Soluble forms of tau are toxic in Alzheimer's disease

Accumulation of neurofibrillary tangles (NFT), intracellular inclusions of fibrillar forms of tau, is a hallmark of Alzheimer Disease. NFT have been considered causative of neuronal death, however, recent evidence challenges this idea. Other species of tau, such as soluble misfolded, hyperphosphorylated, and mislocalized forms, are now being implicated as toxic. Here we review the data supporting soluble tau as toxic to neurons and synapses in the brain and the implications of these data for development of therapeutic strategies for Alzheimer’s disease and other tauopathies

Twist1 Influences the Expression of Leading Members of the IL-17 Signaling Pathway in HER2-Positive Breast Cancer Cells

Breast cancer (BC) is a heterogeneous disease composed of multiple subtypes with different molecular characteristics and clinical outcomes. The metastatic process in BC depends on the transcription factors (TFs) related to epithelial-mesenchymal transition (EMT), including the master regulator Twist1. However, its role beyond EMT in BC subtypes remains unclear. Our study aimed to investigate the role of Twist1, beyond EMT, in the molecular subtypes of BC. In patients, we observed the overexpression of TWIST1 in the HER2+ group. The silencing of TWIST1 in HER2+ BC cells resulted in the upregulation of 138 genes and the downregulation of 174 genes compared to control cells in a microarray assay. In silico analysis revealed correlations between Twist1 and important biological processes such as the Th17-mediated immune response, suggesting that Twist1 could be relevant for IL-17 signaling in HER2+ BC. IL-17 signaling was then examined, and it was shown that TWIST1 knockdown caused the downregulation of leading members of IL-17 signaling pathway. Taken together, our findings suggest that Twist1 plays a role on IL-17 signaling in HER2+ BC

Parental Depressive Symptoms and Adolescent Adjustment: A Prospective Test of an Explanatory Model for the Role of Marital Conflict

Despite calls for process-oriented models for child maladjustment due to heightened marital conflict in the context of parental depressive symptoms, few longitudinal tests of the mechanisms underlying these relations have been conducted. Addressing this gap, the present study examined multiple factors longitudinally that link parental depressive symptoms to adolescent adjustment problems, building on a conceptual model informed by emotional security theory (EST). Participants were 320 families (158 boys, 162 girls), including mothers and fathers, who took part when their children were in kindergarten (T1), second (T2), seventh (T3), eighth (T4) and ninth (T5) grades. Parental depressive symptoms (T1) were related to changes in adolescents’ externalizing and internalizing symptoms (T5), as mediated by parents’ negative emotional expressiveness (T2), marital conflict (T3), and emotional insecurity (T4). Evidence was thus advanced for emotional insecurity as an explanatory process in the context of parental depressive symptoms