Frontostriatal circuit dysfunction leads to cognitive inflexibility in neuroligin-3 R451C knockin mice.

Cognitive and behavioral rigidity are observed in various psychiatric diseases, including in autism spectrum disorder (ASD). However, the underlying mechanism remains to be elucidated. In this study, we found that neuroligin-3 (NL3) R451C knockin mouse model of autism (KI mice) exhibited deficits in behavioral flexibility in choice selection tasks. Single-unit recording of medium spiny neuron (MSN) activity in the nucleus accumbens (NAc) revealed altered encoding of decision-related cue and impaired updating of choice anticipation in KI mice. Additionally, fiber photometry demonstrated significant disruption in dynamic mesolimbic dopamine (DA) signaling for reward prediction errors (RPEs), along with reduced activity in medial prefrontal cortex (mPFC) neurons projecting to the NAc in KI mice. Interestingly, NL3 re-expression in the mPFC, but not in the NAc, rescued the deficit of flexible behaviors and simultaneously restored NAc-MSN encoding, DA dynamics, and mPFC-NAc output in KI mice. Taken together, this study reveals the frontostriatal circuit dysfunction underlying cognitive inflexibility and establishes a critical role of the mPFC NL3 deficiency in this deficit in KI mice. Therefore, these findings provide new insights into the mechanisms of cognitive and behavioral inflexibility and potential intervention strategies.

Analyzing the factors associated with efficacy among teriparatide treatment in postmenopausal women with osteoporosis.

BACKGROUND: Teriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment. METHODS: In this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months. RESULTS: Twelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and ß-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P < 0.10). In the multiple regression model, postmenopausal women with vitamin K2 supplementation, higher baseline serum 25(OH)D level, and higher PINP concentration at 3 months indicated a good reaction of LS BMD at 12 months (P < 0.05). Patients with gastrointestinal disease, prior bisphosphonate and glucocorticoid treatment, vegetarian diet pattern, and higher baseline BMD were significantly more likely to have a lower absolute LS BMD response compared to patients without these characteristics (P < 0.05). Further analysis confirmed the negative effect of unhealthy lifestyle on TPTD treatment. CONCLUSION: Our results emphasize the significance of a comprehensive assessment of clinical or lifestyle-related characteristics of postmenopausal women with osteoporosis in the management of TPTD therapy in routine care.

Physical activity and its fluctuations in relation to depressive symptoms: A national longitudinal study among Chinese adults.

BACKGROUND: Physical activity (PA) may prevent depressive symptoms, however, PA fluctuations may have different effects. Using three waves of nationally representative data, this study aimed to examine the effects of PA fluctuations on depressive symptoms. METHODS: Participants comprised 7633 adults free of depressive symptoms at the first two waves (Mage = 45.26, 54.70 % males). They completed the China Family Panel Study in 2016 (T1), 2018 (T2), and 2020 (T3), respectively. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression (CES-D) scale using a cutoff of 16. Participants' PA levels were split into regular PA or infrequent PA groups. Changes in PA levels between T1 and T2 were classified into four groups: maintained infrequent PA, initiated regular PA, ceased regular PA, and persisted regular PA. RESULTS: The incidence of depressive symptoms was 20.22 % (19.05 % possible and 1.17 % severe depression). After multivariate adjustment, Poisson regression showed that persistent regular PA had 17.8 % (95 % CI: 0.724, 0.934) lower risks of incident depressive symptoms compared to maintained infrequent PA. And adults who ceased regular PA were more likely to experience depressive symptoms than those who persisted in regular PA (RR = 1.188, 95 % CI: 1.010, 1.398). LIMITATIONS: All items were self-reported. CES-D only examined self-diagnosed depressive symptoms, not medical diagnoses. CONCLUSION: Adults who persisted in regular PA may have a lower possibility of developing depressive symptoms. The finding might serve as an empirical reference to depression prevention.

Empathy and bystander helping behavior in cyberbullying among adolescents: the mediating role of internet moral judgment and the moderating role of internet self-efficacy.

Introduction: Cyberbullying poses a significant challenge among adolescents. If bystanders stand up and help victims, their helping behavior may be able to reduce the frequency and negative impact of cyberbullying. This study investigates the association of empathy, internet moral judgment, and internet self-efficacy with bystander helping behavior among adolescents, building upon the empathy-altruism hypothesis, bystander intervention model, and dual-process model of morality. Methods: A sample of 919 Chinese adolescents from 3 schools in Hunan, Jiangxi and Guangdong provinces completed the Basic Empathy Scale, Internet Moral Judgment Questionnaire, Internet Self-Efficacy Questionnaire and Styles of Bystander Intervention Scale. And we constructed a moderated mediation model to examine the relationship between empathy and bystander helping behavior in cyberbullying and assessed the mediating role of internet moral judgment and the moderating role of internet self-efficacy. Results: Our findings revealed a significant positive correlation between empathy and bystander helping behavior in cyberbullying. Internet moral judgment mediated the relationship between empathy and helping behavior, whereas internet self-efficacy moderated the latter half of the mediation pathway. Specifically, the association between internet moral judgment and helping behavior was stronger for bystanders with higher levels of internet self-efficacy compared with those that have lower levels. Discussion: These results further deepen our understanding of the mechanisms involved in bystander helping behavior in cyberbullying, thus providing a basis for future interventions to encourage more helping actions from bystanders during cyberbullying incidents.

Ginsenoside Rh4 Improves Hepatic Lipid Metabolism and Inflammation in a Model of NAFLD by Targeting the Gut Liver Axis and Modulating the FXR Signaling Pathway.

Non-alcoholic fatty liver disease (NAFLD) is a series of disorders of liver metabolism caused by the accumulation of lipids in the liver, which is considered the main cause of hepatocellular carcinoma. Our previous study demonstrated the promising efficacy of ginsenoside Rh4 in improving the intestinal tract and its related metabolites. Meanwhile, many studies in the literature have investigated the gut microbiota and its metabolites, such as bile acids (BAs) and short-chain fatty acids (SCFAs), which play a key role in the pathogenesis of NAFLD. Therefore, this study focused on whether Rh4 could achieve therapeutic effects on NAFLD through the gut-liver axis. The results showed that Rh4 exhibited sound therapeutic effects on the NAFLD model induced by the Western diet and CCl4 in mice. In the liver, the degrees of hepatic steatosis, lobular inflammation levels, and bile acid in the liver tissue were improved after Rh4 treatment. At the same time, Rh4 treatment significantly increased the levels of intestinal SCFAs and BAs, and these changes were accompanied by the complementary diversity and composition of intestinal flora. In addition, correlation analysis showed that Rh4 affected the expression of proteins involved in the farnesoid X receptor (FXR) signaling pathway in the liver and intestine, which modulates hepatic lipid metabolism, inflammation, and proteins related to bile acid regulation. In conclusion, our study provides a valuable insight into how Rh4 targets the gut-liver axis for the development of NAFLD, which indicates that Rh4 may be a promising candidate for the clinical therapy of NAFLD.

Life Stress and Cyberbullying: Examining the Mediating Roles of Expressive Suppression and Online Disinhibition.

Life stress is a significant predictor of cyberbullying. However, previous studies have not investigated the roles of emotional and cognitive characteristics, such as expressive suppression and online disinhibition, in explaining the associations between life stress and cyberbullying perpetration/victimization. To fill this gap, a two-wave longitudinal design was used to investigate these two mediating variables as the underlying mechanisms among adolescents after controlling for possible covariates. A total of 724 Chinese adolescents (female: 41.2%) aged 12 to 16 years old (M = 13.36, SD = 0.77) participated in this survey. They completed self-report questionnaires on life stress, expressive suppression, online disinhibition (including benign and toxic disinhibition), cyberbullying perpetration, and cyberbullying victimization. The survey was conducted in two waves, six months apart. The correlational analyses showed that life stress was positively associated with cyberbullying perpetration/victimization cross-sectionally and longitudinally. After controlling other variables, life stress did not predict cyberbullying perpetration cross-sectionally or longitudinally, but cross-sectionally predicted cyberbullying victimization. The results only revealed the significant mediation effects of expressive suppression and online disinhibition at the first time point. Specifically, toxic disinhibition mediated the relationship between life stress and cyberbullying perpetration/victimization, and benign disinhibition mediated the relationship between life stress and cyberbullying victimization. In addition, life stress cross-sectionally and positively predicted cyberbullying victimization through the serial mediating roles of expressive suppression and benign disinhibition. The results of the multi-group analysis showed that there was no significant difference in the hypothesized model for the male and female groups. This study reveals how life stress is related to cyberbullying perpetration/victimization. Reducing expressive suppression and online disinhibition may be effective in preventing cyberbullying among adolescents.

Family Matters More Than Friends on Problematic Social Media Use Among Adolescents: Mediating Roles of Resilience and Loneliness.

Problematic social media use (PSMU) among adolescents has raised global concern in the current digital age. Despite the important role of perceived social support in adolescents' PSMU has been examined, possible different influences between perceived support from family and friends are still unknown. To address the gap, the present study aimed to examine how perceived support from family and friends is associated differently with PSMU and the mediating roles of resilience and loneliness therein. A sample of 1056 adolescents was recruited to complete standard questionnaires. Mediation analysis showed that resilience and loneliness mediated this association partially between perceived support from family and PSMU but totally between perceived support from friends and PSMU. Further, ANOVA-based analysis showed that influences of perceived support from family and friends on PSMU were mutually independent, and there was no interaction between them. Our results not only highlight different and independent impacts of perceived support from family and friends on PSMU, but also clarify the mediating mechanisms linking perceived social support to adolescent PSMU.

Parental attachment and cyberbullying among college students: the mediating role of loneliness and the moderating role of interdependent self.

Although considerable research has shown that attachment is a protective factor for cyberbullying, little research has investigated the mechanisms underlying this relationship among college students. This study examined whether loneliness mediates the association between parental attachment and cyberbullying and whether this process is moderated by interdependent self. A sample of 1125 college students (Mage = 19.14, SDage = 1.52 years) in China completed a questionnaire measuring parental attachment, cyberbullying, loneliness, and interdependent self. Loneliness partially mediated the relationship between parental attachment and cyberbullying. Moreover, the mediation effect of loneliness was moderated by interdependent self. A moderated mediation analysis further revealed that interdependent-self moderated the predictive effect of loneliness on cyberbullying. Specifically, the predictive effect of loneliness on cyberbullying was only significant among college students with low interdependent self. The study highlights the complex nature of the association between parental attachment and cyberbullying. These findings provide new perspectives for intervention and prevention of cyberbullying among college students.

Ginsenoside Rh3 Inhibits Lung Cancer Metastasis by Targeting Extracellular Signal-Regulated Kinase: A Network Pharmacology Study.

Lung cancer has a high mortality rate and is very common. One of the main reasons for the poor prognosis of patients with lung cancer is the high incidence of metastasis. Ginsenoside Rh3, a rare ginsenoside extracted from Panax notoginseng, exhibits excellent anti-inflammatory and anti-tumor effects. Nonetheless, the inhibitory potential of Rh3 against lung cancer remains unknown. The target genes of Rh3 were screened by the PharmMapper database; the proliferation of lung cancer cells was detected by MTT assay; the migration and invasion of cells were detected by the Transwell method; and the expression of extracellular signal-regulated kinase (ERK) and EMT-related proteins in vivo and in vitro were detected by Western blotting. In addition, we established a lung metastasis model in nude mice using A549 cells to assess the effect of Rh3 on NSCLC tumor metastasis in vivo. Our findings suggest that Rh3 significantly inhibited lung cancer metastasis both in vivo and in vitro. It was determined by flow cytometry analysis that Rh3 notably inhibited cell proliferation by blocking the G1 phase. In addition, Rh3 inhibited metastasis in lung cancer cells and regulated the expression of metastasis-related proteins under hypoxia. Mechanistic studies suggested that Rh3 targeted ERK to inhibit lung cancer metastasis. The ERK inhibitor U0126 or siRNA-mediated knockdown of ERK had an enhanced effect on Rh3's ability to inhibit lung cancer metastasis. The studies revealed that the inhibitory effect of Rh3 on the metastatic ability of lung cancer cells may be supported by ERK-related signaling pathways.

Development and Validation of an Autonomy Questionnaire for Chinese Adolescents From the Perspective of Network Culture.

This study developed a measure of autonomy for adolescents in contemporary China. First, data from 44 interviewees-40 secondary school students, 2 parents, and 2 secondary school teachers-were used to explore the connotation and theoretical structure of autonomy in adolescents in China. Next, a preliminary Adolescent Autonomy Questionnaire was created from the interview data and administered to 775 secondary school students. Exploratory factor analysis and confirmatory factor analysis (CFA) were conducted to verify the factor structure. Finally, 614 secondary school students completed the Adolescent Autonomy Questionnaire, Personal Growth Initiative Scale-II, and Adolescence Ego Identity Crisis Scale to evaluate criterion validity. The final version of the Adolescent Autonomy Questionnaire included 16 items and four subscales: autonomous decision-making, autonomous regulation, autonomous protection, and autonomous problem-solving. The total variance of the cumulative interpretation questionnaire was 62.54%. The CFA results showed that the four-factor model fits the data well: χ 2/df = 2.340, CFI = 0.949, RMSEA = 0.042, SRMR = 0.046. Evaluation of the psychometric properties of the Adolescent Autonomy Questionnaire provided support for the reliability and validity of the measure. Thus, it serves as an effective measurement tool for assessing the autonomy of adolescents in China.

GRIN2A Variants Associated With Idiopathic Generalized Epilepsies.

Objective: The objective of this study is to explore the role of GRIN2A gene in idiopathic generalized epilepsies and the potential underlying mechanism for phenotypic variation. Methods: Whole-exome sequencing was performed in a cohort of 88 patients with idiopathic generalized epilepsies. Electro-physiological alterations of the recombinant N-methyl-D-aspartate receptors (NMDARs) containing GluN2A mutants were examined using two-electrode voltage-clamp recordings. The alterations of protein expression were detected by immunofluorescence staining and biotinylation. Previous studies reported that epilepsy related GRIN2A missense mutations were reviewed. The correlation among phenotypes, functional alterations, and molecular locations was analyzed. Results: Three novel heterozygous missense GRIN2A mutations (c.1770A > C/p.K590N, c.2636A > G/p.K879R, and c.3199C > T/p.R1067W) were identified in three unrelated cases. Electrophysiological analysis demonstrated R1067W significantly increased the current density of GluN1/GluN2A NMDARs. Immunofluorescence staining indicated GluN2A mutants had abundant distribution in the membrane and cytoplasm. Western blotting showed the ratios of surface and total expression of the three GluN2A-mutants were significantly increased comparing to the wild type. Further analysis on the reported missense mutations demonstrated that mutations with severe gain-of-function were associated with epileptic encephalopathy, while mutations with mild gain of function were associated with mild phenotypes, suggesting a quantitative correlation between gain-of-function and phenotypic severity. The mutations located around transmembrane domains were more frequently associated with severe phenotypes and absence seizure-related mutations were mostly located in carboxyl-terminal domain, suggesting molecular sub-regional effects. Significance: This study revealed GRIN2A gene was potentially a candidate pathogenic gene of idiopathic generalized epilepsies. The functional quantitative correlation and the molecular sub-regional implication of mutations helped in explaining the relatively mild clinical phenotypes and incomplete penetrance associated with GRIN2A variants.

Does bullying victimization really influence adolescents' psychosocial problems? A three-wave longitudinal study in China.

BACKGROUND: Traditional bullying and cyberbullying victimization are associated with adolescents' mental health problems, but the temporal sequence of these relations remains unclear. The present study analyzed the temporal and reciprocal relationships between both types of bullying victimization and six frequent psychosocial problems during adolescence: depression, general anxiety, stress, low self-esteem, social anxiety, and loneliness. METHODS: A total of 661 Chinese adolescents in grades 7 and 8 at the initial wave of the study responded to the survey items assessing their bullying victimization experiences and self-reported psychosocial problems. This research was conducted at three separate time points, over a year and a half period. RESULTS: Bullying victimization did not predict adolescents' psychosocial problems. Instead, adolescents with psychosocial problems were more likely to experience bullying victimization. Depression and general anxiety were two common predictors of traditional bullying and cyberbullying victimization. Stress was a specific predictor of traditional bullying victimization, whereas self-esteem, social anxiety, and loneliness were specific predictors of cyberbullying victimization. Psychosocial problems did not differentially predict the two types of bullying victimization. Boys with higher levels of loneliness were more likely than girls to experience cyberbullying victimization. LIMITATIONS: The present study is limited in terms of its sample selection and self-reported instruments. CONCLUSIONS: This study emphasizes adolescents' psychosocial problems as the potential risk factors for their future bullying victimization. Education professionals should pay special attention to adolescents' mental health problems when formulating bullying interventions and programs.

Are Narcissists More Likely to Be Involved in Cyberbullying? Examining the Mediating Role of Self-Esteem.

Although cyberbullying, a new type of aggressive behavior via electronic means, has been found to be strongly linked with individuals' personality characteristics, few studies to date have investigated its relationship with narcissism, especially overt and covert narcissism. The current study tested the associations between overt and covert narcissism on one hand and cyberbullying perpetration and victimization on the other. To explain these differences further, self-esteem was tested as a mediator through which the two types of narcissism may exert their influences on cyberbullying. An anonymous questionnaire was completed by 814 Chinese adolescents aged 11 to 18. Results of multiple regression analyses indicated that after controlling for gender and student status (middle or high school students), covert narcissism positively predicted both cyberbullying perpetration and victimization, whereas overt narcissism had no association with either perpetration or victimization. Furthermore, when gender and student status were controlled, self-esteem mediated the relationships between overt/covert narcissism and cyberbullying perpetration and victimization, highlighting the possibility that self-esteem is an explanatory mechanism for the associations between the two types of narcissism and cyberbullying. These findings suggest that interventions aimed at reducing engagement in cyberbullying may be more urgent and important for individuals with high levels of covert narcissism. Boosting self-esteem needs to be particularly highlighted in developing anti-bullying measures and policies.

Personality and life satisfaction in middle school students / 中国学校卫生

Objective@#The aim of the study was to identify the personality types of middle school students and its association with life satisfaction,and to provide a reference for improving personality and mental health of middle school students.@*Methods@#A total of 1 409 students randomly selected form 4 middle schools of a rural area in Wuhan city by cluster stratified sampling method were taken as the object of the research. Adolescents completed the Chinese version of NEO Five-Factor Inventory (NEO-FFI) and the Satisfaction with Life Scale. Latent profile analysis (LPA) was used to identify personality types. ANOVA analyses were used to explore the associations between personality types and life satisfaction.@*Results@#Three profiles were identified: resilient (5.32%), overcontrolled (32.86%) and undercontrolled (61.82%),the differences were of statistical significance(P<0.05). Resilient adolescents had the highest scores (M=5.10, SD=1.34) whereas undercontrolled had the lowest scores (M=3.66, SD=1.09) on life satisfaction.@*Conclusion@#Schools, families and society should pay attention to the high proportion of overcontrolled and undercontrolled in middle school students and take actions to promote the positive development of personality and mental health.

Social networking site addiction and undergraduate students' irrational procrastination: The mediating role of social networking site fatigue and the moderating role of effortful control.

With the popularity of social networking sites (SNSs), the problems of SNS addiction have been increasing. Research has revealed the association between SNS addiction and irrational procrastination. However, the mechanism underlying this relation is still unclear. The present study aimed to examine the mediating role of social networking site fatigue and the moderating role of effortful control in this link among Chinese undergraduate students. The Social Networking Site Addiction Scale, Social Networking Service Fatigue Scale, Effortful Control Scale and Irrational Procrastination Scale were completed by 1,085 Chinese undergraduate students. Results indicated that SNS addiction, SNS fatigue and irrational procrastination were positively correlated with each other, and negatively correlated with effortful control. Further analyses revealed that, SNS addiction has a direct effect on irrational procrastination. SNS fatigue mediated the relationship between SNS addiction and irrational procrastination. Both direct and indirect effects of SNS addiction on irrational procrastination were moderated by effortful control. Specifically, this effect was stronger for people with lower effortful control. These findings help clarify the mechanism underlying the association between SNS addiction and irrational procrastination, which have potential implications for intervention.

Stability and Change of Bullying Roles in the Traditional and Virtual Contexts: A Three-Wave Longitudinal Study in Chinese Early Adolescents.

Traditional bullying and cyberbullying are two prevalent phenomena among adolescents around the world. Typically, bullying incidents involve distinct perpetrator and victim roles. However, the question whether participants' roles in bullying situation remain stable or changeable is unclear. The present study examined the developmental stability and change of bullying roles by simultaneously investigating adolescents' bullying behaviors both in the traditional and virtual contexts. Participants were 661 seventh- and eighth-grade students (39.0% girls) aged 11-15 years (M = 12.86, SD = .73) in China. They completed a survey measuring their experiences in perpetration and victimization of traditional bullying and cyberbullying at three time points with 6-month intervals. A cross-lagged panel design was used to test for the temporal sequence of research variables. The results showed a moderate consistency in the bullying roles that students took on (i.e., perpetrator and victim) over time. Traditional bullying perpetrators continued to bully others online, whereas cyberbullying victims continued to be bullied offline. Regarding role change in bullying, perpetrators and victims did not change their roles in traditional bullying situation, but they tended to change their roles to the opposites in cyberbullying situation. Traditional bullying victims were more likely to become cyberbullying perpetrators, and vice versa. Traditional bullying perpetrators also had a greater tendency of being bullied online, but not vice versa. The findings suggest that interventions aimed at reducing adolescents' bullying behaviors should focus on the stability and change of bullying roles in the traditional and virtual contexts.

Functional Investigation of a GRIN2A Variant Associated with Rolandic Epilepsy.

N-methyl-D-aspartate receptors (NMDARs), a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2A (a gene encoding the NMDAR GluN2A subunit) mutations in patients with epilepsy. Phenotypes of GRIN2A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment. Here we identified a heterozygous GRIN2A mutation (c.1341T>A, p.N447K) from a boy with Rolandic epilepsy by whole-exome sequencing. The patient became seizure-free with a combination of valproate and lamotrigine. Functional investigation was carried out using recombinant NMDARs containing a GluN2A-N447K mutant that is located in the ligand-binding domain of the GluN2A subunit. Whole-cell current recordings in HEK 293T cells revealed that the N447K mutation increased the NMDAR current density by ~1.2-fold, enhanced the glutamate potency by 2-fold, and reduced the sensitivity to Mg2+ inhibition. These results indicated that N447K is a gain-of-function mutation. Interestingly, alternative substitutions by alanine and glutamic acid at the same residue (N447A and N447E) did not change NMDAR function, suggesting a residual dependence of this mutation in altering NMDAR function. Taken together, this study identified human GluN2A N447K as a novel mutation associated with epilepsy and validated its functional consequences in vitro. Identification of this mutation is also helpful for advancing our understanding of the role of NMDARs in epilepsy and provides new insights for precision therapeutics in epilepsy.

Structural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer.

Mammalian shelterin proteins POT1 and TPP1 form a stable heterodimer that protects chromosome ends and regulates telomerase-mediated telomere extension. However, how POT1 interacts with TPP1 remains unknown. Here we present the crystal structure of the C-terminal portion of human POT1 (POT1C) complexed with the POT1-binding motif of TPP1. The structure shows that POT1C contains two domains, a third OB fold and a Holliday junction resolvase-like domain. Both domains are essential for binding to TPP1. Notably, unlike the heart-shaped structure of ciliated protozoan Oxytricha nova TEBPα-ß complex, POT1-TPP1 adopts an elongated V-shaped conformation. In addition, we identify several missense mutations in human cancers that disrupt the POT1C-TPP1 interaction, resulting in POT1 instability. POT1C mutants that bind TPP1 localize to telomeres but fail to repress a DNA damage response and inappropriate repair by A-NHEJ. Our results reveal that POT1 C terminus is essential to prevent initiation of genome instability permissive for tumorigenesis.

Self-relevant beauty evaluation: Evidence from an event-related potentials study.

This study examines the electrophysiological correlates of beauty evaluation when participants performed the self-reference task. About 13 (7 men, 6 women) undergraduates participated in the experiment using event-related potentials. Results showed that the response to self-relevant information was faster compared to other-relevant information and no significant differences for self-relevant relative to mother-relevant information were observed. Both physical and interior beauty words for self-relevant information showed an enhanced late positive component as compared to other-relevant information. Physical beauty for self-relevant information yielded a larger late positive component in contrast to mother-relevant information but not for interior beauty. This study indicates that beauty is specific to the person who judges it though an individual and one's mother may hold similar views of interior beauty.

Friendship quality, social preference, proximity prestige, and self-perceived social competence: interactive influences on children's loneliness.

The purpose of this study was to test an integrative model in which peer relations at different levels of social complexity (friendship quality, social preference, and proximity prestige) are associated with children's loneliness, with children's self-perceived social competence acting as a mediator of these associations. A middle childhood sample of 509 Chinese children (233 girls and 276 boys; 3rd to 6th grade) completed a battery of sociometric and self-report questionnaires. Bootstrap analysis showed that self-perceived social competence mediated the relations between each peer variable and loneliness. In the integrative model tested with SEM, the mediating effect of self-perceived social competence in the relation between friendship quality and loneliness and between social preference and loneliness remained significant. However, self-perceived social competence no longer mediated the association between proximity prestige and loneliness, when considering the simultaneous influences of the three peer variables (friendship quality, social preference, and proximity prestige). The whole model accounted for 56% of the variance in loneliness. These findings suggest that self-perceived social competence played an important role in children's loneliness, that the quality and the quantity of direct peer relations (friendship quality, social preference, and part of proximity prestige) were associated with loneliness, and that indirect friends had a relatively lower but significant influence on children's loneliness. The results are discussed in terms of their implications for preventing children's loneliness.