Reducing Molecular Flexibility by Cyclization for Elucidation of Absolute Configuration by CD Calculations: Daurichromenic Acid

Circular dichroism (CD) calculations of flexible natural products have been difficult because of the large number of low‐energy conformers and ambiguous Boltzmann distributions. In this article, through electronic (ECD) and vibrational (VCD) studies on a natural product, (+)‐daurichromenic acid, we demonstrate that derivatization of a flexible molecule can dramatically reduce its flexibility. This work also shows the usefulness of derivatization for diminishing computational expenses required for optimization and CD calculations, and for increasing the reliability of the assignment of absolute configuration. Chirality 28:453–459, 2016. © 2016 Wiley Periodicals, Inc.     

Facile Diastereoseparation of Glycosyl Sulfoxides by Chiral Stationary Phase

Separation of the diastereomers of glycosyl sulfoxides differing in the sulfur chirality has been difficult. This article presents a fast and scalable method for their diastereoseparation using a chiral stationary phase. The usefulness of this method was demonstrated in a 500‐mg scale separation within 20 min, and in the separation of trisaccharyl sulfoxide diastereomers. Chirality 28:534–539, 2016. © 2016 Wiley Periodicals, Inc.     

Urinary D-serine level as a predictive biomarker for deterioration of renal function in patients with atherosclerotic risk factors

Background: D-serine, the enantiomer of L-serine, was identified in mammals 20?years ago. Although a close relationship between D-serine and renal dysfunction has been shown, the clinical implications of urinary D- and L-serine in humans are poorly understood. The aim of this study was to evaluate the relationship between urinary D- and L-serine with well-known renal biomarkers, and clarify the prognostic value of D- and L-serine for renal events.

Methods: This cross-sectional, prospective study included 65 patients with atherosclerotic risk factors, who were followed up for a median of 16?months. The primary endpoint was a composite of end-stage renal disease and a decline in estimated glomerular filtration rate (eGFR)?≥?25% from baseline.

Results: Urinary D-serine concentrations showed a better correlation with eGFR than did urinary L-serine, whereas neither urinary D- nor L-serine correlated with tubular markers such as urinary liver-type fatty acid-binding protein and N-acetyl-beta-D-glucosaminidase. A Cox regression analysis revealed that low urinary D-serine levels were significantly associated with the primary endpoint after adjusting for confounding factors (hazard ratio 12.60; 95% confidence interval, 3.49–45.51).

Conclusions: Urinary D-serine is associated with glomerular filtration and can be a prognostic biomarker of renal dysfunction in patients with atherosclerotic risk factors.     

Searching for potent and specific antibiotics against pathogenic Helicobacter and Campylobacter strains

Journal of Industrial Microbiology & Biotechnology - Menaquinone is an obligatory component of the electron-transfer pathway in microorganisms. Its biosynthetic pathway was established by...     

Multiscale spatial genetic structure within and between populations of wild cherry trees in nuclear genotypes and chloroplast haplotypes

Spatial genetic structure (SGS) of plants mainly depends on the effective population size and gene dispersal. Maternally inherited loci are expected to have higher genetic differentiation between populations and more intensive SGS within populations than biparentally inherited loci because of smaller effective population sizes and fewer opportunities of gene dispersal in the maternally inherited loci. We investigated biparentally inherited nuclear genotypes and maternally inherited chloroplast haplotypes of microsatellites in 17 tree populations of three wild cherry species under different conditions of tree distribution and seed dispersal. As expected, interpopulation genetic differentiation was 6–9 times higher in chloroplast haplotypes than in nuclear genotypes. This difference indicated that pollen flow 4–7 times exceeded seed flow between populations. However, no difference between nuclear and chloroplast loci was detected in within‐population SGS intensity due to their substantial variation among the populations. The SGS intensity tended to increase as trees became more aggregated, suggesting that tree aggregation biased pollen and seed dispersal distances toward shorter. The loss of effective seed dispersers, Asian black bears, did not affect the SGS intensity probably because of mitigation of the bear loss by other vertebrate dispersers and too few tree generations after the bear loss to alter SGS. The findings suggest that SGS is more variable in smaller spatial scales due to various ecological factors in local populations.     

Nucleocytoplasmic shuttling of the zinc finger protein EZI Is mediated by importin-7-dependent nuclear import and CRM1-independent export mechanisms

Nucleocytoplasmic translocation constitutes a foundation for nuclear proteins to exert their proper functions and hence for various biological reactions to occur normally in eukaryotic cells. We reported previously that EZI/Zfp467, a 12 zinc finger motif-containing protein, localizes predominantly in the nucleus, yet the underlying mechanism still remains elusive. Here we constructed a series of mutant forms of EZI and examined their subcellular localization. The results delineated a non-canonical nuclear localization signal in the region covering the 9th to the 12th zinc fingers, which was necessary for nuclear accumulation of EZI as well as sufficient to confer nuclear localizing ability to a heterologous protein. We also found that the N-terminal domain of EZI is necessary for its nuclear export, the process of which was not sensitive to the CRM1 inhibitor leptomycin B. An interaction proteomics approach and the following co-immunoprecipitation experiments identified the nuclear import receptor importin-7 as a molecule that associated with EZI and, importantly, short interfering RNA-mediated knockdown of importin-7 expression completely abrogated nuclear accumulation of EZI. Taken together, these results identify EZI as a novel cargo protein for importin-7 and demonstrate a nucleocytoplasmic shuttling mechanism that is mediated by importin-7-dependent nuclear localization and CRM1-independent nuclear export.     

Determination of muscimol and ibotenic acid in Amanita mushrooms by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry

A reliable analytical method was developed for the quantification and identification of muscimol (MUS) and ibotenic acid (IBO), the toxic constituents of Amanita muscaria and Amanita pantherina. MUS and IBO were extracted from mushrooms by aqueous methanol and derivatized with dansyl chloride (DNS-Cl). After extraction with ethyl acetate and evaporation of the solvent, the residue was ethylated with 1.25 M hydrogen chloride in ethanol. The resulting derivatives were quantified by high-performance liquid chromatography with UV detection and identified by liquid chromatography electrospray ionization tandem mass spectrometry. Calibration curves were linear in the range of 25-2500 ppm for MUS and 40-2500 ppm for IBO, respectively. This method was successfully applied to identify and quantify MUS and IBO in Amanita mushrooms naturally grown and circulated in the drug market.     

Genome-wide association study of idiopathic hypersomnia in a Japanese population

Sleep and Biological Rhythms - Idiopathic hypersomnia (IH) is a rare sleep disorder characterized by excessive daytime sleepiness, great difficulty upon awakening, and prolonged sleep time. In...     

Ergothioneine production with Aspergillus oryzae

To establish a reliable and practical ergothioneine (ERG) supply, we employed fermentative ERG production using Aspergillus oryzae, a fungus used for food production. We heterologously overexpressed the egt-1 and -2 genes of Neurospora crassa in A. oryzae and succeeded in producing ERG (231.0 mg/kg of media, which was 20 times higher than the wild type).

Abbreviations: ERG: ergothioneine; HER: hercynine; Cys-HER: hercynylcysteine-sulfoxide; SAM: S-adenosylmethionine; SAH: S-adenosylhomocysteine; l-His: l-histidine; l-Cys: l-cysteine; LC-ESI-MS: liquid chromatography-electrospray ionization-mass spectrometry