GPR34 is a recently identified G-protein coupled receptor, which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative ligand. Here, we report cryo-electron ...microscopy structures of human GPR34-G
complex bound with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or M1, a derivative of S3E-LysoPS in which oleic acid is substituted with a metabolically stable aromatic fatty acid surrogate. The ligand-binding pocket is laterally open toward the membrane, allowing lateral entry of lipidic agonists into the cavity. The amine and carboxylate groups of the serine moiety are recognized by the charged residue cluster. The acyl chain of S3E-LysoPS is bent and fits into the L-shaped hydrophobic pocket in TM4-5 gap, and the aromatic fatty acid surrogate of M1 fits more appropriately. Molecular dynamics simulations further account for the LysoPS-regioselectivity of GPR34. Thus, using a series of structural and physiological experiments, we provide evidence that chemically unstable 2-acyl LysoPS is the physiological ligand for GPR34. Overall, we anticipate the present structures will pave the way for development of novel anticancer drugs that specifically target GPR34.
The asymmetric total synthesis of a newly proposed structure of (3S,16E,20E,23S)-(+)-eushearilide was achieved primarily through an asymmetric Mukaiyama aldol reaction, Schlosser-modified Wittig ...reaction and 2-methyl-6-nitrobenzoic anhydride-mediated macrolactonization. Based on detailed spectroscopic analyses, the obtained synthetic compound was found to be identical to natural eushearilide. Therefore, we were able to determine the true structure of eushearilide. Moreover, the synthetic compound was found to exhibit significant in vitro antifungal activity against various fungi and bacteria.
The sky exhibits a unique spatial polarization pattern by scattering the unpolarized sun light. Just like insects use this unique angular pattern to navigate, we use it to map pixels to directions on ...the sky. That is, we show that the unique polarization pattern encoded in the polarimetric appearance of an object captured under the sky can be decoded to reveal the surface normal at each pixel. We derive a polarimetric reflection model of a diffuse plus mirror surface lit by the sun and a clear sky. This model is used to recover the per-pixel surface normal of an object from a single polarimetric image or from multiple polarimetric images captured under the sky at different times of the day. We experimentally evaluate the accuracy of our shape-from-sky method on a number of real objects of different surface compositions. The results clearly show that this passive approach to fine-geometry recovery that fully leverages the unique illumination made by nature is a viable option for 3D sensing. With the advent of quad-Bayer polarization chips, we believe the implications of our method span a wide range of domains.
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An asymmetric total synthesis of the proposed structure of (16Z,20E)-eushearilide, a novel 24-membered macrolide, was achieved via an enantioselective aldol reaction and ...2-methyl-6-nitrobenzoic anhydride-mediated macrolactonization. The obtained synthetic compounds were not identical to the natural product. The newly proposed most likely structure of eushearilide, (±)-(16E,20E)-eushearilide, was determined on the basis of detailed NMR analysis, and (3R,16E,20E,23R)-(−)-eushearilide was successfully synthesized. A comparison of the optical rotation of (3R,16E,20E,23R)-(−)-eushearilide with that of the natural product confirmed that the true structure of naturally occurring eushearilide is the (3S,16E,20E,23S)-(+)-form.
This paper presents an underwater active stereo system that realizes 3D capture of dynamic objects in water such as swimming fish. The key idea on realizing a practical underwater 3D sensing is to ...model the refraction process by our pixel-wise varifocal camera model that provides efficient forward (3D to 2D) projections as well as an underwater projector–camera calibration. Evaluations demonstrate that our method achieves reasonable calibration accuracy using off-the-shelf cameras and projectors, and provides a 3D capture of real swimming fish in water.
•A practical underwater active stereo system for dynamic 3D capture of object in water with explicit refraction modeling.•A practical projector–camera calibration in water.•An efficient projection computation of 3D points in water to 2D camera images.
A depsipeptidic analogue of FE399 was efficiently synthesized mainly through macrolactamization using 2-methyl-6-nitrobenzoic anhydride (MNBA), and a detailed investigation of the desired 16-membered ...macrolactam core of FE399 was performed. It was determined that the combination of MNBA and a catalytic amount of 4-(dimethylamino)pyridine N-oxide exhibits much higher activity than that of conventionally used coupling reagents such as hexafluorophosphate azabenzotriazole tetramethyl uronium and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate.
► Tipepidine produces an antidepressant like effect in the forced swimming test. ► The effect of tipepidine may be produced via dopamine D
1 and alpha2 adrenoceptor. ► The properties of the effect ...may be different from those of known antidepressants.
We previously reported that the centrally acting non-narcotic antitussive, tipepidine, produces a novel antidepressant-like effect in the forced swimming test in rats, but the mechanism of the antidepressant-like effect of tipepidine is not clear. We investigated the pharmacological mechanism of the antidepressant-like effect of tipepidine in the forced swimming test in rats. A catecholamine-depleting agent, alpha-methyl-
p-tyrosine (AMPT; 300
mg/kg, s.c.), was given 6
h before the first injection and with the last injection of tipepidine (40
mg/kg, i.p.). A serotonin (5-HT)-depleting agent,
p-chlorophenylalanine (PCPA; 350
mg/kg, i.p.), was given 72
h and 48
h before the pretest session. The dopamine D
1 receptor antagonist, SCH23390 (0.02
mg/kg, s.c.) was given 15
min before each of the three injections of tipepidine. The dopamine D
2 receptor antagonist raclopride (0.2
mg/kg, s.c.), the alpha 1 adrenoceptor antagonist prazosin (1
mg/kg, i.p.), the alpha 2 adrenoceptor antagonist yohimbine (2
mg/kg, i.p.) and the beta adrenoceptor antagonist propranolol (2
mg/kg, i.p.) were given 30
min before each of the three injections of tipepidine. AMPT, but not PCPA, significantly inhibited the immobility time-reducing effect of tipepidine in the forced swimming test. Furthermore, the effect of tipepidine was significantly inhibited by SCH23390 and yohimbine. However, raclopride, prazosin, and propranolol failed to block the effect of tipepidine. The results suggest that the antidepressant-like effect of tipepidine in the forced swimming test may be due at least in part to the effects of dopamine and noradrenaline released at the dopamine D
1 receptor and alpha 2 adrenoceptor, respectively.
We investigated the potential toxicity of gum ghatti, which is added to food for emulsifying, thickening, and stabilizing, after 4 weeks of repeated oral administration at a dose of 8000 mg/kg/day to ...male and female SD rats. Although food consumption was significantly reduced in males in the gum ghatti group compared with those in the distilled water group from Day 18 onwards, the change was minor, there was no pathological evidence of digestive tract abnormalities, and there were no significant changes in body weight; therefore, the change in food consumption was judged to be of no toxicological significance. Hematology and blood biochemistry revealed statistically significant differences in some parameters between the gum ghatti group and the distilled water group. These changes were all within the normal range of physiological variation and therefore were not considered to represent the effects of gum ghatti. In addition, general signs, body weight, and pathology showed no changes in either sex attributable to gum ghatti. Thus, all changes observed were of no toxicological significance and within the normal range of physiological variation, suggesting gum ghatti has no toxic effects in rats.
The first total synthesis and structural determination of benzopyrenomycin has been achieved. This synthesis contains remarkable transformations including cyclization to afford the benzanthrone ...skeleton,
syn-selective vinylogous Mukaiyama aldol reaction, and radical cyclization with the benzanthrone attaching the iodoalkane chain.
This paper is aimed at presenting a 3D surface capture algorithm of underwater objects using multiple projectors and cameras with flat housings. We use a pixel-wise varifocal model to realize an ...efficient forward projection in order to explicitly account for refractions caused by flat housings and to improve appearance-based correspondence estimations. We propose a practical calibration procedure of underwater projectors, and show a real system which proves our concept.
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