Chromosome-dependent aneuploid formation in Spo11-less meiosis.

Deficiency in meiotic recombination leads to aberrant chromosome disjunction during meiosis, often resulting in the lethality of gametes or genetic disorders due to aneuploidy formation. Budding yeasts lacking Spo11, which is essential for initiation of meiotic recombination, produce many inviable spores in meiosis, while very rarely all sets of 16 chromosomes are coincidentally assorted into gametes to form viable spores. We induced meiosis in a spo11∆ diploid, in which homolog pairs can be distinguished by single nucleotide polymorphisms and determined whole-genome sequences of their exceptionally viable spores. We detected no homologous recombination in the viable spores of spo11∆ diploid. Point mutations were fewer in spo11∆ than in wild-type. We observed spo11∆ viable spores carrying a complete diploid set of homolog pairs or haploid spores with a complete haploid set of homologs but with aneuploidy in some chromosomes. In the latter, we found the chromosome-dependence in the aneuploid incidence, which was positively and negatively influenced by the chromosome length and the impact of dosage-sensitive genes, respectively. Selection of aneuploidy during meiosis II or mitosis after spore germination was also chromosome dependent. These results suggest a pathway by which specific chromosomes are more prone to cause aneuploidy, as observed in Down syndrome.

The benzylisoquinoline alkaloids, berberine and coptisine, act against camptothecin-resistant topoisomerase I mutants.

DNA replication inhibitors are utilized extensively in studies of molecular biology and as chemotherapy agents in clinical settings. The inhibition of DNA replication often triggers double-stranded DNA breaks (DSBs) at stalled DNA replication sites, resulting in cytotoxicity. In East Asia, some traditional medicines are administered as anticancer drugs, although the mechanisms underlying their pharmacological effects are not entirely understood. In this study, we screened Japanese herbal medicines and identified two benzylisoquinoline alkaloids (BIAs), berberine and coptisine. These alkaloids mildly induced DSBs, and this effect was dependent on the function of topoisomerase I (Topo I) and MUS81-EME1 structure-specific endonuclease. Biochemical analysis revealed that the action of BIAs involves inhibiting the catalytic activity of Topo I rather than inducing the accumulation of the Topo I-DNA complex, which is different from the action of camptothecin (CPT). Furthermore, the results showed that BIAs can act as inhibitors of Topo I, even against CPT-resistant mutants, and that the action of these BIAs was independent of CPT. These results suggest that using a combination of BIAs and CPT might increase their efficiency in eliminating cancer cells.

Effects of ramelteon on cardiac injury and adipose tissue pathology in rats with metabolic syndrome.

Melatonin regulates circadian rhythms but also has antioxidative and anti-inflammatory effects that ameliorate metabolic disorders. We investigated the effects of the selective melatonin agonist ramelteon on cardiac and adipose tissue pathology in the DahlS.Z-Leprfa /Leprfa (DS/obese) rat, a model of metabolic syndrome (MetS). Rats were treated with a low (0.3 mg/kg per day) or high (8 mg/kg per day) dose of ramelteon from 9 to 13 weeks of age. Ramelteon treatment at either dose attenuated body weight gain, left ventricular fibrosis, and diastolic dysfunction, as well as cardiac oxidative stress and inflammation, without affecting hypertension or insulin resistance. Although ramelteon did not affect visceral white adipose tissue (WAT) mass, it attenuated inflammation and downregulated insulin signaling in this tissue. In contrast, ramelteon reduced fat mass, adipocyte hypertrophy, and inflammation, and ameliorated impaired insulin signaling in subcutaneous WAT. In addition, ramelteon attenuated adipocyte hypertrophy, downregulated mitochondrial uncoupling protein 1, and upregulated 11ß-hydroxysteroid dehydrogenase type 1 expression in interscapular brown adipose tissue (BAT). In summary, ramelteon treatment attenuated obesity and cardiac injury, improved insulin signaling in visceral and subcutaneous WAT, and inhibited the whitening of BAT in rats with MetS.

Detection of DNA double-strand breaks by pulsed-field gel electrophoresis.

A DNA double-strand break (DSB) is one of the most cytotoxic DNA lesions because unrepaired DSBs cause chromosomal aberrations and cell death. Although many physiological DSBs occur at DNA replication sites, the molecular mechanisms underlying this remain poorly understood. There was therefore a need to develop a highly specific method to detect DSB fragments containing DNA replication sites. Here we investigated whether pulsed-field gel electrophoresis (PFGE) combined with visualization of DNA replication sites by immunoblotting using halogenized deoxyuridines, such as BrdU and IdU, was sufficient for this detection. Our methodology enabled us to reproduce previously reported data. In addition, this methodology was also applied to the detection of bacterial infection-induced DSBs on human chromosomal DNA. Based on our findings, we propose that this strategy combining PFGE with immunoblot analysis will be applicable to studies analyzing the mechanistic details of DNA repair, the DNA damage response and the activity of DNA-damaging agents.

Suppression of postsurgical recurrence of hepatocellular carcinoma treated with autologous formalin-fixed tumor vaccine, with special reference to glypican-3.

Autologous formalin-fixed tumor vaccine (AFTV) suppressed re-recurrence for more than 32 months of multiple-recurrent hepatocellular carcinoma based on hepatitis C virus-induced liver cirrhosis in a case with previous recurrence interval, 51-, 28-, 12-, and 4-months. We detected glypican-3-specific cytotoxic T lymphocytes in the peripheral blood at 12 months after AFTV.

Implications of social competence among thirty-month-old toddlers: a theory of mind perspective.

BACKGROUND: The purpose of this study was to examine the relations between children's social competence and initial index of theory of mind at 30 months of age. METHODS: The participants of the study were 322 toddlers and parents/caregivers who were registered with the Japan Science and Technology Agency (JST) project. They completed a five-minute interaction session, which was coded using the Interaction Rating Scale (IRS) as an evidence-based practical index of children's social competence. In addition, the children were asked to complete a diverse-desire task as a ToM (theory of mind) index. RESULTS: The results showed that the ToM index was related to the total score and subscales of the IRS, such as Empathy and Emotional regulation. CONCLUSIONS: These findings show that the IRS score was related to ToM task performance at 30 months of age.

The trajectory patterns of parenting and the social competence of toddlers: a longitudinal perspective.

BACKGROUND: Many studies have suggested that the daily emotional interactions between a child and his/her caregiver play a significant role in his/her development. The purpose of this study was to determine whether the trajectory patterns of parenting patterns of caregivers raising toddlers affect the social competence of the toddlers. METHODS: The study participants were 246 dyads of 18-month-old children (baseline) and their caregivers, which was conducted as part of a Japan Science and Technology Agency (JST) project. We used the Interaction Rating Scale (IRS) to evaluate the children's social competence. We assessed the child rearing environments by analyzing the caregivers' responses to the Index of Child Care Environment (ICCE). RESULTS: Multiple logistic regression analysis showed that the children's total score on the IRS was significantly related to how frequently they sang songs together with their caregivers. Their score was also significantly related to how closely their caregiver worked with his/her partner in raising the child. These relationships did not change according to demographic information. CONCLUSIONS: The results confirm previous findings on the relationship between parenting patterns and children's social competence. In particular, the study shows that varied and continual parenting significantly affects a child's social competence.

Interaction Rating Scale (IRS) as an evidence-based practical index of children's social skills and parenting.

BACKGROUND: The purpose of this paper is to describe the features of the Interaction Rating Scale (IRS) as an evidence-based practical index of children's social skills and parenting. METHODS: The participants in our study, which was conducted as part of a Japan Science and Technology Agency (JST) project, were 370 dyads of children (aged 18, 30, and 42 month) and 81 dyads of 7-year-old children with their caregivers. The participants completed the five minute interaction session and were observed using the IRS. RESULTS: The results indicated that the IRS can measure children's social skill development and parenting with high validity. Along with the discriminate validity for pervasive development disorder (PDD), attention-deficit/hyperactivity disorder (ADHD), abuse and maltreatment, a high correlation with the SDQ (Strength and Difficulties Questionnaire), and high reliability, the IRS is effective in describing features of social skill development. CONCLUSIONS: The IRS provides further evidence of the fact that in order to study children's social skill development, it is important to evaluate various features of the caregiver-child interaction as a predictor of social skills.

The trajectory of children's social competence from 18 months to 30 months of age and their mother's attitude towards the praise.

BACKGROUND: Praise from caregivers has been shown as an important influence on the development of social competence in early adolescence. However, the effects of praise in younger children have not been investigated. We examined how the trajectory of children's social competence from 18 months to 30 months of age was related to their caregiver's attitude towards the importance of praise at times when their child was 4 months and 9 months old. METHODS: We studied 155 mother-child dyads, whose interactions during play were observed both when the child was 18 months and 30 months old, which was conducted as part of a Japan Science and Technology Agency (JST) project. The child's social competence was assessed using the Interaction Rating Scale (IRS). Demographic data was obtained when the child was 4 months old, and the caregiver's attitude towards the importance of praise when the child was both 4 months and 9 months old. A logistic regression analysis controlling for the effects of demographic variables was performed. RESULTS: We found that children who had received continuous praise from their mother when they were 4-9 months of age had a decreased risk of low social competence at 18-30 months of age. CONCLUSIONS: A mother's attitude towards the importance of praise at early stages of her child's development has an important influence on the later trajectory of social competence.

A longitudinal study on social competence development and sleeping habits.

BACKGROUND: It is known that sleep problems impact children's health, learning, and school performance. The purpose of this paper is to examine the association between sleeping habits and social competence development. METHODS: Three hundred and nine caregiver-child dyads participated in this study, which was conducted as part of a Japan Science and Technology Agency (JST) project. The caregivers answered some questionnaires about sleeping habits when the child was 9 months and 18 months old. Caregiver-child interaction was observed when the child was 30 months old, and the features of the interaction were examined using the Interaction Rating Scale (IRS) as a measure of social competence. RESULTS: The caregivers' attitude toward sleeping in the 9-month period was found to be significantly correlated with the children's social competence at 30 months. Moreover the caregivers' attitude toward sleeping in the 9-month period significantly correlated with the children's sleeping habits at 9 and 18 months. CONCLUSIONS: These findings show that the caregivers' attitude toward sleeping is an important factor influencing the development of children's social competence.

Relationship between children's intelligence and their emotional/behavioral problems and social competence: gender differences in first graders.

BACKGROUND: The present study examines gender differences in the correlations between intelligence and developmental problems as well as social competence in first graders. METHODS: Ninety parent-child dyads participated in this study. The children comprised 7-year-olds recruited from the first grade of an elementary school. All the children were administered the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), Parent-child Interaction Rating Scale (IRS), and the parent report version of Strength and Difficulties Questionnaire (SDQ). RESULTS: The findings clarified that the processing speed of boys significantly correlated with their peer relationship. On the other hand, the emotional symptoms exhibited by girls had a more common association with their intellectual abilities. The correlations between parenting and intellectual abilities differed in boys and girls. CONCLUSIONS: Children's gender should be taken into account when assessing the diversity in their intellectual abilities and developmental problems. Moreover, parenting also influences the development of children in various ways.