Effect of Brewer's Yeast-Induced Pyrexia on Aminophylline-Elicited Convulsions in Mice

Theophylline-associated convulsions have been observed most frequently in children with fever, but the mechanism is not fully understood. In this study, we investigated the basic mechanism of aminophylline [theophylline-2-ethylenediamine]-induced convulsions and the effects of Brewer's yeast-induced pyrexia in mice. Diazepam (5-10mg/kg, i.p.), a benzodiazepine receptor agonist, significantly prolonged the onset and significantly decreased the incidence of convulsions induced by aminophylline (350mg/kg, i.p.). However, the gamma aminobutyric acid (GABA)A receptor agonist muscimol (1-4mg/kg, i.p.), the GABAB receptor agonist baclofen (2-4mg/kg, i.p.) and the N-methyl-D-aspartic acid receptor antagonist dizocilpine (0.1-0.3mg/kg, i.p.) failed to protect against the convulsions. 20% Brewer's yeast (0.02ml/g, s.c.) increased body temperature by 1.03, and also significantly shortened the onset and significantly increased the incidence of convulsions induced by aminophylline. The anticonvulsant action of diazepam (2.5-10mg/kg, i.p.) on the convulsions induced by aminophylline was reduced by Brewer's yeast-induced pyrexia. The proconvulsant actions of the GABAA receptor antagonists picrotoxin (3-4mg/kg, i.p.) and pentylenetetrazol (40-60mg/kg, i.p.) were enhanced by Brewer's yeast. These results suggest that the anticonvulsant action of diazepam against aminophylline is reduced by Brewer's yeast-induced pyrexia, and that GABAA receptors are involved in the aggravation of the convulsions by Brewer's yeast in mice.</p

First-step experiment in developing optical-spring quantum locking for DECIGO: sensitivity optimization for simulated quantum noise by completing the square

DECi-hertz Interferometer Gravitational Wave Observatory (DECIGO) is a future mission for a space-borne laser interferometer. DECIGO has 1,000-km-long arm cavities mainly to detect the primordial gravitational waves (PGW) at lower frequencies around 0.1 Hz. Observations in the electromagnetic spectrum have lowered the bounds on the upper limit of PGW energy density ($\Omega_{\rm gw} \sim 10^{-15} \to 10^{-16}$). As a result, DECIGO's target sensitivity, which is mainly limited by quantum noise, needs further improvement. To maximize the feasibility of detection while constrained by DECIGO's large diffraction loss, a quantum locking technique with an optical spring was theoretically proposed to improve the signal-to-noise ratio of the PGW. In this paper, we experimentally verify one key element of the optical-spring quantum locking: sensitivity optimization by completing the square of multiple detector outputs. This experiment is operated on a simplified tabletop optical setup with classical noise simulating quantum noise. We succeed in getting the best of the sensitivities with two different laser powers by the square completion method.Comment: 10 pages, 14 figure

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

Mechanical Behavior of Molecular Crystals Induced by Combination of Photochromic Reaction and Reversible Single-Crystal-to-Single-Crystal Phase Transition

We herein report a unique mechanical behavior of a molecular crystal induced by combination of a photochromic reaction and a reversible single-crystal-to-single-crystal (SCSC) phase transition. A crystal of a diarylethene having octyl group at both sides (<b>1a</b>) was found to undergo a reversible thermodynamic SCSC phase transition accompanying a change in crystal length, which was clarified by differential scanning calorimetry measurement, X-ray crystallographic analysis, and direct microscopic observation of the crystal length. Furthermore, upon irradiation with ultraviolet light, the diarylethene crystal exhibited an unusual photomechanical behavior. The mechanism of the behavior was proposed based on photoisomerization of the diarylethene from the open-ring isomer to the closed-ring isomer and a reversible thermodynamic SCSC phase transition, which was well-supported by thermal bending behavior of a photoirradiated crystal