Erratum Re: “Coping With Racism: Moderators of the Discrimination—Distress Link Among Mexican-Origin Adolescents”

The publisher's final edited version of this article is available at Child Dev This corrects the article "Coping With Racism: Moderators of the Discrimination—Adjustment Link Among Mexican-Origin Adolescents" in Child Dev, volume 89 on page e293

Testing a Multiple Mediation Model of Asian American College Students’ Willingness to See a Counselor

Adapting the theory of reasoned action (TRA), the present study examined help-seeking beliefs, attitudes, and intent among Asian American college students (N = 110). A multiple mediation model was tested to see if the relation between Asian values and willingness to see a counselor was mediated by attitudes toward seeking professional psychological help and subjective norm. A bootstrapping procedure was used to test the multiple mediation model. Results indicated that subjective norm was the sole significant mediator of the effect of Asian values on willingness to see a counselor. The findings highlight the importance of social influences on help-seeking intent among Asian American college students

The Role of Culture, Family Processes, and Anger Regulation in Korean American Adolescents’ Adjustment Problems

Using an ecologically informed, developmental psychopathology perspective, the present study examined contextual and intrapersonal predictors of depressive symptoms and externalizing problems among Korean American adolescents. Specifically, the role of cultural context (selfconstruals), family processes (family cohesion and conflict), and anger regulation (anger control, anger suppression, and outward anger expression) were examined. Study participants were N = 166 Korean American adolescents ranging from 11-15 (M = 13.0; SD = 1.2) years old. Results showed that depressive symptoms were significantly associated with lower levels of perceived family cohesion, higher levels of perceived family conflict intensity, and higher levels of anger suppression. Externalizing problems were associated with male gender, a weaker interdependent self-construal, higher levels of perceived family conflict, lower levels of anger control, and higher levels of outward anger expression. The distinction between specific vs. common factors associated with depressive symptoms and externalizing problems was discussed with an eye towards prevention or intervention strategies targeting specific coping mechanisms (e.g., generating alternatives to anger suppression) or developing psychoeducational approaches to facilitate family processes

Does anger regulation mediate the discrimination-mental health link among Mexican-origin adolescents? A longitudinal mediation analysis using multilevel modeling

Although prior research has consistently documented the association between racial/ethnic discrimination and poor mental health outcomes, the mechanisms that underlie this link are still unclear. The present three-wave longitudinal study tested the mediating role of anger regulation in the discrimination—mental health link among 269 Mexican-origin adolescents (Mage = 14.1 years, SD = 1.6; 57% girls), 12 – 17 years old. Three competing anger regulation variables were tested as potential mediators: outward anger expression, anger suppression, and anger control. Longitudinal mediation analyses were conducted using multilevel modeling that disaggregated within-person effects from between-person effects. Results indicated that outward anger expression was a significant mediator; anger suppression and anger control were not significant mediators. Within a given individual, greater racial/ethnic discrimination was associated with more frequent outward anger expression. In turn, more frequent outward anger expression was associated with higher levels of anxiety and depression at a given time point. Gender, age, and nativity status were not significant moderators of the hypothesized mediation models. By identifying outward anger expression as an explanatory mechanism in the discrimination-distress link among Latino youths, this study points to a malleable target for prevention and intervention efforts aimed at mitigating the detrimental impact of racism on Latino youths’ mental health during the developmentally critical period of adolescence

Racial/Ethnic Discrimination and Mental Health in Mexican-Origin Youths and Their Parents: Testing the "Linked Lives" Hypothesis

PURPOSE: Using a life course perspective, the present study tested the concept of "linked lives" applied to the problem of not only how racial/ethnic discrimination may be associated with poor mental health for the target of discrimination but also how discrimination may exacerbate the discrimination-distress link for others in the target's social network-in this case, the family. METHODS: The discrimination-distress link was investigated among 269 Mexican-origin adolescents and their parents both cross-sectionally and longitudinally. It was hypothesized that parents' discrimination experiences would adversely affect their adolescent children's mental health via a moderating effect on the target adolescent discrimination-distress link. The converse was also hypothesized for the target parents. Multilevel moderation analyses were conducted to test the moderating effect of parents' discrimination experiences on the youth discrimination-distress link. We also tested the moderating effect of youths' discrimination experiences on the parent discrimination-distress link. RESULTS: Parents' discrimination experiences significantly moderated the longitudinal association between youths' discrimination stress appraisals and mental health, such that the father's discrimination experiences exacerbated the youth discrimination-depression link. Youths' discrimination stress appraisals were not a significant moderator of the cross-sectional parent discrimination-mental health association. CONCLUSIONS: Implications of these findings are discussed from a linked lives perspective, highlighting how fathers' discrimination experiences can adversely affect youths who are coping with discrimination, in terms of their mental health

Intermediate filament–membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength

By tethering intermediate filaments (IFs) to sites of intercellular adhesion, desmosomes facilitate formation of a supercellular scaffold that imparts mechanical strength to a tissue. However, the role IF–membrane attachments play in strengthening adhesion has not been directly examined. To address this question, we generated Tet-On A431 cells inducibly expressing a desmoplakin (DP) mutant lacking the rod and IF-binding domains (DPNTP). DPNTP localized to the plasma membrane and led to dissociation of IFs from the junctional plaque, without altering total or cell surface distribution of adherens junction or desmosomal proteins. However, a specific decrease in the detergent-insoluble pool of desmoglein suggested a reduced association with the IF cytoskeleton. DPNTP-expressing cell aggregates in suspension or substrate-released cell sheets readily dissociated when subjected to mechanical stress whereas controls remained largely intact. Dissociation occurred without lactate dehydrogenase release, suggesting that loss of tissue integrity was due to reduced adhesion rather than increased cytolysis. JD-1 cells from a patient with a DP COOH-terminal truncation were also more weakly adherent compared with normal keratinocytes. When used in combination with DPNTP, latrunculin A, which disassembles actin filaments and disrupts adherens junctions, led to dissociation up to an order of magnitude greater than either treatment alone. These data provide direct in vitro evidence that IF–membrane attachments regulate adhesive strength and suggest furthermore that actin- and IF-based junctions act synergistically to strengthen adhesion

Inhibiting the oncogenic translation program is an effective therapeutic strategy in multiple myeloma

Published in final edited form as: Sci Transl Med. 2017 May 10; 9(389). https://doi.org/10.1126/scitranslmed.aal2668.Multiple myeloma (MM) is a frequently incurable hematological cancer in which overactivity of MYC plays a central role, notably through up-regulation of ribosome biogenesis and translation. To better understand the oncogenic program driven by MYC and investigate its potential as a therapeutic target, we screened a chemically diverse small-molecule library for anti-MM activity. The most potent hits identified were rocaglate scaffold inhibitors of translation initiation. Expression profiling of MM cells revealed reversion of the oncogenic MYC-driven transcriptional program by CMLD010509, the most promising rocaglate. Proteome-wide reversion correlated with selective depletion of short-lived proteins that are key to MM growth and survival, most notably MYC, MDM2, CCND1, MAF, and MCL-1. The efficacy of CMLD010509 in mouse models of MM confirmed the therapeutic relevance of these findings in vivo and supports the feasibility of targeting the oncogenic MYC-driven translation program in MM with rocaglates

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management