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21.
A series of new piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives were synthesized. Among these compounds, 4-methyl-2-(1,2,3,6-tetrahydropyridin-4-yl)pyrimidine derivative 23 (SUN N5147) exhibited sub-nanomolar affinity for 5-HT1A receptor with 1000-fold selectivity over both dopamine D2 and alpha1-adrenergic receptors and remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model.  相似文献   
22.

Background

Although delayed sleep timing causes many socio-psycho-biological problems such as sleep loss, excessive daytime sleepiness, obesity, and impaired daytime neurocognitive performance in adults, there are insufficient data showing the clinical significance of a ‘night owl lifestyle’ in early life. This study examined the association between habitual delayed bedtime and sleep-related problems among community-dwelling 2-year-old children in Japan.

Methods

Parents/caregivers of 708 community-dwelling 2-year-old children in Nishitokyo City, Tokyo, participated in the study. The participants answered a questionnaire to evaluate their child’s sleep habits and sleep-related problems for the past 1 month.

Results

Of the 425 children for whom complete data were collected, 90 (21.2%) went to bed at 22:00 or later. Children with delayed bedtime showed significantly more irregular bedtime, delayed wake time, shorter total sleep time, and difficulty in initiating and terminating sleep. Although this relationship indicated the presence of sleep debt in children with delayed bedtime, sleep onset latency did not differ between children with earlier bedtime and those with delayed bedtime. Rather, delayed bedtime was significantly associated with bedtime resistance and problems in the morning even when adjusting for nighttime and daytime sleep time.

Conclusions

Even in 2-year-old children, delayed bedtime was associated with various sleep-related problems. The causal factors may include diminished homeostatic sleep drive due to prolonged daytime nap as well as diurnal preference (morning or night type) regulated by the biological clock.  相似文献   
23.
The complete genome of the unicellular motile cyanobacterium Synechocystis sp. PCC 6803 harbors seven putative genes for a subfamily Pkn2 of the eukaryotic-type (or "Hanks-type") protein kinase. Previously, SpkA and SpkB were shown to have protein kinase activity and to be required for cell motility. Here, the other five genes were examined. These genes, except for spkG (slr0152), were successfully expressed in Escherichia coli. Eukaryotic-type protein kinase activity of the expressed SpkC (Slr0599), SpkD (S110776) and SpkF (Slr1225) was demonstrated as autophosphorylation and phosphorylation of the general substrate proteins. SpkE (Slr1443) did not show any activity, a finding consistent with its lack of several key amino acid residues in its kinase motif. Gene-disrupted mutants showed no discernible defect in phenotype except that spkD was apparently essential for survival.  相似文献   
24.

Aim

This study aimed to evaluate the treatment result of intensity-modulated radiation therapy (IMRT) in a large number of Japanese patients with prostate cancer.

Background

A total of 1091 patients with localized prostate cancer were recruited between March 2006 and July 2014. The patients were stratified into low- (n = 205 [18.8%]), intermediate- (n = 450 [41.2%]), high- (n = 345 [31.6%]), and very high-risk (n = 91 [8.3%]) groups according to the National Comprehensive Cancer Network classification. All patients were irradiated via IMRT at a dose of 74–78 Gy with or without androgen-deprivation therapy. The mean follow-up period was 50 months (range, 2–120 months).

Results

The biochemical failure-free rate (BFFR), the clinical failure-free rate, and the overall survival rate at the 5-year follow-up for all patients was 91.3%, 96.2%, and 99.1%, respectively. In univariate analysis, the prostate-specific antigen (PSA) levels (≤20 vs. >20 ng/ml) were significantly correlated with BFFR. A trend toward higher BFFR was noted in patients with a Gleason score (GS) of ≤7 than in patients with GS ≥8. In multivariate analysis, only PSA (≤20 vs. >20 ng/ml) was significantly correlated with BFFR. The cumulative incidence rate of gastrointestinal and genitourinary toxicity (≥grade 2) at the 5-year follow-up was 11.4% and 4.3%, respectively.

Conclusions

The findings of this study indicate that IMRT is well tolerated and is associated with both good long-term tumor control and excellent outcomes in patients with localized prostate cancer.  相似文献   
25.
Animals respond to adverse environments by slowing down or arresting growth and development. Upon returning to normal conditions, they often show compensatory acceleration in growth and developmental rate. This phenomenon, known as `catch-up' growth, is widely documented in the animal kingdom. The underlying molecular mechanisms, however, are poorly understood. Using the zebrafish embryo as an experimental model system, we tested the hypothesis that changes in IGF signaling activities play an important role in the accelerated growth and temporal development resulting from re-oxygenation following hypoxia. We show that chronic hypoxia reduced, and re-oxygenation accelerated, embryonic growth and developmental rate. Whereas hypoxia repressed the Igf1 receptor and its downstream Erk1/2 and Akt signaling activities, re-oxygenation restored their activities. Specific inhibition of Igf1 receptor signaling during re-oxygenation by genetic and pharmacological approaches attenuated catch-up growth. Further analysis showed that whereas PI3K-Akt is required in both normal and catch-up growth, Mek1/2-Erk1/2 activation induced by elevated IGF signaling during re-oxygenation is particularly crucial for catch-up growth. These results suggest that the evolutionarily conserved IGF signaling pathway coordinates growth and temporal development in zebrafish embryos in response to oxygen availability.  相似文献   
26.
Basic studies and applications on bioremediation of DDT: A review   总被引:2,自引:0,他引:2  
The persistent insecticide DDT (1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane) has been widely used for pest control in the management of mosquito-borne malaria and is still used for that purpose in some tropical countries. Considering the potential for negative effects due to DDT contamination, it is necessary to determine effective methods of remediation. Several methods have been used to degrade or transform DDT into less toxic compounds. Bacteria and white-rot fungi (WRF) have been shown to enhance the degradation process in soil using both pure and mixed cultures. Recently, a biological approach has been used as an environmentally-friendly treatment, using new biological sources to degrade DDT, e.g. brown-rot fungi (BRF), cattle manure compost (CMC) and spent mushroom waste (SMW). In this review, the abilities of BRF, CMC and SMW to degrade DDT are discussed, including the mechanisms and degradation pathways. Furthermore, application of these sources to contaminated soil is also described. The review discusses which is the best source for bioremediation of DDT.  相似文献   
27.
AC54 monoclonal antibody (MAb), an anti-desmin MAb, recognizes both intermediate filaments (IFs) and nuclear granules in BHK21/C13 cells. To investigate nuclear granules, similar MAbs were obtained by using desmin fraction as an antigen. Among them, DSB389 MAb recognized mainly nuclear granules in HeLa and rat liver cells. The nuclear granules in HeLa cells were aligned in arrays, sometimes connected by, or part of, a rope-like structure, and stable against treatment with 0.5% Triton X-100 and 2 M NaCl. They located on or around the chromosomes during mitosis. Essentially the same results were obtained with DSB860 and AC54 MAbs. The distribution of the granules in liver nuclei recognized by DSB389 MAb was similar to that of DNA and was different from that of the nuclear pore complexes. The biological significance of the nuclear granules is discussed.  相似文献   
28.
Mulberry is commonly used to feed silkworms. Here we examined whether a dietary intake of mulberry leaf (ML) could affect atherogenesis in vivo and in vitro. Apolipoprotein E-deficient mice were fed either normal chow (control group) or a diet containing 1% ML powder (ML group) from 6 weeks of age. The mice were sacrificed after 12 weeks. The susceptibility of plasma lipoprotein to oxidation was assessed using diene formation. A significant increase in the lag time of lipoprotein oxidation was detected in the ML group compared with the control group. Furthermore, the ML group showed a 40% reduction in atherosclerotic lesion size in the aortae compared with the control. We also examined the direct anti-oxidative activity of ML in vitro. Aqueous extract of ML had a strong scavenging effect on 1,1-diphenyl-2-picrylhydrazyl and inhibited lipoprotein oxidation. These results confirm that ML contains anti-oxidative substances that might help prevent atherosclerosis.  相似文献   
29.
30.
Monocyte chemoattractant protein-1 (MCP-1), an important chemokine whose expression is increased during the course of obesity, plays a role in macrophage infiltration into obese adipose tissue. This study was designed to elucidate the role of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in the induction of MCP-1 during the course of adipocyte hypertrophy. We examined the time course of MKP-1 and MCP-1 mRNA expression and extracellular signal-regulated kinase (ERK) phosphorylation in the adipose tissue from mice rendered mildly obese by a short term high fat diet. We also studied the role of MKP-1 in the induction of MCP-1 in 3T3-L1 adipocytes during the course of adipocyte hypertrophy. MCP-1 mRNA expression was increased, followed by ERK activation and down-regulation of MKP-1, an inducible dual specificity phosphatase to inactivate ERK, in the adipose tissue at the early stage of obesity induced by a short term high fat diet, when macrophages are not infiltrated. Down-regulation of MKP-1 preceded ERK activation and increased production of MCP-1 in 3T3-L1 adipocytes in vitro during the course of adipocyte hypertrophy. Adenovirus-mediated restoration of MKP-1 in hypertrophied 3T3-L1 adipocytes reduced the otherwise increased ERK phosphorylation, thereby leading to the significant reduction of MCP-1 mRNA expression. This study provides evidence that the down-regulation of MKP-1 is critical for increased production of MCP-1 during the course of adipocyte hypertrophy.  相似文献   
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