Meis Cofactors Control HDAC and CBP Accessibility at Hox-Regulated Promoters during Zebrafish Embryogenesis

SummaryHox proteins form complexes with Pbx and Meis cofactors to control gene expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx, and Meis in zebrafish tissues where these promoters are active. Inhibition of Meis blocks gene expression and reduces AcH4 levels at these promoters, suggesting a role for Meis in maintaining AcH4. Within Hox transcription complexes, Meis binds directly to Pbx and we find that this binding displaces histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos. Accordingly, Pbx mutants that cannot bind Meis act as repressors by recruiting HDACs and reducing AcH4 levels, while Pbx mutants that bind neither HDAC nor Meis are constitutively active and recruit CBP to increase AcH4 levels. We conclude that Meis acts, at least in part, by controlling access of HDAC and CBP to Hox-regulated promoters

Nlz1/Znf703 acts as a repressor of transcription

<p>Abstract</p> <p>Background</p> <p>Members of the NET subfamily of zinc-finger proteins are related to the Sp-family of transcription factors and are required during embryogenesis. In particular, Nlz1/Znf703 and Nlz2/Znf503 are required for formation of rhombomere 4 of the vertebrate hindbrain. While NET family proteins have been hypothesized to regulate transcription, it remains unclear if they function as activators or repressors of transcription.</p> <p>Results</p> <p>Here we demonstrate that Nlz proteins repress transcription both in cell lines and in developing zebrafish embryos. We first use standard cell culture-based reporter assays to demonstrate that Nlz1/Znf703 represses transcription of a luciferase reporter in four different cell lines. Structure-function analyses and pharmacological inhibition further reveal that Nlz1-mediated repression requires histone deacetylase activity. We next generate a stable transgenic zebrafish reporter line to demonstrate that Nlz1 promotes histone deacetylation at the transgenic promoter and repression of transgene expression during embryogenesis. Lastly, taking a genetic approach we find that endogenous Nlz proteins are required for formation of hindbrain rhombomere 4 during zebrafish embryogenesis by repressing expression of non-rhombomere 4 genes.</p> <p>Conclusion</p> <p>We conclude that Nlz1/Znf703 acts as a repressor of transcription and hypothesize that other NET family members function in a similar manner.</p

Validation and Factor Analysis of the Japanese Version of the Highs Scale in Perinatal Women

Background: The Highs scale has been developed to evaluate hypomanic symptoms in the first postpartum week. However, it has not been elucidated whether this scale is also applicable to pregnant women. To address this issue, we confirmed the factor structure, reliability, and validity of the Japanese version of the Highs scale for pregnant and postpartum women.Methods: 418 women provided effective responses to both the Highs scale and the Edinburgh Postnatal Depression Scale (EPDS) during early pregnancy (before week 25), late pregnancy (around week 36), at 5 days and at 1 month after delivery. Subjects were randomly divided into two groups, and exploratory and confirmatory factor analyses were performed for each group. Cronbach's alpha was calculated and the correlation of the Highs scale with EPDS was analyzed. The correlation between the subscales was analyzed at four time points, and the correlation of subscales between the four time points was confirmed.Results: This scale was found to have the two-factor structure with elation and agitation subscales. The two subscales had reasonable internal consistency at all time points (Cronbach's alpha range: Factor 1, 0.696–0.758; Factor 2, 0.553–0.694). The overall scale had reasonable internal consistency at all time points (Cronbach's alpha range: 0.672–0.738). Based on the correlation analysis of the two subscales and EPDS, discriminative and convergent validity were indicated at all time points, confirming the construct validity of the Highs scale. Subscale scores showed a significant correlation with EPDS at all time points (r = 0.388, 0.384, 0.498, and 0.442, p &lt; 0.01).Conclusions: The Japanese version of the Highs scale is reliable and valid, and can be applied for evaluating the hypomanic symptoms during pregnancy and postpartum period

Breastfeeding history and metabolic syndrome in parous women

Objective The aim of the present study was to investigate the associations between breastfeeding and the prevalence of metabolic syndrome in community-dwelling parous women and to clarify whether the associations depend on age. Methods The present cross-sectional study included 11,118 women, aged 35–69 years. Participants’ longest breastfeeding duration for one child and their number of breastfed children were assessed using a self-administered questionnaire, and their total breastfeeding duration was approximated as a product of the number of breastfed children and the longest breastfeeding duration. The longest and the total breastfeeding durations were categorized into none and tertiles above 0 months. Metabolic syndrome and cardiovascular risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) were defined as primary and secondary outcomes, respectively. Associations between breastfeeding history and metabolic syndrome or each cardiovascular risk factor were assessed using multivariable unconditional logistic regression analysis. Results Among a total of 11,118 women, 10,432 (93.8%) had ever breastfed, and 1,236 (11.1%) had metabolic syndrome. In participants aged <55 years, an inverse dose–response relationship was found between the number of breastfed children and the prevalence of metabolic syndrome; multivariable-adjusted odds ratios for 1, 2, 3, and ≥4 breastfed children were 0.60 (95% confidence interval [CI]: 0.31 to 1.17), 0.50 (95% CI: 0.29 to 0.87), 0.44 (95% CI: 0.24 to 0.84), and 0.35 (95% CI: 0.14 to 0.89), respectively. The longest and total breastfeeding durations of longer than 0 months were also associated with lower odds of metabolic syndrome relative to no breastfeeding history in participants aged <55 years. In contrast, all measures of breastfeeding history were not significantly associated with metabolic syndrome and cardiovascular risk factors in participants aged ≥55 years old. Conclusions Breastfeeding history may be related to lower prevalence of metabolic syndrome in middle-aged parous women

Metabolic syndrome and metabolically unhealthy obesity with cancer mortality

Purpose The association between metabolic syndrome (MetS) and the risk of death from cancer is still a controversial issue. The purpose of this study was to examine the associations of MetS and metabolically unhealthy obesity (MUHO) with cancer mortality in a Japanese population. Methods We used data from the Japan Multi-Institutional Collaborative Cohort Study. The study population consisted of 28,554 eligible subjects (14,103 men and 14,451 women) aged 35–69 years. MetS was diagnosed based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and the Japan Society for the Study of Obesity (JASSO), using the body mass index instead of waist circumference. The Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total cancer mortality in relation to MetS and its components. Additionally, the associations of obesity and the metabolic health status with cancer mortality were examined. Results During an average 6.9-year follow-up, there were 192 deaths from cancer. The presence of MetS was significantly correlated with increased total cancer mortality when the JASSO criteria were used (HR = 1.51, 95% CI 1.04–2.21), but not when the NCEP-ATP III criteria were used (HR = 1.09, 95% CI 0.78–1.53). Metabolic risk factors, elevated fasting blood glucose, and MUHO were positively associated with cancer mortality (P <0.05). Conclusion MetS diagnosed using the JASSO criteria and MUHO were associated with an increased risk of total cancer mortality in the Japanese population

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

A novel subfamily of zinc finger genes involved in embryonic development

C2H2 zinc finger proteins make up one of the largest protein families in eukaryotic organisms. Recent study in several different systems has identified a set of novel zinc finger proteins that appear to form a distinct subfamily that we have named the NET family. Members of the NET family (Noc, Nlz, Elbow, and Tlp-1) share two protein motifs--a buttonhead box and an Sp motif--with zinc finger proteins from the Sp family. However, the NET family is uniquely characterized by a single atypical C2H2 zinc finger, in contrast to the Sp family that contains three tandem C2H2 fingers. Here, we review current information about the biochemical function and in vivo role for members of this subfamily. In general, NET family proteins are required during embryonic development. They appear to act by regulating transcription, most likely as repressors, although they are unlikely to bind DNA directly. In the future, it will be important to directly test if NET family proteins control transcription of specific target genes, perhaps via interactions with DNA-binding transcription factors, as well as to further explore their function in vivo

Directly mounted sol-gel composite piezoelectric devices by spray coating technique for high temperature ultrasonic transducers

In this paper, we propose a fabrication method of a high temperature-resistant ultrasonic transducer for non-destructive tests. In typical pipe non-destructive wall thickness measurements, couplant material and backing material which do not have heat resistance are necessary. Therefore, there are restrictions for the practical online pipe thickness monitoring in chemical and power plants. To avoid a limitation of these non-heat-resistant material, we propose a couplant-less transducer fabrication method by attaching a piezoelectric film directly on the tested object with the spray coating method. Our method is based on the sol-gel spray technique to fabricate a piezoelectric ceramic film. With the sensor fabricated with this method, we measured the wall thickness under high temperature (100, 200, 300, 400, 500, 600°C) conditions. From the results of the high-temperature experiment, it was found that the sensitivity decrease due to temperature rise was limited to 3dB and the difference of frequency response was also limited to 2 MHz at the second peak frequency at the maximum. According to the results, the performance deterioration due to high temperature was within an acceptable range. Additionally, the wall thickness could be calculated from reflected pulse waves. We concluded that sufficient availability of the piezoelectric film under high temperature were confirmed. This paper describes the effectiveness of piezoelectric film attached directly on the tested object