Patterns of Gender Development Across Intersections of Age, Gender, and Ethnicity-Race.

Two components of gender identity are gender similarity, how one's self-concept relates to the major gender collectives (i.e., female, male), and felt pressure to conform to gender norms. The development of these components across ages and contexts has been understudied. The focus of this study was to examine variations in gender similarity and felt pressure across multiple intersecting contexts: developmental stage, gender, and ethnic-racial group. Six data sets were harmonized and means were compared across 2628 participants (51% girls, 49% boys) from four different developmental cohorts (childhood n = 678, early adolescence n = 1322, adolescence n = 415, and young adulthood n = 213) from diverse ethnic-racial backgrounds (45% White, 23% Latinx/Hispanic, 11% Black/African-American, 7% Asian-American, 5% American Indian, and 5% Multiracial). Results revealed nuanced patterns: Gender intensification was supported in early adolescence, primarily for boys. Young adult men reported lower levels of pressure and gender typicality than younger boys, but young adult women's levels were generally not different than younger girls. Surprisingly, young adult women's levels of own-gender similarity and pressure from parents were higher than adolescent girls. Expectations of gender differences in gender typicality and felt pressure were supported for all ages except young adults, with higher levels for boys. Finally, there were more similarities than differences across ethnic-racial groups, though when there were differences, minoritized participants reported heightened gender typicality and pressure (largely accounted for by higher scores for Black and Latinx participants and lower scores for White and Multiracial participants). These results add to what is understood about contextually dependent gender development.

Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis.

Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish "condensinopathies" as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.

cGAS surveillance of micronuclei links genome instability to innate immunity.

DNA is strictly compartmentalized within the nucleus to prevent autoimmunity; despite this, cyclic GMP-AMP synthase (cGAS), a cytosolic sensor of double-stranded DNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. Such micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by its own nuclear membrane. Breakdown of the micronuclear envelope, a process associated with chromothripsis, leads to rapid accumulation of cGAS, providing a mechanism by which self-DNA becomes exposed to the cytosol. cGAS is activated by chromatin, and consistent with a mitotic origin, micronuclei formation and the proinflammatory response following DNA damage are cell-cycle dependent. By combining live-cell laser microdissection with single cell transcriptomics, we establish that interferon-stimulated gene expression is induced in micronucleated cells. We therefore conclude that micronuclei represent an important source of immunostimulatory DNA. As micronuclei formed from lagging chromosomes also activate this pathway, recognition of micronuclei by cGAS may act as a cell-intrinsic immune surveillance mechanism that detects a range of neoplasia-inducing processes.

Similarity in transgender and cisgender children's gender development.

Gender is one of the central categories organizing children's social world. Clear patterns of gender development have been well-documented among cisgender children (i.e., children who identify as a gender that is typically associated with their sex assigned at birth). We present a comprehensive study of gender development (e.g., gender identity and gender expression) in a cohort of 3- to 12-y-old transgender children (n = 317) who, in early childhood, are identifying and living as a gender different from their assigned sex. Four primary findings emerged. First, transgender children strongly identify as members of their current gender group and show gender-typed preferences and behaviors that are strongly associated with their current gender, not the gender typically associated with their sex assigned at birth. Second, transgender children's gender identity (i.e., the gender they feel they are) and gender-typed preferences generally did not differ from 2 comparison groups: cisgender siblings (n = 189) and cisgender controls (n = 316). Third, transgender and cisgender children's patterns of gender development showed coherence across measures. Finally, we observed minimal or no differences in gender identity or preferences as a function of how long transgender children had lived as their current gender. Our findings suggest that early sex assignment and parental rearing based on that sex assignment do not always define how a child identifies or expresses gender later.

Power in Aggressor-Victim Relationships: Exploring Social, Physical, Gender- and Ethnicity-Based Power.

Theory highlights power in aggressor-victim relationships, yet empirical work assessing dyadic power is largely absent. Variability in power balance versus imbalance within aggressor-victim dyads (based on social, physical, gender- and ethnicity-based power) was explored. Participants (N = 952; grade 6-8; 50% girls, 44% Hispanic/Latina/o) nominated aggressors and victims (4662 aggressor-victim dyads; 642 strong dyads [based on reputational strength]; 169 sustained dyads [based on longevity]). Dyadic social power (social network centrality and prestige) was calculated from friendship nominations. Self-report was used for dyadic physical (body mass index), gender- and ethnicity-based power. Across power indicators, there were more power-balanced than imbalanced dyads (particularly for strong and sustained dyads). The findings challenge theoretical notions that aggressors are more powerful than their victims and have implications for aggressor-victim relationships.

Mutations in TOP3A Cause a Bloom Syndrome-like Disorder.

Bloom syndrome, caused by biallelic mutations in BLM, is characterized by prenatal-onset growth deficiency, short stature, an erythematous photosensitive malar rash, and increased cancer predisposition. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges (SCEs) on cytogenetic testing. Here, we describe biallelic mutations in TOP3A in ten individuals with prenatal-onset growth restriction and microcephaly. TOP3A encodes topoisomerase III alpha (TopIIIα), which binds to BLM as part of the BTRR complex, and promotes dissolution of double Holliday junctions arising during homologous recombination. We also identify a homozygous truncating variant in RMI1, which encodes another component of the BTRR complex, in two individuals with microcephalic dwarfism. The TOP3A mutations substantially reduce cellular levels of TopIIIα, and consequently subjects' cells demonstrate elevated rates of SCE. Unresolved DNA recombination and/or replication intermediates persist into mitosis, leading to chromosome segregation defects and genome instability that most likely explain the growth restriction seen in these subjects and in Bloom syndrome. Clinical features of mitochondrial dysfunction are evident in several individuals with biallelic TOP3A mutations, consistent with the recently reported additional function of TopIIIα in mitochondrial DNA decatenation. In summary, our findings establish TOP3A mutations as an additional cause of prenatal-onset short stature with increased cytogenetic SCEs and implicate the decatenation activity of the BTRR complex in their pathogenesis.

Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.

PURPOSE: Lamins are the major component of nuclear lamina, maintaining structural integrity of the nucleus. Lamin A/C variants are well established to cause a spectrum of disorders ranging from myopathies to progeria, termed laminopathies. Phenotypes resulting from variants in LMNB1 and LMNB2 have been much less clearly defined. METHODS: We investigated exome and genome sequencing from the Deciphering Developmental Disorders Study and the 100,000 Genomes Project to identify novel microcephaly genes. RESULTS: Starting from a cohort of patients with extreme microcephaly, 13 individuals with heterozygous variants in the two human B-type lamins were identified. Recurrent variants were established to be de novo in nine cases and shown to affect highly conserved residues within the lamin ɑ-helical rod domain, likely disrupting interactions required for higher-order assembly of lamin filaments. CONCLUSION: We identify dominant pathogenic variants in LMNB1 and LMNB2 as a genetic cause of primary microcephaly, implicating a major structural component of the nuclear envelope in its etiology and defining a new form of laminopathy. The distinct nature of this lamin B-associated phenotype highlights the strikingly different developmental requirements for lamin paralogs and suggests a novel mechanism for primary microcephaly warranting future investigation.

Quantifying gender norm resistance.

INTRODUCTION: Qualitative and mixed-methods researchers have described the experience of gender norm resistance in adolescence and identified potential types of resistance including indirect resistance (motivated by a preference for gender-atypicality) and direct resistance (motivated by dislike of gender norms and a desire to change them). Building on this work, we developed the Gender Norm Resistance measure to operationalize indirect and direct gender norm resistance. We explored how gender norm resistance aligns with and differs from other gender self-concepts (e.g., felt pressure to conform to gender norms) and peer relations (e.g., contact with peers) and tested for gender differences. METHODS: Participants included 484 early adolescents (girls = 234; Mage = 11.44 years, SD = 0.56). Analyses included factor analyses (EFA, CFA) and bivariate correlations to gather validity evidence, and ANOVAs to determine mean level differences. RESULTS: Evidence that validated using the proposed measure as intended was found including confirmation of the two types of gender norm resistance (indirect and direct). Mean differences were found across participant gender as well as across types of gender norm resistance. CONCLUSIONS: The findings highlight the strengths and weaknesses of the Gender Norm Resistance measure, the different ways adolescents experience indirect and direct gender norm resistance, and the limited role of felt pressure in gender norm resistance.

Cerebral organoids model human brain development and microcephaly.

The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.

Early Adolescent Gender Development: The Differential Effects of Felt Pressure from Parents, Peers, and the Self.

Most empirical research examining youth's gender development measures felt pressure to conform to gender norms using a composite value of felt pressure from multiple sources; however, because of the different socialization processes at work from parents, peers, and the self, analyzing these sources separately may elucidate different effects on gender development. Thus, the purpose of this study was to (a) differentiate the effects of perceived gender socialization pressure from parents, peers, and the self on early adolescents' own- and other-gender typicality, and (b) to examine whether a bi-directional relation between gender typicality and felt pressure is evident when distinguished across sources. With a sample of 212 early adolescents (54% girls; Mage = 11.11 years), felt pressure was found to be distinguishable by socialization source: adolescents' perceptions of parents, peers, and their own pressures were distinct, and each contributed differently to gender development. Pressure from self and peers were both found to relate concurrently to typicality (i.e., positively to own-gender typicality, negatively to other-gender typicality); only pressure from the self was found to have a longitudinal effect on adolescents' developing gender identity (i.e., an increase in own-gender typicality). Interestingly, other-gender typicality did not elicit higher felt pressure; in fact, it was negatively related to later felt pressure from the self, suggesting that adolescents may be developing self-acceptance of their levels of gender typicality. The findings suggest that the development of gender identity may involve a complex interplay with various sources of socialization pressures (e.g., parent, peers, self), and may further shift in relation to the adolescent's own levels of gender typicality.

The Influence of Peers During Adolescence: Does Homophobic Name Calling by Peers Change Gender Identity?

Adolescents actively evaluate their identities during adolescence, and one of the most salient and central identities for youth concerns their gender identity. Experiences with peers may inform gender identity. Unfortunately, many youth experience homophobic name calling, a form of peer victimization, and it is unknown whether youth internalize these peer messages and how these messages might influence gender identity. The goal of the present study was to assess the role of homophobic name calling on changes over the course of an academic year in adolescents' gender identity. Specifically, this study extends the literature using a new conceptualization and measure of gender identity that involves assessing how similar adolescents feel to both their own- and other-gender peers and, by employing longitudinal social network analyses, provides a rigorous analytic assessment of the impact of homophobic name calling on changes in these two dimensions of gender identity. Symbolic interaction perspectives-the "looking glass self"-suggest that peer feedback is incorporated into the self-concept. The current study tests this hypothesis by determining if adolescents respond to homophobic name calling by revising their self-view, specifically, how the self is viewed in relation to both gender groups. Participants were 299 6th grade students (53% female). Participants reported peer relationships, experiences of homophobic name calling, and gender identity (i.e., similarity to own- and other-gender peers). Longitudinal social network analyses revealed that homophobic name calling early in the school year predicted changes in gender identity over time. The results support the "looking glass self" hypothesis: experiencing homophobic name calling predicted identifying significantly less with own-gender peers and marginally more with other-gender peers over the course of an academic year. The effects held after controlling for participant characteristics (e.g., gender), social network features (e.g., norms), and peer experiences (e.g., friend influence, general victimization). Homophobic name calling emerged as a form of peer influence that changed early adolescent gender identity, such that adolescents in this study appear to have internalized the messages they received from peers and incorporated these messages into their personal views of their own gender identity.

Kindergarten School Engagement: Linking Early Temperament and Academic Achievement at the Transition to School.

RESEARCH FINDINGS: Although children's temperament contributes to their academic success, little is known regarding the mechanisms through which temperament is associated withacademic achievement during the transition to elementary school. One such mechanism may be school engagement, but findings are inconsistent and limited. Across two waves of data at the transition to school, we examined the role of kindergarten emotional and behavioral engagement as links between preschool temperament (positive emotionality, anger, andeffortful control), and kindergartenacademic achievement, among a predominantlyMexican/Mexican-Americansample of 241children drawn from Head Start classrooms. Significant direct effects indicated that preschool anger was negatively,and positive emotionality and effortful control werepositively,associated withkindergarten behavioralengagement.Only preschool anger was significantly associatedwithkindergarten emotional engagement. In turn, kindergarten behavioral, but not emotional, engagement was directly, positively associated withkindergartenacademic achievement. All three preschool temperament measures were indirectly related to kindergarten achievement via kindergarten behavioral engagement, and anger was indirectly related to kindergarten achievement via emotional engagement. PRACTICE OR POLIC: Findings highlight the importance of understanding the role of engagement as a mechanismthat can foster children'sacademic achievement at a key developmental transition.

A Dual Identity Approach for Conceptualizing and Measuring Children's Gender Identity.

The goal was to test a new dual identity perspective on gender identity by asking children (n = 467) in three grades (Mage  = 5.7, 7.6, 9.5) to consider the relation of the self to both boys and girls. This change shifted the conceptualization of gender identity from one to two dimensions, provided insights into the meaning and measurement of gender identity, and allowed for revisiting ideas about the roles of gender identity in adjustment. Using a graphical measure to allow assessment of identity in young children and cluster analyses to determine types of identity, it was found that individual and developmental differences in how similar children feel to both genders, and these variations matter for many important personal and social outcomes.

Traditional Masculinity During the Middle School Transition: Associations with Depressive Symptoms and Academic Engagement.

Culturally prescribed social scripts for traditional masculinity that emphasize social dominance are frequently linked to diminished well-being for men across a variety of psychological domains. However, few studies have examined the role of traditional masculinity scripts in the lives of early adolescent boys and girls, despite their relevance during this period and their potential developmental implications. To address this need, we examined the development of early adolescents' conformity to traditional masculinity across the middle school transition, as well as its links with depressive symptoms and academic engagement. Using a diverse sample of 280 adolescents (M age = 11.13, SD = 0.51; 54.3 % Female; 44 % Latina/o) assessed at the beginning (fall 2014) and end (spring 2015) of their first year of middle school, we found an increase in conformity to traditional masculinity scripts among boys, but not among girls. For boys and girls alike, conformity to traditional masculinity predicted greater depressive symptoms and decreased academic engagement. Depressive symptoms also mediated the association between traditional masculinity and academic engagement for boys and girls. This study is among the first to study conformity to traditional masculinity from a developmental lens. The findings suggest that traditional masculinity scripts are relevant for early adolescents (particularly boys) transitioning to middle school. However, for both boys and girls, conformity to these scripts can compromise psychological and academic well-being.

Assessing the Impact of Homophobic Name Calling on Early Adolescent Mental Health: A Longitudinal Social Network Analysis of Competing Peer Influence Effects.

The goal of the current study was to improve our understanding of why adolescence is a critical period for the consideration of declining mental health. We did this by focusing on the impact of homophobic name calling on early adolescent mental health after the transition to middle school. Because we know that homophobic name calling emerges within a dynamic peer group structure, we used longitudinal social network analysis to assess the relation between homophobic name calling, depressive symptoms, and self-esteem while simultaneously limiting bias from alternative peer socialization mechanisms. A sample of adolescents who recently transitioned to a large public middle school (N = 299; 53 % girls; M age = 11.13 years, SD = 0.48) were assessed. Longitudinal assessments of peer relationship networks, depressive symptoms, and self-esteem were collected during the fall and spring of the academic year. The results suggest that, after accounting for the simultaneous effect of alternative peer socialization processes, adolescent experiences of homophobic name calling in the fall predict higher levels of depressive symptoms and lower levels of self-esteem over the course of the academic year. These findings provide evidence of a significant influence of homophobic name calling on adolescent mental health.

On the Association Between Self-Reported Own- and Other-Gender Similarity and the Use of Physical and Relational Aggression in Sixth Grade Children.

The goal was to assess the association between felt similarity to each gender (an aspect of gender identity) and girls' and boys' differential use of relational versus physical aggression. We extend past research on gender differences in the use of aggression by expanding the gender dichotomy and allowing for more variations in an individual's gender identity. Students (N = 414, 47 % female, 6th grade) reported how similar they felt to both their own- and other-gender peers, from which cluster analyses derived four typologies of perceived gender similarity (those who feel similar to their own-gender group; those who feel similar to the other-gender group; those who feel similar to both gender groups; those who feel similar to neither gender group). Peers reported which classmates were relationally and physically aggressive. Analyses compared how girls and boys in each typology of gender similarity differed in their use of relational and physical aggression. Results indicated that most children were engaged in gender normative aggression more than gender non-normative aggression (with the notable exception of low-gender similar girls). Findings were discussed in terms of their importance both for examining a broad spectrum of gender similarity and for understanding the use of aggressive behavior among children.

Development of Expectancies About Own- and Other-Gender Group Interactions and Their School-Related Consequences.

This study examined children's expectancies about interactions with own- and other-gender peers. Goals were to examine expectancies about the outcomes related to own- versus other-gender group interactions, assess cohort and temporal changes in expectancies, and assess the effect of expectancies on school-related outcomes. Students in second and fourth grades (N = 412, 47% girls, Mage  = 7.15 and 9.10 years, respectively) were followed longitudinally for 1 year. Results supported hypotheses that social costs and inclusion-enjoyment that children expect in interactions with own- and other-gender peers represent four constructs. Expectancies varied by gender, age, and differentially predicted school outcomes with inclusion expectancies more strongly relating to outcomes than cost expectancies. Implications of children's expectancies about gendered contexts are discussed.