Separation of item and context in item-method directed forgetting.

Contextual information plays a critical role in directed forgetting (DF) of lists of items, whereas DF of individual items has been primarily associated with item-level processing. This study was designed to investigate whether context processing also contributes to the forgetting of individual items. Participants first viewed a series of words, with task-irrelevant scene images (used as "context tags") interspersed between them. Later, these words reappeared without the scenes and were followed by an instruction to remember or forget that word. Multivariate pattern analyses of fMRI data revealed that the reactivation of context information associated with the studied words (i.e., scene-related activity) was greater whereas the item-related information diminished after a forget instruction compared to a remember instruction. Critically, we found the magnitude of the separation between item information and context information predicted successful forgetting. These results suggest that the unbinding of an item from its context may support the intention to forget, and more generally they establish that contextual processing indeed contributes to item-method DF.

Eye movement analyses of strong and weak memories and goal-driven forgetting.

Research indicates that eye movements can reveal expressions of memory for previously studied relationships. Specifically, eye movements are disproportionately drawn to test items that were originally studied with the test scene, compared to other equally familiar items in the test display - an effect known as preferential viewing (e.g., Hannula, Ryan, Tranel, & Cohen, 2007). Across four studies we assessed how strength-based differences in memory are reflected in preferential viewing. Participants studied objects superimposed on background scenes and were tested with three-object displays superimposed on the scenes viewed previously. Eye movements were monitored at test. In Experiment 1 we employed an item-method directed forgetting (DF) procedure to manipulate memory strength. In Experiment 2, viewing patterns were examined across differences in memory strength assessed through subjective confidence ratings. In Experiment 3, we used spaced repetitions to objectively strengthen items, and Experiment 4 involved a list-method DF manipulation. Across all experiments, eye movements consistently differentiated the effect of DF from other strength-based differences in memory, producing different viewing patterns. They also differentiated between incidental and successful intentional forgetting. Finally, despite a null effect in recognition accuracy in list-method DF, viewing patterns revealed both common as well as critical differences between list-method DF and item-method DF. We discuss the eye movement findings from the perspective of theoretical accounts of DF and other strength-based differences in memory.

Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis.

Mitochondrial Lon is a chaperone protein whose upregulation increases the production of mitochondrial reactive oxygen species (ROS). However, there is a lack of information in detail on how mitochondrial Lon regulates cancer metastasis through ROS production in the tumor microenvironment (TME). Our results show that elevated Lon promotes epithelial-mesenchymal transition (EMT) via ROS-dependent p38 and NF-κB-signaling. We further identified pyrroline-5-carboxylate reductase 1 (PYCR1) as a client of chaperone Lon, which induces mitochondrial ROS and EMT by Lon. Mitochondrial Lon induces ROS-dependent production of inflammatory cytokines, such as TGF-ß, IL-6, IL-13, and VEGF-A, which consequently activates EMT, angiogenesis, and M2 macrophage polarization. In addition, Lon expression is induced upon the activation and M2 polarization of macrophages, which further promotes M2 macrophages to enhance the immunosuppressive microenvironment and metastatic behaviors in the TME. This raises the possibility that manipulation of the mitochondrial redox balance in the TME may serve as a therapeutic strategy to improve T cell function in cancer immunotherapy.

Design of New n-Type Porphyrin Acceptors with Subtle Side-Chain Engineering for Efficient Nonfullerene Solar Cells with Low Energy Loss and Optoelectronic Response Covering the Near-Infrared Region.

A series of tailor-made highly efficient and near-infrared (NIR) porphyrin-based acceptors is designed and synthesized for fullerene-free bulk-heterojunction (BHJ) organic solar cells. Constructing BHJ active layers using a PTB7-Th donor and porphyrin acceptors (P-x), which have complementary absorption, accomplishes panchromatic photon-to-current conversion from 300 to 950 nm. Our study shows that side chains of the porphyrin acceptors fairly influence the molecular ordering and nanomorphology of the BHJ active layers. Significantly, the porphyrin acceptor with four dodecoxyl side chains (P-2) achieves an open-circuit voltage (VOC) of 0.80 V, short-circuit current density (JSC) of 13.94 mA cm-2, fill factor of 64.8%, and overall power conversion efficiency of 7.23%. This great performance is attributable to the ascendant light-harvesting capability in the visible and near-infrared region, a high-lying LUMO energy level, a relatively high and more balanced carrier mobilities, and more ordered face-on molecular packing, which is beneficial for obtaining high VOC and JSC.

Mitochondrial Lon protease controls ROS-dependent apoptosis in cardiomyocyte under hypoxia.

Apoptosis of cardiomyocytes, under ischemic conditions, has been identified as an essential process in the progression of heart failure. Under hypoxic conditions, mitochondria can become a threat to the cell because of their capacity to generate reactive oxygen species (ROS). As ROS appear to have a critical role in heart failure, there has been considerable interest in identifying the candidate proteins involved and in developing strategies to reduce oxidative stress. Lon protease (Lon) is a multifunctional protein that mediates protein quality control and stress response in mitochondria. However, comprehensive and detailed studies, on the role of Lon in hypoxia-induced cardiomyocyte apoptosis, have yet to be carried out. In the present study, we demonstrated that hypoxia induced ROS-dependent cardiomyocyte apoptosis. Lon was upregulated in hypoxia-induced cardiomyocytes. Lon downregulation attenuated hypoxia-induced cardiomyocyte apoptosis through a reduction of ROS level. Moreover, overexpression of Lon stimulated ROS production and induced apoptosis under normoxic conditions in cardiomyocytes. Our results identify Lon as a novel regulator of cardiomyocyte fate and offers exciting new insights into the therapeutic potential of hypoxia-induced cardiomyocyte apoptosis.

Unintentional memory inhibition is weakened in non-clinical dissociators.

Although participants with dissociation proneness showed inefficient cognitive inhibition, whether and under what stimulus-task contexts dissociators show inefficient memory inhibition remains inconclusive. This study investigated the relationship between trait dissociation and basic operation of memory control using a non-clinical sample. To reduce the involvement of strategic control and the influence of emotionality, the retrieval-practice paradigm was adopted to examine unintentional memory inhibition of neutral materials. Both the low- and middle-dissociation groups showed the forgetting effect, resulting from suppressing competing memories while retrieving a target. In contrast, the high-dissociation group did not show the forgetting effect although their performance in the baseline condition and in recalling practiced items was comparable to the other two groups. High dissociation proneness is linked with weakened memory inhibition that may cause diverse memory problems in clinical patients.

The set switching function of nonclinical dissociators under negative emotion.

Rapid switching may underlie the disruption of some integrated thought processes that characterize dissociation in both nonclinical and clinical populations. We investigated the set switching function under negative emotion with three groups of nonclinical participants that had different degrees of dissociation proneness. In the experiment, participants judged whether the digit in a predefined target color was odd or even on the preswitch trials. In a perseverance condition, participants were required to switch to a new target color while the previous target color became the distractor color. In a learned irrelevance condition, the previously ignored color became the new target color. The results showed that the three groups did not differ in focusing attention in the preswitch trials, for set switching in the baseline condition (in which emotion was not engaged), or for switching in the learned irrelevance condition under negative emotion. However, high dissociators under negative emotion showed faster switching in the perseverance condition. This enhanced ability to divert attention to a new mental set under negative emotion may be a coping strategy related to cognitive symptoms in dissociative disorders.

An amygdala response to fearful faces with covered eyes.

Findings of amygdala responsiveness to the eye region of fearful faces raise the question of whether eye widening is the only facial cue involved. We used fMRI to investigate the differential amygdala response to fearful versus neutral stimuli for faces, eyes, and for faces in which the eye region was masked. For maximum sensitivity, a block design was used, with a region of interest (ROI) centred on the amygdala which included peri-amygdalar areas. Evidence of amygdala responsiveness to fear compared to neutral stimuli was found for whole faces, eye region only, and for faces with masked eyes. The amygdala can therefore use information from facial regions other than the eyes, allowing it to respond differentially to fearful compared to neutral faces even when the eye region is hidden.