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Purpose: Despite growing recognition that unfortunately common maternal stress exposures in childhood and pregnancy may have intergenerational impacts on children's psychiatric health, studies rarely take a life course approach. With child psychopathology on the rise, the identification of modifiable risk factors is needed to promote maternal and child well-being. In this study, we examined associations of maternal exposure to childhood traumatic events (CTE) and pregnancy stressful life events (PSLE) with child mental health problems in a large, sociodemographically diverse sample. Methods: Participants were mother–child dyads in the ECHO-PATHWAYS consortium's harmonized data across three U.S. pregnancy cohorts. Women completed questionnaires regarding their own exposure to CTE and PSLE, and their 4–6-year-old child's mental health problems using the Child Behavior Checklist (CBCL). Regression analyses estimated associations between stressors and child total behavior problems, adjusting for confounders. Results: Among 1948 dyads (child age M = 5.13 (SD = 1.02) years; 38% Black, 44% White; 8.5% Hispanic), maternal history of CTE and PSLE were independently associated with children's psychopathology: higher CTE and PSLE counts were related to higher total problems ([ßCTE = 0.11, 95% CI [.06,.16]; ßSLE = 0.21, 95% CI [.14, 0.27]) and greater odds of clinical levels of problems (ORCTE = 1.41; 95% CI [1.12, 1.78]; ORPSLE = 1.36; 95% CI [1.23, 1.51]). Tests of interaction showed PSLEs were more strongly associated with child problems for each additional CTE experienced. Conclusion: Findings confirm that maternal exposure to CTE and PSLE are independently associated with child mental health, and history of CTE exacerbates the risk associated with PSLE, highlighting intergenerational risk pathways for early psychopathology. Given the prevalence of these exposures, prevention and intervention programs that reduce childhood trauma and stress during pregnancy will likely positively impact women's and their children's health. [ABSTRACT FROM AUTHOR]

Women's social experiences can have long-term implications for their offspring's health, but little is known about the potential independent contributions of multiple periods of stress exposures over time. This study examined associations of maternal exposure to adversity in childhood and pregnancy with children's anxiety and depression symptoms in a large, sociodemographically diverse sample. Participants were 1389 mother-child dyads (child age M = 8.83 years; SD = 0.66; 42% Black, 42% White; 6% Hispanic) in the ECHO-PATHWAYS Consortium's three U.S. pregnancy cohorts. Women reported their exposure to childhood traumatic events (CTE) and pregnancy stressful life events (PSLE). Children self-reported on their symptoms of anxiety and depression at age 8–9 years. Regression analyses estimated associations between maternal stressors and children's internalizing problems, adjusting for confounders, and examined child sex as a modifier. Exploratory interaction analyses examined whether geospatially-linked postnatal neighborhood quality buffered effects. In adjusted models, PSLE counts positively predicted levels of children's anxiety and depression symptoms ([ßAnxiety=0.08, 95%CI [0.02, 0.13]; ßDepression=0.09, 95%CI [0.03, 0.14]); no significant associations were observed with CTE. Each additional PSLE increased odds of clinically significant anxiety symptoms by 9% (95%CI [0.02, 0.17]). Neither sex nor neighborhood quality moderated relations. Maternal stressors during pregnancy appear to have associations with middle childhood anxiety and depression across diverse sociodemographic contexts, whereas maternal history of childhood adversity may not. Effects appear comparable for boys and girls. Policies and programs addressing prevention of childhood internalizing symptoms may benefit from considering prenatal origins and the potential two-generation impact of pregnancy stress prevention and intervention. [ABSTRACT FROM AUTHOR]

Social media has increasingly enabled "fake news" to circulate widely, most notably during the 2016 U.S. presidential campaign. These intentionally false or misleading stories threaten the democratic goal of a well-informed electorate. This study evaluates the effectiveness of strategies that could be used by Facebook and other social media to counter false stories. Results from a pre-registered experiment indicate that false headlines are perceived as less accurate when people receive a general warning about misleading information on social media or when specific headlines are accompanied by a "Disputed" or "Rated false" tag. Though the magnitudes of these effects are relatively modest, they generally do not vary by whether headlines were congenial to respondents' political views. In addition, we find that adding a "Rated false" tag to an article headline lowers its perceived accuracy more than adding a "Disputed" tag (Facebook's original approach) relative to a control condition. Finally, though exposure to the "Disputed" or "Rated false" tags did not affect the perceived accuracy of unlabeled false or true headlines, exposure to a general warning decreased belief in the accuracy of true headlines, suggesting the need for further research into how to most effectively counter false news without distorting belief in true information. [ABSTRACT FROM AUTHOR]

The PTEN tumor suppressor is a lipid phosphatase that has a central role in regulating the phosphatidylinositol-3-kinase (PI3K) signal transduction cascade. Nevertheless, the mechanism by which the PTEN activity is regulated in cells needs further elucidation. Although previous studies have shown that ubiquitination of PTEN can modulate its stability and subcellular localization, the role of ubiquitination in the most critical aspect of PTEN function, its phosphatase activity, has not been fully addressed. Here, we identify a novel E3 ubiquitin ligase of PTEN, Ret finger protein (RFP), that is able to promote atypical polyubiquitinations of PTEN. These ubiquitinations do not lead to PTEN instability or relocalization, but rather significantly inhibit PTEN phosphatase activity and therefore modulate its ability to regulate the PI3K signal transduction cascade. Indeed, RFP overexpression relieves PTEN-mediated inhibitory effects on AKT activation; in contrast, RNAi-mediated knockdown of endogenous RFP enhances the ability of PTEN to suppress AKT activation. Moreover, RFP-mediated ubiquitination of PTEN inhibits PTEN-dependent activation of TRAIL expression and also suppresses its ability to induce apoptosis. Our findings demonstrate a crucial role of RFP-mediated ubiquitination in controlling PTEN activity. [ABSTRACT FROM AUTHOR]

Reliable long-term cell culture in microfluidic system is limited by air bubble formation and accumulation. In this study, we developed a bubble removal system capable of both trapping and discharging air bubbles in a consistent and reliable manner. Combined with PDMS (Polydimethylsiloxane) hydrophilic surface treatment and vacuum filling, a microfluidic perifusion system equipped with the bubble trap was successfully applied for long-term culture of mouse pancreatic islets with no bubble formation and no flow interruption. In addition to demonstrating normal cell viability and islet morphology, post-cultured islets exhibited normal insulin secretion kinetics, intracellular calcium signaling, and changes in mitochondrial potentials in response to glucose challenge. This design could be easily adapted by other microfluidic systems due to its simple design, ease of fabrication, and portability. [ABSTRACT FROM AUTHOR]