Multifaceted regulation of Sirtuin 2 (Sirt2) Deacetylase Activity.

Sirtuin 2 (Sirt2) is a member of the sirtuin family of NAD-dependent lysine deacylases and plays important roles in regulation of the cell cycle and gene expression. As a nucleocytoplasmic deacetylase, Sirt2 has been shown to target both histone and non-histone acetylated protein substrates. The central catalytic domain of Sirt2 is flanked by flexible N- and C-termini, which vary in length and composition with alternative splicing. These termini are further subject to post-translational modifications (PTMs) including phosphorylation. Here we investigate the function of the N- and C-termini on deacetylation of nuclear substrates by Sirt2. Remarkably, we find that the C-terminus autoinhibits deacetylation, while the N-terminus enhances deacetylation of proteins and peptides, but not nucleosomes-a chromatin model substrate. Using protein semisynthesis we characterize the effect of cell cycle-linked N-terminal phosphorylation at two major phosphorylation sites (Ser23/Ser25) and find that these further enhance protein/peptide deacetylation, with no effect on nucleosome deacetylation. Additionally, we find that VRK1, an established binding partner of both Sirt2 and nucleosomes, can stimulate deacetylation of nucleosomes by Sirt2, likely through an electrostatic mechanism. Taken together, these findings reveal multiple mechanisms regulating the activity of Sirt2, which allow for a broad range of activities across its multiple biological roles.

Uncoupling histone modification crosstalk by engineering lysine demethylase LSD1.

Biochemical crosstalk between two or more histone modifications is often observed in epigenetic enzyme regulation, but its functional significance in cells has been difficult to discern. Previous enzymatic studies revealed that Lys14 acetylation of histone H3 can inhibit Lys4 demethylation by lysine-specific demethylase 1 (LSD1). In the present study, we engineered a mutant form of LSD1, Y391K, which renders the nucleosome demethylase activity of LSD1 insensitive to Lys14 acetylation. K562 cells with the Y391K LSD1 CRISPR knockin show decreased expression of a set of genes associated with cellular adhesion and myeloid leukocyte activation. Chromatin profiling revealed that the cis-regulatory regions of these silenced genes display a higher level of H3 Lys14 acetylation, and edited K562 cells show diminished H3 mono-methyl Lys4 near these silenced genes, consistent with a role for enhanced LSD1 demethylase activity. These findings illuminate the functional consequences of disconnecting histone modification crosstalk for a key epigenetic enzyme.

The Growth of Problematic Media Use Over Early Childhood: Associations with Long-Term Social and Emotional Outcomes.

Problematic media use (PMU) tends to be related to significant social, emotional, and behavioral problems throughout life. Little research, however, has examined the development of PMU during early childhood, where media habits begin to form. The current longitudinal study examines the growth of PMU across early childhood (between 2.5 and 5.5 years of age) with a focus on predictors and outcomes (social, emotional, and parenting) of the intercept and slope of PMU over time. Participants (N = 269 children and their parents; 4.9% Asian American, 8.2% Black, 21% Hispanic or Latino, 63% White, 7% Mixed or Other race) completed questionnaires assessing PMU, media parenting, parental warmth and connection, and child social and emotional problems. Results indicated slight overall increases in PMU from ages 2.5 to 5.5. Emotional reactivity, aggression, and overall TV time predicted initial levels of PMU. Additionally, initial levels of PMU were related to social and emotional problems four years later. An increasing trajectory of PMU was associated with later aggression in childhood, even when controlling for initial levels of aggression. Implications for parents and prevention efforts aimed at reducing PMU are discussed.

Who's most at risk? A person-centered approach to understanding the long-term relationship between early social media use and later depression across adolescence.

INTRODUCTION: Person-centered analyses examined the relationship between social media use and depression over an 8-year period. The purpose was to examine the varying ways early social media use was associated with the development of depressive symptoms with a hypothesis that social media would not have a uniform association with depressive symptoms across adolescents. METHODS: Participants included 488 adolescents (52% female), living in the United States, who were surveyed once a year for 8 years (beginning in 2010 when the average age for participants was 13.33 years old). RESULTS: Longitudinal mixture regression was used to identify classes of adolescents representing unique ways their early social media use was related to the development of depressive symptoms over an 8-year period. Five classes were found representing unique ways social media use was related to depression. Findings suggest social media use does not impact all adolescents in the same way. Social media use was related to increased depression for adolescents with greater parental hostility, peer bullying, anxiety, reactivity to stressors, and lower parental media monitoring. In other instances, social media use was related to less depression or was unrelated to depression. CONCLUSIONS: By identifying which adolescents may be most at risk from social media use, health providers, schools, and caregivers can tailor interventions to fit the needs of each adolescent.

Coenzyme A biosynthesis: mechanisms of regulation, function and disease.

The tricarboxylic acid cycle, nutrient oxidation, histone acetylation and synthesis of lipids, glycans and haem all require the cofactor coenzyme A (CoA). Although the sources and regulation of the acyl groups carried by CoA for these processes are heavily studied, a key underlying question is less often considered: how is production of CoA itself controlled? Here, we discuss the many cellular roles of CoA and the regulatory mechanisms that govern its biosynthesis from cysteine, ATP and the essential nutrient pantothenate (vitamin B5), or from salvaged precursors in mammals. Metabolite feedback and signalling mechanisms involving acetyl-CoA, other acyl-CoAs, acyl-carnitines, MYC, p53, PPARα, PINK1 and insulin- and growth factor-stimulated PI3K-AKT signalling regulate the vitamin B5 transporter SLC5A6/SMVT and CoA biosynthesis enzymes PANK1, PANK2, PANK3, PANK4 and COASY. We also discuss methods for measuring CoA-related metabolites, compounds that target CoA biosynthesis and diseases caused by mutations in pathway enzymes including types of cataracts, cardiomyopathy and neurodegeneration (PKAN and COPAN).

Corrigendum/Erratum to "Teens, screens and quarantine; The relationship between adolescent media use and mental health prior to and during COVID-19" [Heliyon 8(7), July 2022 e09898].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e09898.].

Links between parent-child conversations about emotions and changes in children's emotion knowledge across early childhood.

This study examined different sources of emotion socialization. Children (N = 256, 115 girls, 129 boys, 12 child gender not reported) and parents (62% White, 9% Black, 19% Hispanic, 3% Asian American, and 7% "Other") were recruited from Denver, Colorado. In waves 1 (Mage = 2.45 years, SD = 0.26) and 2 (Mage = 3.51 years, SD = 0.26), parents and children discussed wordless images of children experiencing an emotion (e.g., sad after dropping ice cream). Children's emotion knowledge was assessed at waves 2 and 3 (Mage = 4.48 years, SD = 0.26). Structural equation modeling found concurrent and prospective relations between parents' questions, parents' emotion talk, children's emotion talk, and children's emotion knowledge, highlighting the multidimensional nature of early emotion socialization.

Trajectories of parents' gendered play attitudes during early childhood and implications for children's gender development.

This study examined associations between parents' gendered attitudes about play and children's gender development. The sample was 501 families from a large US city followed annually for 4 years (501 mothers, 383 fathers; 69% White, 16% Latinx, 8% African American; children Mage = 5.67 months, 53% boys). Latent trajectories examined change in parents' attitudes toward same- and other-gender play during first 4 years of the child's life. On a subsample (n = 252), trajectories were examined in relation to children's later gender-typed preferences and gender constancy. Parents grew more gender-flexible in their attitudes, particularly parents of boys. Trajectories reflecting more stereotypic attitudes showed some associations (small in magnitude) with children's gender-typed preferences and gender constancy by age 4.

Longitudinal associations between parents' prosocial behavior and media use and young children's prosocial development: The mediating role of children's media use.

Research has found that media is associated with children's prosocial behavior (PB) from an early age, and that parents play a key role in children's media use and behavior. However, few studies explore these relations as early as infancy while also controlling for well-established predictors of PB (e.g., empathic concern). Thus, the present study examined longitudinal associations between parents' PB and media use, and prosocial development during early childhood, mediated by children's own media use. Participants were 519 children (M age at Time 1 = 17.77 months) and parents who participated in three timepoints of an ongoing, longitudinal study. A longitudinal path model suggested that children's media use was still significantly associated with PB 1 year later after accounting for factors such as parents' PB, media use, and empathy. These findings have important implications for the early development of behaviors that serve as a foundation for social and moral development.

Attachment security and problematic media use in infancy: A longitudinal study in the United States.

Media use during childhood has quickly become a norm across the United States and in other countries. One area still not well understood is the development of problematic (or maladaptive and disruptive) media use in children. This research examines the role of attachment security as a central component in the development of problematic media use over time in a sample of 248 parent-child dyads (9.50% African American, 20.66% Hispanic, 62.81% White, 2.07% Asian, 4.96% other ethnicities). We examined the relationship between attachment security and problematic media use one and 2 years later. We then constructed a mediation model examining parent responsiveness while jointly engaging in media use and during play as mediators between infant attachment security and problematic media use over time. Results suggest that while infant attachment security may be protective against developing problematic media use patterns, this relationship does not seem to be mediated by parent-child interactions while engaging in media or during play.

Structures for Screens: Longitudinal associations between parental media rules and problematic media use in early childhood.

Media use is increasingly becoming an important facet of early childhood, and while professional organizations and researchers have attempted to present guidelines to parents to help them structure their children's media use, many parents either are not aware of these guidelines, or struggle to effectively implement them into their children's daily routine. This research aimed to examine what rules parents of young children are implementing to structure their children's media use and how specific media rules affected development of children's problematic media use (an early indicator of media dependence) longitudinally from ages 2-4 (three time points, each one year apart) in a sample of n = 435 children. We found that more parents have rules around their child's TV use than tablet use when children are around age 2 ½ years old, and that a sizable minority of parents (n = 45; 10.30%) or parents do not allow their child to use tablets at this same age. There was no relationship between media rules and problematic media use at Time 2. However, parents who did not allow their child to use tablets at Time 1 had lower levels of child problematic media use at Time 3, implying that the rules parents set around young children's use of tablets and other personal media devices may be impactful in protecting children from the development of problematic media use.

"I'll Walk with You": LGBTQ+ Individuals and Religious Belonging.

Research on LGBTQ+ individuals, belonging, and religiosity has been mixed. Some studies have illustrated the ways religion can harm LGBTQ+ individuals while others suggest religion has positive impacts. In the current study, we sought to understand this complexity by examining the experiences of LGBTQ+ individuals who have been or currently are affiliated with The Church of Jesus Christ of Latter-day Saints (i.e. Mormon, LDS). A thematic analysis of 100 interviews with LGBTQ+ individuals currently or previously affiliated with the Church revealed various ways they feel belonging or the lack thereof in Latter-day Saint congregations and communities. These include sharing physical space, being invited to and included at events, receiving gifts or acts of service, seeing others' safety signals, hearing accepting and character-affirming language, and having others listen to them and give them voice. With the intent of fostering belonging, we discuss implications of this research for church communities and propose the belonging in practice: LGBTQ+ and religion model.

Masters of Media: A longitudinal study of parental media efficacy, media monitoring, and child problematic media use across early childhood in the United States.

The development of problematic media use in early childhood is not well understood. The current study examined long-term associations between parental media efficacy, parental media monitoring, and problematic media use across a three-year period of time during early childhood. Participants included 432 parents who reported on their own parenting and their child's use of problematic media once a year for three years (M age of child at Wave 1 = 29.68 months, SD = 3.73 months). Results revealed that early parental media efficacy predicted lower levels of child problematic media use over time. Restrictive media monitoring was also related to lower levels of child problematic media use over time. Additionally, general parental efficacy was related to parental media efficacy and lower child problematic media use, both at the cross-sectional and longitudinal levels. Discussion focuses on encouraging early parental media efficacy (and exploring other potential mechanisms) as a way to mitigate the development of problematic media use over time.

Parents' judgments of children's gender-typed play indicate qualities of the early-life caregiving environment.

Play is critical for children's development but is the target of significant gender stereotyping. Early in life, parents must navigate these stereotypes on behalf of their children. This study examined typologies of caregivers' judgments toward their infants' future engagement with toys and activities considered typical of same- and different-gender peers, and whether these judgments indicated qualities of the child-rearing environment. We conducted a latent profile analysis on a sample of 501 families with infant children in a large city in the Western United States (501 mothers, 388 fathers; 69% White, 16% Latinx, 8% African American). Results showed that parents could be classified as androgynous, stereotyped, counterstereotyped, or gender-impartial in their preferences for their child's toys and activities. Mothers who displayed androgynous and counterstereotyped preferences-primarily conveying approval different-gender-typed play-were rated higher on objective assessments of the quality of the home environment and parent-child interactions. How parents orient to cultural gendered messages for children's play may have implications for the overall parenting environment. We discuss implications for research and practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

"Oh no! What happened?" an investigation of parent-child conversations about self-conscious emotions.

Parents play an important role in socializing children's emotion understanding. Previous research shows that parents emphasize different aspects of emotion contexts depending on the discrete emotion. However, there is limited research on how parents and children discuss self-conscious emotions, such as embarrassment, guilt, and shame, and what socialization practices parents employ to elicit children's talk about these emotions. In this study, children (N = 166, 78 females, 88 males) ages 2-3 years (M = 2.46, SD = 0.26) and their parents (65.5% White, 10.2% Black, 17.5% Hispanic, 2.4% Asian American, and 5.4% other) from a large city in the Western United States discussed a wordless storybook depicting different female and male characters experiencing self-conscious emotions (embarrassment, guilt, shame, awe, and pride). Parents' and children's emotion talk and parents' questions were coded from their conversations about each emotion scenario and subsequently analyzed by discrete emotion, child gender, and the depicted character's gender. Parents and children differentially focused on different aspects of each self-conscious emotion as a function of discrete emotion and picture gender, and elements of children's talk about self-conscious emotions were related to children's expressive language and age. Additionally, parents' emotion talk and questions about emotions were directly related to children's emotion talk, even after controlling for children's age, expressive language, and parental education. Taken together, these findings suggest that parent-child emotion conversations may be one context that facilitates the development of children's understanding of self-conscious emotions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Toddlers and the Telly: A latent profile analysis of children's television time and content and behavioral outcomes one year later in the U.S.

Despite the ubiquity of tablets and smartphones, television remains the most frequently used screen media consumed by young children. However, it is likely that variability exists in how young children use media; for example, while some may view small amounts of aggressive content, others may view many hours each day of aggressive and prosocial media content. It is possible that differences in toddler television time and content also impact behavioral outcomes. The aims of this study were two-fold; first, we examined profiles of children's time spent watching television and media content viewed. Second, we examined longitudinal relations between media use profiles and outcomes including aggression, prosocial behavior, and problematic media use. Results suggested a three-profile solution of children's television time and content, including "Low TV content," "High child-centered content," and "High aggressive content" profiles. The "High aggressive content" group experienced higher levels of problematic media use and aggressive behavior one year later compared to other classes. The discussion focuses on implications of these findings. We urge parents to become aware of both television time and media content as they may relate to problematic media use behaviors in young children.

Analysis of Social Media Use, Mental Health, and Gender Identity Among US Youths.

Importance: Mental health among children and adolescents is a critical public health issue, and transgender and gender nonbinary youths are at an even greater risk. Social media has been consistently associated with youth mental health, but little is known about how gender identity interacts with this association. Objective: To use a risk and resilience approach to examine the association between social media use and mental health among transgender, gender nonbinary, and cisgender youths. Design, Setting, and Participants: This cross-sectional study analyzed data collected from an online survey between May and August 2021. Participants included a random sample of US youths; eligibility requirements included being aged 10 to 17 years and residing in the US. Statistical analysis was performed from February to April 2022. Main Outcomes and Measures: Social media use (time, type of use, favorite site, social comparisons, mindfulness, taking intentional breaks, cleaning and curating feeds, problematic use, and media literacy programs at their school) and mental health (depression, emotional problems, conduct problems, and body image) as main outcomes. Results: Participants included 1231 youths aged 10 to 17 years from a national quota sample from the United States; 675 (54.8%) identified as cisgender female, 479 (38.9%) as cisgender male, and 77 (6.3%) as transgender, gender nonbinary, or other; 4 (0.3%) identified as American Indian or Alaska Native, 111 (9.0%) as Asian, 185 (15.0%) as Black, 186 (15.1%) as Hispanic or Latinx, 1 (0.1%) as Pacific Islander, 703 (57.1%) as White, and 41 (3.3%) as mixed and/or another race or ethnicity. Gender identity moderated both the strength and the direction of multiple associations between social media practices and mental health: active social media use (eg, emotional problems: B = 1.82; 95% CI, 0.16 to 3.49; P = .03), cleaning and/or curating social media feeds (eg, depression: B = -0.91; 95% CI, -1.98 to -0.09; P = .03), and taking intentional breaks (eg, depression: B = 1.03; 95% CI, 0.14 to 1.92; P = .02). Conclusions and Relevance: In this cross-sectional study of gender identity, social media, and mental health, gender identity was associated with youths' experiences of social media in ways that may have distinct implications for mental health. These results suggest that research about social media effects on youths should attend to gender identity; directing children and adolescents to spend less time on social media may backfire for those transgender and gender nonbinary youths who are intentional about creating safe spaces on social media that may not exist in their offline world.

Learning to cyberbully: Longitudinal relations between cyberbullying attitudes and perpetration and the moderating influence of participant sex: A brief report.

Scholars have contended that cyberbullying perpetration is a learned social behavior, and one way to show evidence for cyberbullying learning is to test the longitudinal reciprocal relationships between cyberbullying behavior and related cyberbullying-related cognitions (e.g., attitudes). A paucity of research has tested these learning tenets, and no research that we are aware of has examined the moderating role of sex. The current study used a two-wave longitudinal design with US youth. Participants completed measures of cyberbullying attitudes and perpetration. Results showed that early cyberbullying attitudes and behavior predicted later cyberbullying attitudes and behavior; however, and most importantly, sex moderated those relationships. Males had stronger longitudinal relationships than females. Results are interpreted regarding theory.

Silencing screaming with screens: The longitudinal relationship between media emotion regulation processes and children's emotional reactivity, emotional knowledge, and empathy.

Many parents use screens to regulate their young children's emotions. We know very little, however, about how this parenting practice is related to the development of emotional competencies (i.e., emotional reactivity, emotion knowledge, and empathy) over time. The current longitudinal study examined bidirectional associations between media emotion regulation and various emotional competencies across a 1-year period during early childhood (between ages 3.5 and 4.5 on average). Participants included 269 child/parent dyads who completed a number of in-home tasks and questionnaires. Results revealed that higher levels of media emotion regulation were associated with worse emotional knowledge and empathy and higher emotional reactivity at the cross-sectional level. However, early media emotion regulation was associated with higher levels of child empathy 1 year later. We discuss these results in the context of general parenting practices and encourage future research on the topic with a focus on how these processes develop over time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Who is Most at Risk for Developing Physical Aggression After Playing Violent Video Games? An Individual Differences Perspective From Early Adolescence to Emerging Adulthood.

Many theories of development suggest that playing violent video games would not impact all adolescents the same way, yet empirical research is sparse. To date there have been no within-subjects analyses that examine which adolescents are most at risk for developing aggression after playing violent video games and under what context, and no longitudinal studies encompassing multiple developmental stages (i.e., early adolescence to emerging adulthood) that examine the long-term effects of playing violent video games. To address this gap, the current study used a longitudinal design (spanning 8 years and encompassing multiple developmental periods) with a sample of U.S. adolescents who completed questionnaires on aggression, video gaming, and multiple risk and protective factors for aggression. Participants included 488 adolescents (M age = 13.82, SD = 1.03 at the initial wave, 51% female, with 65% being White, 12% Black, 19% multiethnic, and 4% other). Mixture regression was utilized to model physical aggression over time and to examine how playing violent video games might be related to aggression on an individual level. There were four classes: "Multi-risk", "High Gaming, High Aggression" (both of which had high levels of aggression over time), "Moderate Risk", and "Low Risk, High Privilege" (both of which had lower levels of aggression over time). Individuals were most aggressive with multiple risk factors or higher levels of violent game play and playing violent video games likely increased aggression more in individuals with other gaming problems and in males with low self-regulation. The results are discussed using a balanced perspective and recognize that violent video games do not affect all adolescents the same way. This research has direct implications for designing interventions around reducing aggressive behavior among adolescents.