Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions.

Transcription factors (TFs) activate enhancers to drive cell-specific gene programs in response to signals, but our understanding of enhancer assembly during signaling events is incomplete. Here, we show that androgen receptor (AR) forms condensates through multivalent interactions mediated by its N-terminal intrinsically disordered region (IDR) to orchestrate enhancer assembly in response to androgen signaling. AR IDR can be substituted by IDRs from selective proteins for AR condensation capacity and its function on enhancers. Expansion of the poly(Q) track within AR IDR results in a higher AR condensation propensity as measured by multiple methods, including live-cell single-molecule microscopy. Either weakening or strengthening AR condensation propensity impairs its heterotypic multivalent interactions with other enhancer components and diminishes its transcriptional activity. Our work reveals the requirement of an optimal level of AR condensation in mediating enhancer assembly and suggests that alteration of the fine-tuned multivalent IDR-IDR interactions might underlie AR-related human pathologies.

Cross-generational bacterial strain transfer to an infant after fecal microbiota transplantation to a pregnant patient: a case report.

BACKGROUND: Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment. METHODS: A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults. RESULTS: The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient's gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer. CONCLUSIONS: The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding. Video Abstract.

The influence of family cohesion on self-regulation and anxiety problems among African American emerging adults.

Although African Americans have lower rates of anxiety in childhood than other racial and ethnic minority groups, they seem to experience escalating rates during emerging adulthood. Despite this, few studies have examined factors associated with anxiety during emerging adulthood among African American populations. The current study investigated the extent to which late adolescent family relationships affect anxiety problems among African American emerging adults. Informed by family development theory, family cohesion was hypothesized to indirectly effect anxiety problems through self-regulation. This model was tested with three waves of data (ages 17, 19, 21) from African Americans participating in the Maryland Adolescent Development in Context Study. Study findings were consistent with the hypothesized model: family cohesion forecasted decreased anxiety problems, indirectly, via increased self-regulation. This finding suggests that families may be an important promotive process for anxiety problems during emerging adulthood. Prevention programs that target family processes may be able to reduce anxiety problems in emerging adult African Americans.

Exploring Racial-Ethnic Pride & Perceived Barriers in PYD: A Latent Profile Analysis.

This study sought to identify profiles of positive youth development (PYD) integrating racial-ethnic factors, specifically racial-ethnic pride and perceived racial-ethnic barriers in a sample of African American (77%) and Latino (23%) children (N = 234, Mean age = 8). Using a latent profile analysis, we found three profiles: The High PYD, Proud & Optimistic (High PYD, racial-ethnic pride, and low perceived racial-ethnic barriers), the High PYD, Proud & Aware (high PYD, pride, and perceived barriers), and the Low PYD and Disconnected (low PYD, pride and high barriers). The Optimistic profile exhibited fewer overall adjustment problems and higher standardized achievement at Time 2 than both the Aware and the Disconnected profiles. The Aware and the Disconnected showed similar adjustments. This study highlights the critical role of helping youth to feel competent, caring, connected, and proud, further supporting the role of socio-cultural factors in the PYD of African American and Latino children.

Positive Youth Development in 2020: Theory, Research, Programs, and the Promotion of Social Justice.

We use Hamilton's (1999) tripartite conception of the positive youth development (PYD) literature - that is, PYD as a theoretical construct, PYD as a frame for program design, and PYD as an instance of specific youth development programs - as a framework for reviewing scholarship involved in the PYD field across the second decade of the 21st century. Advances were made in all three domains and, as well, new issues emerged; chief among them was a focus on the promotion of social justice. We discuss ways in which social justice issues are being addressed within each of these domains and we present a vision for enhancing the PYD-social justice relation in future scholarship involving theory, research, program design, and community-based PYD programs.

The "Haves, Have Some, and Have Nots:" a Latent Profile Analysis of Capacity, Quality, and Implementation in Community-Based Afterschool Programs.

Implementation of evidence-based practices is a critical factor in whether afterschool programs are successful in having a positive impact upon risk reduction and positive youth development. However, important prevention research reveals that contextual and organizational factors can affect implementation (Bradshaw & Pas in School Psychology Review, 40, 530-548, 2011) (Flaspohler et al., in American Journal of Community Psychology, 50(3-4), 271-281, 2012) (Gottfredson et al., Prevention Science, 3, 43-56, 2002) (McIntosh et al., Journal of Positive Behavior Interventions, 18(4), 209-218, 2016) (Payne in Prevention Science, 10, 151-167, 2009). Using a latent profile approach (LPA), this paper examines multiple organizational and neighborhood contextual factors that might affect the degree to which afterschool programs effectively implement evidence-based practices in the context of a cluster-randomized trial of the Paxis Good Behavior Game (PaxGBG). The Interactive Systems Framework (ISF) explores dimensions of capacity that might matter for prevention efforts. As expected, we found that well-resourced and high-quality programs performed well in terms of implementation (the Haves) and, in neighborhood contexts rich in racial-ethnic diversity. Yet, we found that some programs with less physical and material capacity (the Have Nots), demonstrated greater program quality (i.e., supportive adult and peer relationships, engagement, a sense of belonging) and implementation, relative to programs with better capacity (e.g., space, material resources, staffing, and leadership, the Have Somes). While capacity matters, intentional prevention initiatives that seek to promote evidence-based practices are helpful to sites in supporting organizations that might otherwise fail to provide quality programming for youth. This paper addresses a conundrum in prevention science, namely, how to make programming accessible to those who need it with a focus on organizational processes, program quality, and implementation of evidence-based practices.

Racism and preparation for bias within African American families.

Objectives: Exposure to racism experienced by caregivers poses a threat to child developmental outcomes. The current study examines the effects of caregiver-experienced racism on the development of internalizing behaviors for African American children during a sensitive period in their development of racial awareness. Two aspects of caregiver-provided ethnic racial socialization (ERS), cultural socialization and preparation for bias, were assessed as moderators. Supported by prior research, cultural socialization was hypothesized to be protective. Given that research on preparation for bias in early childhood is sparse or inconclusive, no directional hypothesis was formulated for the moderation effect of preparation for bias. Method: A community-recruited, low-income sample of 130 African American caregivers and their children (T3 Mage = 6.20, T4 Mage = 7.17) reported on past-year experiences with racism, ERS practices, and child internalizing behaviors. Path analyses were utilized to assess the influence of caregivers' racist experiences and ERS practices on children's first grade internalizing behaviors after controlling for kindergarten levels. Results: Cultural socialization was not a significant protective factor as hypothesized. However, caregivers' past-year experiences with racism predicted more anxious and sad behaviors in children when caregivers reported using more preparation for bias. Conclusions: The effects of caregivers' racism experiences on their 6-year-old children's internalizing behaviors were contingent on their use of preparation for bias socialization. This study adds to the literature on racism and further elucidates the role preparation for discrimination plays in developmental outcomes for young African American children. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Child Maltreatment and Resilience: The Promotive and Protective Role of Future Orientation.

Maltreatment is associated with risk for a wide range of socio-emotional and behavioral problems in adolescence. Despite this risk, many maltreated youth adjust well through the process of resilience. Extant research demonstrates that future orientation is linked to reduced risks for maladjustment in adolescence. Few studies, however, have tested the protective and promotive role of future orientation using positive and negative developmental outcomes among maltreated youth. The present study aimed to investigate the promotive and moderating role of future orientation among a longitudinal sample of maltreated and demographically comparable non-maltreated youth (N = 1354, 51.5% female, 53.2% African American). Data collected from Time 1 (Mage = 4.56, SDage = 0.70) to Time 8 (Mage = 18.514, SDage = 0.615) were used. Compared to the non-maltreated youth, maltreated youth showed increased delinquent behaviors and reduced self-esteem. In addition, future orientation significantly predicted higher levels of social competence and attenuated the adverse effects of maltreatment on youth delinquency and substance use. The findings highlight the role of future orientation in the development of resilience among maltreated youth, bearing significant contributions to prevention and intervention programs designed to protect youth against risks linked to child maltreatment and promote their positive development.

Severe Poverty and Growth in Behavioral Self-Regulation: The Mediating Role of Parenting.

This study examined how exposure to severe poverty related to behavioral self-regulation growth during early childhood as mediated by parenting practices. Ethnic differences were tested. Data were collected across 4 waves from 359 low-income African American and Latino families. The frequency of exposure to severe poverty was indicated by how many times family income fell below 50% of the federal poverty line across 4 waves. Behavioral self-regulation was assessed when children were 3½, 6, and 7 years old (Wave 2-4), and parenting was observed when children were age 2½ years old (Wave 1). More frequent exposure to severe poverty was associated with slower behavioral self-regulation growth, and the effect was partially mediated through less sensitive and supportive parenting practices for Latino families. The mediation was not observed for African American families. Targeting the promotion of sensitive and supportive parenting practices may be an effective strategy for accelerating self-regulation development.

Fathering quality in early childhood and kindergarten achievement in low-income racial-ethnic minority children.

The relative lack of attention to fathers' effects on children's achievement is even more apparent when examining fathering among low-income racial-ethnic minorities. We examined relations of fathering qualities when children were 2-3 years old with subsequent reading and mathematics achievement in kindergarten in a sample of low-income African American (n = 119) and primarily Mexican-origin Latino children (n = 193) from multiple neighborhood areas of a large city in the southwestern United States. Measures of parenting qualities were based on qualitative ratings of videotaped observations of father-child and mother-child interactions collected in the home during semistructured play activities. Mathematics and reading achievement scores were based on administration of the Woodcock-Johnson Revised (Woodcock & Muñoz-Sandoval, 1993) or the Batería Woodcock-Muñoz (Woodcock & Munoz-Sandoval, 1996), as appropriate depending upon the child's language. A structural equations model in which kindergarten mathematics and reading achievement were regressed on early childhood fathering displayed good model fit, χ2(72) = 131.30, p < .001, comparative fit index = .954, root mean square error of approximation = .051, standardized root mean square residual = .079. Results indicated that sensitive support from African American and Latino resident fathers was associated with their children's mathematics achievement even after controlling for mothers' sensitive support, but fathering quality was not associated with reading achievement. The implications of these findings for the study of fathering in racial-ethnic minority populations as well as for the development of early preventive interventions to support academic achievement are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Cultural Values and Behavior Among African American and European American Children.

OBJECTIVES: This study explores the relationships of individualistic (e.g., competition, material success) and collectivistic values (e.g., familism, respect) with risky and prosocial behavior among African-American and European-American youth. While previous work has focused upon immigrant adolescents, this study expands the research exploring cultural values to other racial-ethnic groups and to a younger developmental period. This study builds upon culture as individually experienced beliefs and practices, potentially espousing multiple cultural orientations and relationships to behavior. METHODS: Data from Cohort 3 of a study of 219 urban, suburban, and rural children included African-American (42%) and European-American(58%) children, 54% female, ranging from grades 1-5 (mean age = 9). Multigroup structural equation models were tested resulting in a measurement model that fit similarly across groups (RMSEA=.05, CFI =.94). RESULTS: African-American children reported higher levels of individualism, and African-American and European-American children reported espousing similar levels of collectivism. Children in higher grades were found to be more collectivistic and less individualistic. Individualistic values were related to children's lower prosocial and higher rates of problem and delinquent behavior. Collectivistic cultural values were associated with reduced rates of problem behaviors, controlling for race-ethnicity, gender and grade. CONCLUSIONS: Results provide support for the assertion that youth espouse multiple cultural orientations and that collectivistic cultural values can serve as promotive factors for children of diverse backgrounds. Practice and policy should seek to understand the role of family, school, and community socialization of multiple cultural orientations and nuanced associations with risk and resilience.

Using Connected Technologies in a Continuous Quality Improvement Approach in After-school Settings: The PAX Good Behavior Game.

This demonstration study explored the use of connected technologies in a continuous quality improvement (CQI) approach to implementing evidence-based practices in after-school. Focus-group with staff indicated enjoyment of technology and offered feedback for future development. Ecological momentary assessments (EMA) were gathered daily. Three randomized conditions were compared among 4 programs and 12 staff implementing PAX Good Behavior Game (PAX GBG). ANOVA, Post-Hoc Tukey and Chi-square analyses indicated that the tech-enhanced condition showed better implementation using scoreboards than the in-person, while similar in game length. Both were superior to the control in behavioral strategies; highlighting the promise of technology in capacity-building.

Symptoms and synchrony: Mother and child internalizing problems moderate respiratory sinus arrhythmia concordance in mother-preadolescent dyads.

Physiological synchrony, or concordance, among caregiver-child dyads involves the matching of biological states. Understanding this process is critical for enhancing our knowledge of the ways that the caregiver-child relationship supports child development. However, the meaning of physiological synchrony for child adjustment is poorly understood. This study examined physiological synchrony in respiratory sinus arrhythmia (RSA), an indicator of parasympathetic activity, between 87 mothers (M age = 35.30 years, SD = 6.71 years) and their preadolescent children (M age = 10.36 years, SD = 1. 19 years, 52.9% girls). Dyads, all of which were from economically impoverished backgrounds, participated in 3 tasks that varied in the level of interaction that was required between the partners. Mothers self-reported their own depressive symptoms and rated their children's externalizing and internalizing symptoms. Physiological synchrony was generally strongest in tasks requiring the greatest levels of interaction among partners. Further, RSA synchrony was positive in the context of low levels of maternal depressive and child internalizing symptoms, and negative in the context of high levels of such symptoms, though results varied by task. Child externalizing symptoms did not moderate the RSA concordance process. The results identify both proximal and distal contexts in which physiological synchrony occurs, which ultimately broadens our understanding of the meaning and significance of parent-child physiological synchrony. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Ethical Challenges in Promoting the Implementation of Preventive Interventions: Report of the SPR Task Force.

Prevention science researchers and practitioners are increasingly engaged in a wide range of activities and roles to promote evidence-based prevention practices in the community. Ethical concerns invariably arise in these activities and roles that may not be explicitly addressed by university or professional guidelines for ethical conduct. In 2015, the Society for Prevention Research (SPR) Board of Directors commissioned Irwin Sandler and Tom Dishion to organize a series of roundtables and establish a task force to identify salient ethical issues encountered by prevention scientists and community-based practitioners as they collaborate to implement evidence-based prevention practices. This article documents the process and findings of the SPR Ethics Task Force and aims to inform continued efforts to articulate ethical practice. Specifically, the SPR membership and task force identified prevention activities that commonly stemmed from implementation and scale-up efforts. This article presents examples that illustrate typical ethical dilemmas. We present principles and concepts that can be used to frame the discussion of ethical concerns that may be encountered in implementation and scale-up efforts. We summarize value statements that stemmed from our discussion. We also conclude that the field of prevention science in general would benefit from standards and guidelines to promote ethical behavior and social justice in the process of implementing evidence-based prevention practices in community settings. It is our hope that this article serves as an educational resource for students, investigators, and Human Subjects Review Board members regarding some of the complexity of issues of fairness, equality, diversity, and personal rights for implementation of preventive interventions.

Promoting Afterschool Quality and Positive Youth Development: Cluster Randomized Trial of the Pax Good Behavior Game.

This randomized trial tested a strategy originally developed for school settings, the Pax Good Behavior Game (PAX GBG), in the new context of afterschool programs. We examined this approach in afterschool since 70% of all juvenile crime occurs between the hours of 3-6 pm, making afterschool an important setting for prevention and promotion. Dual-career and working families need monitoring and supervision for their children in quality settings that are safe and appropriately structured. While substantial work has identified important features of afterschool programs, increasing attention is being given to how to foster quality. PAX GBG, with its focus on shared norms, cooperative teams, contingent activity rewards, and liberal praise, could potentially enhance not only appropriate structure and supportive relationships, but also youth self-regulation, co-regulation, and socio-emotional development. This study examined the PAX GBG among 76 afterschool programs, serving 811 youth ages 5-12, who were diverse in race-ethnicity, socio-economic status, and geographic locale. Demographically matched pairs of afterschool programs were randomized to PAX GBG or treatment-as-usual. Independent observers conducted ratings of implementation fidelity and program quality across time; along with surveys of children's problem and prosocial behavior. Interaction effects were found using hierarchical linear models such that experimental programs evidencing higher implementation fidelity demonstrated better program quality than controls, (i.e., less harshness, increased appropriate structure, support, and engagement), as well as reduced child-reported hyperactivity and intent-to-treat effects on prosocial behavior. This study demonstrates that best practices fostered by PAX GBG and implemented with fidelity in afterschool result in higher quality contexts for positive youth development.

Design, synthesis and biological evaluation of renin inhibitors guided by simulated annealing of chemical potential simulations.

We have applied simulated annealing of chemical potential (SACP) to a diverse set of ∼150 very small molecules to provide insights into new interactions in the binding pocket of human renin, a historically difficult target for which to find low molecular weight (MW) inhibitors with good bioavailability. In one of its many uses in drug discovery, SACP provides an efficient, thermodynamically principled method of ranking chemotype replacements for scaffold hopping and manipulating physicochemical characteristics for drug development. We introduce the use of Constrained Fragment Analysis (CFA) to construct and analyze ligands composed of linking those fragments with predicted high affinity. This technique addresses the issue of effectively linking fragments together and provides a predictive mechanism to rank order prospective inhibitors for synthesis. The application of these techniques to the identification of novel inhibitors of human renin is described. Synthesis of a limited set of designed compounds provided potent, low MW analogs (IC50s<100nM) with good oral bioavailability (F>20-58%).

Introduction to the Special Section of Child Development on Positive Youth Development in Diverse and Global Contexts.

Positive youth development (PYD) research seeks to understand and promote positive aspects of development in young people. In this the special section, focused upon youth from diverse racial-ethnic backgrounds around the globe, we describe the origins and development of the field, identify key and emerging themes, and present the challenges for work in the area in the years ahead. Central to these are elements that are inherent in many of the articles that constitute the section: These include a need to articulate more clearly the role of social and cultural context in positive development, a need to refine the measures and methods used for collecting data, the significance of social identities, and engagement with other fields of study and with policymakers.

Positive Youth Development Among Diverse Racial-Ethnic Children: Quality Afterschool Contexts as Developmental Assets.

Positive youth development (PYD) deserves more empirical attention, particularly among children of diverse racial-ethnic backgrounds. Given the need among families for monitoring and supervision during out-of-school time, community-based afterschool is a potentially promotive ecological setting. This study explores the quality of afterschool experiences upon PYD. This multimethod study includes over 500 elementary school children in Grades 2-5 (Mage  = 8.80, SD = 1.12). The sample comprises of 49% White, 27% African American, 7% Latino, and 17% mixed race/others with 45% free/reduced lunch eligible children. In multilevel models, independently observed quality across time positively impacted competence, connection, caring for all youth, and cultural values for racial-ethnic minority youth. Afterschool fosters PYD, including sociocultural dimensions, when comprised of appropriately structured, supportive, and engaging interactions.

Promoting Nurturing Environments in Afterschool Settings.

Given the rise in dual-career and single-parent families, and the need for monitoring and supervision during out-of-school time, afterschool settings are becoming important contexts for the prevention of problem behaviors and the promotion of the positive development of youth. Research indicates that high-quality afterschool programs can have positive effects on children's academic, socio-emotional, and behavioral outcomes. But less is known about how these influences occur and potential mechanisms involved in this nurturing and promotion process. This paper draws upon the current theoretical and empirical literature in school settings and beyond to examine ways in which afterschool settings can be leveraged as a potential nurturing environment. We apply the conceptualization of nurturing environments put forth by Biglan et al. (Am Psychol 67(4):257-271, 2012. doi: 10.1037/a0026796 ), which attends to the minimization of toxic social and biological conditions, reinforcement of diverse prosocial behaviors, limiting opportunities and influences for problem behavior, and promoting psychological flexibility in the pursuit of one's values and goals. This paper concludes by identifying potential future research directions and practice implications regarding afterschool settings as nurturing environments for all youth.

Racial-ethnic Identity in Context: Examining Mediation of Neighborhood Factors on Children's Academic Adjustment.

Research consistently shows that neighborhood socio-demographic characteristics and residents' neighborhood perceptions matter for youth well-being, including a positive sense of racial-ethnic identity. Although elementary-school children are likely in the earlier phases of identity formation, the authors examined whether objective and subjective neighborhood characteristics are related to their racial-ethnic identity and, in turn, their academic adjustment. A diverse sample (30.4% African American, 35.2% White, 12.3% Latino, & 22.0% Other) of 227 children in Grades 2 through 5 were surveyed in afterschool programs. Bivariate correlations showed that youth living in disadvantaged neighborhoods reported more barriers due to their race-ethnicity, but these barriers were not related to their sense of academic efficacy. Residing in a disadvantaged neighborhood was unrelated to youth's academic self-efficacy. However, path analyses showed that positive neighborhood perceptions were associated with a stronger sense of race-ethnicity (i.e., affirmation and belonging), which was in turn related to greater academic efficacy. These results suggest that neighborhood connection provides a source of affirmation and value for young children, helping them to understand who they are as part of a racial-ethnic group and helping to foster a sense of future achievement opportunities. This study provides additional evidence that along with other important proximal contexts (e.g., family, school), young children's neighborhood context is important for development. Results are discussed to highlight environmental influences on young children's awareness of race-ethnicity and the implications of the combined impact of neighborhood and racial-ethnic identity on psychosocial adjustment.