Background-Hematopoietic cytokines, granulocyte colony-stimulating factor (G-CSF), and stem cell factor (SCF) were reported to show a neuroprotective effect or to support neurogenesis. These cytokines also mobilize bone marrow (BM) cells into the brain, and the BM-derived cells differentiate into neuronal cells. We administered these hematopoietic cytokines after focal cerebral ischemia and assessed their effects and the therapeutic time window for neuronal regeneration. Methods and Results-We induced permanent middle cerebral artery occlusion in mice whose BM had been replaced with BM cells from green fluorescent protein (GFP)-transgenic mice. The occluded mice were treated with G-CSF and SCF in the acute phase (days 1 to 10) or subacute phase (days 11 to 20), and the brain functions and histological changes were evaluated. Separately, we injected bromodeoxyuridine during cytokine treatment to assess cell kinetics in the brain. Six mice were prepared for each experimental group. Administration of G-CSF and SCF in the subacute phase effectively improved not only motor performance but also higher brain function, compared with acute-phase treatment. Acute-phase and subacute-phase treatments identically reduced the infarct volume relative to vehicle treatment. However, subacute-phase treatment significantly induced transition of BM-derived neuronal cells into the peri-infarct area and stimulated proliferation of intrinsic neural stem/progenitor cells in the neuroproliferative zone. Conclusions-Administration

This mini-review focuses on the effects of exercise on sleep. In its early days, sleep research largely focused on central nervous system (CNS) physiology using standardized tabulations of several sleep-specific landmark electroencephalogram (EEG) waveforms. Though coarse, this method has enabled the observation and inspection of numerous uninterrupted sleep phenomena. The research on the effects of exercise on sleep began, in the 1960s, with a focus primarily on sleep related EEG changes (CNS sleep). Those early studies found only small effects of exercise on sleep. However, more recent sleep research has explored not only CNS functioning, but somatic physiology as well. Sleep should be affected by daytime exercise, as physical activity alters endocrine, autonomic nervous system (ANS), and somatic functions. Since endocrinological, metabolic, and autonomic changes can be measured during sleep, it should be possible to assess exercise effects on somatic physiology in addition to CNS sleep quality, evaluated by standard polysomnographic (PSG) techniques. Additional measures of somatic physiology have provided enough evidences to conclude that the auto-regulatory, global regulation of sleep is not the exclusive domain of the CNS, but it is heavily influenced by inputs from the rest of the body.

We previously isolated a mutant which showed a high tolerance to freezing that correlated with higher levels of intracellular L-proline derived from L-proline analogue-resistant mutants. The mutation responsible for the analogue resistance and L-proline accumulation was a single nuclear dominant mutation. By introducing the mutant-derived genomic library into a non-L-proline-utilizing strain, the mutant was found to carry an allele of the wild-type PRO1 gene encoding ␥-glutamyl kinase, which resulted in a single amino acid replacement; Asp (GAC) at position 154 was replaced by Asn (AAC). Interestingly, the allele of PRO1 was shown to enhance the activities of ␥-glutamyl kinase and ␥-glutamyl phosphate reductase, both of which catalyze the first two steps of L-proline synthesis from L-glutamate and which together may form a complex in vivo. When cultured in liquid minimal medium, yeast cells expressing the mutated ␥-glutamyl kinase were found to accumulate intracellular L-proline and showed a prominent increase in cell viability after freezing at ؊20°C compared to the viability of cells harboring the wild-type PRO1 gene. These results suggest that the altered ␥-glutamyl kinase results in stabilization of the complex or has an indirect effect on ␥-glutamyl phosphate reductase activity, which leads to an increase in L-proline production in Saccharomyces cerevisiae. The approach described in this paper could be a practical method for breeding novel freeze-tolerant yeast strains.Frozen-dough technology has recently been used in the baking industry to supply oven-fresh bakery products to consumers. Many freeze-tolerant yeasts have been isolated from natural sources and under natural culture conditions, and many have also been constructed by conventional mutation techniques (11,13,21,23,25). However, the mechanism of freeze tolerance is not well understood, and a baker's yeast that provides good leavening qualities for both sweet-and lean-thawed doughs after frozen storage has not yet been developed.We previously investigated the cryoprotective effects of amino acids on freezing stress in the yeast Saccharomyces cerevisiae and found that L-proline, which is known to be an osmoprotectant (5, 9), has cryoprotective activity that is nearly equal that of glycerol or trehalose (38). In bacteria, L-proline biosynthesis from L-glutamate has been shown to be regulated by end product inhibition of ␥-glutamyl kinase (␥-GK) activity (26, 35). L-Proline-overproducing mutants of Escherichia coli (7), Salmonella enterica serovar Typhimurium (4), and Serratia marcescens (27) have mutations which result in desensitization of L-proline feedback inhibition of ␥-GK. S. cerevisiae synthesizes L-proline from L-glutamate via the intermediates ␥-glutamyl phosphate (␥-GP), glutamate-␥-semialdehyde (GSA), and ⌬ 1 -pyrroline-5-carboxylate (P5C) by almost the same pathway found in bacteria (Fig. 1). Three enzymes, ␥-GK (the PRO1 gene product), ␥-GP reductase (␥-GPR) (the PRO2 gene product), and P5C reductase (the PRO3 gene product), are involved...

The present study examined whether three‐ball cascade juggling was improved by sleep. To elucidate sleep functions related to motor memory consolidation, sleep EEG spectral analysis was performed for each recorded sleep stage. Sixteen female college students practiced juggling in the morning, and were tested immediately afterward. Eight of the subjects took a 2‐hour nap after practice juggling (nap group), while another 8 stayed awake (control group). Juggling performance was then re‐tested in the evening. Juggling performance improved after the 2‐hour nap, while subjects in the control group did not show improvement. Slow oscillation, delta wave, and sigma wave EEG spectral power all increased significantly during non‐REM sleep, especially during slow‐wave sleep, after the post‐motor learning nap (mNap) compared to an earlier baseline nap that preceded learning the task. Such EEG alterations have been suggested to relate to explicit declarative (hippocampus‐dependent) memory consolidation; however, motor learning is considered to rely upon implicit procedural memory. We found that while sleep facilitated the consolidation of motor memory similar to that following real sport activities, the alterations in sleep EEG suggest that the initial motor learning of complex, highly coordinated 3‐ball cascade juggling may involve substantial use of explicit memory.