Nonphotic entrainment of an overt sleep-wake rhythm and a circadian pacemaker-driving temperature/melatonin rhythm suggests existence of feedback mechanisms in the human circadian system. In this study, the authors constructed a phase dynamics model that consisted of two oscillators driving temperature/melatonin and sleep-wake rhythms, and an additional oscillator generating an overt sleep-wake rhythm. The feedback mechanism was implemented by modifying couplings between the constituent oscillators according to the history of correlations between them. The model successfully simulated the behavior of human circadian rhythms in response to forced rest-activity schedules under free-run situations: the sleep-wake rhythm is reentrained with the circadian pacemaker after release from the schedule, there is a critical period for the schedule to fully entrain the sleep-wake rhythm, and the forced rest-activity schedule can entrain the circadian pacemaker with the aid of exercise. The behavior of human circadian rhythms was reproduced with variations in only a few model parameters. Because conventional models are unable to reproduce the experimental results concerned here, it was suggested that the feedback mechanisms included in this model underlie nonphotic entrainment of human circadian rhythms.

Limited data are available on the background levels of exposure to synthetic pyrethroid (PYR) in Japan despite their frequent application for agriculture and indoor extermination and possible effects of chronic and/or low-dose PYR exposure on human health. This study was conducted to describe the level and distribution of one of the major PYR metabolites, 3-phenoxybenzoic acid (3-PBA), in urine samples collected from a general population in Japan. The subjects were 535 individuals (184 men and 351 women; 61.5 ± 9.8 years of age, mean ± S.D.) residing in a town in Hokkaido, a dairy and agricultural area. Urinary 3-PBA was found detectable in 98% of samples above the limit of detection of 0.02 μg/L. The geometric mean values of urinary 3-PBA in occupationally exposed farmers (n = 87) and the remaining general group without occupational exposure (n = 448) were 0.38 μg/L and 0.29 μg/L, respectively, ranging from < LOD to 17.09 μg/L. No significant differences in urinary 3-PBA concentrations were shown between these two groups. Moreover, 3-PBA concentrations were found comparable to those reported in some countries. The present study is, to our knowledge, the first report of a biological monitoring study of urinary 3-PBA, which elucidated the background environmental exposure level of PYR in the Japanese general population without occupational exposure. Further nationwide studies covering different seasons and age distribution are needed to monitor the urinary 3-PBA levels in Japan.

Nucleotide-binding, leucine-rich repeat containing X1 (NLRX1) is a mitochondria-located innate immune sensor that inhibits major pro-inflammatory pathways such as type I interferon and nuclear factor-κB signaling. We generated a novel, spontaneous, and rapidly progressing mouse model of multiple sclerosis (MS) by crossing myelin-specific T-cell receptor (TCR) transgenic mice with Nlrx1−/− mice. About half of the resulting progeny developed spontaneous experimental autoimmune encephalomyelitis (spEAE), which was associated with severe demyelination and inflammation in the central nervous system (CNS). Using lymphocyte-deficient mice and a series of adoptive transfer experiments, we demonstrate that genetic susceptibility to EAE lies within the innate immune compartment. We show that NLRX1 inhibits the subclinical stages of microglial activation and prevents the generation of neurotoxic astrocytes that induce neuronal and oligodendrocyte death in vitro. Moreover, we discovered several mutations within NLRX1 that run in MS-affected families. In summary, our findings highlight the importance of NLRX1 in controlling the early stages of CNS inflammation and preventing the onset of spontaneous autoimmunity.

No abstract

Minority-carrier lifetime improvement by a two-step annealing has been demonstrated using MOS capacitors fabricated on Czochralski-grown (CZ) silicon wafers. It is shown that an intrinsic gettering effect does not always follow a single annealing in an oxygen-free ambient, even in the wafers containing high oxygen content (∼1018 cm−3). This is probably because nuclei of precipitate-dislocation complexes (PDC) are two small in size to grow into PDC during a single annealing of recent high-grade CZ wafers. In the present study, an additional low-temperature annealing at 800 °C is performed in order to improve the situation. A few critical conditions to the effectiveness of the intrinsic gettering are discussed in connection with the crystalline quality of the wafer.