Comparison of structural effects of cholesterol, lanosterol, and oxysterol on phospholipid (POPC) bilayers.

Membrane sterols contribute to the function of biomembranes by regulating the physical properties of the lipid bilayers. Cholesterol, a typical mammalian sterol, is biosynthesized by oxidation of lanosterol. From a molecular evolutionary perspective, lanosterol is considered the ancestral molecule of cholesterol. Here, we studied whether cholesterol is superior to lanosterol in regulating the physical properties of the lipid bilayer in terms of the structural effect on model biomembranes composed of a phospholipid. For comparison, oxysterol, which is formed by oxidation of cholesterol, was also studied. The phospholipid used was 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), which is abundantly found in mammalian biomembranes, and 7ß-hydroxycholesterol, which is highly cytotoxic, was used as the oxysterol. The apparent molecular volume was calculated from the mass density determined by the flotation method using H2O and D2O, and the bilayer thickness was determined by reconstructing the electron density distribution from X-ray diffraction data of the POPC/sterol mixtures at a sterol concentration of 30 mol%. The apparent occupied area at the bilayer surface was calculated from the above two structural data. The cholesterol system had the thickest bilayer thickness and the smallest occupied area of the three sterols studied here. This indicates that the POPC/cholesterol bilayer has a better barrier property than the other two systems. Compared to cholesterol, the effects of lanosterol and 7ß-hydroxycholesterol on lipid bilayer properties can be interpreted as suboptimal for the function of mammalian biomembranes.

CDX2-positive Cancer of Unknown Primary With Upper-body Paralysis Was Dramatically Improved by Colorectal Cancer Chemotherapy.

BACKGROUND: Caudal-related homeobox transcription factor 2 (CDX2) is expressed in intestinal epithelial cells. CDX2 is a very sensitive marker for the identification of small and large intestine tumors, which is expressed in 85.7-100% of colorectal cancer (CRC) cases. CASE REPORT: A 61-year-old female had been suffering from left shoulder pain for one month. Computed tomography showed osteolytic masses extending to the vertebral arch in the C5, C6, C7, and Th3 vertebral bodies. In addition, a thickening of the sigmoid colon was observed from the rectal-sigmoid colon, suggesting CRC. A colon biopsy revealed poorly differentiated adenocarcinoma and the vertebra excision was metastatic adenocarcinoma. However, immunohistochemically, the vertebra tumor was negative for CK7 and CK20 but positive for CDX2. Therefore, we made the diagnosis of CRC with bone metastasis and decided to start treatment for CRC. Posterior stabilization was performed for the spinal tumor 6 days after admission. About one month after admission, she started treatment with chemotherapy. Initially, her left hand could not move, and she could barely hold the pen with her right hand. After adding cetuximab for the third time, she became able to bend the dorsiflexion of her right wrist joint, grasp a stick with her right hand, and move the fingertips of her left hand a little. CONCLUSION: The presented case could not be diagnosed as CRC unless CDX2 was examined. Upper body paralysis due to CRC bone metastasis was improved by chemotherapy.

Diaryliodonium Salt-Mediated Intramolecular C-N Bond Formation Using Boron-Masking N-Hydroxyamides.

Intramolecular aromatic C-N bond formation reactions using electron-rich aromatic tethered boron-masking N-hydroxyamide as substrate were realized. These new C-N bond formation reactions involve the in situ generation of a diaryliodonium salt by treatment with hypervalent iodine, deborylation by base treatment, spontaneous N → O acyl migration, cyclization, reductive elimination, elimination of benzoic acid, and tautomerization to indole formation. Hereby, we obtained highly functionalized electron-rich indoles and quinoline in practical yields.

Total syntheses and stereochemical reassignments of mollenines A and B.

Total syntheses of prenylated pyrrolidinoindoline alkaloids, (-)-mollenines A [(-)-1'] and B (2'), were accomplished via three- and four-step sequences including a bioinspired indole prenylation reaction followed by dioxomorpholine ring formation. Then, the stereochemistry of mollenines A and B was reassigned to 3S,6S,14S,16S by analysis of spectroscopic data and chemical syntheses with different approaches along with the comparison of calculated and experimental ECD spectra. In addition, a thermodynamically controlled epimerization reaction on the dioxomorpholine ring was observed in our synthesis.

Orexin A enhances locomotor activity and induces anxiogenic-like action in the goldfish, Carassius auratus.

Orexin acts as an orexigenic factor for the regulation of appetite and rhythmicity in rodents. In goldfish, intracerebroventricular (ICV) administration of orexin A has been shown to affect not only food intake, but also locomotor activity. However, as there is still no information regarding the effect of orexin A on emotional behavior in goldfish, we investigated the effect of orexin A on psychomotor activity in this species. Intracerebroventricular administration of synthetic orexin A at 2 and 4pmol/g body weight (BW) enhanced locomotor activity, and this enhancement by orexin A at 4pmol/g BW was attenuated by treatment with the orexin receptor 1 antagonist, SB334867, at 10pmol/g BW. Since intact goldfish prefer a black to a white background area, or the lower to the upper area of a tank, we used two types of preference tests (black/white and upper/lower tests) for measuring anxiety-like behavior in goldfish. Intracerebroventricular administration of orexin A at 4pmol/g BW shortened the time spent in the white background area, and increased the time taken to move from the lower to the upper area. This action of orexin A mimicked that of the central-type benzodiazepine receptor inverse agonist, FG-7142 (an anxiogenic agent), at 4pmol/g BW. The anxiogenic-like effect of orexin A was abolished by treatment with SB334867 at 10pmol/g BW. These results indicate that orexin A potently affects psychomotor activity in goldfish.

Ovine corticotropin-releasing hormone (oCRH) exerts an anxiogenic-like action in the goldfish, Carassius auratus.

Corticotropin-releasing hormone (CRH) is a member of the hypothalamic neuropeptide family that includes urocortins, urotensin I and sauvagine in vertebrates. CRH and urocortin act as anorexigenic factors for satiety regulation in rodents. In a goldfish model, intracerebroventricular (ICV) administration of ovine CRH (oCRH) affects not only food intake, but also locomotor activity. However, there is no information regarding the psychophysiological roles of CRH in goldfish. Therefore, we investigated the effect of oCRH on psychomotor activity in this species. ICV administration of synthetic oCRH at 20 pmol/g body weight (BW) enhanced locomotor activity. Since intact goldfish prefer the lower to the upper area of a tank, we developed a method for measuring the time taken for fish to move from the lower to the upper area. ICV administration of oCRH at 20 pmol/g BW and the central-type benzodiazepine receptor inverse agonist FG-7142 (an anxiogenic agent) at 1-4 pmol/g BW both increased the time taken to move from the lower to the upper area. This anxiogenic-like effect of oCRH was abolished by the CRH receptor antagonist α-helical CRH(9-41) (100 pmol/g BW). These results indicate that CRH can potently affect locomotor and psychomotor activities in goldfish.

CaCu3Pt4O12: the first perovskite with the B site fully occupied by Pt(4+).

A novel A-site ordered perovskite CaCu(3)Pt(4)O(12) was synthesized under high pressure and high temperature of 12 GPa and 1250 degrees C. CaCu(3)Pt(4)O(12) is the first perovskite in which the B site is fully occupied by Pt(4+). The crystal structure refinement based on the synchrotron powder X-ray diffraction data shows that CaCu(3)Pt(4)O(12) crystallizes in the space group Im3 (cubic) with a lattice constant of a = 7.48946(10) A. The magnetic susceptibility data show the antiferromagnetic transition at T(N) = 40 K, which is attributed to the magnetic ordering of Cu(2+) spins with S = 1/2.

The anorexigenic action of the octadecaneuropeptide (ODN) in goldfish is mediated through the MC4R- and subsequently the CRH receptor-signaling pathways.

Intracerebroventricular (ICV) administration of the octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor, reduces food intake in goldfish as in rodents. However, the neurochemical pathways involved in the anorexigenic action of ODN have not yet been identified in goldfish. Alpha-melanocyte-stimulating hormone (alpha-MSH), corticotropin-releasing hormone (CRH), and CRH-related peptides play a major role in the control of food consumption in goldfish. In this species, the anorexigenic action of alpha-MSH is mediated via the CRH/CRH receptor neuronal system. Therefore, in the present study, we examined whether the anorexigenic effect of ODN in goldfish could be mediated through alpha-MSH and/or CRH neuronal pathways. ICV injection of ODN (10 pmol/g body weight (BW)) significantly reduced food intake, and the anorexigenic effect of ODN was suppressed by ICV preinjection of the melanocortin 4 receptor (MC4R) antagonist HS024 (40 pmol/g BW) or the CRH receptor 1/receptor 2 antagonist alpha-helical CRH((9-41)) (100 pmol/g BW). ICV injection of ODN (10 pmol/g BW) induced a significant increase of proopiomelanocortin mRNA level but had no effect on CRH mRNA level, while ICV injection of the MC4R agonist, melanotan II (100 pmol/g BW), significantly enhanced CRH mRNA expression. These results suggest that, in goldfish, the anorexigenic action of ODN is mediated by the MC4R- and subsequently through the CRH receptor-signaling pathways.

Neuromedin U-induced anorexigenic action is mediated by the corticotropin-releasing hormone receptor-signaling pathway in goldfish.

Our recent research has indicated that neuromedin U (NMU) orthologs exist in goldfish, and that NMU consisting of 21 amino acid residues (NMU-21) can potently inhibit food intake in goldfish, as is the case in rodents. However, the anorexigenic pathway of NMU-21 has not yet been clarified in this species. Corticotropin-releasing hormone (CRH), CRH-related peptides and alpha-melanocyte-stimulating hormone (alpha-MSH), which exert potent anorexigenic effects, are important mediators involved in feeding regulation in fish. We examined whether CRH or alpha-MSH mediates NMU-21-induced anorexigenic action in goldfish. We first investigated the effect of intracerebroventricular (ICV) administration of NMU-21 at 100 pmol/g body weight (BW), which is enough to suppress food intake, on expression levels of mRNA for CRH and proopiomelanocortin (POMC) in the hypothalamus. ICV-injected NMU-21 induced a significant increase in the expression level of CRH mRNA, but not that of POMC mRNA. We also examined the effects of ICV administration of the CRH 1/2 receptor antagonist, alpha-helical CRH((9-41)), and the melanocortin 4 receptor antagonist, HS024, on the anorexigenic action of ICV-injected NMU-21. The anorexigenic effect of NMU-21 was blocked by treatment with alpha-helical CRH((9-41)) at 400 pmol/g BW, but not HS024 at 200 pmol/g BW. These results suggest that the anorexigenic action of NMU-21 is mediated by the CRH 1 or 2 receptor-signaling pathway in goldfish.

Corticotropin-releasing hormone mediates alpha-melanocyte-stimulating hormone-induced anorexigenic action in goldfish.

alpha-Melanocyte-stimulating hormone (alpha-MSH) and corticotropin-releasing hormone (CRH) both suppress food intake, and the alpha-MSH- or CRH-signaling pathway has possible potency to mediate anorexigenic actions induced by most other neuropeptides in goldfish. Therefore, using specific receptor antagonists, we examined whether the anorexigenic actions of alpha-MSH and CRH mutually interact. The inhibitory effect of ICV injection of the alpha-MSH agonist, melanotan II (MT II), on food intake was abolished by treatment with a CRH 1/2 receptor antagonist, alpha-helical CRH((9-41)), whereas the anorexigenic action of ICV-injected CRH was not affected by treatment with a melanocortin 4 receptor antagonist, HS024. This led us to investigate whether alpha-MSH-containing neurons in the goldfish brain have direct inputs to CRH-containing neurons, using confocal laser scanning microscopy. alpha-MSH- and CRH-like immunoreactivities were distributed throughout the brain, especially in the diencephalon. alpha-MSH-containing nerve fibers or endings lay in close apposition to CRH-containing neurons in a region of the hypothalamus, the nucleus posterioris periventricularis (NPPv). These results indicate that, in goldfish, alpha-MSH-induced anorexigenic action is mediated by the CRH-signaling pathway, and that CRH plays a crucial role in the regulation of feeding behavior as an integrated anorexigenic neuropeptide in this species.