Changing Relations Among Cognitive Abilities Across Development: Implications for Measurement and Research

The constructs of intelligence and executive function are critical concepts of ability in neuropsychological research, cognitive research, developmental research, and clinical assessment. Yet, we have limited understanding of the changing age-related associations among these cognitive constructs. To better understand the development of these abilities, we compared a child sample and a young-adult sample on several measures of intelligence and executive functions. We used confirmatory factor analysis to estimate models for each developmental period. In addition, the association with ratings of inattention and hyperactivity/impulsivity, a dispositional measure of cognitive and behavioural regulation, was examined. The results indicated that cognitive abilities are more dependent on age in children than in young adults and that these abilities are more highly associated with ratings of cognitive and behavioural regulation in children than in young adults. The results support the integral relationship between intelligence and executive function throughout development, but especially in children

An Examination of the Structure and Common Correlates of Three Domains of Contaminated Mindware in Adolescence and Young Adulthood

Limited research has examined individual differences in the accumulation of misinformation and unwarranted beliefs, known as contaminated mindware. The three unwarranted beliefs examined in this dissertation are paranormal, conspiracy, and anti-science beliefs. These beliefs remain prevalent in the public despite their epistemically suspect or unsubstantiated nature. This dissertation focused on the psychometric properties of items measuring individual differences in unwarranted beliefs to address three research objectives: (1) examine the underlying dimensional structure of unwarranted belief items in adolescents and young adults, (2) examine individual differences predicting susceptibility to these beliefs, and (3) examine differences between adolescents and young adults with respect to these beliefs. Study One examined the underlying structure of individual differences in unwarranted belief scores and its correlates in a sample of young-adults. Study Two confirmed that the same structure and correlates are found in adolescents. Both studies demonstrate the multidimensional nature of unwarranted beliefs that form domains of contaminated mindware. Specifically, the optimal factor model among adolescents and young adults was a hierarchical factor model with three correlated general factors (paranormal, conspiracy, and anti-science beliefs) and four specific paranormal factors (i.e., psi, superstition, spiritualism, and precognition). Further, we observed unique effects of individual differences in thinking and reasoning on individual differences in unwarranted beliefs. In Study Three, we assessed the measurement invariance of these scales across the two developmental groups, to allow for cross-sectional comparisons and age associations. The paranormal and conspiracy scales were characterized by strict invariance and the anti-science scale was characterized by strong invariance. With respect to developmental comparisons, endorsement of the unwarranted beliefs did not differ across development, except for a small difference in paranormal belief. Further, the unwarranted beliefs total scores were not associated with age. We discuss the novelty of the results within the belief literature on contaminated mindware and focus on the utility of this scale for future research

The Role of CCL21/CCR7 Chemokine Axis in Breast Cancer Progression

Tumor-induced lymphangiogenesis facilitates breast cancer progression by generating new lymphatic vessels that serve as conduits for tumor dissemination to lymph nodes and beyond. Given the recent evidence suggesting the implication of C-C chemokine ligand 21/chemokine receptor 7 (CCL21/CCR7) in lymph node metastasis, the aim of our study was to define the role of this chemokine pair in breast cancer-associated lymphangiogenesis. The expression analysis of CCL21/CCR7 pair and lymphatic endothelial cell (LEC) markers in breast cancer specimens was performed by means of quantitative real-time PCR. By utilizing CCR7 and CCL21 gene manipulated breast cancer cell implants into orthotopic sites of nude mice, lymphatic vessel formation was assessed through quantitative real-time PCR, immunohistochemistry and immunofluorescence assays. Finally, the lymphangiogenic potential of CCL21/CCR7 was assessed in vitro with primary LECs through separate functional assays, each attempting to mimic different stages of the lymphangiogenic process. We found that CCR7 mRNA expression in human breast cancer tissues positively correlates with the expression of lymphatic endothelial markers LYVE-1, podoplanin, Prox-1, and vascular endothelial growth factor-C (VEGF-C). We demonstrated that the expression of CCL21/CCR7 by breast cancer cells has the ability to promote tumor-induced lymph-vascular recruitment in vivo. In vitro, CCL21/CCR7 chemokine axis regulates the expression and secretion of lymphangiogenic factor VEGF-C and thereby promotes proliferation, migration, as well as tube formation of the primary human LECs. Finally, we showed that protein kinase B (AKT) signaling pathway is the intracellular mechanism of CCR7-mediated VEGF-C secretion by human breast cancer cells. These results reveal that CCR7 and VEGF-C display a significant crosstalk and suggest a novel role of the CCL21/CCR7 chemokine axis in the promotion of breast cancer-induced lymphangiogenesis

Towards understanding the mechanisms of actions of carcinoembryonic antigen-related cell adhesion molecule 6 in cancer progression

Human carcinoembryonic antigen (CEA) is the prototypic member of a family of highly related cell surface glycoproteins that includes carcinoembryonic antigenrelated cell adhesion molecule 6 (CEACAM6) and others. CEACAM6 (formerly NCA), which belongs to the immunoglobulin superfamily, is a cell adhesion protein of the CEA family. It is normally expressed on the epithelial surfaces and on the surface of myeloid cells (CD66c). CEACAM6 is a multi-functional glycoprotein that mediates homotypic binding with other CEA family members and heterotypic binding with integrin receptors. It functions by organizing tissue architecture and regulating different signal transduction, while aberrant expression leads to the development of human malignancies. It was first discovered in proliferating cells of adenomas and hyperplastic polyps in comparison to benign colonic tissue when overexpressed on the surface of various cell types in model systems. CEACAM6 functions as a paninhibitor of cell differentiation and cell polarization, and it also causes distortion of tissue architecture. Moreover, overexpression of CEACAM6 modulates cancer progression through aberrant cell differentiation, anti-apoptosis, cell growth and resistance to therapeutic agents. In addition, CEACAM6 overexpression in multiple malignancies promotes cell invasion and metastasis, thereby representing an acquired advantage of tumor cells directly responsible for an invasive phenotype. This review focuses on the findings supporting the mechanisms of actions linking the oncogenic potential of CEACAM6 to the onset of cancer progression and pathogenesis, especially in breast cancer, and to validating CEACAM6 as a target to pave the way towards the design of efficient therapeutic strategies against breast cancer

Affective forecasting and psychopathology: a scoping review

Affective forecasting – estimations of future emotional reactions – is an important aspect of future thinking that informs judgement and decision making. Biases in affective forecasting have been noted generally and with people with emotional disturbances specifically. Still, the role of affective forecasting within models of psychopathology has received little attention. Given the state of the literature, a scoping review method was adopted to summarize and synthesize the methodological approaches used in measuring affective forecasting within the context of psychopathology and the scope of the evidence on this association. Three databases were searched for research published on or before November 13th, 2023. Original quantitative research that examined affective forecasting and its association with psychopathology was reviewed. Data were charted using a form designed for this study. Overall, the review highlights the heterogeneity in operationalization of affective forecasting. The majority of the evidence supports an association between severity of psychopathology and intensity of affective forecasts, with notable exceptions, which are discussed within the scope of methodology and operationalization of affective forecasting. This remains an important process to investigate in information processing models of psychopathology to elucidate its role in the development and maintenance of psychopathology and potential as a target for intervention

The cognitive, emotional, and behavioral sequelae of trauma exposure: An integrative approach to examining trauma’s effect

Objective: In this study, we tested direct pathways from trauma exposure to trauma symptomatology and risky and self-destructive behavior and indirect pathways through two cognitive and affective mechanisms: (a) world assumptions and (b) emotion dysregulation. Method: A sample of 270 undergraduate students with an average age of 20.02 years participated in the study (204 women, 65 men, and one participant choosing not to disclose). Participants completed self-report measures assessing trauma exposure, trauma symptoms, emotion dysregulation, world assumptions, and lifetime and past-month engagement in any of 38 risky and self-destructive behaviors. Results: The direct path from trauma exposure to trauma symptoms was significant, and so was the indirect effect of self-worth assumptions on this association. The indirect pathway between trauma symptoms and risky and self-destructive behavior in the past month was significant through difficulties with impulse control when distressed. Trauma symptoms had an indirect effect on the association between trauma exposure and lifetime and past-month engagement in risky and self-destructive behavior, while the direct pathway from trauma exposure to lifetime engagement remained significant. Conclusion: We offer theoretically and empirically supported integrative pathways that explicate some aspects of trauma exposure’s negative sequelae with potential areas for intervention. Clinical Impact Statement: Trauma exposure is widespread and is associated with negative views about oneself and the world and with difficulties in managing one’s emotions, which in part is associated with individuals’ risk for developing psychopathology and engaging in risky and self-destructive behaviors. The findings inform optimal time for intervention and prevention efforts targeting trauma exposure

Novel CD44-downstream signaling pathways mediating breast tumor invasion

CD44, also known as homing cell adhesion molecule is a multi-structural cell molecule involved in cell-cell and cell-extracellular matrix communications. CD44 regulates a number of central signaling pathways, including PI3K/AKT, Rho GTPases and the Ras-MAPK pathways, but also acts as a growth/arrest sensor, and inhibitor of angiogenesis and invasion, in response to signals from the microenvironment. The function of CD44 has been very controversial since it acts as both, a suppressor and a promoter of tumor growth and progression. To address this discrepancy, we have previously established CD44-inducible system both in vitro and in vivo. Next, using microarray analysis, we have identified and validated Survivin, Cortactin and TGF-β2 as novel CD44-downstream target genes, and characterized their signaling pathways underpinning CD44-promoted breast cancer (BC) cell invasion. This report aims to update the literature by adding and discussing the impact of these novel three signaling pathways to better understand the CD44-signaling pathways involved in BC tumor cell invasion

Novel role of BRCA1 interacting C-terminal helicase 1 (BRIP1) in breast tumour cell invasion

Breast cancer (BC) is the most common malignancy and the leading cause of death in women worldwide. Only 5%-10% of mutations in BRCA genes are associated with familial breast tumours in Eastern countries, suggesting the contribution of other genes. Using a microarray gene expression profiling study of BC, we have recently identified BRIP1 (fivefold up-regulation) as a potential gene associated with BC progression in the Omani population. Although BRIP1 regulates DNA repair and cell proliferation, the precise role of BRIP1 in BC cell invasion/metastasis has not been explored yet; this prompted us to test the hypothesis that BRIP1 promotes BC cell proliferation and invasion. Using a combination of cellular and molecular approaches, our results revealed differential overexpression of BRIP1 in different BC cell lines. Functional assays validated further the physiological relevance of BRIP1 in tumour malignancy, and siRNA-mediated BRIP1 knockdown significantly reduced BC cell motility by targeting key motility-associated genes. Moreover, down-regulation of BRIP1 expression significantly attenuated cell proliferation via cell cycle arrest. Our study is the first to show the novel function of BRIP1 in promoting BC cell invasion by regulating expression of various downstream target genes. Furthermore, these findings provide us with a unique opportunity to identify BRIP1-induced pro-invasive genes that could serve as biomarkers and/or targets to guide the design of appropriate BC targeted therapies