Low Frequency Vibrations Disrupt Left-Right Patterning in the Xenopus Embryo

The development of consistent left-right (LR) asymmetry across phyla is a fascinating question in biology. While many pharmacological and molecular approaches have been used to explore molecular mechanisms, it has proven difficult to exert precise temporal control over functional perturbations. Here, we took advantage of acoustical vibration to disrupt LR patterning in Xenopus embryos during tightly-circumscribed periods of development. Exposure to several low frequencies induced specific randomization of three internal organs (heterotaxia). Investigating one frequency (7 Hz), we found two discrete periods of sensitivity to vibration; during the first period, vibration affected the same LR pathway as nocodazole, while during the second period, vibration affected the integrity of the epithelial barrier; both are required for normal LR patterning. Our results indicate that low frequency vibrations disrupt two steps in the early LR pathway: the orientation of the LR axis with the other two axes, and the amplification/restriction of downstream LR signals to asymmetric organs

Gender role orientation is associated with health-related quality of life differently among African-American, Hispanic, and White youth

PurposeThis study examined the association between gender role orientation (GRO) and health-related quality of life (HRQOL) in youth, and how this relationship may differ between males and females as well as among African-American, White, and Hispanic individuals. GRO has been reported to influence serious health outcomes including cancer, heart disease, mental illness, and mortality rates. However, few studies have examined the link between GRO and health outcomes for children, even though gender identity is formed in childhood.MethodsData were examined from 4824 participants in the Healthy Passages™ project, a population-based survey of fifth-grade children in three US metropolitan areas. Children reported their own HRQOL using the PedsQL and degree of female, male, and androgynous GRO using the Children's Sex Role Inventory.ResultsBased on structural equations analysis, male GRO was positively associated with HRQOL for all racial/ethnic groups, regardless of sex, whereas female GRO was associated with better HRQOL for Hispanic and White females and poorer HRQOL for Hispanic males. Androgynous GRO was associated with better HRQOL among Hispanic and White females, but not males nor African-Americans of either sex.ConclusionsRacial/ethnic differences emerged for female and androgynous, but not male, GROs. Hispanic males are the only group for which GRO (female) was associated with poorer HRQOL. Future research should find ways to help youth overcome negative effects on health from gender beliefs and behavior patterns with sensitivity to racial/ethnic membership

Soc Psychiatry Psychiatr Epidemiol

PURPOSE: The present study seeks to examine gender differences in internalizing and externalizing problems either parent/teacher or self-reported and to investigate the influence of country-level gender gap on children's mental health problems across countries with high and low gender gap across Europe. METHODS: The School Children's Mental Health in Europe (SCMHE) survey collected data on primary school children living in six European countries, using self-reports (SR) from children (Dominic Interactive), as well as combination of parent- and teacherreports (P/T C) (Strengths and Difficulties Questionnaire) to assess internalizing and externalizing mental health problems. The World Economic Forum's (WEF's) Global Gender Gap report's Gender Gap Index (GGI) was used to categorize countries with high and low gender gap. RESULTS: Boys had greater odds of externalizing problems (OR = 2.6 P/T C, 1.95 SR), and lower odds of internalizing problems (OR = 0.85 P/T C, 0.63 SR). The gender gap's association with mental health problems was different depending on the informant used to identify these problems. A small gap was a risk factor based on reports from adults for externalizing (OR = 1.53) and internalizing problems (OR = 1.42) while it was a protective factor for SR internalizing problems (OR = 0.72). For these problems the gender gap impacted boys and girls differently: a small gender gap was protective for boys but not for girls, including when controlling for key confounding variables. CONCLUSIONS: The differential impact of country-level gender gap observed between self-reported and parent- or teacher-reported mental health is complex but nevertheless present trough mechanisms that are worthwhile to study in depth, with a special attention to the informants and the type of problems examined

RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1

Abstract Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. Upon ligand binding, the Notch intracellular domain (NOTCH ICD) translocates into the nucleus and forms a complex with the transcription factor RBPJ (also known as CBF1 or CSL) to activate expression of Notch target genes. In the absence of a Notch signal, RBPJ acts as a transcriptional repressor. Using a proteomic approach, we identified L3MBTL3 (also known as MBT1) as a novel RBPJ interactor. L3MBTL3 competes with NOTCH ICD for binding to RBPJ. In the absence of NOTCH ICD, RBPJ recruits L3MBTL3 and the histone demethylase KDM1A (also known as LSD1) to the enhancers of Notch target genes, leading to H3K4me2 demethylation and to transcriptional repression. Importantly, in vivo analyses of the homologs of RBPJ and L3MBTL3 in Drosophila melanogaster and Caenorhabditis elegans demonstrate that the functional link between RBPJ and L3MBTL3 is evolutionarily conserved, thus identifying L3MBTL3 as a universal modulator of Notch signaling in metazoans