pVHL-mediated regulation of the anti-angiogenic protein thrombospondin-1 decreases migration of Clear Cell Renal Carcinoma Cell Lines

Thrombospondin-1 (TSP-1) is a multifunctional matrix protein with antitumor activities due in part to its ability to inhibit angiogenesis, which in turn contributes to determine the fate of many tumours. Previous studies have shown that TSP-1 expression supports normal kidney angiostasis, and decreased TSP-1 levels contribute to the angiogenic phenotype of renal cell carcinomas (RCC). The loss of the von Hippel-Lindau tumour suppressor gene (VHL) in these tumours favours stabilization of the Hypoxia Inducible Factors (HIF), which in turn contribute to adapt tumour cells to hostile environments promoting tumour progression. However, HIF-independent regulation of certain genes might also be involved. We have previously shown that TSP-1 is regulated in hypoxia in clear cell RCC (ccRCC) in a HIF-independent manner; however, the effect of VHL protein (pVHL) on TSP-1 expression has not been evaluated. Our results proved that pVHL loss or mutation in its alpha or beta domain significantly decreased TSP-1 levels in ccRCC in a HIF-independent manner. Furthermore, this regulation proved to be important for ccRCC cells behaviour showing that decreased TSP-1 levels rendered ccRCC cells more migratory. This data substantiates a unique regulation pattern for TSP-1 in a pVHL-dependent manner, which may be relevant in the aggressiveness of ccRCC.This work was supported by grants from the Spanish Government (co-funded by European Regional Development Fund, ERDF/FEDER); PI16/02166 and 2017/EEUU/03 to MJC; Red Temática de Excelencia en Investigación en Hipoxia (SAF 2017-90794-REDT) to MJ

System Dynamics of Cognitive Vulnerabilities and Family Support Among Latina Children and Adolescents

The paper describes an approach to developing a data-driven development of a feedback theory of cognitive vulnerabilities and family support focused on understanding the dynamics experienced among Latina children, adolescents, and families. Family support is understood to be a response to avoidant and maladaptive behaviors that may be characteristic of cognitive vulnerabilities commonly associated depression and suicidal ideation. A formal feedback theory is developed, appraised, and analyzed using a combination of secondary analysis of qualitative interviews (N = 30) and quantitative analysis using system dynamics modeling and simulation. Implications for prevention practice, treatment, and future research are discussed

Preventing Child Maltreatment in the US : The Latinx Community Perspective

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The Mediating Role of Home-School Dissonance in Linking Maternal Discrimination to Latin American-Origin Adolescent Academic Performance

Latin American-origin parents play an important role in supporting the formal education of their youth, but cultural, linguistic, and systemic barriers make parent involvement difficult. The aim of the present study was to examine how Latina mothers\u27 experiences with discrimination were associated with short-term changes in their adolescent children\u27s academic performance, directly and indirectly through mothers\u27 appraisal of home-school dissonance. Data were drawn from an ongoing longitudinal study of 547 mother-youth dyads in suburban Atlanta. Results showed a significant indirect relationship between mothers\u27 experiences of discrimination and declines in adolescents\u27 grade point average by way of increased home-school dissonance. Thus, Latina mothers\u27 discriminatory experiences may have spillover effects on adolescent academic achievement through increasing proximal barriers to parent involvement