Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a catalytic subunit of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some subunits of SWItch/Sucrose Non‐Fermentable (SWI/SNF) chromatin remodeling complexes have been observed. However, little is known about the function of EZH1 in tumorigenesis. Herein, we developed novel, orally bioavailable EZH1/2 dual inhibitors that strongly and selectively inhibited methyltransferase activity of both EZH2 and EZH1. EZH1/2 dual inhibitors suppressed trimethylation of histone H3 lysine 27 in cells more than EZH2 selective inhibitors. They also showed greater antitumor efficacy than EZH2 selective inhibitor in vitro and in vivo against diffuse large B‐cell lymphoma cells harboring gain‐of‐function mutation in EZH2. A hematological cancer panel assay indicated that EZH1/2 dual inhibitor has efficacy against some lymphomas, multiple myeloma, and leukemia with fusion genes such as MLL‐AF9,MLL‐AF4, and AML1‐ETO. A solid cancer panel assay demonstrated that some cancer cell lines are sensitive to EZH1/2 dual inhibitor in vitro and in vivo. No clear correlation was detected between sensitivity to EZH1/2 dual inhibitor and SWI/SNF mutations, with a few exceptions. Severe toxicity was not seen in rats treated with EZH1/2 dual inhibitor for 14 days at drug levels higher than those used in the antitumor study. Our results indicate the possibility of EZH1/2 dual inhibitors for clinical applications.

A chiral Brønsted acid has been developed from cationic gold(I) disphosphine complex in the presence of alcoholic solvent and applied to enantioselective protonation reaction of silyl enol ethers of ketones. Various optically active cyclic ketones were obtained in excellent yields and high enantioselectivities including cyclic ketones bearing aliphatic substrates at the α-position. Furthermore, the application of this Brønsted acid was extended to the first Brønsted acid-catalyzed enantioselective protonation reaction of silyl enol ethers of acyclic substrates, regardless of their E/Z ratio.

Alcohol is key: Regio‐ and enantioselective hydroamination of 1,3‐dienes has been achieved with the dinuclear catalyst (R)‐DTBM‐SEGPHOS. The rate and selectivity of the reaction are enhanced by alcohol additives like menthol, which coordinates the cationic gold(I) to generate a Brønsted acid that can participate in catalysis. Mbs=p‐methoxybenzenesulfonyl.

The effects of triazolam on cognitive function and vigilance on the morning following a nocturnal administration were investigated using event-related potentials (ERP) measurement and a sleep latency test (SLT). We previously reported a significant reducing effect on target N1 amplitude on the morning following triazolam administration, suggesting a residual effect of triazolam. In order to demonstrate, which aspect of cognitive function alteration caused the reducing effect on N1 amplitude, we added the ignore condition for ERP measurement, which enabled us to separate mismatch negativity (MMN) from other subcomponents overlapping N1. As a result, MMN was attenuated and sleep latency was shortened on the morning following triazolam administration. Two possibilities were suggested for the mechanism of MMN attenuation. One is GABAergic activation caused by the residual effect of triazolam per se, and the other is the lowered vigilance level demonstrated in the SLT. Further studies are necessary to determine whether this alteration in physiological bases underlying mismatch detection is specific to triazolam and/or other benzodiazepines or related to nonspecific vigilance level.

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EEG examinations were carried out on 137 patients with thalidomide embryopathy aged between 7 and 22 with a mean age of 17.0. Waking and sleep EEGs were normal in 82 (59.9%), and abnormal in 55 (40.1%). The incidence of abnormal EEG was significantly high in the patients associated with mental retardation, and it increased in proportion to the severity of mental retardation. The most frequent abnormal EEG finding was slowing of the basic activity (35/137; 24.8%).The incidence of slowing was significantly higher in the patients with a sensorineural hearing impairment (26/74; 35.1%) than in those with dysmelia (9/62; 14.5%). Slowing appeared frequently in the patients with various cranial nerve symptoms (30/84; 35.7%). Theincidence of slowing was found significantly high in the patients with borderline or subnormal intelligence (8/16; 50.0%), and it correlated with the severity of mental retardation. Many patients (48/84; 57.1%) showed unilateral or asymmetrical neurological symptoms. However, asymmetry or focal abnormality in EEG was shown in only 8 patients. Positive spikes appeared frequently in the patients with gonadal dysplasia. Other somatic symptoms, past medical history and family history were not related to the incidence of abnormal EEGs. Eight patients had had epileptic seizures prior to this examination. Another 2 patients had noctural enuresis and showed epileptic EEG abnormalities in this examination. The incidence of epilepsy was significantly higher in the patients we examined than among the general population. It is concluded that ingestion of thalidomide during pregnancy affected not only the morphological development of the limbs of the fetus, but the functions of its central nervoussystem, causing hearing impairment, other cranial nerve symptoms, mental retardation or epilepsy.

Previous reports have suggested that human time production of several seconds fluctuates across the day. In order to test whether human time production was controlled by the circadian process or by the homeostatic process, we investigate diurnal fluctuation of human time production under constant routine conditions. We found a common circadian feature in time production tests of 10 s by calculating Z‐score for each subject; afternoon troughs and morning peaks. These results may suggest that human time production was modulated by the circadian process.