Adolescents’ self-control develops in the context of mental health and family functioning, but it is unclear how the interplay of self-control, mental health, and family functioning unfolds across ...time within individuals. Separating within-person from between-person effects, random-intercept cross-lagged panel models were applied to adolescents (from ages 11 to 26) from a Dutch cohort (
n
= 2228, 51% female). Adolescents with low self-control were likely to have mental health problems and poorly functioning families. Although within-person changes in the study variables were not meaningfully associated in a reciprocal manner, changes in self-control and mental health were concurrently associated. This suggests that besides stable connections between self-control, mental health, and family functioning in adolescence and young adulthood, changes in self-control and mental health are developmentally linked as well.
This study tested two opposing hypotheses on the continuity of psychopathology throughout adolescence and young adulthood; differentiation versus dynamic mutualism. Differentiation predicts that ...co-occurrence decreases, while dynamic mutualism predicts that co-occurrence increases due to causal interactions amongst mental health problems.
Using data from the Dutch TRacking Adolescents' Individual Lives Survey (n = 2228, 51% female), we studied the development of self-reported internalizing, externalizing, and attention problems at ages 11 to 26 across six waves. Random-intercept cross-lagged panel modeling was employed to distinguish within-person development from stable between-person processes.
Large stable between-person associations indicated that adolescents with internalizing problems tended to have both externalizing and attention problems as well. On a within-person level, mental health problems showed partial stability and strong cross-sectional co-occurrence. Within-wave associations of internalizing with externalizing or attention problems decreased between age 11 and 16 years, after which they increased again. Little heterotypic continuity was found: age 11 externalizing predicted age 13 attention, which in turn predicted age 16 externalizing problems, and internalizing predicted externalizing problems across ages 22 to 26. Findings were similar for males and females.
Our findings suggest co-occurrence decreases during early and middle adolescence, supporting differentiation. While co-occurrence increased again into young adulthood, this could not be labeled as dynamic mutualism because little evidence for heterotypic continuity was found in this phase of life. The strong stable links between internalizing, externalizing, and attention problems stress the importance of targeting these mental health problems and their shared risk factors together.
Sprint interval training (SIT) increases peak oxygen uptake (V̇O
) but the mechanistic basis is unclear. We have reported that 12 wk of SIT increased V̇O
and peak cardiac output (Q̇
) and the changes ...in these variables were correlated. An exploratory analysis suggested that Q̇
increased in males but not females. The present study incorporated best practices to examine the potential influence of biological sex on the Q̇
response to SIT. Male and female participants (n = 10 each; 21 ± 4 y) performed 33 ± 2 sessions of SIT over 12 wk. Each 10-min session involved 3 × 20-s 'all-out' sprints on an ergometer. V̇O
increased after SIT (3.16 ± 1.0 vs. 2.89 ± 1.0 L/min, η
= 0.53, p < 0.001) with no sex × time interaction (p = 0.61). Q̇
was unchanged after training (15.2 ± 3.3 vs. 15.1 ± 3.0 L/min, p = 0.85), in contrast to our previous study. The peak estimated arteriovenous oxygen difference increased after training (204 ± 30 vs. 187 ± 36 ml/L, p = 0.006). There was no effect of training or sex on measures of endothelial function. We conclude that 12 wk of SIT increases V̇O
but the mechanistic basis remains unclear. The capacity of inert gas rebreathing to assess changes in Q̇
may be limited and invasive studies that use more direct measures are needed.
Social withdrawal and social anxiety are believed to have a bidirectional influence on one another, but it is unknown if their relationship is bidirectional, especially within person, and if peer ...experiences influence this relationship. We investigated temporal sequencing and the strength of effects between social withdrawal and social anxiety, and the roles of peer victimization and acceptance in the pathways. Participants were 2,772 adolescents from the population-based and clinically referred cohorts of the Tracking Adolescents' Individual Lives Survey. Self- and parent-reported withdrawal, and self-reported social anxiety, peer victimization, and perceived peer acceptance were assessed at 11, 13, and 16 years. Random-intercept cross-lagged panel models were used to investigate within-person associations between these variables. There was no feedback loop between withdrawal and social anxiety. Social withdrawal did not predict social anxiety at any age. Social anxiety at 11 years predicted increased self-reported withdrawal at 13 years. Negative peer experiences predicted increased self- and parent-reported withdrawal at 13 years and increased parent-reported withdrawal at 16 years. In turn, self-reported withdrawal at 13 years predicted negative peer experiences at 16 years. In conclusion, adolescents became more withdrawn when they became more socially anxious or experienced greater peer problems, and increasing withdrawal predicted greater victimization and lower acceptance.
Exposure to prenatal tobacco smoke (PTS) has been associated with a number of health outcomes in the offspring, including some childhood cancers. Lower levels of genomic DNA methylation have also ...been associated with several types of cancers. We investigated whether PTS was associated with global DNA methylation levels in the offspring.
Our sample was drawn from a birth cohort of women born between 1959 and 1963 in New York City (n = 90). We measured methylation of repetitive elements (Sat2, Alu, LINE-1) from peripheral blood granulocytes. We combined prospectively collected data on PTS with adult epidemiologic data and blood samples collected in 2001 to 2007 (mean age, 43 years). We used linear regression to assess the association between PTS and repetitive element methylation.
Thirty-six percent of mothers smoked during pregnancy. We observed an inverse association between PTS and Sat2 methylation. This inverse association remained even after adjustment for potential mediators including child environmental tobacco smoke exposure, birth size, postnatal weight and height changes, and adult smoking status and alcohol intake (β = -0.22, 95% confidence interval = -0.40 to -0.03 for ever exposed to PTS vs. never exposed using models of log-transformed methylation levels). PTS exposure was not statistically significantly associated with LINE-1 or Alu methylation.
PTS exposure, measured at the time of pregnancy and not retrospectively reported, was associated with a decrease in Sat2 methylation but not LINE-1 or Alu methylation.
If replicated in larger studies, this study supports a persistent effect of PTS on DNA methylation levels, as measured by Sat2, in adulthood.
The aim of this study was to test a longitudinal, transactional model that describes how social withdrawal and friendship development are interrelated in late adolescence, and to investigate if ...post‐secondary transitions are catalysts of change for highly withdrawn adolescents’ friendships. Unilateral friendship data of 1,019 adolescents (61.3% female, 91% Dutch‐origin) from the Tracking Adolescents’ Individual Lives Survey (TRAILS) cohort were collected five times from ages 17 to 18 years. Social withdrawal was assessed at 16 and 19 years. The transactional model was tested within a Structural Equation Modeling framework, with intercepts and slopes of friendship quantity, quality, and stability as mediators and residential transitions, education transitions, and sex as moderators. The results confirmed the presence of a transactional relation between withdrawal and friendship quality. Whereas higher age 16 withdrawal predicted having fewer, lower‐quality, and less‐stable friendships, only having lower‐quality friendships, in turn, predicted higher age 19 withdrawal, especially in girls. Residential transitions were catalysts of change for highly withdrawn youth's number of friends: higher withdrawal predicted a moderate increase in number of friends for adolescents who relocated, and no change for those who made an educational transition or did not transition. Taken together, these results indicate that the quality of friendships—over and above number of friends and the stability of those friendships—is particularly important for entrenching or diminishing withdrawal in late adolescence, and that relocating provides an opportunity for withdrawn late adolescents to expand their friendship networks.
Platinum resistance is the primary cause of poor survival in ovarian cancer (OC) patients. Targeted therapies and biomarkers of chemoresistance are critical for the treatment of OC patients. Our ...previous studies identified cell surface CD55, a member of the complement regulatory proteins, drives chemoresistance and maintenance of cancer stem cells (CSCs). CSCs are implicated in tumor recurrence and metastasis in multiple cancers.BACKGROUNDPlatinum resistance is the primary cause of poor survival in ovarian cancer (OC) patients. Targeted therapies and biomarkers of chemoresistance are critical for the treatment of OC patients. Our previous studies identified cell surface CD55, a member of the complement regulatory proteins, drives chemoresistance and maintenance of cancer stem cells (CSCs). CSCs are implicated in tumor recurrence and metastasis in multiple cancers.Protein localization assays including immunofluorescence and subcellular fractionation were used to identify CD55 at the cell surface and nucleus of cancer cells. Protein half-life determinations were used to compare cell surface and nuclear CD55 stability. CD55 deletion mutants were generated and introduced into cancer cells to identify the nuclear trafficking code, cisplatin sensitivity, and stem cell frequency that were assayed using in vitro and in vivo models. Detection of CD55 binding proteins was analyzed by immunoprecipitation followed by mass spectrometry. Target pathways activated by CD55 were identified by RNA sequencing.METHODSProtein localization assays including immunofluorescence and subcellular fractionation were used to identify CD55 at the cell surface and nucleus of cancer cells. Protein half-life determinations were used to compare cell surface and nuclear CD55 stability. CD55 deletion mutants were generated and introduced into cancer cells to identify the nuclear trafficking code, cisplatin sensitivity, and stem cell frequency that were assayed using in vitro and in vivo models. Detection of CD55 binding proteins was analyzed by immunoprecipitation followed by mass spectrometry. Target pathways activated by CD55 were identified by RNA sequencing.CD55 localizes to the nucleus of a subset of OC specimens, ascites from chemoresistant patients, and enriched in chemoresistant OC cells. We determined that nuclear CD55 is glycosylated and derived from the cell surface pool of CD55. Nuclear localization is driven by a trafficking code containing the serine/threonine (S/T) domain of CD55. Nuclear CD55 is necessary for cisplatin resistance, stemness, and cell proliferation in OC cells. CD55 S/T domain is necessary for nuclear entry and inducing chemoresistance to cisplatin in both in vitro and in vivo models. Deletion of the CD55 S/T domain is sufficient to sensitize chemoresistant OC cells to cisplatin. In the nucleus, CD55 binds and attenuates the epigenetic regulator and tumor suppressor ZMYND8 with a parallel increase in H3K27 trimethylation and members of the Polycomb Repressive Complex 2.RESULTSCD55 localizes to the nucleus of a subset of OC specimens, ascites from chemoresistant patients, and enriched in chemoresistant OC cells. We determined that nuclear CD55 is glycosylated and derived from the cell surface pool of CD55. Nuclear localization is driven by a trafficking code containing the serine/threonine (S/T) domain of CD55. Nuclear CD55 is necessary for cisplatin resistance, stemness, and cell proliferation in OC cells. CD55 S/T domain is necessary for nuclear entry and inducing chemoresistance to cisplatin in both in vitro and in vivo models. Deletion of the CD55 S/T domain is sufficient to sensitize chemoresistant OC cells to cisplatin. In the nucleus, CD55 binds and attenuates the epigenetic regulator and tumor suppressor ZMYND8 with a parallel increase in H3K27 trimethylation and members of the Polycomb Repressive Complex 2.For the first time, we show CD55 localizes to the nucleus in OC and promotes CSC and chemoresistance. Our studies identify a therapeutic mechanism for treating platinum resistant ovarian cancer by blocking CD55 nuclear entry.CONCLUSIONSFor the first time, we show CD55 localizes to the nucleus in OC and promotes CSC and chemoresistance. Our studies identify a therapeutic mechanism for treating platinum resistant ovarian cancer by blocking CD55 nuclear entry.
Involvement in romantic relationships is a salient developmental task in late adolescence and early adulthood, and deviations from normative romantic development are linked to adverse outcomes. This ...study investigated to what extent social withdrawal contributed to deviations from normative romantic development, and vice versa, and the interplay between withdrawal and couples’ relationship perceptions. The sample included 1710 young adults (55–61% female) from the Tracking Adolescents’ Individual Lives Survey cohort and their romantic partners. Data were collected across 4 waves, covering romantic relationships from ages 17 to 29 years. The results showed that higher withdrawal predicted a higher likelihood of romantic non-involvement by adulthood, consistently being single at subsequent waves, and entering one’s first relationship when older. Withdrawal moderately decreased when youth entered their first relationship. Male’s withdrawal in particular affected romantic relationship qualities and dynamics. These results provide new insights into the developmental sequelae of withdrawn young adults’ romantic relationship development.
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