Development and photo-responsive peptide bond cleavage reaction of two-photon near-infrared excitation-responsive peptide

Two-photon near-infrared excitation-responsive amino acid was developed. It was incorporated into a peptide, and focused near-infrared pulsed laser irradiation-induced peptide bond cleavage reaction at the C-terminal position of the photo-responsive amino acid was observed

Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles

初期化を阻害する転写因子が分化を促進する. 京都大学プレスリリース. 2013-04-02.Transcription factors (TFs) are able to regulate differentiation-related processes, including dedifferentiation and direct conversion, through the regulation of cell type-specific transcriptional profiles. However, the functional interactions between the TFs regulating different transcriptional profiles are not well understood. Here, we show that the TFs capable of inducing cell type-specific transcriptional profiles prevent the dedifferentiation induced by TFs for pluripotency. Of the large number of TFs expressed in a neural-lineage cell line, we identified a subset of TFs that, when overexpressed, strongly interfered with the dedifferentiation triggered by the procedure to generate induced pluripotent stem cells. This interference occurred through a maintenance mechanism of the cell type-specific transcriptional profile. Strikingly, the maintenance activity of the interfering TF set was strong enough to induce the cell line-specific transcriptional profile when overexpressed in a heterologous cell type. In addition, the TFs that interfered with dedifferentiation in hepatic-lineage cells involved TFs with known induction activity for hepatic-lineage cells. Our results suggest that dedifferentiation suppresses a cell type-specific transcriptional profile, which is primarily maintained by a small subset of TFs capable of inducing direct conversion. We anticipate that this functional correlation might be applicable in various cell types and might facilitate the identification of TFs with induction activity in efforts to understand differentiation

Efficacy and Safety of an Ultrasonically Activated Device for Sealing the Bile Ducts During Liver Resection

The use of ultrasonically activated devices (USADs) in hepatic resections may be associated with an increased rate of complications, such as postoperative bile leaks. Nonetheless, the safety of USADs for sealing bile ducts during liver surgery has not yet been established. The purpose of this study was to assess the efficacy of a USAD for sealing bile ducts. In animal experiments, the common bile duct of ten anesthetized dogs was individually occluded using a USAD. Additionally, using the prospective liver surgery database from a single institution, we identified 45 consecutive patients who underwent hepatic resection using a USAD (USAD group) and 45 similar patients who underwent hepatic resection without the use of a USAD (NUSAD group). In the occluded and harvested canine bile ducts, the mean burst pressure was 280mmHg, and the lumen of the bile duct was completely sealed morphologically. In the clinical study, there was no significant difference in postoperative mortality or complications between the two groups, and biliary leakage was observed in only one patient (0.7%) in the USAD group. These data demonstrate that the USAD is a safe, efficient, and practical instrument for use during liver surgery to achieve complete hemobiliary stasis

Development of a New Bioartificial Liver Support System Using a Radial-flow Bioreactor

There is an increasing number of patients with severe liver disease that requires whole organ transplantation or living-related split liver transplantation. This has resulted in a shortage of donor organs, which is particularly problematic and still awaits resolution. Bioartificial liver (BAL) support systems have been developed with the aim of supporting patients with life-threatening liver disease until their liver recovers. Here, we describe a high performance three-dimensional rat hepatocyte culture system using a radial-flow bioreactor (RFB) with a polyvinyl alcohol (PVA) membrane as a small-scale BAL support system. Hepatocytes from male Sprague-Dawley rat livers were isolated and divided into two groups as follows. Group A: isolated hepatocytes were maintained in culture medium as controls; and group B: isolated hepatocytes were injected into the medium chamber of the RFB-PVA culture system. Sampling was carried out every 48 h to analyze the concentrations of ammonia and albumin in the medium. Light and electron microscopic examination of hepatocytes explanted from the PVA membrane was also performed. Albumin production and urea synthesis by cells in group B were both significantly higher than in group A. Hematoxylin-Eosin staining of the cells in group B showed that three-dimensional cell masses were attached to the PVA membrane. It also showed that the cells were stably proliferating in the porous spaces of the PVA. Scanning electron microscopic images of group B also showed clusters of hepatocytes attached to the PVA membrane. Hepatocyte clusters growing in the RFB-PVA culture system retained their biological function and were stable in the porous spaces of the PVA membrane. This cell culture system may be useful for the development of new BAL support systems

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation

Protein S-guanylation by the biological signal 8-nitroguanosine 3\u27,5\u27-cyclic monophosphate

The signaling pathway of nitric oxide (NO) depends mainly on guanosine 3′,5′-cyclic monophosphate (cGMP, 1). Here we report the formation and chemical biology of a nitrated derivative of cGMP, 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP, 2), in NO-mediated signal transduction. Immunocytochemistry demonstrated marked 8-nitro-cGMP production in various cultured cells in an NO-dependent manner. This finding was confirmed by HPLC plus electrochemical detection and tandem mass spectrometry. 8-Nitro-cGMP activated cGMP-dependent protein kinase and showed unique redox-active properties independent of cGMP activity. Formation of protein Cys-cGMP adducts by 8-nitro-cGMP was identified as a new post-translational modification, which we call protein S-guanylation. 8-Nitro-cGMP seems to regulate the redox-sensor signaling protein Keap1, via S-guanylation of the highly nucleophilic cysteine sulfhydryls of Keap1. This study reveals 8-nitro-cGMP to be a second messenger of NO and sheds light on new areas of the physiology and chemical biology of signal transduction by NO

結晶化ガラス顆粒の臨床応用

This reports tha development of bioactive glass ceramic particles and evaluates their use inclinical applications. 1. The subjects of the evaluation were 13 impacted teeth, 17 intramaxillary cysts (not including radicular cysts), and 7 atrophic mandibular alveolar ridges. 2. The results were classified into effective, slightly effective, ineffective, and harmful, a very high proportion, 33 or 89.3%,were judged effective or slightly effective. 3. None were evaluated to be harmful, showing the safety of the present material. Among the ineffective cases there were open wounds due to infection, leakage of the supplied material, and fistulation. In cases where inflammation had not disappeared at the supply there were cases where the particles had to be completely removed due to infection, It was determined the that this was not due to the material, but possidly due to the surgical procedures, as there were no further complications in the tretment. 4. From the results reported here, the bioactive glass ceramic material here was found to be useful in the articial bone needed after atrophic mandibular alveolar ridge surgery

A pristine record of outer Solar System materials from asteroid Ryugu’s returned sample

Volatile and organic-rich C-type asteroids may have been one of the main sources of Earth’s water. Our best insight into their chemistry is currently provided by carbonaceous chondritic meteorites, but the meteorite record is biased: only the strongest types survive atmospheric entry and are then modified by interaction with the terrestrial environment. Here we present the results of a detailed bulk and microanalytical study of pristine Ryugu particles, brought to Earth by the Hayabusa2 spacecraft. Ryugu particles display a close compositional match with the chemically unfractionated, but aqueously altered, CI (Ivuna-type) chondrites, which are widely used as a proxy for the bulk Solar System composition. The sample shows an intricate spatial relationship between aliphatic-rich organics and phyllosilicates and indicates maximum temperatures of ~30 °C during aqueous alteration. We find that heavy hydrogen and nitrogen abundances are consistent with an outer Solar System origin. Ryugu particles are the most uncontaminated and unfractionated extraterrestrial materials studied so far, and provide the best available match to the bulk Solar System composition

A dehydrated space-weathered skin cloaking the hydrated interior of Ryugu

Without a protective atmosphere, space-exposed surfaces of airless Solar System bodies gradually experience an alteration in composition, structure and optical properties through a collective process called space weathering. The return of samples from near-Earth asteroid (162173) Ryugu by Hayabusa2 provides the first opportunity for laboratory study of space-weathering signatures on the most abundant type of inner solar system body: a C-type asteroid, composed of materials largely unchanged since the formation of the Solar System. Weathered Ryugu grains show areas of surface amorphization and partial melting of phyllosilicates, in which reduction from Fe3+ to Fe2+ and dehydration developed. Space weathering probably contributed to dehydration by dehydroxylation of Ryugu surface phyllosilicates that had already lost interlayer water molecules and to weakening of the 2.7 µm hydroxyl (–OH) band in reflectance spectra. For C-type asteroids in general, this indicates that a weak 2.7 µm band can signify space-weathering-induced surface dehydration, rather than bulk volatile loss

A phosphopantetheinyl transferase gene essential for biosynthesis of n-3 polyunsaturated fatty acids from Moritella marina strain MP-1

A phosphopantetheinyl transferase (PPTase) gene (pfaE), cloned from the docosahexaenoic acid (DHA)-producing bacterium Moritella marina strain MP-1, has an open reading frame of 861 bp encoding a 287-amino acid protein. When the pfaE gene was expressed with pfaA–D, which are four out of five essential genes for biosynthesis of eicosapentaenoic acid (EPA) derived from Shewanella pneumatophori SCRC-2738 in Escherichia coli, the recombinant produced 12% EPA of total fatty acids. This suggests that pfaE encodes a PPTase required for producing n−3 polyunsaturated fatty acids, which is probably involved in the synthesis of DHA in M. marina strain MP-1