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 Fe to Fe and dehydration developed.

Soluble organic molecules in samples of the carbonaceous asteroid (162173) Ryugu.

The Hayabusa2 spacecraft collected samples from the surface of the carbonaceous near-Earth asteroid (162173) Ryugu and brought them to Earth. The samples were expected to contain organic molecules, which record processes that occurred in the early Solar System. We analyzed organic molecules extracted from the Ryugu surface samples.

Macromolecular organic matter in samples of the asteroid (162173) Ryugu.

Samples of the carbonaceous asteroid (162173) Ryugu were collected and brought to Earth by the Hayabusa2 spacecraft. We investigated the macromolecular organic matter in Ryugu samples and found that it contains aromatic and aliphatic carbon, ketone, and carboxyl functional groups. The spectroscopic features of the organic matter are consistent with those in chemically primitive carbonaceous chondrite meteorites that experienced parent-body aqueous alteration (reactions with liquid water).

Noble gases and nitrogen in samples of asteroid Ryugu record its volatile sources and recent surface evolution.

The near-Earth carbonaceous asteroid (162173) Ryugu is expected to contain volatile chemical species that could provide information on the origin of Earth's volatiles. Samples of Ryugu were retrieved by the Hayabusa2 spacecraft. We measured noble gas and nitrogen isotopes in Ryugu samples and found that they are dominated by presolar and primordial components, incorporated during Solar System formation.

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.

Samples returned from the asteroid Ryugu are similar to Ivuna-type carbonaceous meteorites.

Carbonaceous meteorites are thought to be fragments of C-type (carbonaceous) asteroids. Samples of the C-type asteroid (162173) Ryugu were retrieved by the Hayabusa2 spacecraft. We measured the mineralogy and bulk chemical and isotopic compositions of Ryugu samples.

Highly porous nature of a primitive asteroid revealed by thermal imaging.

Carbonaceous (C-type) asteroids are relics of the early Solar System that have preserved primitive materials since their formation approximately 4.6 billion years ago. They are probably analogues of carbonaceous chondrites and are essential for understanding planetary formation processes.

Hitomi X-ray studies of Giant Radio Pulses from the Crab pulsar.

To search for giant X-ray pulses correlated with the giant radio pulses (GRPs) from the Crab pulsar, we performed a simultaneous observation of the Crab pulsar with the X-ray satellite Hitomi in the 2 - 300 keV band and the Kashima NICT radio observatory in the 1.4 - 1.7 GHz band with a net exposure of about 2 ks on 25 March 2016, just before the loss of the Hitomi mission.

[Characteristics and Functional Roles of Opioids Originally Present in Vivo].

The characteristics and functional roles of opioids originally present in vivo (endogenous opioids) in guinea-pig ileum were investigated. The release of endogenous opioids was determined by the inhibitory twitch response evoked by 0.1 Hz stimulation after 10 Hz stimulation (post-tetanic twitch inhibition).

Tumor cell-derived secretory factor downregulates Semaphorin-3a in osteoblasts by activating mammalian target of rapamycin pathway.

We found that conditioned medium derived from Lewis Lung Carcinoma cells down-regulated Semaphorin3a (Sema3a) mRNA expression and increased the activity of mammalian target of rapamycin complex 1 (mTORC1) in osteoblast-like MC3T3-E1 cells. Furthermore, mTORC1 inhibition with rapamycin counteracted the effect of conditioned media on Sema3a mRNA expression. These results suggest that tumor cells decrease Sema3a mRNA expression in osteoblast in an mTORC1-dependent manner.

[Study on novel mechanism underlying analgesia targeting TRPV1].

Transient receptor potential protein (TRP) channels are distributed in pain pathways including primary afferent neurons and function as transduction of various noxious stimuli to innocuous stimuli. TRP channels are considered as molecular basis of chronic pain. Targeting TRPs may lead to novel class of analgesics, and so drug-discovery efforts are focused on TRP agonists and its antagonists.

Possible involvement of endogenous opioid system located downstream of α7 nicotinic acetylcholine receptor in mice with physical dependence on nicotine.

We previously reported that nicotine (NIC)-induced analgesia was elicited in part by activation of the endogenous opioid system. Moreover, it is well known that NIC has physical-dependence liability, but its mechanism is unclear. Therefore, we examined whether physical dependence on NIC was mediated by activation of the endogenous opioid system in ICR mice.

HMGB1 as a potential therapeutic target for neuropathic pain.

Neuropathic pain, which is intolerable and persistent, arises as a direct consequence of a lesion or disease affecting the somatosensory system and can be debilitating for the affected patients. Accumulating evidence from animal studies has revealed the potential molecular basis for neuropathic pain, resulting in many promising therapeutic targets. While efforts at drug discovery have been made, conventional pharmacotherapy, including the use of opioid analgesics, is still insufficient for the relief of neuropathic pain.

Activation of nicotinic acetylcholine receptors on bone marrow-derived cells relieves neuropathic pain accompanied by peripheral neuroinflammation.

Emerging evidence indicates that chronic neuroinflammation plays a pivotal role in neuropathic pain. We explored whether activation of the nicotinic acetylcholine receptor (nAChRs) pathway on peripheral immune cells improves neuropathic pain. Mice were subjected to partial sciatic nerve ligation (PSL).

The critical role of spinal ceramide in the development of partial sciatic nerve ligation-induced neuropathic pain in mice.

Recent observations indicate that peripheral nerve injury induces central sensitization through microglial activation and the release of inflammatory cytokines, resulting in the development of neuropathic pain. However, the underlying mechanisms of this phenomenon remain to be fully elucidated. In this study, we examined the involvement of spinal ceramide, a bioactive lipid, in the development of neuropathic pain induced by partial sciatic nerve ligation (PSL).

Increment of activated serine/threonine protein phosphatase in brain membrane fraction synchronized with antinociceptive effect of morphine in mice.

We have examined the involvement of serine/threonine protein phosphatase (PP) sensitive to okadaic acid (OA) in the antinociceptive effect of morphine in mice. The present study was performed to elucidate subcellular distribution and activity of OA-sensitive PPs in the brain when mice exposed to morphine. Subcutaneous administration of morphine (5 mg/kg) produced the antinociceptive effect with the maximum 30 min after its administration, evaluated by tail-pinch test.

Internalization of constitutively active N111G MUTANT of AT1 receptor induced by angiotensin II-receptor antagonists candesartan, losartan, and telmisartan: comparison with valsartan.

Based on radioligand binding and signal transduction assays in our previous study, we have determined the binding pattern and functional efficacy of the constitutively active mutant N111G of angiotensin II type 1 (AT(1)) receptor. We have also shown that the N111G mutant induces homologous internalization through mediation of the AT(1)-receptor antagonist valsartan. In this study we demonstrated that other AT(1)-receptor antagonists, candesartan, losartan, and telmi-sartan, also stimulate internalization of N111G mutant receptor to the same extent.

Constitutively active mutant N111G of angiotensin II type 1 (AT(1)) receptor induces homologous internalization through mediation of AT(1)-receptor antagonist.

The present study investigated the internalization behavior of the constitutively active mutant (CAM) N111G of angiotensin II type 1 (AT(1)) receptor and correlated the result with the mechanism of the constitutive activity of the mutant. The inverse agonist activity of valsartan, losartan, candesartan, and telmisartan was also examined by inositol phosphate (IP) accumulation study as well as receptor-internalization assay. Both wild-type (WT) and N111G mutant receptors were transiently expressed in COS-7 cells and the binding affinities towards the agonist and these four AT(1) antagonists were determined.

Leptin derived from adipocytes in injured peripheral nerves facilitates development of neuropathic pain via macrophage stimulation.

Nerve injury may result in neuropathic pain, characterized by allodynia and hyperalgesia. Accumulating evidence suggests the existence of a molecular substrate for neuropathic pain produced by neurons, glia, and immune cells. Here, we show that leptin, an adipokine exclusively produced by adipocytes, is critical for the development of tactile allodynia through macrophage activation in mice with partial sciatic nerve ligation (PSL).

Mutagenesis of important amino acid reveals unconventional homologous internalization of beta(1)-adrenergic receptor.

Aims: The study was designed to examine the internalization of Asp104Lys mutant of beta(1)-adrenergic receptor (beta(1)-AR) and compared to other mutant (Asp104Ala) and wild type receptors. Moreover, this study needs to perform the role of GRK2 (betaARK1) and beta-arrestin1 on this internalization of Asp104Lys mutant of beta(1)-AR.

Main Methods: Binding affinity, functional potency of agonist and agonist-induced internalization were determined for wild type and both mutants of beta(1)-ARs stably expressed in HEK 293 cells as assessed by [(3)H] CGP12177 radioligand.

Suppressive effect of imipramine on vincristine-induced mechanical allodynia in mice.

Because chronic vincristine (VCR) treatment causes neuropathic pain, as demonstrated by mechanical allodynia, effective therapeutic strategy is required. In this study, we investigated a suppressive effect of imipramine (IMI) on VCR-induced mechanical allodynia in mice. VCR (0.

Binding sites of valsartan, candesartan and losartan with angiotensin II receptor 1 subtype by molecular modeling.

Aims: This study was designed to examine the importance of interaction in the binding of selective angiotensin II receptor antagonists to angiotensin II type 1 receptor using molecular modeling. The AT(1) antagonists used in this study were valsartan, candesartan and losartan.

Main Methods: AT(1) receptor structural model was constructed by homology modeling using structural models of rhodopsin photointermediates.

Mutation of important amino acid residue of Asp104Lys in human beta(1)-adrenergic receptor triggers functional and constitutive inactivation.

Based on our previous molecular modeling and radioligand binding study, we have demonstrated that aspartic acid of 104 in transmembrane helix (TMH) II of beta(1)-adrenergic receptor (beta(1)-AR) is important for functional characteristics of these receptors. We have also showed that mutation of negatively charged aspartic acid to neutral charged alanine exhibited constitutive activity of beta(1)-AR. However, the mutation of negatively charged aspartic acid to positively charged lysine is still remained to be examined, which is very important to know for fully understanding the characteristics of beta(1)-AR.