro culture can contain the cells derived from ICM
and we analyzed its outgrowth as grown embryos like post-implantation stage
Dead cells may be possibly included in post-culture samples
but they are not thought to effect karyotype and mtDNA
Because scale of cells was larger in post-culture sample than embryos’
we were able to evaluate them correctly from post-culture samples
DNA was extracted with a Pico Pure DNA extraction kit (Applied Biosystems Inc.
United States) from all samples individually with modified manufacturer’s protocol
The DNA solution was diluted with DNA RNA free water and used for karyotyping
our decision was based on their uniformity when multiple samples were simultaneously collected from the same embryo
When all results were “euploid” or the same “aneuploidy,” the embryo was determined as “euploid” or “full aneuploid.” When they did not match
the embryo was determined as “mosaic.” When the mosaicism rate was between 20% and 80% for a single sample
karyotype of the sample was determined to be mosaic
We calculated the ratios of each karyotype at pre- and post-culture separately to evaluate the change of karyotype during in vitro culture
we excluded data that resulted in measurements of more than 1 × 106 copies per embryo as measurement errors
As for tRNA mutations with ≥90% heteroplasmy
we included likely pathogenic mutations defined by MitoTIP tool on MITOMAP
and pathogenic mutations confirmed in MITOMAP
We calculated heteroplasmy as the percentage of reads that detected each mutation among all reads at the same detection site
We evaluated the number of these high heteroplasmic and non-synonymous mutations in embryo
When multiple samples were simultaneously collected from the same embryo
the number of mtDNA mutations in each embryo was adjusted by the number of samples as below
We counted the number of mutations per embryo by adding the number of mtDNA mutations on samples of each embryo and dividing it by the number of the samples
number of pre- and post-culture mutations were calculated as 0
and 1-4 had no ≥ 90% heteroplasmic and non-synonymous mutation
number of mutations was calculated to be 0
all samples (2 pre-culture samples and 3 post-culture samples) had one heteroplasmy ≥90% mutation each
Number of mutations at pre-culture stage was calculated as (1 + 1)/2
and that of post-culture stage was calculated as (1 + 1+1)/3
embryo No.10 had one mutation at both of pre- and post-culture stage
The percentage data and means were compared with Fisher’s exact test and two-sided student t-test. All statistical analyses were performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). It is a modified version of the R commander designed to add statistical functions frequently used in biostatistics (Kanda, 2013)
A value of p < 0.05 was chosen as statistical significance
We recruited 17 patients with infertility at Yokohama City University Medical Center. The study was approved by Yokohama City University. The mean patient age was 35.6 years. In total, 27 blastocysts were analyzed, most of which were morphologically evaluated as low-grade (Gardner grade BB, 30%; CB, 11%; CC, 59%, Table 1)
Summary of results from each embryo (culture
TE biopsy was performed on all the 27 embryos 1–3 times per embryos
56 pre-culture samples (2.1 ± 0.8 samples per embryo [mean ± standard deviation (SD)]) were obtained
To confirm the non-uniform development of mosaic embryos, we compared the karyotypes of 27 embryos before and after culturing (Figure 1A)
The success rate for data acquisition of each sample were 89.3% (50/56) for pre-culture samples
The success rate of embryo karyotyping was 100% (27/27) and 92% (24/26) for pre-culture and post-culture stage
These trends did not correlate with indications for ART or female age
Result of Karyotyping and mitochondrial DNA (mtDNA) copy number assay
(A–C) Distribution of karyotypes in pre- and post-culture embryos
C) show karyotype changes in all experimental
A significant increase in euploid embryos and a significant decrease in mosaic embryos can be observed in (A
E) mtDNA copy number in pre-culture samples
D shows the comparison of copy number between each post-culture karyotypes
The mtDNA copy number of each karyotype were 172769 ± 153311 for euploid
and 216284 ± 170297 for full aneuploid
E shows comparison of copy number between each culturability
Although culturable embryos had lower number of mtDNA copy number
the mean mtDNA copy number does not differ significantly between the groups
The mtDNA copy number of each culturability were 159509 ± 126220 for culturable embryos
243872 ± 191082 for non-culturable embryos
mtDNA copy number is presented as mean ± SD
“*” represents p < 0.05
“n.s.” represents not significant
These results suggest that a simple difference in the mtDNA copy number is not critical for post-implantation development
For mtDNA mutation analysis, we selectively amplified mtDNA from all 88 samples derived from 27 embryos using polymerase chain reaction (PCR) and performed mtDNA sequencing via next-generation sequencing. The success rate for data acquisition of each sample were 92.9% (52/56) for pre-culture samples, and 96.9% (31/32) for post-culture samples. Supplementary Table S1 lists mutations for each sample with a heteroplasmy level of ≥90%
The mean number of mtDNA mutations per embryo with a heteroplasmy level of more than 90% were 0.6 ± 0.8 (mean ± SD)
The number of mutations in each embryo was unaltered between pre- and post-culture
We determined the number of mtDNA mutations to examine whether this number was related to post-culture karyotype (13 euploid embryos (embryo No.1
9 aneuploid embryos (including mosaic and full aneuploids
and 18–24)) and culturability (17 culturable embryos (embryo No
and 26)) and clarify the influence of mtDNA mutations on post-implantation development
the post-culture status can be considered as model of post-implantation status
We evaluated the mean number of mtDNA mutations that achieved ≥90% heteroplasmy
given that these mtDNA point mutations generally worsen mitochondrial activity
The number of mtDNA mutations is presented as mean ± SD
Euploid embryos had a significantly low number of pre-culture mtDNA mutations (euploid vs. aneuploid: 0.27 ± 0.57 vs. 1.22 ± 0.66, p = 0.005; Figure 3A). Moreover, a similar trend was observed for post-culture mtDNA mutations (euploid vs. aneuploid: 0.36 ± 0.61 vs. 1.22 ± 0.79, p = 0.010; Figure 3A)
Number and location of mtDNA mutations in pre- and post-culture embryos
C) Number of mutations per embryo in each post-culture karyotype and culturability at the pre- and post-culture stages
Post-culture euploid embryos exhibit a significantly lower number of mutations than post-culture aneuploid embryos at both pre- and post-culture stages
The number of mutations is lower in culturable embryos than in non-culturable embryos at both pre- and post-culture stages
(B) Comparing the distribution of post-culture karyotype between pre-culture mosaic embryos with lower number of mtDNA mutations and pre-culture mosaic embryos with higher number of mtDNA mutations
(D) Comparing the distribution of culturability between embryos with lower number of mtDNA mutations and embryos with higher number of mtDNA mutations
F) Distribution of mtDNA mutations in protein-coding genes and OXPHOS complexes
and complexes III and V are more frequent in post-culture aneuploid embryos
COII and ND3 are more frequent in non-culturable embryos
To clarify the role of each mtDNA gene, we determined the number and location of ≥90% heteroplasmic and non-synonymous mtDNA mutations to establish their potential relationship with post-culture karyotype and culturability (Table 2). The number of mtDNA mutations at each gene site was adjusted based on the number of pre-culture samples collected from each embryo. We also counted the number of embryos showing mtDNA mutation on each gene (Table 3)
we detected mutations in seven mtDNA genes (ND1
The ND5 mutation was the most frequent per embryo at all locations (33.3%)
and embryos with other mutations were 1 (10%) for each gene
The number and rate of embryos which had mtDNA mutations on each gene
In embryos diagnosed as pre-culture mosaic embryos
only post-culture aneuploid embryos had mutations in COII
Our mtDNA analysis revealed that mtDNA mutations partly impacted the post-implantation development of human embryos
whereas mtDNA copy number exhibited no such impact
it is suspected that the aneuploid cell decrease also occurred in their study and participated with the discordancy
suggest that aneuploid cell numbers are reduced during post-implantation embryonic development
we select mosaic embryos to be transferred or not by mosaicism level and the detail of chromosome with aneuploidy in clinical practice
we considered the relationship between the level of mosaicism and embryo development
and tried to classify mosaic embryos by the maximum level of mosaicism of the embryo
We classified mosaic embryos with 20%–50% mosaicism as low-level mosaicism
and embryos with 50%–80% mosaicism as high-level mosaicism
Although there was no significant difference due to the small number of embryos
high-level mosaicism embryos obtained 8/12 (66.7%) of the embryos that changed mosaic to euploid during culture
7/9 (77.8%) of the culturable embryos were high-level mosaicism
the number of mtDNA mutations tended to be lower in high-level mosaicism embryos than that in low-level mosaicism embryos
but the difference was also not significant (high-level vs
we could suggest high-level mosaicism embryos also have possibility to develop well after implantation
further studies are required to clarify this
It should be noted that the mechanism underlying the decrease in aneuploid cell number remains elusive. Mitochondria possess critical functions in human embryonic development, such as ATP synthesis and OXPHOS. Disrupting OXPHOS and low ATP content can hinder oocyte maturation, along with chromosomal misalignment, fertilization, and implantation (Van Blerkom et al., 1995; Takeuchi et al., 2005)
we speculated that mitochondrial functions play an important role in post-implantation embryonic development and participate in aneuploid cell reduction
This unequal division of mitochondria will be one of the disturbances of embryonic mtDNA copy number analysis and further innovation of the technologies to measure mtDNA copy number of embryos is required
Owing to the generation of reactive oxygen species in mitochondria, lack of DNA protective histones, and limited mtDNA repair mechanisms, mtDNA has a higher number of mutations than nuclear DNA (Payne and Chinnery, 2015), and these mtDNA mutations can result in pathological dysfunctions (Schon et al., 2012)
Although not all mtDNA mutations induce mitochondrial dysfunction
non-synonymous and highly heteroplasmic mtDNA mutations can impact mitochondrial function
Analysis of these mtDNA mutations can facilitate the prediction of mitochondrial function in limited cells
we focused on mtDNA mutations to determine whether mitochondria are associated with human embryonic development
mtDNA mutations in embryos may have same effect and influence the mitosis
These reports suggest that non-synonymous and highly heteroplasmic mtDNA mutations may influence unequal blastomere proliferation and the remaining of aneuploid cells
The mtDNA mutations may also relate with a part of these implantation failure and miscarriage which is independent with embryo karyotypes
Our mtDNA evaluation of peri-implantation embryos with non-synonymous and highly heteroplasmic mtDNA mutations revealed that euploid and culturable embryos had fewer mtDNA mutations than aneuploid and non-culturable embryos
We concluded that the number of non-synonymous and highly heteroplasmic mtDNA mutations at pre-implantation stage would importantly influence post-implantation development by altering OXPHOS
Further investigation of this influence may enable us to predict post-implantation development
The number and location of mtDNA mutations
may play a critical role in the mitochondrial function during post-implantation embryonic development
our results and those of previous studies suggest that specific mtDNA gene mutations may critically impact embryonic development and karyotype
Further human studies are required to clarify the relationship between mtDNA mutations and human embryonic development
The detailed establishment of this relationship could help to predict post-implantation embryonic development in more detail using the number and location of non-synonymous and highly heteroplasmic mtDNA mutations
we need to analyze the embryos with this deletion in next step
The relationship between mtDNA mutations and mitochondrial function has not been directly assessed
given that only a few cells can be obtained via TE biopsy
further innovations and advancements in this field are needed to address these limitations
our findings revealed that some human mosaic embryos can develop into euploids
and suggested the number of aneuploid cells decreases in human mosaic embryos during post-implantation development
post-culture euploid and culturable embryos had fewer non-synonymous and highly heteroplasmic mtDNA mutations than aneuploid embryos and non-culturable embryos
mitochondrial function may be one of important factor in reducing aneuploid cells and in the development of post-implantation human embryos
Further studies of this area may enable us to select better mosaic embryos for transfer
and may also enable us to transfer better embryos among euploid embryos
which could increase clinical pregnancy rates
The data presented in the study are deposited in the DDBJ repository
accession number “DRR491368-DRR491450” further inquiries can be directed to the corresponding author
The studies involving human participants were reviewed and approved by the ethics committee of Yokohama City University (approval number: A171130002) the Japan Society of Obstetrics and Gynecology (approval number: 192)
The patients/participants provided their written informed consent to participate in this study
HU directed the cryopreservation of embryos
MS helped with the cryopreservation of embryos and blastocyst biopsies
and SS explained to embryo provider and performed helpful discussions
All authors contributed to the article and approved the submitted version
This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research C (Grant Number JP21K09474) and Early-Career Scientists (Grant Number JP20K18169) and the Grants of 2019 from Yamaguchi Endocrine Research Foundation (to TH)
We are grateful to Ryoko Asano for special advice on our manuscript, Mizuki Yamamoto and Mayuko Nishi for cooperation for our study as members of our team, and Rei Yanagihara (OVUS Co., Ltd.) for advice on the experimental design. We gratefully acknowledge the assistance of our laboratory technician, Mae Inada. We would like to thank Editage (www.editage.com) for English language editing
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations
Any product that may be evaluated in this article
or claim that may be made by its manufacturer
is not guaranteed or endorsed by the publisher
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcell.2023.1215626/full#supplementary-material
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PubMed Abstract | CrossRef Full Text | Google Scholar
Sakakibara H and Murase M (2023) Mitochondrial DNA mutations can influence the post-implantation development of human mosaic embryos
Received: 02 May 2023; Accepted: 25 July 2023;Published: 11 August 2023
Copyright © 2023 Ijuin, Ueno, Hayama, Miyai, Miyakoshi, Hamada, Sueyoshi, Tochihara, Saito, Hamanoue, Takeshima, Yumura, Miyagi, Kurahashi, Sakakibara and Murase. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use
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*Correspondence: Tomonari Hayama, dG9tbXlfaEB5b2tvaGFtYS1jdS5hYy5qcA==
†These authors have contributed equally to this work and share first authorship
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TOKYO (Jiji Press) — Japanese prize-winning author Shizuka Ijuin died Friday
announced last month that he was suffering intrahepatic bile duct cancer
Ijuin won the prestigious Naoki Prize for his novel “Ukezuki” in 1992 after working as a commercial video director
married Masako Natsume in 1984 before the actress died of leukemia the following year
Our weekly ePaper presents the most noteworthy recent topics in an exciting
© 2025 The Japan News - by The Yomiuri Shimbun
While relations between Japan and South Korea have been improving for years
concerns have also been mounting that bilateral ties might worsen again in the future
casting a shadow over the security environment in East Asia
Japan and South Korea have been bolstering security relations with the United States
Russia and North Korea have been deepening military cooperation
especially since the Russian invasion of Ukraine began in February 2022
given that South Korean politicians have often used anti-Japan sentiment to increase their popularity at home
which brings up negative memories between the two Asian countries
As the minority ruling party of South Korean President Yoon Suk Yeol
who has extended an olive branch to Japan since taking office in May 2022
suffered a crushing defeat in April's general election
he might change his favorable attitude toward the neighboring nation
Yoon's conservative People Power Party has been regarded as pro-Japan
while the left-leaning Democratic Party has adopted a hardline stance against the country that colonized Korea from 1910 through the end of the war in 1945
"There is a risk" that Yoon's ability to "promote policy will decline significantly down the road with his political standing weakening," said Atsushi Ijuin
a senior researcher at the Japan Center for Economic Research
the Japan-South Korea relationship is "inherently fragile" as each of them have alliances with the United States but are not allies of each other
A Japanese government source well-versed in East Asian affairs said a worsening of ties between Tokyo and Seoul would "definitely benefit" China
which would be "the worst-case scenario" for the region
South Korea and China held their trilateral summit for the first time in more than four years
The last time that the leaders of the three countries met was in December 2019
before the COVID-19 pandemic began in early 2020
Japanese Prime Minister Fumio Kishida and Chinese Premier Li Qiang
who took up the current position in March 2023
agreed to work together in addressing common challenges
including epidemics and the graying of their populations
said at a joint press announcement with Yoon and Li
which share a great responsibility for peace and prosperity in the region
reaffirmed our determination to cooperate in a wide range of fields."
South Korea and China are supposed to hold trilateral summits annually on a rotating basis
but they have occasionally been suspended as Japan's relations with its two neighbors have chilled over historical and territorial spats
Some analysts point out that even though trilateral summits take place
the outcomes only cover what the three nations can easily agree on
meaning such gatherings have become more meaningless as a way to resolve serious regional issues
The latest summit was held as Tokyo and Beijing have been at odds over the Chinese ban on all Japanese seafood imports following the start of the release of treated radioactive water from the crippled Fukushima nuclear power plant in August 2023
Kishida and Li traded barbs over China's increased military activities
days after Beijing conducted two-day drills around Taiwan
which it called a "strong punishment" for those seeking the island's independence
have recovered after Seoul proposed a solution in March 2023 for a long-standing wartime labor compensation dispute
Kishida and Yoon resumed reciprocal visits by countries' leaders for the first time in 12 years
Kishida and Yoon agreed at their bilateral summit to join hands in further developing Japan-South Korea relations ahead of the 60th anniversary of the normalization of diplomatic ties in 2025
demonstrating a personal rapport between them
At the previous trilateral summit in December 2019
Japan had been in a position where it had been "bullied by China and South Korea," but this time China was apparently "grilled" by the other two nations
even if the wartime labor dispute is resolved
Tokyo and Seoul are likely to keep facing several bilateral issues
such as a territorial row in the Sea of Japan and the treatment of Korean women in Japanese military brothels during World War II
Japan has claimed that all problems stemming from its colonization of the Korean Peninsula were "completely and finally" settled under a bilateral agreement signed in 1965
but South Korea's anti-Japan politicians continue to brush aside the argument
South Korea's majority opposition Democratic Party criticized the government in a statement released after Yoon's meeting with Kishida on Sunday
"Is President Yoon Suk Yeol planning to sell out not only our past but also our future?"
"South Koreans have been expressing their frustration with President Yoon's unrequited love for Japan
saying that it has gone too far and is pathological."
a fellow at the Japan Institute of International Affairs
who serves a five-year term with no opportunity for reelection
is "prone to becoming a lame duck" after the ruling party loses the general election
Given the possibility that a policy shift by South Korea's president could "directly affect" relations with Japan
Tokyo must continue "managing" issues with Seoul "in a cautious manner," the researcher said
Japan needs to maintain close communication with South Korea "at various levels" in a bid to strengthen their trilateral cooperation with the United States
Japan, South Korea, China businesses groups to study cooperation
Japan, South Korea, China to pursue North Korea denuclearization: Kishida
Japan, South Korea to deepen ties ahead of 60th anniv.: Kishida
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Metrics details
Fraser syndrome (FS) involves multiple malformations and has a 25% recurrence risk among siblings
these malformations are difficult to detect prenatally
we describe a fetus with FS diagnosed using ultrasonography
Ultrasonography revealed congenital high airway obstruction syndrome and renal agenesis
Syndactyly of both hands and cryptophthalmos were noted postnatally
and the diagnosis was confirmed by genetic analysis
which showed novel compound heterozygous variants of FREM2
The authors suggested that a diagnosis of FS can be made if either three major
or one major and three minor symptoms are present in a patient
As FS is an autosomal recessive disease and has a recurrence risk of 25% among siblings
both prenatal and postnatal diagnoses are important in affected families
are difficult to detect via prenatal ultrasonography
especially in the presence of oligohydramnios
we report a case of FS prenatally suspected at 19 weeks of gestation and diagnosed via genetic analysis
which uncovered novel compound heterozygous FREM2 variants
This study was approved by the Institutional Review Board of Kanagawa Children’s Medical Center
and clinical information was collected after obtaining written informed consent from the parents
Bilateral renal agenesis: color Doppler image of the renal artery (a)
a hyperechogenic lung with an inverted diaphragm (c)
and a distended trachea (d) were observed at 19 weeks of gestation
Fetal facial features included cryptophthalmos
Bilateral cutaneous syndactyly of the hands was also observed (g)
Candidate variants were subsequently confirmed by Sanger sequencing
FREM2 contains chondroitin sulfate proteoglycan (CSPG) repeats and the calcium-binding loop of Na2+–Ca2+ exchange (Calx) beta domains (https://www.uniprot.org/)
Electropherograms revealed biallelic variants
c.3628_3628dupA:p.(Thr1210Asnfs*8) and c.6203 T > A:p.(Leu2068*)
derived from the father and mother of the patient
this is the first report of a Japanese FS patient carrying FREM2 pathogenic variants
we did not detect these features in a subsequent fetal scan owing to severe oligohydramnios
Postmortem examinations of fetal and neonatal cases
may confirm diagnoses and consequently improve genetic counseling
and sonographic screening during subsequent pregnancies
The relevant data from this Data Report are hosted at the Human Genome Variation Database at
https://doi.org/10.6084/m9.figshare.hgv.2882
https://doi.org/10.6084/m9.figshare.hgv.2885
Fraser syndrome: a clinical study of 59 cases and evaluation of diagnostic criteria
Fraser syndrome: features suggestive of prenatal diagnosis in a review of 38 cases
Fraser syndrome: review of the literature illustrated by a hystorical adult case
Fraser syndrome: frequency in our environment and clinical-epidemiological aspects of a consecutive series of cases
Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein
The role of Tras1/Frem proteins in the structure and function of basement membrane
A female patient with X-linked Ohdo syndrome of the Maat-Kievit-Brunner phenotype caused by a novel variant of MED12
Molecular study of 33 families with Fraser syndrome new data and mutation review
Prenatal sonographic appearance of cryptophthalmos in Fraser syndrome
Prospective prenatal diagnosis of Fraser syndrome variant in a family with negative history
Identification of a new gene mutated in Fraser syndrome and mouse myelencephalic blebs
Fras1 deficiency results in cryptophthalmos
renal agenesis and blebbed phenotype in mice
The genetics of Fraser syndrome and the blebs mouse mutants
Congenital high airway obstruction syndrome (CHAOS): a potential for perinatal intervention
Diagnostic echographic findings in cryptophthalmos syndrome (Fraser syndrome)
Congenital high airway obstruction syndrome (CHAOS) as part of Fraser syndrome: Ultrasound and autopsy findings
Prenatal diagnosis of Fraser syndrome using routine ultrasound examination
confirmed by exome sequencing: report of a novel homozygous missense FRAS1 mutation
Intrafamilial variability in Fraser synderome
Download references
We thank the parents for agreeing to participate in this research
This work was supported by the Initiative on Rare and Undiagnosed Diseases (IRUD) (18ek0109301) from the Japan Agency for Medical Research and Development (AMED) (KK)
The authors declare that they have no conflict of interest
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
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DOI: https://doi.org/10.1038/s41439-020-00119-5
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Vox Populi
Vox Dei is a daily column that runs on Page 1 of The Asahi Shimbun
I look forward to Suntory Holdings Ltd.’s newspaper ad
I saw it in the April 1 edition of The Asahi Shimbun
Addressed to young people who started working this spring
The message must have meant: “Since all the glasses are the same size now
your school records don’t mean much anymore
The important thing is to understand the ‘core’ of your job
which is that making money is never your only goal.”
And this was actually the very first ad copy he wrote for Suntory
The words reached the depth of my heart and lingered like fine
But Ijuin was hardly a paragon of virtue during his life
There are stories galore of his misbehavior
such as gambling with money borrowed from publishers and even getting his editors to deliver the cash to his place
Roguery and naivete existed in him side by side and that made his charm irresistible
His words were straightforward yet deeply nuanced
which must have reflected his checkered lifestyle
there are things we can learn even when we are utterly inefficient
I recall when I started working 30 years ago
made mistakes that were so terrible they caused the blood to drain from my face and I just resented everything
I still believed that experience would make writing my stories easy
Things haven’t changed much since then and I still struggle
Singer-songwriter Mariya Takeuchi once noted
“The more I look at myself objectively as a professional
the deeper my predicament gets because of my inability to reach the standard I’ve set for myself.”
Newcomers and veterans alike are all in the process of development
Vox Dei is a popular daily column that takes up a wide range of topics
the column provides useful perspectives on and insights into contemporary Japan and its culture
VOX POPULI: Suga looks sure to win LDP race
VOX POPULI: Already broken your New Year’s resolution
No reproduction or republication without written permission
Haikara-san: Here Comes Miss Modern is one of the latest adaptations of the manga series of the same name, written by Waki Yamato and published between 1975 and 1977. The series has largely become Yamato's defining work, and with good reason: she won the first Kodansha Book Award for shōjo manga in 1977 for this series
including live-action and the 1978-79 anime series
That seems like a better approach with this series because a lot is going on
and it doesn't always feel like the film's two-hour-and-a-half runtime has the space to develop everything the story wants to do
That doesn't mean there isn't plenty to enjoy about this version, however. The story is the sort of luscious melodrama that 1970s shōjo excelled at – taking place between 1917 and 1923; it tells the tale of Benio Hanamura
a young woman fully ready to embrace the modern era
As an enthusiastic adherent of the “New Woman” philosophy
Benio is much more interested in climbing trees
and looking forward to a career rather than becoming a traditional married woman
and to say that she's not thrilled when her father announces that she is engaged due to an old family promise is an understatement
The first part of the story features Benio trying her damndest to horrify her fiancé
and his family; she very nearly succeeds with his sexist pig of a grandfather
It turns out that she and Shinobu are much better suited than she initially thought
But this wouldn't be a melodrama if the course of true love ran smooth
and Shinobu finds himself on the front lines of the war in Manchuria after he upsets a superior
The first film ends with Benio vowing never to marry anyone who is not Shinobu
and becoming that staple of 1920s fiction: a girl reporter
The second film has her discovering that a Russian noblewoman has a husband who looks suspiciously like the missing Shinobu
It wouldn't be 70s historical fiction without a good dose of amnesia
Benio and Shinobu find themselves kept apart by the consumptive Russian noblewoman to whom Shinobu feels indebted
it looks as if Benio will give in to her editor's affections and marry him
But as you may have guessed from the dates the story takes place between
the Great Kanto Earthquake may have something to say about the finale of Benio and Shinobu's story
If that sounds like a lot to put into two films
There is more than three hours worth of story going on here
which results in both films having some uneven pacing
who for much of the first film comes off as rather dull
the template for the princely shōjo romance hero
and its beating heart is still easily found
it feels very apparent that we are missing some information
One of the plot's better elements is the way we see Benio grow up
It's important to note that she doesn't object to getting married someday; she objects to her father picking her future husband for her
she feels much more in control of her future
That control is something that she prizes and that we see her struggle to maintain over the story
We see her learning to be less impulsive and to make more considered decisions
her trying to bob her hair after Shinobu is missing and presumed dead marks the moment when she truly takes control
History students will also point to this as indicative of her genuinely moving into the modern era
Bobbed hair is one of the signifiers of women of the 1920s who have cast off the shackles of the Victorian era
Benio's friend Tamaki mentions that they read Bluestocking Magazine
an early feminist publication that ran from 1911 to 1916
The magazine is credited with jumpstarting Japanese feminism
it contained translations of western feminist works
This means that we can largely take the cutting of Benio's hair in the same way we would in a western novel because her choice of reading material clearly shows that she is fully aware of what's happening in other countries and wants to be a part of that
Her choice of profession is another nod to new opportunities for women that the 20th century brought about; starting in the late 19th century
American newspapers began hiring what they called “girl reporters,” women who started to report outside of the previously constricted field of social columns
as we can see from the stories she is assigned to cover
These aren't perfect films, and the first one especially has moments that feel like it's dragging. They are, however, beautifully animated, and the attempts to update Yamato's art style work quite well. The story itself holds up, and fans of old-school shōjo and soapy melodrama don't want to miss this. Both sub and dub tracks are well done
and overall the films present a very nice package
Haikara-san: Here Comes Miss Modern is a snapshot of two times – the early 20th century when the world was beginning to change very quickly and the heyday of 70s shōjo manga
Full encyclopedia details aboutHaikara-San: Here Comes Miss Modern Part 1 (movie)
Love Flops original anime revealed a new key visual ahead of the second half of the series. The anime has been airing since October 12
with studio Passione in charge of the animation
Reason Why!!” by Konomi Suzuki (opening) and “Flop Around” by Miku Ito
These voice actresses are also a part of the cast
Love Flops anime is scheduled to start airing on October 12 in Japan, while advance screening of the first and second episodes will take place on September 25 at the EJ Anime Theater in Tokyo.. The previously-announced original anime by Kadokawa Corporation
with Midori Yui and Fujiaki Asari assisting with the direction
Kazuyuki Ueda as both the chief animation director and character designer
The main cast includes:Ryota Osaka as Asahi KashiwagiMiku Ito as Aoi IzumisawaAyana Taketatsu as Amelia IrvingRie Takahashi as Ilya IlyukhinHisako Kanemoto as Bai MongfaMarika Kouno as Karin IstelJun Fukuyama as Yoshio IjuinLove Flops anime – Key VisualLove Flops (Renai Flops) is a coming-of-age romantic comedy series
all of which attend or work in the same high school
Asahi Kashiwagi and his friend Yoshio Ijuin meet Aoi Izumisawa
as well as three transfer students – Amelia Irving
A young teacher named Bai Mongfa is also involved in their interactions
The anime has also received a manga adaptation, with illustrations by Ryudai Ishizaka, which has been serialized in Hakusensha’s Young Animal magazine since June this year.Source: Comic Natalie© Love Flops Project
Also Read:Keiken Zumi na Kimi To Light Novel Gets Anime AdaptationComedy Anime The Little Lies We All Tell Reveals New Key Visual and Trailer
est em (IPPO, Age Called Blue) launched the spinoff on the manga website Comic Tatan of Monthly Comic Zenon in April 2018
The manga was one of three new titles and nine overall manga that launched with the website
The spinoff manga centers on the character Umibōzu from Tsukasa Hōjō's original City Hunter manga
titled "Bubbly Time," the Cat's Eye café's master Umibōzu listens and responds to the troubles of his customers
Tsukasa's original City Hunter manga follows Ryō Saeba
a sniper and a private eye ("sweeper") based in Tokyo's Shinjuku Ward with unrivaled marksmanship and an over-the-top obsession for the opposite sex
He serves as a bodyguard and other duties for his clients
Source: Monthly Comic Zenon's Twitter account
Capcom's next-gen Panta Rhei engine was unveiled at Sony's PS4 reveal over a year ago
and we're yet to see the extent of its potential
that the company's senior manager Masaru Ijuin has discussed the engine in a new blog post
It follows the release of a new Deep Down PS4 screenshot
Over on the Capcom business site
Ijuin explained that the company's MT Framework engine started to run into problems as tech advanced
"We believe MT Framework is a powerful rendering engine
But it's clear that heightened game quality leads to a rise in the number of man hours
"The amount of work involved in making games for next-gen consoles is eight to ten times greater than what is required for the current generation of consoles."
Ijuin explained that Capcom had considered simply updating the MT Framework engine
but decided to build Panta Rhei from the ground up to meet the demands of next-generation development
"We won't use Panta Rhei to develop games for the current generation of consoles," he stressed
"We intend to continue using MT Framework'to do that
and use MT Framework Mobile for handhelds and smartphones
These engines provide the optimum development environments for hardware with different characteristics and specifications."
means that Capcom developers will have to learn a new engine over again
I'm afraid creators will have to start back at square one when they learn how develop games using 'Panta Rhei'
Next-gen consoles have drastically redefined the way games are rendered
"If we create games the same way as before
we won't be able to give our fans what they want
and that's games unlike any they have ever played
We think we should view this new hardware as an opportunity to tackle new challenges."
Injuin and his team aren't blind to the potential negatives of having to start over however
"there were people who were initially against the introduction of "Panta Rhei"
I think everyone's a little apprehensive about changing the development environment
People frequently asked us why we felt the need to replace a smoothly running engine with a new one
and moved ahead with the development of 'Panta Rhei'
Currently we're working with the "deep down" development team and using this engine to make the game."
"Panta Rhei is designed to unlock the full potential of hardware and maximize the rendering power of next-gen consoles
It also reduces the iterations in developing games for next-gen consoles
we need to go through a process of trial and error
such as adjusting parameters and considering how games are played
"This process needs to be completed in the shortest amount of time possible
Reducing the iteration time from ten minutes to one minute delivers a tenfold increase on the amount of work we can do."
On how the engine has been used to enhance the play experience in PS4 exclusive Deep Down
"One of the main features is 'parallelization'
The characters are then placed on the map and the created game is played
This is what you would call a serial process
"Panta Rhei" transforms this into a parallel process
thereby minimizing work loss through the coordination of efforts."
"The players of Deep down"will be surprised to see realistic fire rendered by fluids," he continued
fire is rendered by arranging a large number of so-called billboards
but this method fails to depict the motion of fire
We can now make fire look more realistic by using fluids and simulating the flow of the flames
Imagine a T junction at the end of a narrow corridor
The fire rendered through the use of billboards ends at the wall of the T junction
the fire rendered with fluids fans out to the left and right when it hits the wall
"The effects staff were extremely excited when they discovered this was possible with Panta Rhei (laugh)
I think this change will also affect different elements of gameplay
in traditional games a player can run away to safety by turning at a T junction
but in the future that fire might actually chase them around the corner."
There's tons more over at the Capcom business site
what do you make of Panta Rhei and Deep Down
Via OXM
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Sentai Filmworks announced the English dub cast for the Tada Never Falls in Love (Tada-kun wa Koi o Shinai) anime with a video on Friday
The first English-dubbed episode will debut on HIDIVE on September 30
The anime premiered on April 5 and streamed on HIDIVE with English subtitles as a simulcast
is taking pictures of the cherry blossoms in full bloom when he meets Teresa Wagner
Mitsuyoshi helps her and brings her to his grandfather's coffee shop
Source: Sentai Filmworks, Sentai Filmworks' YouTube channel
The website opened on Sunday with nine manga
The spinoff manga centers on the character Umibōzu from Tsukasa Hōjō's original City Hunter manga
The series will run on the website on the third and fourth Sundays of every month
The other two new manga on the website are Yua Kotegawa's Satsujin Purgatorium (Murderer's Purgatorium) and Satono Okazaki's Ihō no Ozwald (Other Land Ozwald)
Satsujin Purgatorium centers on a 46-year-old hitman who dies with regret and wakes up as a 16-year-old boy again
The paranormal science-fiction romance Ihō no Ozwald centers on a boy who dreams of encountering intelligent extraterrestrial life and becomes the assistant of a nonconformist in the world of astronomy
Tsukasa's original City Hunter manga follows Ryō Saeba
Hojo's Angel Heart 2nd Season manga ended in May, and Sokura Nijiki launched a spinoff manga titled Kyō kara City Hunter on July 25
Source: Comic Natalie
It’s probably fair to say that last week’s episode of Tada-kun wa Koi wo Shinai was the weakest so far
I have two thoughts predominating in my mind at the moment:
I had a feeling from the beginning where the “Ijuin Kaoru Show” was headed
but that didn’t stop it from totally working for me
Friendship is something we sometimes take for granted and never should
and that we never appreciate so much as when we’re at our lowest point
and you have to wonder whether someone like that has a breaking point
but maybe Kaoru’s general sense of goofiness acts as a kind of visceral steam valve for Tada – letting some of that pressure off without having to act in a way that doesn’t come naturally to him
I certainly get why Kaoru could be a bit much for some viewers
There are many times I feel Miyano-san (and the writers) taking the schtick right to the edge of where it becomes grating
and sometimes they keep going one more step
But I still feel he works much better as a focus character than Pin-sempai and Hina
at least based on the evidence of the last two eps (though as much as anything
I keep waiting for Nyanko-big to start talking again)
What Kaoru needs is a romance subplot of his own – whether he gets that with Alec remains to be seen
but she at least acknowledged (through her appetite) his cooking
Her pointed questions certainly caught Teresa off guard
and it’s pretty clear how Teresa feels – but something about the incident ten years ago is stopping her from acting on it
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Brisbane and Adelaide were lit up to honour Japan’s longest serving prime minister.The Sails of the Sydney Opera House were lit up with the red and white of the Japanese hinomaru in honour of the late Shinzo Abe
Assassination of former PM Shinzo Abe shook Japan
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The film will open in France on February 6, 2019. The film stars Philippe Lacheau as Nicky Larson. Tarek Boudali and Élodie Fontan also star in the film. Philippe Lacheau and Pierre Lacheau wrote the film alongside writer and actor Julien Arruti
A separate Chinese live-action film adaptation has been green-lit for December 2018 or later in China
The manga is also inspiring a new anime film that will open in Japan on February 8
Hayato Ijuin's not peaceful life) in April
Source: Sony Pictures France's YouTube channel via Hachima Kikō