PI3K drives the de novo synthesis of coenzyme A from vitamin B5.

In response to hormones and growth factors, the class I phosphoinositide-3-kinase (PI3K) signalling network functions as a major regulator of metabolism and growth, governing cellular nutrient uptake, energy generation, reducing cofactor production and macromolecule biosynthesis1. Many of the driver mutations in cancer with the highest recurrence, including in receptor tyrosine kinases, Ras, PTEN and PI3K, pathologically activate PI3K signalling2,3. However, our understanding of the core metabolic program controlled by PI3K is almost certainly incomplete. Here, using mass-spectrometry-based metabolomics and isotope tracing, we show that PI3K signalling stimulates the de novo synthesis of one of the most pivotal metabolic cofactors: coenzyme A (CoA). CoA is the major carrier of activated acyl groups in cells4,5 and is synthesized from cysteine, ATP and the essential nutrient vitamin B5 (also known as pantothenate)6,7. We identify pantothenate kinase 2 (PANK2) and PANK4 as substrates of the PI3K effector kinase AKT8. Although PANK2 is known to catalyse the rate-determining first step of CoA synthesis, we find that the minimally characterized but highly conserved PANK49 is a rate-limiting suppressor of CoA synthesis through its metabolite phosphatase activity. Phosphorylation of PANK4 by AKT relieves this suppression. Ultimately, the PI3K-PANK4 axis regulates the abundance of acetyl-CoA and other acyl-CoAs, CoA-dependent processes such as lipid metabolism and proliferation. We propose that these regulatory mechanisms coordinate cellular CoA supplies with the demands of hormone/growth-factor-driven or oncogene-driven metabolism and growth.

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.

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 nonhistone 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 posttranslational modifications 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.

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.

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.

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.

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.

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.

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.

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.

"Katerina gets mad": Infants' physiological and behavioral responses to co-viewing educational, self-regulatory media.

A growing body of research has focused on the physiological impact of media on older children and adolescents. Less research has been focused on the potential physiological impact of media on infants and younger children, especially media designed to be age appropriate and educational in content. In this study, we examined respiratory sinus arrhythmia (RSA) in infants (N = 269, Mage  = 17.13 months) while they co-viewed an educational video clip that modeled emotion regulation and contrasted their physiological response to an unoccupied baseline and a frustration paradigm (arm-restraint). Given parent reports showing the calming effect of educational media viewing in young children, we anticipated that a similar pattern of calming would be observed physiologically in infants. Results showed that relative to baseline, most infants demonstrated an increase in RSA while co-viewing, suggesting greater parasympathetic (regulatory) activation consistent with behavioral calming. However, infants who demonstrated vagal withdrawal during co-viewing (decrease in RSA) were more likely to have parents who used a tablet to help infants go to sleep at night. Vagal withdrawal was also associated with increased levels of negative affect observed during the co-viewing task. Findings are discussed in relation to the contextual effect of co-viewing age-appropriate, educational media on children's physiological responses.

Survivors' perceptions of support following a parent's suicide.

Children who experience a parent's suicide are vulnerable to an increased risk for mental health disorders and suicide attempts. In this study, 17 adults, each a child survivor of their parent's suicide, shared their perceptions of support following the suicide. Helpful experiences included opening communication about suicide and offering individualized support. Unhelpful experiences included judgment and blame, silence regarding suicide, and a heightened awareness of the surviving parent's challenges. Individuals most helpful in meeting the child's needs included those with preexisting relationships. In particular, our findings emphasize the critical need for honest, open, and age-appropriate communication about the parent's suicide.

Speaking of State of Mind: Maternal Mental Health Predicts Children's Home Language Environment and Expressive Language.

Maternal depression and anxiety are potential risk factors to children's language environments and development. Though existing work has examined relations between these constructs, further work is needed accounting for both depression and anxiety and using more direct measures of the home language environment and children's language development. We examined 265 mother-infant dyads (49.6% female, Mage = 17.03 months) from a large city in the Western United States to explore the relations between self-reports of maternal depression and anxiety and observational indices of the home language environment and expressive language as captured by Language Environment Analysis (LENA) and parent-reported language comprehension and production. Results revealed maternal depressive symptoms to be negatively associated with home language environment and expressive language indices. Maternal anxiety symptoms were found to be negatively associated with children's parent-reported language production. These findings provide further evidence that maternal mental health modulates children's home language environments and expressive language.

Princess Power: Longitudinal Associations Between Engagement With Princess Culture in Preschool and Gender Stereotypical Behavior, Body Esteem, and Hegemonic Masculinity in Early Adolescence.

Princess culture is criticized for contributing to gender stereotypes and poor body esteem, however, there is little longitudinal research examining these claims. This study examines associations between engagement with princess culture during early childhood and gender stereotypes, body esteem, and adherence to hegemonic masculinity in early adolescence. Participants included 307 children (51% female, Mage = 4.83 years, 87% White) who completed questionnaires at two time points, 5 years apart. The results indicated that early engagement with princess culture was not associated with later adherence to female gender stereotypes. However, princess engagement was associated with lower adherence to norms of hegemonic masculinity and higher body esteem. Socioeconomic status and gender moderated the results. Effect sizes were small to moderate. The changing nature of Disney princesses is discussed in the context of gender development across childhood.

The impact of parent and child media use on early parent-infant attachment.

With the rise in affordability of digital media and mobile devices, children under age 2 on average spend significantly more time with digital media than is recommended. Although concerns have been expressed about how parent and child media use might negatively impact parent-child attachment, there continues to be a scarcity of research on the topic. The current study assessed both the amount and the way in which children (11-26 months) and their parents engage with digital media and the impact on early attachment after controlling for temperament, parent income, parent age, marital status, and access to support. The study utilizes data from a diverse sample: 248 parents of infants completed an attachment q-sort and surveys assessing the amount of media use, parental absorption in media, types of parental mediation, temperament, and demographics. Results showed that for both parent and child, time using digital media and co-viewing was not predictive of attachment insecurity. Parental absorption in media was found to significantly predict attachment insecurity. Greater child TV media use was associated with poorer attachment security when there was limited to no parental active mediation. Active mediation served as a protective factor for attachment while parental absorption in media serves as a risk factor for attachment.

Suicide Risk in Emerging Adulthood: Associations with Screen Time over 10 years.

Suicide rates have increased over the past decade, and screen media (and social media in particular) are often blamed for this marked increase. However, there is little longitudinal research on this topic. The current study examined the link between various types of screen media use over a 10-year period (from adolescence to emerging adulthood) to suicide risk in emerging adulthood. Participants included 500 adolescents (51% female) who were first surveyed in 2009, when they were an average of 13.82 years old (range 12-15 years). For girls, a high level of social media or television use in early adolescence followed by a marked increase over time was most predictive of suicide risk in emerging adulthood. Additionally, video game use that increased over time was also associated with a higher risk for developing suicide risk for girls. A passive sensing measurement was also included at the final wave of data collection to obtain a more accurate and complete picture of phone use in particular. The use of entertainment apps was risky for girls while reading apps were risky for boys. Additionally, video game use (for boys) was associated with suicide risk when cyberbullying was also high. Identifying nonnormative patterns of media during adolescence may be instructive in terms of suicide prevention efforts.

Look Who's Talking: Mediums of Contact Among Mid-to Later-Life Siblings.

Adult siblings maintain contact and remain close to one another. The current study used participants recruited via Amazon Mechanical Turk (n = 491) to conduct regression analyses examining five methods of contact (in person, telephone, email, texting, and social media) predicting sibling closeness and conflict. Further, two- and three-way interactions assessed the role of sibling dyad composition (e.g., women with a sister and women with a brother). Results suggested that as contact in person, through social media, the telephone, or email increased, sibling closeness increased, while increased contact through email indicated less conflict. Assessing sibling dyad composition suggested as telephone contact increased, sibling closeness increased for all sibling dyads, especially for women with a sister compared to men with a brother. In-person and texting contacts were beneficial for women with a brother. Even in mid- to later-life, siblings connect through synchronous and asynchronous mediums, and this contact appears beneficial for sisters.

Large-Scale, In-House Production of Viral Transport Media To Support SARS-CoV-2 PCR Testing in a Multihospital Health Care Network during the COVID-19 Pandemic.

The COVID-19 pandemic has severely disrupted worldwide supplies of viral transport media (VTM) due to widespread demand for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription-PCR (RT-PCR) testing. In response to this ongoing shortage, we began production of VTM in-house in support of diagnostic testing in our hospital network. As our diagnostic laboratory was not equipped for reagent production, we took advantage of space and personnel that became available due to closure of the research division of our medical center. We utilized a formulation of VTM described by the CDC that was simple to produce, did not require filtration for sterilization, and used reagents that were available from commercial suppliers. Performance of VTM was evaluated by several quality assurance measures. Based on cycle threshold (CT ) values of spiking experiments, we found that our VTM supported highly consistent amplification of the SARS-CoV-2 target (coefficient of variation = 2.95%) using the Abbott RealTime SARS-CoV-2 Emergency Use Authorization (EUA) assay on the Abbott m2000 platform. VTM was also found to be compatible with multiple swab types and, based on accelerated stability studies, able to maintain functionality for at least 4 months at room temperature. We further discuss how we met logistical challenges associated with large-scale VTM production in a crisis setting, including use of a staged assembly line for VTM transport tube production.

Bored and online: Reasons for using social media, problematic social networking site use, and behavioral outcomes across the transition from adolescence to emerging adulthood.

INTRODUCTION: The current study examined motivations for social networking site use across three years during the transition from late adolescence to emerging adulthood. While research has been conducted examining reasons for social networking site usage and behavior, the clear majority have focused on samples of undergraduate college students and are cross-sectional. METHODS: Changes in motivations for using social networking sites were examined in relation to problematic social networking site use and several behavioral and mental health outcomes in a sample of adolescents over three years. RESULTS: Using social networking sites to connect with others was relatively stable over a three-year period. However, using social networking sites to seek information increased from late adolescence to emerging adulthood and was not related to any negative outcomes across three years. Using social networking sites to alleviate boredom also increased over time. Initial levels of social media use to alleviate boredom were associated with problematic social networking site use, financial stress, anxiety, and empathy at year three. Increases in using social networking sites to socially connect over time was related to problematic social networking site use, anxiety, delinquency, and empathy at year three. Using social networking sites for any reason was not related to depressive symptoms over three years. CONCLUSIONS: The current study supports the growing body of literature suggesting that using social networking sites to alleviate boredom and socially connect, may place individuals at increased risk for developing pathological tendencies and patterns of behavior towards social networking sites.

The growth of gossip: Socialization of relational aggression from adolescence to emerging adulthood.

The extant literature suggests that relational aggression appears in early childhood, and gradually increases throughout adolescence. However, very little research has examined the growth of relational aggression from adolescence to emerging adulthood. In addition, research generally examines socializing factors of relational aggression, such as parenting, peers, siblings, or media in isolation. Accordingly, the aim of the current study was to examine these socializing factors conjunctively as predictors of the growth of relational aggression over time. Participants consisted of 500 adolescents who completed several questionnaires over a 7-year period (between ages 14-20 on average). Results revealed that the vast majority of individuals (88%) showed low levels of relational aggression that decreased over time. Conversely, a small proportion of individuals (12%) had high, increasing levels of relational aggression between adolescence and emerging adulthood. High levels of maternal psychological control, sibling hostility, and relational aggression in the media at the initial time point all predicted being in the high and increasing group.