ABSTRACT
Theories of emotion-cognition interactions suggest that emotional valence can both facilitate or limit cognitive performance. One cause for the mixed findings may be the order (random versus non-random presentation) in which emotional stimuli are presented. To investigate the impact of stimuli order on cognitive control processing, EEG data were recorded as 130 undergraduate students (M age = 22.2, SD = 5.4; 79 female) completed a modified version of the AX-Continuous Performance Task in which the cue was followed by an emotionally-valenced image (positive, negative, and neutral). Specifically, the task was designed so that valenced images were presented in either a block or random order, prior to probe presentation. We examined two event-related potentials (ERPs), the N2, which reflects aspects of cognitive control, and the late positive potential (LPP), which reflects attention allocation to emotional stimuli. We assessed the impact of emotionally oriented attention (LPP) on downstream cognitive control (N2) and how this relationship might differ for a block versus random (order of emotional image) task design. Consistent with the LPP literature, we found a main effect of image valence with the negative trials showing larger LPPs than the positive and neutral trials. For N2s, we found that the negative trials were associated with smaller N2s than both the positive and neutral trials. We observed that as LPP amplitude increased, subsequent N2 amplitude was reduced, specifically for negative trials in the random design. These results suggest an emotion-related depletion of neural cognitive resources. Lastly, we found larger N2s for the block design versus the random design. Together, these results indicate the importance of paying attention to both trial order (block versus random) and within trial stimulus sequence when designing emotion induction tasks.
Subject(s)
Electroencephalography , Evoked Potentials , Adult , Cognition , Emotions , Female , Humans , Neuropsychological Tests , Young AdultABSTRACT
Human colorectal cancers are known to possess multiple mutations, though how these mutations interact in tumor development and progression has not been fully investigated. We have previously described the FCPIK3ca* murine colon cancer model, which expresses a constitutively activated phosphoinositide-3 kinase (PI3K) in the intestinal epithelium. The expression of this dominantly active form of PI3K results in hyperplasia and invasive mucinous adenocarcinomas. These cancers form via a non-canonical mechanism of tumor initiation that is mediated through activation of PI3K and not through aberrations in WNT signaling. Since the Adenomatous Polyposis Coli (APC) gene is mutated in the majority of human colon cancers and often occurs simultaneously with PIK3CA mutations, we sought to better understand the interaction between APC and PIK3CA mutations in the mammalian intestine. In this study, we have generated mice in which the expression of a constitutively active PI3K and the loss of APC occur simultaneously in the distal small intestine and colon. Here, we demonstrate that expression of a dominant active PI3K synergizes with loss of APC activity resulting in a dramatic change in tumor multiplicity, size, morphology and invasiveness. Activation of the PI3K pathway is not able to directly activate WNT signaling through the nuclear localization of CTNNB1 (ß-catenin) in the absence of aberrant WNT signaling. Alterations at the transcriptional level, including increased CCND1, may be the etiology of synergy between these activated pathways.
Subject(s)
Adenocarcinoma/genetics , Adenomatous Polyposis Coli Protein/genetics , Colorectal Neoplasms/genetics , Phosphatidylinositol 3-Kinases/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adenomatous Polyposis Coli Protein/metabolism , Animals , Cell Nucleus/metabolism , Class I Phosphatidylinositol 3-Kinases , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Cyclin D1/metabolism , Disease Models, Animal , Epistasis, Genetic , Female , Gene Expression , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microsatellite Instability , Phosphatidylinositol 3-Kinases/metabolism , Tumor Burden , Wnt Signaling Pathway , beta Catenin/metabolismABSTRACT
Paclitaxel, a relatively new antineoplastic agent, is associated with numerous side effects, including two reported cases of pancreatitis. Our patient also developed paclitaxel-associated pancreatitis. Several companion drugs, including steroids, diphenhydramine, histamine2 blockers, serotonin type 3 antagonists, and other chemotherapeutic agents administered with paclitaxel, must be considered as possible causes of pancreatitis. In addition, paclitaxel is a hydrophobic agent that requires a vehicle, cremophor (CrEL), for solubility. Intravenous cyclosporine also requires CrEL and has been associated with pancreatitis. In the cerulein-induced pancreatitis rat model, paclitaxel with dimethyl sulfoxide as a vehicle prevents pancreatitis, suggesting that another causal agent is responsible. Animal studies of CrEL as a single agent may be required to settle this question, but for now, awareness that paclitaxel may be associated with pancreatitis may lead to earlier treatment of this potentially fatal complication.
