Educational Interventions and Evaluation for Obesity Prevention in Preschool Children in Local Communities.

Educational interventions for obesity prevention from early childhood is one of the important measures in health promotion policies, especially in locations where obesity and overweight in school and preschool children are prevalent, such as in the Aomori Prefecture. The Aomori Prefecture government started a new demonstration project in FY 2014 that targeted children in nursing schools for the prevention of obesity through both population approaches (nutrition/physical activity education and nutrition management in lunch programs) and individual approaches to solving overweight in children. Our study group developed a data management tool to routinely accumulate data on measured body height and weight. We also developed educational materials with growth charts for nutritional education of guardians, and summary sheets showing the distributions of degree of obesity and prevalence of overweight/obesity in age-sex groups for use in assessment in each nursing school. To promote and evaluate the demonstration project, we offered the data management tool to all nursing schools in the prefecture for nutritional education and management in the nursing schools and asked them to anonymously submit data to build a prefecture-based monitoring dataset. Around 70% (310 institutes) of the institutes responded to this request, and we developed a longitudinal dataset with about 4,000 children in each of the 3-, 4-, and 5-year-old cohorts. This first revealed the prevalence of overweight in preschool children in the entire prefecture. The dataset will be further utilized for evaluating the effectiveness of educational interventions in preschool settings in local communities.

pH- and salt-dependent self-assembly of human Rad51 protein analyzed as fluorescence resonance energy transfer between labeled proteins.

Human HsRad51 protein assembles on a DNA molecule through cooperative binding and forms a long filament for homologous recombination. We have characterized the self-assembly of HsRad51 by measuring the fluorescence resonance energy transfer from the fluorescein-labeled protein to the rhodamine-labeled protein. Self-assembly quickly reached equilibrium and can be described by the head-to-tail polymerization of monomers, like that of its procaryotic homologue, RecA. It depended strongly on pH and was inhibited by high salt concentrations, indicating that ionic interactions between negatively and positively charged aminoacid residues are important. By contrast, neither ATP nor ADP significantly affected the reaction.

[Effects of gender-related weight reduction on the physical condition of male and female college judoists].

OBJECTIVE: In order to study the gender-related effects of weight reduction on the physical condition of male and female college judoists during weight reduction periods, we examined changes in anthropometric, nutritional intake and biochemical parameters in 43 male and female college judoists 20 days (pre-weight reduction) before and one day (post-weight reduction) before the game. METHODS: Subjects were divided into two groups. Thirty subjects (22 males, 8 females) who required weight reduction were defined as the weight reduction (WR) group, and the remaining 13 subjects (5 males, 8 females) were defined as the non-reduction (non-WR) group. RESULTS: In both WR groups, anthropometric parameters and nutritional intake significantly decreased after weight reduction compared to the pre-values. The change ratios of nutritional intake during the weight reduction period in the female WR group were higher than those in the male WR group. Serum lipids and electrolytes significantly decreased after the weight reduction compared to the pre-values in both WR groups. In the female WR group, Cr and UA significantly increased after the weight reduction compared to the pre-values. Although it was not significant, Ht increased after the weight reduction compared to the pre-values only in the female WR group. TP, Cr, UA, BUN, CK, LDH and IgA significantly increased after the weight reduction compared to the pre-values in the weight reduction compared to the pre-values in the male WR group. In contrast, in both non-WR groups, these parameters did not change significantly during the research period. CONCLUSIONS: Our findings suggest that nutritional exhaustion and dehydration may be the major effects brought about by energy and fluid restriction in female college judoists during a weight reduction period. On the other hand, in male college judoists undergoing weight reduction, the data suggest that muscle damage and myogenic protein catabolism may be caused chiefly by exercise. These differences may be due to the difference in the method of weight reduction for the different genders, namely, mainly exercise in males and mainly energy and fluid restriction in females.

Onset of quiescence following p53 mediated down-regulation of H2AX in normal cells.

Normal cells, both in vivo and in vitro, become quiescent after serial cell proliferation. During this process, cells can develop immortality with genomic instability, although the mechanisms by which this is regulated are unclear. Here, we show that a growth-arrested cellular status is produced by the down-regulation of histone H2AX in normal cells. Normal mouse embryonic fibroblast cells preserve an H2AX diminished quiescent status through p53 regulation and stable-diploidy maintenance. However, such quiescence is abrogated under continuous growth stimulation, inducing DNA replication stress. Because DNA replication stress-associated lesions are cryptogenic and capable of mediating chromosome-bridge formation and cytokinesis failure, this results in tetraploidization. Arf/p53 module-mutation is induced during tetraploidization with the resulting H2AX recovery and immortality acquisition. Thus, although cellular homeostasis is preserved under quiescence with stable diploidy, tetraploidization induced under growth stimulation disrupts the homeostasis and triggers immortality acquisition.

DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development.

During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploidy/aneuploidy generation in association with mitotic aberration. Although oncogene acceleration primarily induces DNA replication stress and the resulting lesions in the S phase, these lesions are carried over into the M phase and cause cytokinesis failure and genomic instability. Unlike directly induced DNA double-strand breaks, DNA replication stress-associated lesions are cryptogenic and pass through cell-cycle checkpoints due to limited and ineffective activation of checkpoint factors. Furthermore, since damaged M-phase cells still progress in mitotic steps, these cells result in chromosomal mis-segregation, cytokinesis failure and the resulting tetraploidy generation. Thus, our results reveal a process of genomic instability generation triggered by precancerous DNA replication stress.

ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts.

S(N)1-type alkylating agents that produce cytotoxic O(6)-methyl-G (O(6)-meG) DNA adducts induce cell cycle arrest and apoptosis in a manner requiring the DNA mismatch repair (MMR) proteins MutSalpha and MutLalpha. Here, we show that checkpoint signaling in response to DNA methylation occurs during S phase and requires DNA replication that gives rise to O(6)-meG/T mispairs. DNA binding studies reveal that MutSalpha specifically recognizes O(6)-meG/T mispairs, but not O(6)-meG/C. In an in vitro assay, ATR-ATRIP, but not RPA, is preferentially recruited to O(6)-meG/T mismatches in a MutSalpha- and MutLalpha-dependent manner. Furthermore, ATR kinase is activated to phosphorylate Chk1 in the presence of O(6)-meG/T mispairs and MMR proteins. These results suggest that MMR proteins can act as direct sensors of methylation damage and help recruit ATR-ATRIP to sites of cytotoxic O(6)-meG adducts to initiate ATR checkpoint signaling.

Gender differences in the psychological response to weight reduction in judoists.

We examined gender-related differences in the psychological response to weight reduction in 43 judoists. Twenty-two males and 8 females who required weight reduction [weight reduction (WR) group] (the average percentages of weight reduction observed for males and females were 3.4% and 4.9%, respectively), and 5 males and 8 females who did not require weight reduction (non-WR group). The POMS scores were measured before and after weight reduction. The TMD (total mood disturbance) score in POMS significantly increased after weight reduction only in WR group males. In the female WR group, the anger and depression scores decreased after weight reduction, and the pre-value of the TMD score in thisgroup was relatively high. The psychological stress may be caused by anxiety engendered by the overall concept of weight reduction before actual weight reduction in females, whereas in males it may be caused by the actual weight reduction.

Structure-based design, synthesis and biochemical testing of novel and potent Smac peptido-mimetics.

Structure-based design, chemical synthesis and biochemical testing of a series of novel Smac peptido-mimetics as inhibitors of XIAP protein are described. The most potent compound, 6j, has a binding affinity (K(i) value) of 24 nM to XIAP BIR3 protein and is 24 times more potent than the native Smac AVPI peptide. Further optimization of these potent Smac mimetics may ultimately lead to the development of a novel class of anticancer drugs for the treatment of human cancer by overcoming apoptosis-resistance of cancer cells through targeting the inhibitor of apoptosis proteins.

Trends in dietary fiber intake in Japan over the last century.

BACKGROUND: Insufficient intake of dietary fiber (DF) is currently a major problem in the overall promotion of health in the general population in Japan. AIM OF THE STUDY: To analyze the time trends in DF intake, including DF density (total DF intake/1,000 kcal), and the ratio of water-insoluble fiber to water-soluble fiber (IS ratio) in Japan. METHODS: The time trend in DF intake in Japan was calculated from data compiled in the Japanese National Nutrition Survey. RESULTS: The mean daily DF intake (total DF intake) in 1952 was 20.5 g/day, which rapidly declined to about 70 % of the 1952 level in 1970, after which there was little change to 1998. DF density in 1952 was 9.7 g/1000 kcal, which declined by about 30 % in 1970, and remained at about the same level to 1998. The IS ratio has remained stable over this period. Whereas total DF intake and DF density in Japan are similar to those in Western countries, the IS ratios are higher in Japan. Therefore, the higher incidence of, and mortality from, colon diverticulosis, coronary heart disease, hyperlipidemia, etc., which are all thought to be related to fiber deficiency, in Western countries compared to Japan might be due to the differences in the IS ratio. CONCLUSIONS: A decline in total DF intake and DF density is predicted for Japan in the future, because these parameters were lower among the younger generation. This may be due to the marked changes in the dietary habits of the younger generation, and is a problematic trend for Japanese health.

Structure-based design of potent, conformationally constrained Smac mimetics.

A successful structure-based design and synthesis of a class of highly potent conformationally constrained Smac mimetics is described. The most potent compound has a Ki value of 25 nM binding to the XIAP BIR3 protein and is 23 times more potent than natural Smac peptides. These potent Smac mimetics can serve as powerful chemical and pharmacological tools to further elucidate the role of Smac and its cellular binding partners in apoptosis regulation and may be developed as a new class of anti-cancer drugs.