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All life on Earth contains amino acids and carbonaceous chondrite meteorites have been suggested as their source at the origin of life on Earth. While many meteoritic amino acids are considered indigenous, deciphering the extent of terrestrial contamination remains an issue. The Ryugu asteroid fragments (JAXA Hayabusa2 mission), represent the most uncontaminated primitive extraterrestrial material available. Here, the concentrations of amino acids from two particles from different touchdown sites (TD1 and TD2) are reported. The concentrations show that N,N-dimethylglycine (DMG) is the most abundant amino acid in the TD1 particle, but below detection limit in the other. The TD1 particle mineral components indicate it experienced more aqueous alteration. Furthermore, the relationships between the amino acids and the geochemistry suggest that DMG formed on the Ryugu progenitor body during aqueous alteration. The findings highlight the importance of aqueous chemistry for defining the ultimate concentrations of amino acids in primitive extraterrestrial samples. Amino acid concentrations from 2 particles returned from different touchdown sites on the surface of Ryugu are reported. Differences in chemistry suggest different levels of aqueous alteration are recorded at the 2 sampled locations.

The pristine sample from the near-Earth carbonaceous asteroid (162173) Ryugu collected by the Hayabusa2 spacecraft enabled us to analyze the pristine extraterrestrial material without uncontrolled exposure to the Earth’s atmosphere and biosphere. The initial analysis team for the soluble organic matter reported the detection of wide variety of organic molecules including racemic amino acids in the Ryugu samples. Here we report the detection of uracil, one of the four nucleobases in ribonucleic acid, in aqueous extracts from Ryugu samples. In addition, nicotinic acid (niacin, a B 3 vitamer), its derivatives, and imidazoles were detected in search for nitrogen heterocyclic molecules. The observed difference in the concentration of uracil between A0106 and C0107 may be related to the possible differences in the degree of alteration induced by energetic particles such as ultraviolet photons and cosmic rays. The present study strongly suggests that such molecules of prebiotic interest commonly formed in carbonaceous asteroids including Ryugu and were delivered to the early Earth. Uracil was identified in the sample returned from the asteroid Ryugu. Having been provided to the early Earth as a component in such asteroidal materials, these molecules might have played a role for prebiotic chemical evolution on the early Earth

The tumor suppressor p53 functions as a pioneer transcription factor that binds a nucleosomal target DNA sequence. However, the mechanism by which p53 binds to its target DNA in the nucleosome remains elusive. Here we report the cryo-electron microscopy structures of the p53 DNA-binding domain and the full-length p53 protein complexed with a nucleosome containing the 20 base-pair target DNA sequence of p53 (p53BS). In the p53-nucleosome structures, the p53 DNA-binding domain forms a tetramer and specifically binds to the p53BS DNA, located near the entry/exit region of the nucleosome. The nucleosomal position of the p53BS DNA is within the genomic p21 promoter region. The p53 binding peels the DNA from the histone surface, and drastically changes the DNA path around the p53BS on the nucleosome. The C-terminal domain of p53 also binds to the DNA around the center and linker DNA regions of the nucleosome, as revealed by hydroxyl radical footprinting. These results provide important structural information for understanding the mechanism by which p53 binds the nucleosome and changes the chromatin structure for gene activation.

C-type asteroids 1 are considered to be primitive small Solar System bodies enriched in water and organics, providing clues to the origin and evolution of the Solar System and the building blocks of life. C-type asteroid 162173 Ryugu has been characterized by remote sensing 2 – 7 and on-asteroid measurements 8 , 9 with Hayabusa2 (ref.  10 ). However, the ground truth provided by laboratory analysis of returned samples is invaluable to determine the fine properties of asteroids and other planetary bodies. We report preliminary results of analyses on returned samples from Ryugu of the particle size distribution, density and porosity, spectral properties and textural properties, and the results of a search for Ca–Al-rich inclusions (CAIs) and chondrules. The bulk sample mainly consists of rugged and smooth particles of millimetre to submillimetre size, confirming that the physical and chemical properties were not altered during the return from the asteroid. The power index of its size distribution is shallower than that of the surface boulder observed on Ryugu 11 , indicating differences in the returned Ryugu samples. The average of the estimated bulk densities of Ryugu sample particles is 1,282 ± 231 kg m −3 , which is lower than that of meteorites 12 , suggesting a high microporosity down to the millimetre scale, extending centimetre-scale estimates from thermal measurements 5 , 9 . The extremely dark optical to near-infrared reflectance and spectral profile with weak absorptions at 2.7 and 3.4 μm imply a carbonaceous composition with indigenous aqueous alteration, matching the global average of Ryugu 3 , 4 and confirming that the sample is representative of the asteroid. Together with the absence of submillimetre CAIs and chondrules, these features indicate that Ryugu is most similar to CI chondrites but has lower albedo, higher porosity and more fragile characteristics. The Hayabusa2 spacecraft returned 5.4 g of material from the asteroid Ryugu. A first analysis of the samples found an estimated density of 1,282 ± 231 kg m −3 , considerably lower than even the most porous meteorites. Together with preliminary spectral analysis, these results indicate that Ryugu is similar to CI chondrites, but darker, more porous and more brittle.

Vascular endothelial cell growth factor-C (VEGF-C) is a member of the VEGF family and plays a role in various biological activities. VEGF-C enhances proliferation and migration of lymphatic endothelial cells and vascular endothelial cells through VEGF receptor 2 (VEGFR2) and/or receptor 3 (VEGFR3), and thereby induces lymphangiogenesis or angiogenesis. However, it remains unclear whether VEGF-C promotes the migration of mesenchymal stem cells (MSCs). Here, we investigated the effects of VEGF-C on the migration of MSCs and evaluated the underlying molecular mechanisms. VEGF-C treatment significantly induced the migration of MSCs, which is accompanied by the promotion of actin cytoskeletal reorganization and focal adhesion assembly. VEGF-C treatment enhanced the phosphorylation of VEGFR2 and VEGFR3 proteins in MSCs, and pretreatment with VEGFR2 and VEGFR3 kinase inhibitors effectively suppressed the VEGF-C-induced MSC migration. In addition, VEGF-C treatment promoted phosphorylation of ERK and FAK proteins in MSCs, and inhibition of VEGFR2 and VEGFR3 signaling pathways abolished the VEGF-C-induced activation of ERK and FAK proteins. Furthermore, treatment with ERK and FAK inhibitors suppressed VEGF-C-induced actin cytoskeletal reorganization and focal adhesion assembly, and then significantly inhibited MSCs migration. These results suggest that VEGF-C-induced MSC migration is mediated via VEGFR2 and VEGFR3, and follows the activation of the ERK and FAK signaling pathway. Thus, VEGF-C may be valuable in tissue regeneration and repair in MSC-based therapy.

This study aimed to evaluate the effectiveness of passive stretch training (PST) using electromyographic analysis and the pain visual analogue scale (VAS), and to investigate changes in mouth opening, masseter activity, and pain level before and after PST in patients with myofascial pain and temporomandibular joint disc displacement. The study sample comprised 37 patients with Temporomandibular disorders (TMD) and limited mouth opening (LMO, < 40 mm) and 27 healthy volunteers. Patients were divided into three groups: disc displacement (DD), disc displacement with myofascial pain (DD + M), and myofascial pain (M). At the first visit, all participants were instructed to perform three repetitions of maximum mouth opening (O max ), each held for 5 s. After a brief rest period, they underwent PST using finger-generated force to support mouth opening, holding each stretch for 5 s and repeating the task 15 times. Three additional O max repetitions were then performed. After the first experiment, all patients were instructed to continue PST at home for three months before returning for the second experiment. The masseter muscle activity in the DD + M and M groups exhibited significantly lower electromyographic potentials after PST in both the first and second experiments ( p < .05). Furthermore, mouth opening significantly increased and pain VAS scores significantly decreased after three months of home-based PST in the DD + M and M groups ( p < .05). These electromyographic findings confirm the short- and long-term effectiveness of PST in TMD patients with myofascial pain and limited mouth opening.

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. The sample taken from carbonaceous asteroid Ryugu and brought back to Earth by the Hayabusa2 spacecraft contains outer Solar System-derived materials uncontaminated by terrestrial processes. Even CI carbonaceous chondrites, despite their closeness to solar abundances, are not pristine.

Chondrule-like objects and Ca-Al-rich inclusions (CAIs) are discovered in the retuned samples from asteroid Ryugu. Here we report results of oxygen isotope, mineralogical, and compositional analysis of the chondrule-like objects and CAIs. Three chondrule-like objects dominated by Mg-rich olivine are 16 O-rich and -poor with Δ 17 O (=δ 17 O – 0.52 × δ 18 O) values of ~ –23‰ and ~ –3‰, resembling what has been proposed as early generations of chondrules. The 16 O-rich objects are likely to be melted amoeboid olivine aggregates that escaped from incorporation into 16 O-poor chondrule precursor dust. Two CAIs composed of refractory minerals are 16 O-rich with Δ 17 O of ~ –23‰ and possibly as old as the oldest CAIs. The discovered objects (<30 µm) are as small as those from comets, suggesting radial transport favoring smaller objects from the inner solar nebula to the formation location of the Ryugu original parent body, which is farther from the Sun and scarce in chondrules. The transported objects may have been mostly destroyed during aqueous alteration in the Ryugu parent body. Chondrule-like objects and CAIs in the Ryugu samples are early generations of chondrules and possibly oldest solids in the Solar System. They were transported from the inner solar nebula to the formation location of the Ryugu original parent body.

Background Kaempferia parviflora Wall. ex. Baker (KP) has been reported to exhibit anti-obesity effects. However, the detailed mechanism of the anti-obesity effect of KP extract (KPE) is yet to be clarified. Here, we investigated the effect of KPE and its component polymethoxyflavones (PMFs) on the adipogenic differentiation of human mesenchymal stem cells (MSCs). Methods and results KPE and PMFs fraction (2.5 µg/mL) significantly inhibited lipid and triacylglyceride accumulation in MSCs; lipid accumulation in MSCs was suppressed during the early stages of differentiation (days 0–3) but not during the mid (days 3–7) or late (days 7–14) stages. Treatment with KPE and PMFs fractions significantly suppressed peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and various adipogenic metabolic factors. Treatment with KPE and PMFs fraction induced the activation of AMP-activated protein kinase (AMPK) signaling, and pretreatment with an AMPK signaling inhibitor significantly attenuated KPE- and PMFs fraction-induced suppression of lipid formation. Conclusions Our findings demonstrate that KPE and PMFs fraction inhibit lipid formation by inhibiting the differentiation of undifferentiated MSCs into adipocyte lineages via AMPK signaling, and this may be the mechanism underlying the anti-obesity effects of KPE and PMFs. Our study lays the foundation for the elucidation of the anti-obesity mechanism of KPE and PMFs.