Who is hiromitsu arakawa

A long tremor registering 6. Search teams from more than a dozen nations were bound for Japan, including a unit from New Zealand, which suffered a devastating quake last month in Christchurch.

A Japanese team that had been working in New Zealand also was called home. Assistance teams also were due from China and South Korea, two of Japan's traditional and most bitter rivals. Tokyo's acceptance of these offers of help - along with a parade of senior officials offering updates at televised news conferences on Sunday - was in marked contrast to government policies after the Kobe earthquake that killed more than 6, people. The government refused most offers of aid at the time, put restrictions on foreign aid operations and offered little information about the disaster.

I think they should all go in an airplane to a safe place. I am very sorry it happened. I just think we should all at least have the heart to help them out. See next articles.

European Pressphoto Agency Survivors walked through a devastated area of Onagawa. Go to related article » Go to related slide show ». Antonio C. Japan is a great nation of great people it will survive and make a come back soon.

Emily M. Maziah D. Kiana F. As a result, highly expanded T cells have not proven to be particularly effective for treatments. This exhaustion issue could be overcome due to rejuvenation of T cells by reprogramming to pluripotency and redifferentiation to T cells.

This is a potential therapeutic strategy for combating various types of cancer. For scientists working within the field of induced pluripotent stem cells iPSCs , this protocol will provide a thorough walk-through on how to conduct in vitro and in vivo experiments that validate the function of a particular safeguard system technology. In short, we provide instructions on how to generate inducible Caspase-9 iC9 safeguard system with human iPSCs that act as normal or abnormal models of the cells for therapeutics to be tried after differentiation.

These iC9-iPSCs should be modified prior to beginning this protocol by constitutively expressing luciferase, an enzyme capable of generating bioluminescent signals through the oxidation of the substrate luciferin. Monitoring the bioluminescent signal over time provides the information on whether a safeguard system is working or not.

The current paradigm that a single long-term hematopoietic stem cell can regenerate all components of the mammalian immune system has been challenged by recent findings in mice. These findings show that adult tissue-resident macrophages and innate-like lymphocytes develop early in fetal hematopoiesis from progenitors that emerge prior to, and apparently independently of, conventional long-term hematopoietic stem cells.

Here, we discuss these recent findings, which show that an early and distinct wave of hematopoiesis occurs for all major hematopoietic lineages. These data provide evidence that fetal hematopoietic progenitors not derived from the bona fide long-term hematopoietic stem cells give rise to tissue-resident immune cells that persist throughout adulthood.

We also discuss recent insights into B lymphocyte development and attempt to synthesize seemingly contradictory recent findings on the origins of innate-like B-1a lymphocytes during fetal hematopoiesis.

The liver parenchyma is composed of hepatocytes and bile duct epithelial cells BECs. Controversy exists regarding the cellular origin of human liver parenchymal tissue generation during embryonic development, homeostasis or repair. Here we report the existence of a hepatobiliary hybrid progenitor HHyP population in human foetal liver using single-cell RNA sequencing. HHyPs are anatomically restricted to the ductal plate of foetal liver and maintain a transcriptional profile distinct from foetal hepatocytes, mature hepatocytes and mature BECs.

Our study suggests that hepatobiliary progenitor cells previously identified in mice also exist in humans, and can be distinguished from other parenchymal populations, including mature BECs, by distinct gene expression profiles. An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Scarless genome editing in human pluripotent stem cells hPSCs represents a goal for both precise research applications and clinical translation of hPSC-derived therapies.

Here we established a versatile and efficient method that combines CRISPR-Cas9-mediated homologous recombination with positive-negative selection of edited clones to generate scarless genetic changes in hPSCs. However, large modifications, such as gene replacement or gene fusions, are still difficult to introduce in embryos without costly micromanipulators.

Moreover, micromanipulation techniques for intra-embryo genome editing have been established in only a small set of animals. To overcome these issues, we developed a method of large-fragment DNA knockin without micromanipulation.

By this method, we can exchange large DNA fragments conveniently in various animal species without micromanipulation. A major limitation in the field of liver transplantation is the shortage of transplantable organs.

Chimeric animals carrying human tissue have the potential to solve this problem. However, currently available chimeric organs retain a high level of xenogeneic cells, and the transplantation of impure organs needs to be tested. Rat hepatocytes fully replaced mouse hepatocytes starting from day 56 absence of detectable mouse serum albumin, histological clearance of mouse hepatocytes.

In addition, rat albumin levels reached those of syngeneic recipients. Taken together, these data demonstrate the efficacy of transplanting rat-to-mouse chimeric livers into rats, with a high potential for post-transplant recipient-oriented graft remodelling.

Validation in a large animal model is still needed. Chimeric animals are composed of cells from different species. Chimeric animals carrying human tissue have the potential to increase the availability of transplantable organs. We transplanted rat-to-mouse liver grafts into newly weaned rats. In addition, we observed the post-transplant development of diffuse mature rat bile ducts through the transformation of hepatocytes, and patchy areas of portal endothelium originating from the host.

These data demonstrate the efficacy of transplanting rat-to-mouse chimeric livers into rats, with a high potential for post-transplant graft remodelling. Lifelong maintenance of the blood system requires equilibrium between clearance of damaged hematopoietic stem cells HSCs and long-term survival of the HSC pool. Severe perturbations of cellular homeostasis result in rapid HSC loss to maintain clonal purity. However, normal homeostatic processes can also generate lower-level stress; how HSCs survive these conditions remains unknown.

These findings identify a link between the ISR and stem cell survival in the normal and leukemic contexts. To study development of the conceptus in xenogeneic environments, we assessed interspecies chimera formation as well as tetraploid complementation between mouse and rat.

Overall contribution of donor PSC-derived cells was lower in interspecies chimeras than in intraspecies chimeras, and high donor chimerism was associated with anomalies or embryonic death. Organ to organ variation in donor chimerism was greater in interspecies chimeras than in intraspecies chimeras, suggesting species-specific affinity differences among interacting molecules necessary for organogenesis. In interspecies tetraploid complementation, embryo development was near normal until the stage of placental formation, after which no embryos survived.

In the case of organ transplantation accompanied by vascular anastomosis, major histocompatibility complex mismatched vascular endothelial cells become a target for graft rejection. Production of a rejection-free, transplantable organ, therefore, requires simultaneous generation of vascular endothelial cells within the organ. To generate pluripotent stem cell PSC -derived vascular endothelial cells, we performed blastocyst complementation with a vascular endothelial growth factor receptor-2 homozygous mutant blastocyst.

This mutation is embryonic lethal at embryonic E day 8. The Flk-1 homozygous knockout chimeric mice survived to adulthood for over 1 year without any abnormality, and all vascular endothelial cells and hematopoietic cells were derived from the injected PSCs. This approach could be used in conjunction with other gene knockouts which induce organ deficiency to produce a rejection-free, transplantable organ in which all the organ's cells and vasculature are PSC derived.

The production of knock-out KO livestock models is both expensive and time consuming due to their long gestational interval and low number of offspring. One alternative to increase efficiency is performing a genetic screening to select pre-implantation embryos that have incorporated the desired mutation. PDX1 is a critical gene for pancreas development and the target gene required for the creation of pancreatogenesis-disabled sheep.

We evaluated the viability of biopsied embryos in vitro and in vivo, and we determined the mutation efficiency using PCR combined with gel electrophoresis and digital droplet PCR ddPCR. While the use of biopsies did not compromise embryo viability, the presence of mosaicism diminished the diagnostic value of the technique. If mosaicism could be overcome, pre-implantation embryo biopsies for mutation screening represents a powerful approach that will streamline the creation of KO animals.

However, lifelong dependency on HAART is a continuing challenge, and an effective therapeutic is much desired. The technology is expected to be applied with hemato-lymphopoietic cell transplantation of HIV patients to suppress HIV transcription in transplanted hemato-lymphopoietic cells. Combination of the TGS technology with new cell transplantation strategy with induced pluripotent stem cell iPSC -derived hemato-lymphopoietic cells might contribute to new gene therapy in the HIV field.

The shPromA-transfected iPSCs were successfully differentiated into functional macrophages, and they exhibited strong protection against HIV-1 replication with alteration in the histone structure of the HIV-1 promoter region to induce heterochromatin formation. These results indicated that iPS-derived macrophage is a useful tool to investigate HIV infection and protection, and that the TGS technology targeting the HIV promoter is a potential candidate of new gene therapy.

The aim of the present study is to develop in vitro experimental analytical method for the electrophysiological properties of allogeneic induced pluripotent stem cell-derived cardiomyocytes CMs in cardiac conduction defect model. Cardiomyocytes were derived from rat induced pluripotent stem cells CMs riPSC-CMs using an embryoid body-based differentiation method with the serial application of growth factors including activin-A, bone morphogenetic protein 4 BMP-4 , and inhibitor of wnt production 2 IWP Flow cytometry analysis showed that Generation of human organoids from induced pluripotent stem cells iPSCs offers exciting possibilities for developmental biology, disease modelling and cell therapy.

Significant advances towards those goals have been hampered by dependence on animal derived matrices e. Matrigel , immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal ICC whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development.

The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularise and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFbeta and hedgehog signalling pathways.

The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications. The understanding of signaling events is critical for attaining long-term expansion of hematopoietic stem cells ex vivo.

In this study, we aim to analyze the contribution of multiple signaling molecules in proliferation of hematopoietic stem cells. To this end, we design a bottom-up engineered receptor with multiple tyrosine motifs, which can recruit multiple signaling molecules of interest. This is followed by a top-down approach, where one of the multiple tyrosine motifs in the bottom-up engineered receptor is functionally knocked out by tyrosine-to-phenylalanine mutation.

By probing early embryogenesis and regeneration, interspecies chimeras provide a unique platform for discovery and clinical use. Although efficient generation of human:animal chimeric embryos remains elusive, recent advancements attempt to overcome incompatibilities in xenogeneic development and transplantation.

Stem cell self-renewal is critical for tissue homeostasis, and its dysregulation can lead to organ failure or tumorigenesis. While obesity can induce varied abnormalities in bone marrow components, it is unclear how diet might affect hematopoietic stem cell HSC self-renewal.

Under steady-state conditions, Spred1 negatively regulates HSC self-renewal and fitness, in part through Rho kinase activity. Spred1 deficiency mitigates HSC failure induced by infection mimetics and prolongs HSC lifespan, but it does not initiate leukemogenesis due to compensatory upregulation of Spred2.

HFD-induced hematopoietic abnormalities are mediated partly through alterations to the gut microbiota. Together, these findings reveal that diet-induced stress disrupts fine-tuning of Spred1-mediated signals to govern HSC homeostasis. Use of hepatocytes derived from induced pluripotent stem cells i-Heps is limited by their functional differences in comparison with primary cells.

Extracellular niche factors likely play a critical role in bridging this gap. Using image-based characterization high content analysis; HCA of freshly isolated hepatocytes from 17 human donors, we devised and validated an algorithm Hepatocyte Likeness Index; HLI for comparing the hepatic properties of cells against a physiological gold standard.

The HLI was then applied in a targeted screen of extracellular niche factors to identify substrates driving i-Heps closer to the standard.

Cumulatively, these data provide a reference method to control and screen for i-Hep differentiation, identify Laminin as a key niche protein, and underscore the importance of combining substrates, soluble factors, and HCA when developing iPSC applications. Splicing factor mutations are characteristic of myelodysplastic syndromes MDS and related myeloid neoplasms and implicated in their pathogenesis, but their roles in the development of MDS have not been fully elucidated.

In the present study, we investigated the consequence of mutant Srsf2 expression using newly generated Vav1-Cre-mediated conditional knockin mice. Mice carrying a heterozygous Srsf2 P95H mutation showed significantly reduced numbers of hematopoietic stem and progenitor cells HSPCs and differentiation defects both in the steady-state condition and transplantation settings.

Srsf2-mutated hematopoietic stem cells HSCs showed impaired long-term reconstitution compared with control mice in competitive repopulation assays. Although the Srsf2 mutant mice did not develop MDS under the steady-state condition, when their stem cells were transplanted into lethally irradiated mice, the recipients developed anemia, leukopenia, and erythroid dysplasia, which suggests the role of replicative stress in the development of an MDS-like phenotype in Srsf2-mutated mice.

Hematopoietic stem cells HSCs are a valuable resource in transplantation medicine. Cytokines are often used to culture HSCs aiming at better clinical outcomes through enhancement of HSC reconstitution capability.

Roles for each signal molecule downstream of receptors in HSCs, however, remain puzzling due to complexity of the cytokine-signaling network.

Engineered receptors that are non-responsive to endogenous cytokines represent an attractive tool for dissection of signaling events.

We here tested a previously developed chimeric receptor CR system in primary murine HSCs, target cells that are indispensable for analysis of stem cell activity. Each CR contains tyrosine motifs that enable selective activation of signal molecules located downstream of the c-Mpl receptor upon stimulation by an artificial ligand. Signaling through a control CR with a wild-type c-Mpl cytoplasmic tail sufficed to enhance HSC proliferation and colony formation in cooperation with stem cell factor SCF.

Among a series of CRs, only one compatible with selective Stat5 activation showed similar positive effects. The HSCs maintained ex vivo in these environments retained long-term reconstitution ability following transplantation. This ability was also demonstrated in secondary recipients, indicating effective transmission of stem cell-supportive signals into HSCs via these artificial CRs during culture.

Selective activation of Stat5 through CR ex vivo favored preservation of lymphoid potential in long-term reconstituting HSCs, but not of myeloid potential, exemplifying possible dissection of signals downstream of c-Mpl. Genetically engineered pigs play an indispensable role in the study of rare monogenic diseases. Pigs harboring a gene responsible for a specific disease can be efficiently generated via somatic cell cloning.

The generation of somatic cell-cloned pigs from male cells with mutation s in an X chromosomal gene is a reliable and straightforward method for reproducing X-linked genetic diseases XLGDs in pigs. However, the severe symptoms of XLGDs are often accompanied by impaired growth and reproductive disorders, which hinder the reproduction of these valuable model animals.

Here, we generated unique chimeric boars composed of mutant cells harboring a lethal XLGD and normal cells. The chimeric boars exhibited the cured phenotype with fertility while carrying and transmitting the genotype of the XLGD. This unique reproduction system permits routine production of XLGD model pigs through the male-based breeding, thereby opening an avenue for translational research using disease model pigs.

Transplanting iPSCs into the embryos of another species can generate functional organs for basic research and translational applications. We discuss forward-looking approaches and address key remaining challenges of generating iPSC-derived human organs in vivo.

Hematopoietic stem cells HSCs are used clinically in bone marrow BM transplantation due to their unique ability to reform the entire hematopoietic system. Recently, we reported that HSCs are highly sensitive to valine, one of the three branched-chain amino acids BCAAs in addition to isoleucine and leucine.

Dietary depletion of valine could even be used as a conditioning regimen for HSC transplantation. Importantly, in vivo depletion of all three BCAAs was significantly less toxic than depletion of valine only. In summary, by determining HSC metabolic requirements, we can improve metabolic approaches to BM conditioning. One of the ultimate goals of regenerative medicine is the generation of patient-specific organs from pluripotent stem cells PSCs.

Sheep are potential hosts for growing human organs through the technique of blastocyst complementation. MII oocyte microinjection reduced lysis, improved blastocyst rate, increased the number of targeted bi-allelic mutations, and resulted in similar degree of mosaicism when compared to zygote microinjection.

While the use of a single sgRNA was efficient at inducing mutated fetuses, the lack of complete gene inactivation resulted in animals with an intact pancreas.

The present study was conducted to establish haploid embryonic stem ES cell lines using fluorescent marker-carrying rats. In the first series, 7 ES cell lines were established from 26 androgenetic haploid blastocysts.

No chimeras were detected among the 10 fetuses and 41 offspring derived from blastocyst injection with the FACS-purified haploid cells. Following blastocyst injection with the FACS-purified haploid cells, no chimera was observed among the 11 fetuses; however, 1 chimeric male was found among the 47 offspring.

Although haploid rat ES cell lines can be established from both blastocyst sources, FACS purification may be necessary for maintenance and chimera production. Interspecies chimeric assays are a valuable tool for investigating the potential of human stem and progenitor cells, as well as their differentiated progeny.

This Spotlight article discusses the different factors that affect interspecies chimera generation, such as evolutionary distance, developmental timing, and apoptosis of the transplanted cells, and suggests some possible strategies to address them. A refined approach to generating interspecies chimeras could contribute not only to a better understanding of cellular potential, but also to understanding the nature of xenogeneic barriers and mechanisms of heterochronicity, to modeling human development, and to the creation of human transplantable organs.

While this induces bone marrow BM -localized inflammation, how this BM environmental change affects transplanted HSCs in vivo remains largely unknown. We here report that, depending on interval between irradiation and HSCT, residence within lethally irradiated recipient BM compromises donor-HSC reconstitution ability.

Importantly, pre-transplantation exposure to NAC successfully demonstrats protective effects in inflammatory BM on graft-HSCs, exhibiting better reconstitution capability than that of nonprotected control grafts.

We thus suggest that in vivo protection of graft-HSCs from BM inflammation is a feasible and attractive approach, which may lead to improved hematopoietic reconstitution kinetics in transplantation with myeloablative conditioning that inevitably causes inflammation in recipient BM. Stem Cells Macrophage activation syndrome MAS is a life-threatening disorder characterized by a cytokine storm and multiorgan dysfunction due to excessive immune activation.

Although abnormalities of coagulation and fibrinolysis are major components of MAS, the role of the fibrinolytic system and its key player, plasmin, in the development of MAS remains to be solved. We found plasmin was excessively activated during the progression of fulminant MAS in mice. Genetic and pharmacological inhibition of plasmin counteracted MAS-associated lethality and other related symptoms.

Collectively, our findings identify plasmin as a decisive checkpoint in the inflammatory response during MAS and a potential novel therapeutic target for MAS. Adoptive T-cell therapy to target and kill tumor cells shows promise and induces durable remissions in selected malignancies. However, for most cancers, clinical utility is limited. Cytotoxic T lymphocytes continuously exposed to viral or tumor antigens, with long-term expansion, may become unable to proliferate "exhausted".

To exploit fully rejuvenated induced pluripotent stem cell iPSC -derived antigen-specific cytotoxic T lymphocytes is a potentially powerful approach. We review recent progress in engineering iPSC-derived T cells and prospects for clinical translation. We also describe the importance of introducing a suicide gene safeguard system into adoptive T-cell therapy, including iPSC-derived T-cell therapy, to protect from unexpected events in first-in-humans clinical trials.

Human induced pluripotent stem cells iPSCs are promising in regenerative medicine. However, the risks of teratoma formation and the overgrowth of the transplanted cells continue to be major hurdles that must be overcome. Here, we examined the efficacy of the inducible caspase-9 iCaspase9 gene as a fail-safe against undesired tumorigenic transformation of iPSC-derived somatic cells.

We used a lentiviral vector to transduce iCaspase9 into two iPSC lines and assessed its efficacy in vitro and in vivo. All transplanted cells whose mass effect was hindering motor function recovery were ablated upon transduction of iCaspase9. Our results suggest that the iCaspase9 system may serve as an important countermeasure against post-transplantation adverse events in stem cell transplant therapies. Hematopoietic stem cells HSCs are considered one of the most promising therapeutic targets for the treatment of various blood disorders.

However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Subsequent molecular analysis revealed that HPX reduces intracellular reactive oxygen species levels within cultured HSCs.

Furthermore, bone marrow immunostaining and 3D immunohistochemistry revealed that HPX is expressed in non-myelinating Schwann cells, known HSC niche constituents.

These results highlight the utility of this fully defined all-recombinant protein-based culture system for reproducible in vitro HSC culture and its potential to contribute to the identification of factors responsible for in vitro maintenance, expansion, and differentiation of stem cell populations. The nature of hematopoietic stem cells under normal hematopoiesis remained largely unknown due to the limited assays available to monitor their behavior in situ.

We succeeded in transferring a GFP reporter gene into adult hematopoietic stem cells in vivo, which are predominantly quiescent, by generating pseudotyped-lentivirus. Furthermore, we demonstrate the utility of this system to study neonatal hematopoiesis, a developmental stage that has been difficult to analyze to date. Using the system developed in this study, we observed continuous multi-lineage hematopoietic cell supply in peripheral blood from Krt7-positive hematopoietic stem cells during unperturbed homeostatic condition.

His immense bravery and desire to become a hero were also important factors in giving him the mentality to protect others. Having been trained by his father for 10 months in order to properly utilized his quirk Hiro became a versatile hand-to-hand combatant and learning several martial arts.

Hiro's fighting also incorporates and takes full advantage of his proper use of physical forces, momentum, and leverage, with the hero staying low and mobile while utilizing the momentum of frequent spins to come crashing down on to his opponents. During the Quirk Apprehension Test, he demonstrated a grip strength of 85 kilograms and the ability to run the meter dash in 4. After acquiring his own Quirk he was granted the ability to shapeshifted and a tremendous amount of raw strength and power agility, speed, and dexterity which allows him to take down an enormous villain bot in a single punch.

Keen Intellect : Hiro has proven to be exceptionally intelligent on many occasions and is very observant over his surrounding. He has a keen eye for details and can spot any unusual aspects and his fastidious attention to detail allows him to notice minor inconsistencies.

Transhift : Hiro's Quirk was something like mutation he gains from Vrak who injected with his Quirk formula which grants him shapeshifting abilities. He also gains a tremendous amount of raw strength and agility via by biomass ejection and manipulation. Due to his inexperience, Hiro has a lot of trouble learning how to properly use it and has difficulty controlling it especially when each time he unlocks a new power.

His Quirk gives him the power to change any and all parts of his body into weapons like his hands turning into blades, claws, or huge mechanical gauntlets. His quirk also grants him a psychological awareness which allows him to detect danger before it happens and warns him of it in no time. The greater the danger or how close the danger increases the tingling sensation it can also allow him to find a target in a crowded populated area.