High-dose zolpidem abuse in a patient with insomnia comorbid with major depressive disorder

Sleep and Biological Rhythms - A 39-year-old married woman was referred to a psychiatry outpatient clinic for treatment of major depressive disorder (MDD). The dose of zolpidem she had been taking...     

Ophiocordyceps sessilis sp. nov., a new species of Ophiocordyceps on Camponotus ants in Japan

Ophiocordyceps sessilis, a new species of Ophiocordycipitaceae, Hypocreales, was found on Camponotus obscuripes ants, where the ants were primarily infected by another close relative, O. pulvinata. Morphological observation clearly indicated that O. sessilis and O. pulvinata are distinct species. Ophiocordyceps sessilis exhibited superficial development of perithecia and ascospore disarticulation into part-spores, not known in O. pulvinata. Nucleotide sequence data suggested that O. sessilis belongs in Ophiocordyceps, Ophiocordycipitaceae. Molecular data also indicated that O. sessilis is a close relative of O. cuboidea, O. prolifica, O. paracuboidea, and O. ryogamiensis, which are all known to produce part-spores. Since O. sessilis is always associated with ants infected by O. pulvinata, O. sessilis may be a hyperparasite of O. pulvinata.     

CLE2 regulates light-dependent carbohydrate metabolism in Arabidopsis shoots

Plant Molecular Biology - This study focused on the role of CLE1-CLE7 peptides as environmental mediators and indicated that root-induced CLE2 functions systemically in light-dependent carbohydrate...     

Mutations in SERPINB7, Encoding a Member of the Serine Protease Inhibitor Superfamily,Cause Nagashima-type Palmoplantar Keratosis

“Nagashima-type” palmoplantar keratosis (NPPK) is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis characterized by well-demarcated diffuse hyperkeratosis with redness, expanding on to the dorsal surfaces of the palms and feet and the Achilles tendon area. Hyperkeratosis in NPPK is mild and nonprogressive, differentiating NPPK clinically from Mal de Meleda. We performed whole-exome and/or Sanger sequencing analyses of 13 unrelated NPPK individuals and identified biallelic putative loss-of-function mutations in SERPINB7, which encodes a cytoplasmic member of the serine protease inhibitor superfamily. We identified a major causative mutation of c.796C>T (p.Arg266^∗) as a founder mutation in Japanese and Chinese populations. SERPINB7 was specifically present in the cytoplasm of the stratum granulosum and the stratum corneum (SC) of the epidermis. All of the identified mutants are predicted to cause premature termination upstream of the reactive site, which inhibits the proteases, suggesting a complete loss of the protease inhibitory activity of SERPINB7 in NPPK skin. On exposure of NPPK lesional skin to water, we observed a whitish spongy change in the SC, suggesting enhanced water permeation into the SC due to overactivation of proteases and a resultant loss of integrity of the SC structure. These findings provide an important framework for developing pathogenesis-based therapies for NPPK.     

Discovery of TAK-960: An orally available small molecule inhibitor of polo-like kinase 1 (PLK1)

Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies.     

Isolation and Identification of Native Auxins in Marine Algae

Endosperm cell walls were isolated from rice grains and their chemical composition was analyzed. The cell walls were composed of cellulose microfibrils and matrix phase which consisted of hemicellulose and pectic substances. Hemicellulose mainly comprised arabinoxylan, accompanied by a small amount of glucose-containing polysaccharide. Pectic substances contained polygalacturonides, some of which had side chains containing neutral sugars such as galactose and arabinose. Amino acid analysis of these fractions suggested that hydroxyproline-containing glycoproteins were contained in these cell walls and firmly bound to cellulose microfibrils.     

Studies on Kojic Acid and its Related γ-Pyrone Compounds

The Mannich reaction of kojic acid in both acidic and basic media was studied. Mono-Mannich derivatives (substitution at position 6) were obtained; the reactivity in basic medium was found to be somewhat greater than in acidic medium. Reduction of the Mannich derivatives with zinc dust and acetic acid gave a 6-methyl kojic acid (6-methyl-5-hydroxy-2-hydroxymethyl-γ-pyrone).

Mono-Mannich base of pyromeconic acid was also prepared in a manner similar to that of kojic acid. From this Mannich base, maltol (2-methyl-3-hydroxy-γ-pyrone) was obtained by the reduction with zinc dust and acetic acid.     

Conformational Change of a Natto Mucin in Solution

The mucin obtained from a natto sample was found to be composed of 58 % of γ-polyglutamic acid and 40% of polysaccharide. The ratio of l- and d-glutamic acid was determined to be 58:42 using l-glutamic acid decarboxylase. The weight- and z-average molecular weight were 2.08 × 10⁵ and 2.22 × 10⁵, respectively. The distribution curve of the sedimentation coefficient showed a small heterogeneity. The mucin molecule was considered to be randomly coiled at pH 5.0 ~ 8.8 and to be a rod-like molecule in the lower pH region.     

Relative Cytokinin Activity of 3-Methyl Substituted Adenylate Cytokinins

More than 100 multi-component lures consisting of primary straight chain alkenols, their acetates and alkenals were prepared and tested as attractants of male lepidopterous insects. In field trials, male moths of 52 species were specifically attracted to two- or three-component lures. Further 35 lepidopterous species were found to be attracted to single component lures used as control. The main families captured by the multi-component lures were Tortricidae (24 species), Noctuidae (11 species) and Acrolepiidae (3 species). This successful attraction of so many species indicates the usefulness of systematic field tests using multi-component lures of selected synthetic chemicals.