Differential effects of valence and encoding strategy on internal source memory and judgments of source: exploring the production and the self-reference effect

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpsyg.2019.01326/full#supplementary-materialItem memory studies show that emotional stimuli are associated with improved memory performance compared to neutral ones. However, emotion-related effects on source memory are less consistent. The current study probed how emotional valence and specific encoding conditions influence internal source memory performance and judgments of source (JOSs). In two independent experiments, participants were required to read silently/aloud (Experiment 1) or to perform self-reference/common judgments (Experiment 2) on a list of negative/neutral/positive words. They also performed immediate JOSs ratings for each word. The study phase was followed by a test phase in which participants performed old-new judgments. In Experiment 1, the production effect was replicated for item memory, but the effects of valence on item and source memory were not significant. In Experiment 2, self-referential processing effects on item and source memory differed as a function of valence. In both experiments, JOSs ratings were sensitive to valence and encoding conditions, although they were not predictive of objective memory performance. These findings demonstrate that the effects of valence on internal source memory and JOSs are modulated by encoding strategy. Thus, the way information is encoded can shed light on how emotion might enhance, impair or exert no influence on source memory.This work was supported by a Ph.D. Fellowship (PD/BD/105964/2014), awarded to DP, funded by the Portuguese Science Foundation (FCT) through national funds and cofunded by the European Social Fund (ESF) through the Operational Programme for Human Capital (POCH). It was also supported by a research grant (PTDC/MHC-PCN/0101/2014) funded by FCT and awarded to AP. The study was conducted at the Psychology Research Centre (PSI/01662), School of Psychology, University of Minho, and supported by FCT and the Portuguese Ministry of Science, Technology and Higher Education (UID/PSI/01662/2019), through the national funds (PIDDAC) and co-funded by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653)

MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model

Human embryonic stem cells (hESCs) can potentially differentiate into any cell type, including dopaminergic neurons to treat Parkinson's disease (PD), but hyperproliferation and tumor formation must be avoided. Accordingly, we use myocyte enhancer factor 2C (MEF2C) as a neurogenic and anti-apoptotic transcription factor to generate neurons from hESC-derived neural stem/progenitor cells (NPCs), thus avoiding hyperproliferation. Here, we report that forced expression of constitutively active MEF2C (MEF2CA) generates significantly greater numbers of neurons with dopaminergic properties in vitro. Conversely, RNAi knockdown of MEF2C in NPCs decreases neuronal differentiation and dendritic length. When we inject MEF2CA-programmed NPCs into 6-hydroxydopamine—lesioned Parkinsonian rats in vivo, the transplanted cells survive well, differentiate into tyrosine hydroxylase-positive neurons, and improve behavioral deficits to a significantly greater degree than non-programmed cells. The enriched generation of dopaminergic neuronal lineages from hESCs by forced expression of MEF2CA in the proper context may prove valuable in cell-based therapy for CNS disorders such as PD

Classification of current anticancer immunotherapies

© 2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.info:eu-repo/semantics/publishedVersio

Neurofibromin regulates somatic growth through the hypothalamic–pituitary axis

To study the role of the neurofibromatosis-1 (NF1) gene in mammalian brain development, we recently generated mice in which Nf1 gene inactivation occurs in neuroglial progenitor cells using the brain lipid binding protein (BLBP) promoter. We found that Nf1BLBPCKO mice exhibit significantly reduced body weights and anterior pituitary gland sizes. We further demonstrate that the small anterior pituitary size reflects loss of neurofibromin expression in the hypothalamus, leading to reduced growth hormone releasing hormone, pituitary growth hormone (GH) and liver insulin-like growth factor-1 (IGF1) production. Since neurofibromin both negatively regulates Ras activity and positively modulates cAMP levels, we examined the signaling pathway responsible for these abnormalities. While BLBP-mediated expression of an activated Ras molecule did not recapitulate the body weight and hypothalamic/pituitary defects, treatment of Nf1BLBPCKO mice with rolipram to increase cAMP levels resulted in a partial restoration of the body weight phenotype. Furthermore, conditional expression of the Ras regulatory GAP domain of neurofibromin also did not rescue the body weight or Igf1 mRNA defects in Nf1BLBPCKO mice. Collectively, these data demonstrate a critical role for neurofibromin in hypothalamic–pituitary axis function and provide further insights into the short stature and GH deficits seen in children with NF1