Deep sequencing shows multiple oligouridylations are required for 3' to 5' degradation of histone mRNAs on polyribosomes.

Histone mRNAs are rapidly degraded when DNA replication is inhibited during S phase with degradation initiating with oligouridylation of the stem loop at the 3' end. We developed a customized RNA sequencing strategy to identify the 3' termini of degradation intermediates of histone mRNAs. Using this strategy, we identified two types of oligouridylated degradation intermediates: RNAs ending at different sites of the 3' side of the stem loop that resulted from initial degradation by 3'hExo and intermediates near the stop codon and within the coding region. Sequencing of polyribosomal histone mRNAs revealed that degradation initiates and proceeds 3' to 5' on translating mRNA and that many intermediates are capped. Knockdown of the exosome-associated exonuclease PM/Scl-100, but not the Dis3L2 exonuclease, slows histone mRNA degradation consistent with 3' to 5' degradation by the exosome containing PM/Scl-100. Knockdown of No-go decay factors also slowed histone mRNA degradation, suggesting a role in removing ribosomes from partially degraded mRNAs.

The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation.

Widespread changes in gene expression drive tumorigenesis, yet our knowledge of how aberrant epigenomic and transcriptome profiles arise in cancer cells is poorly understood. Here, we demonstrate that metabolic transformation plays an important role. Butyrate is the primary energy source of normal colonocytes and is metabolized to acetyl-CoA, which was shown to be important not only for energetics but also for HAT activity. Due to the Warburg effect, cancerous colonocytes rely on glucose as their primary energy source, so butyrate accumulated and functioned as an HDAC inhibitor. Although both mechanisms increased histone acetylation, different target genes were upregulated. Consequently, butyrate stimulated the proliferation of normal colonocytes and cancerous colonocytes when the Warburg effect was prevented from occurring, whereas it inhibited the proliferation of cancerous colonocytes undergoing the Warburg effect. These findings link a common metabolite to epigenetic mechanisms that are differentially utilized by normal and cancerous cells because of their inherent metabolic differences.

Toward a Developmental Science of Politics.

In this monograph, we argue for the establishment of a developmental science of politics that describes, explains, and predicts the formation and change of individuals' political knowledge, attitudes, and behavior beginning in childhood and continuing across the life course. Reflecting our goal of contributing both theoretical conceptualizations and empirical data, we have organized the monograph into two broad sections. In the first section, we outline theoretical contributions that the study of politics may make to developmental science and provide practical reasons that empirical research in the domain of politics is important (e.g., for identifying ways to improve civics education and for encouraging higher voting rates among young adults). We also review major historical approaches to the study of political development and provide an integrative theoretical framework to ground future work. Drawing on Bronfenbrenner's ecological systems model as an organizing scheme and emphasizing social justice issues, we describe how factors rooted in cultural contexts, families, and children themselves are likely to shape political development. In the second section of the monograph, we argue for the importance and utility of studying major political events, such as presidential elections, and introduce the major themes, rationales, and hypotheses for a study of U.S. children's views of the 2016 U.S. presidential election. In addition, we apply a social-justice lens to political thought and participation, addressing the role of gender/sex and race/ethnicity in children's political development broadly, and in their knowledge and views of the 2016 U.S. presidential election specifically. In interviews conducted within the month before and after the election, we examined two overarching categories of children's political attitudes: (a) knowledge, preferences, and expectations about the 2016 election, and (b) knowledge and attitudes concerning gender/sex and politics, particularly relevant for the 2016 election given Hillary Clinton's role as the first female major-party candidate for the presidency. Participants were 187 children (101 girls) between 5 and 11 years of age (M = 8.42 years, SD = 1.45 years). They were recruited from schools and youth organizations in five counties in four U.S. states (Kansas, Kentucky, Texas, and Washington) with varying voting patterns (e.g., Trump voters ranged from 27% to 71% of county voters). The sample was not a nationally representative one, but was racially diverse (35 African American, 50 Latinx, 81 White, and 21 multiracial, Asian American, Middle Eastern, or Native American children). In addition to several child characteristics (e.g., age, social dominance orientation [SDO]), we assessed several family and community characteristics (e.g., child-reported parental interest in the election and government-reported county-level voting patterns, respectively) hypothesized to predict outcome variables. Although our findings are shaped by the nature of our sample (e.g., our participants were less likely to support Trump than children in larger, nationwide samples were), they offer preliminary insights into children's political development. Overall, children in our sample were interested in and knowledgeable about the presidential election (e.g., a large majority identified the candidates correctly and reported some knowledge about their personal qualities or policy positions). They reported more information about Donald Trump's than Hillary Clinton's policies, largely accounted for by the substantial percentage of children (41%) who referred to Trump's immigration policies (e.g., building a wall between the United States and Mexico). Overall, children reported as many negative as positive personal qualities of the candidates, with negative qualities being reported more often for Trump than for Clinton (56% and 18% of children, respectively). Most children (88%) supported Clinton over Trump, a preference that did not vary by participants' gender/sex or race/ethnicity. In their responses to an open-ended inquiry about their reactions to Trump's win, 63% of children reported negative and 18% reported positive emotions. Latinx children reacted more negatively to the election outcome than did White children. Girls' and boys' emotional responses to the election outcome did not differ. Children's personal interest in serving as U.S. president did not vary across gender/sex or racial/ethnic groups (overall, 42% were interested). Clinton's loss of the election did not appear to depress (or pique) girls' interest in becoming U.S. president. With respect to the role of gender/sex in politics, many children (35%) were ignorant about women's absence from the U.S. presidency. Only a single child was able to name a historical individual who worked for women's civil rights or suffrage. Child characteristics predicted some outcome variables. For example, as expected, older children showed greater knowledge about the candidates than did younger children. Family and community characteristics also predicted some outcome variables. For example, as expected, participants were more likely to support Trump if they perceived that their parents supported him and if Trump received a greater percentage of votes in the children's county of residence. Our data suggest that civic education should be expanded and reformed. In addition to addressing societal problems requiring political solutions, civics lessons should include the histories of social groups' political participation, including information about gender discrimination and the women's suffrage movement in U.S. political history. Providing children with environments that are rich in information related to the purpose and value of politics, and with opportunities and encouragement for political thought and action, is potentially beneficial for youth and their nations.

The inherence heuristic: a key theoretical addition to understanding social stereotyping and prejudice.

Prior work has detailed the constructivist processes that lead individuals to categorize others along particular dimensions (e.g., gender) and generate the content (e.g., stereotypes) and affect (e.g., prejudices) associated with social groups. The inherence heuristic is a novel mechanism that appears to shape the content and rigidity of children's social stereotypes and prejudices.

Specific and modular binding code for cytosine recognition in Pumilio/FBF (PUF) RNA-binding domains.

Pumilio/fem-3 mRNA-binding factor (PUF) proteins possess a recognition code for bases A, U, and G, allowing designed RNA sequence specificity of their modular Pumilio (PUM) repeats. However, recognition side chains in a PUM repeat for cytosine are unknown. Here we report identification of a cytosine-recognition code by screening random amino acid combinations at conserved RNA recognition positions using a yeast three-hybrid system. This C-recognition code is specific and modular as specificity can be transferred to different positions in the RNA recognition sequence. A crystal structure of a modified PUF domain reveals specific contacts between an arginine side chain and the cytosine base. We applied the C-recognition code to design PUF domains that recognize targets with multiple cytosines and to generate engineered splicing factors that modulate alternative splicing. Finally, we identified a divergent yeast PUF protein, Nop9p, that may recognize natural target RNAs with cytosine. This work deepens our understanding of natural PUF protein target recognition and expands the ability to engineer PUF domains to recognize any RNA sequence.

Relations between colorblind socialization and children's racial bias: evidence from European American mothers and their preschool children.

To examine European American parents' racial socialization, mothers (n = 84) were videotaped while reading 2 race-themed books to their 4- to 5-year-old children and completed surveys concerning their racial attitudes and behaviors. Children completed measures of their racial attitudes and both groups (mothers and preschoolers) predicted the others' racial attitudes. Results indicated that nearly all mothers adopted "colormute" and "colorblind" approaches to socialization. Furthermore, neither children nor mothers accurately predicted the others' views. Children's racial attitudes were unrelated to their mothers' attitudes but were predicted by their mothers' cross-race friendships; those children whose mothers had a higher percentage of non-European American friends showed lower levels of racial biases than those children whose mothers had a lower percentage of non-European American friends.

White Parents' Socialization of Racial Attitudes: A Commentary on Scott et al. (2020).

In the September 2020 issue of Perspectives, Scott et al. argued that there is insufficient empirical work on White parents' racial-socialization strategies to support generalizations about the topic and, therefore, that journalists' recommendation that White parents discuss race and racism with their children represents a case of speculation without evidence. Although we strongly support Scott et al.'s call for additional, rigorous research on racial socialization in White families, we argue that their critique of popular-press pieces was unwarranted. Specifically, we argue that, although definitive tests of the effects of specific White parental racial-socialization strategies are lacking, the recommendation for parents to discuss race and racism with their children is both appropriate and empirically grounded. We describe research on racial socialization, intergroup contact, and cognitive development that is consistent with recommendations from developmental scientists reported in the popular press. Furthermore, we argue that parents may be the ideal socializers of racial attitudes. We conclude with a discussion of the broad context concerning media reports of findings from psychological science.

When multiracial individuals are the numerical majority: Children's racial attitudes in the Dominican Republic.

The Dominican Republic is a uniquely valuable context in which to study children's racial stereotyping and prejudice, in part because multiracial individuals comprise the majority of the population and race is viewed largely as a continuous rather than dichotomous construct. In two studies, we use developmental and social theories to ground an exploration of Dominican children's racial biases. In studies 1 (n = 54; ages 6-11) and 2 (n = 122; ages 6-11), children were given measures of racial identity, preference, stereotyping, and/or status. As expected, children identified their own race in a manner consistent with others (e.g., their teachers). Across a variety of tasks, children failed to consistently favor members of a specific racial group-as indicated by differing levels of racial stereotyping and associations of social status with different races. They did, however, sometimes systematically express greater liking of individuals of mixed racial heritage, a finding that was contingent on the modality of assessment (i.e., whether race was framed as a continuous vs. dichotomous category, and measured via nonforced vs. forced-choice methods). Implications for current theories of racial attitude development are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Gender, values, and occupational interests among children, adolescents, and adults.

Work fulfills personal values, perhaps differently for males and females. Explored here was the role values play in shaping occupational interests. Study 1 examined children's, adolescents', and adults' (N = 313) occupational values (regarding money, power, family, altruism), occupational interests, and perceptions of values afforded by traditionally masculine and feminine occupations. Results revealed sex differences in occupational values and interests. Furthermore, participants' values predicted their own interests in culturally masculine and feminine occupations. Study 2 used novel jobs and experimentally manipulated prototypical sex of worker and value affordances to disentangle their effects on occupational interests. At all ages, participants' (N = 240) occupational interests were affected by the depicted sex of the workers and by the stated value affordances of the jobs.

An experimental study of the correlates and consequences of perceiving oneself to be the target of gender discrimination.

An experimental methodology was used to test hypotheses concerning the effects of contextual, cognitive-developmental, and individual difference factors on children's views of whether they have been the target of gender discrimination and the possible consequent effect of such views on two forms of state self-esteem: performance and social acceptance. Children (N=108, 5-11 years of age) completed theory of mind and gender attitude measures and a drawing task. Next, children received feedback that was designed to appear either gender biased (discrimination condition) or nonbiased (control condition). Children's attributions for the feedback and state self-esteem were assessed. As expected, children reported having been the target of gender discrimination more often in the discrimination condition than in the control condition. Older and more cognitively advanced children made fewer attributions to discrimination than their peers. Perceptions of discrimination were associated with higher performance state self-esteem and, among egalitarian children, lower social state self-esteem.

An experimental test of the effects of gender constancy on sex typing.

This study provides an experimental test of the hypothesis that level of gender constancy understanding affects children's sex typing. Preschool-age children (N=62, mean age=47 months) were randomly assigned to experimental lessons that taught that biological traits (including gender) are either fixed (pro-constancy condition) or mutable (anti-constancy condition). Posttests revealed that the lessons were effective; children in the pro-constancy condition showed higher gender constancy and appearance-reality distinction scores than did children in the anti-constancy condition. Sex typing did not, however, differ between treatment conditions at immediate and 3-month posttesting.

The future of sex and gender in psychology: Five challenges to the gender binary.

The view that humans comprise only two types of beings, women and men, a framework that is sometimes referred to as the "gender binary," played a profound role in shaping the history of psychological science. In recent years, serious challenges to the gender binary have arisen from both academic research and social activism. This review describes 5 sets of empirical findings, spanning multiple disciplines, that fundamentally undermine the gender binary. These sources of evidence include neuroscience findings that refute sexual dimorphism of the human brain; behavioral neuroendocrinology findings that challenge the notion of genetically fixed, nonoverlapping, sexually dimorphic hormonal systems; psychological findings that highlight the similarities between men and women; psychological research on transgender and nonbinary individuals' identities and experiences; and developmental research suggesting that the tendency to view gender/sex as a meaningful, binary category is culturally determined and malleable. Costs associated with reliance on the gender binary and recommendations for future research, as well as clinical practice, are outlined. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Messenger RNAs localized to distal projections of human stem cell derived neurons.

The identification of mRNAs in distal projections of model organisms has led to the discovery of multiple proteins that are locally synthesized for functional roles such as axon guidance, injury signaling and regeneration. The extent to which local protein synthesis is conserved in human neurons is unknown. Here we used compartmentalized microfluidic chambers to characterize the transcriptome of distal projections of human embryonic stem cells differentiated using a protocol which enriched for glutamatergic neurons (hESC-neurons). Using gene expression analysis, we identified mRNAs proportionally enriched in these projections, representing a functionally unique local transcriptome as compared to the human neuronal transcriptome inclusive of somata. Further, we found that the most abundant mRNAs within these hESC-neuron projections were functionally similar to the axonal transcriptome of rat cortical neurons. We confirmed the presence of two well characterized axonal mRNAs in model organisms, ß-actin and GAP43, within hESC-neuron projections using multiplexed single molecule RNA-FISH. Additionally, we report the novel finding that oxytocin mRNA localized to these human projections and confirmed its localization using RNA-FISH. This new evaluation of mRNA within human projections provides an important resource for studying local mRNA translation and has the potential to reveal both conserved and unique translation dependent mechanisms.

Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling.

Injury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynaptic excitability, and inhibitory inputs at injured neurons. Our findings show that intrinsic signaling within damaged neurons regulates synaptic remodeling and involves netrin-1 signaling.Spinal cord injury can induce synaptic reorganization and remodeling in the brain. Here the authors study how severed distal axons signal back to the cell body to induce hyperexcitability, loss of inhibition and enhanced presynaptic release through netrin-1.

Children's Intergroup Relations and Attitudes.

The existence of warm, intimate, supportive, and egalitarian relationships between members of differing social outgroups is likely, at the societal level, to facilitate cooperation and cohesion, and at the individual level, to promote positive social, educational, and occupational outcomes. The developmental pathway from intergroup contact to intergroup attitudes as it operates among children is not, however, well understood. In our chapter, we review and integrate selected social and developmental science related to intergroup relations and attitudes with the goal of proposing a conceptual model of the pathway from intergroup contact to positive intergroup attitudes among youth.

Children's perceptions of gender discrimination.

Children (N = 76; ages 5-10 years) participated in a study designed to examine perceptions of gender discrimination. Children were read scenarios in which a teacher determined outcomes for 2 students (1 boy and 1 girl). Contextual information (i.e., teacher's past behavior), the gender of the target of discrimination (i.e., student), and the gender of the perpetrator (i.e., teacher) were manipulated. Results indicated that older children were more likely than younger children to make attributions to discrimination when contextual information suggested that it was likely. Girls (but not boys) were more likely to view girls than boys as victims of discrimination, and children with egalitarian gender attitudes were more likely to perceive discrimination than were their peers.

Race and the workforce: occupational status, aspirations, and stereotyping among African American children.

This study examined whether African American children's perceptions of occupational status and their own vocational interests are affected by racial segregation of the workforce. Children (N = 92) rated familiar occupations with respect to status, desirability, and stereotyping. Children also rated novel jobs that had been depicted with African Americans, European Americans, or both African and European Americans. As predicted, for familiar jobs, children's judgments were linked to their knowledge of racial segregation of these jobs. In addition, novel occupations that had been depicted with African Americans were judged as lower in status than the identical occupations that had been depicted with European Americans, demonstrating a causal influence of workers' race on children's judgments. Children's age and socioeconomic background moderated their occupational judgments.

Analysis and evaluation of the rationales for single-sex schooling.

Amendments passed as part of the No Child Left Behind Act in 2006 made some forms of single-sex (SS) public education legal in the United States. Proponents offer a host of arguments in favor of such schooling. This chapter identifies and evaluates five broad rationales for SS schooling. We conclude that empirical evidence fails to support proponents' claims but nonetheless suggests ways in which to improve coeducation. Specifically, we (a) show that the purported benefits of SS schooling arise from factors confounded with, but not causally linked to, single-sex composition; (b) challenge claims that biological sex is an effective marker of differences relevant to instruction; (c) argue that sexism on the part of teachers and peers persists in SS contexts; and (d) critique the notion that gender per se "disappears" in SS contexts. We also address societal implications of the use of sex-segregated education and conclude that factors found to be beneficial for students should be implemented within coeducational schools.

Predictors of African American and European American adolescents' endorsement of race-conscious social policies.

To examine the predictors of adolescents' evaluations of affirmative action and school desegregation policies, African American and European American students (ns = 94 and 116, respectively; aged 14 to 17 years) attending a racially diverse high school in the Midwestern United States completed measures of (a) implicit racial attitudes, (b) knowledge about historical racism, and (c) perceptions of and attributions for racial disparities. The following day, adolescents learned about either a proposed affirmative action policy (n = 101) or a school desegregation policy (n = 109) and completed measures of their attitudes toward the policy. Results indicated racial differences in policy support and in the factors predicting policy support. Theoretical implications of the findings are discussed.