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#29036701   2017/10/16 Save this To Up

Mismatch Negativity But Not P300 Is Associated With Functional Disability in Schizophrenia.

Mismatch negativity (MMN) and P300 event-related potential (ERP) reductions in schizophrenia (SZ) reflect preattentive and attention-mediated auditory processing deficits, respectively. Although both have been linked to cognitive deficits in SZ, their relative contributions to real-world functioning are unclear. We sought to determine the functional significance of disrupted auditory processing in SZ by examining MMN and P300 in typically disabled low-functioning patients and in patients with high levels of independent role functioning. MMN to auditory deviants and P300 to infrequent auditory target and nontarget novel stimuli were assessed in 20 high-functioning SZ patients (HF-SZ), 17 low-functioning patients (LF-SZ), and 35 healthy comparison (HC) subjects. There was a group effect on MMN and P300 amplitudes across stimulus types. MMN was significantly diminished in LF-SZ compared to HF-SZ and HC, and HF-SZ demonstrated comparable MMN to HC. In contrast, P300 was significantly reduced in both LF-SZ and HF-SZ compared to HC. Logistic regression suggested independent sensitivity of MMN to functioning in SZ over and above P300 measures. Neither MMN nor P300 were associated with positive or negative symptom severity. Results replicate MMN and P300 abnormalities in SZ, and also suggest that the neural mechanisms associated with the preattentive detection of auditory deviance are most compromised in patients with functional disability. MMN may index pathophysiological processes that are critical for optimal functioning in SZ.

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#29033323   2017/10/16 Save this To Up

mTORC1 Phosphorylates Acetyltransferase p300 to Regulate Autophagy and Lipogenesis.

Acetylation is increasingly recognized as one of the major post-translational mechanisms for the regulation of multiple cellular functions in mammalian cells. Acetyltransferase p300, which acetylates histone and non-histone proteins, has been intensively studied in its role in cell growth and metabolism. However, the mechanism underlying the activation of p300 in cells remains largely unknown. Here, we identify the homeostatic sensor mTORC1 as a direct activator of p300. Activated mTORC1 interacts with p300 and phosphorylates p300 at 4 serine residues in the C-terminal domain. Mechanistically, phosphorylation of p300 by mTORC1 prevents the catalytic HAT domain from binding to the RING domain, thereby eliminating intra-molecular inhibition. Functionally, mTORC1-dependent phosphorylation of p300 suppresses cell-starvation-induced autophagy and activates cell lipogenesis. These results uncover p300 as a direct target of mTORC1 and suggest that the mTORC1-p300 pathway plays a pivotal role in cell metabolism by coordinately controlling cell anabolism and catabolism.

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#29031761   2017/10/16 Save this To Up

Reduced P300 amplitude during a visuospatial attention task in idiopathic rapid eye movement sleep behavior disorder.

Idiopathic rapid eye movement sleep behavior disorder (IRBD) patients are prone to cognitive deficits, which include attention, executive, and visuospatial dysfunctions. Even patients with normal cognition may exhibit subclinical electrophysiological dysfunction. This study aimed to evaluate visuospatial attention processing in IRBD patients with normal cognition and to compare their findings with those of age- and sex-matched healthy controls.

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#29027071   2017/10/13 Save this To Up

The Brain's Reward Response Occurs Even Without Actual Reward!

What if the brain's response to reward occurs even when there is no reward? Wouldn't that be a further concern for people prone to problem gambling and other forms of addiction, like those related to eating? Electroencephalography was employed to investigate this possibility using probabilistic feedback manipulations and measures of known event-related potentials (ERPs) related to reward processing. We tested the hypothesis-that reward-based ERPs would occur even in the absence of a tangible reward and when manipulations on expectation are implicit. The well-known P300 response potential was a key focus, and was assessed in non-gambling volunteer undergraduates on a task involving experimentally-manipulated probabilities of positive or negative feedback comprising three trial types-80, 50, or 20% positive feedback. A feedback stimulus (F1) followed a guess response between two possible outcomes (implicit win/loss), and then a second feedback stimulus (F2) was presented to confirm an alleged 'win' or 'loss' (explicit win/loss). Results revealed that amplitude of the P300 in F1-locked data (implicit manipulation) was larger (more positive) on average for feedback outcomes that were manipulated to be less likely than expected. The effect is pronounced after increased time on task (later trials), even though the majority of participants were not explicitly aware of our probability manipulations. For the explicit effects in F2-locked data, no meaningful or significant effects were observed. These findings point to the existence of proposed success-response mechanisms that operate not only explicitly but also with implicit manipulations that do not involve any direct indication of a win or loss, and are not associated with tangible rewards. Thus, there seems to be a non-explicit form of perception (we call 'implicit') associated with an internal experience of wins/losses (in the absence of actual rewards or losses) that can be measured in associated brain processes. The potential significance of these findings is discussed in terms of implications for problem gambling.

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#29025858   2017/10/13 Save this To Up

Histone modifications regulate the developmental expression of human hepatic UGT1A1.

Human UDP-glucuronosyltransferase 1A1 (UGT1A1) is a unique enzyme involved in bilirubin conjugation. We previously characterized the hepatic expression of transcription factors affecting UGT1A1 expression during development. Accordingly, in this study, we characterized the ontogenetic expression of hepatic UGT1A1 from the perspective of epigenetic regulation. We observed significant histone-3-lysine-4 dimethylation (H3K4me2) enrichment in the adult liver and histone-3-lysine-27 trimethylation (H3K27me3) enrichment in the fetal liver, indicating that dynamic alterations of histone methylation were associated with ontogenetic UGT1A1 expression. We further showed that the transcription factor hepatocyte nuclear factor 1 alpha (HNF1A) affects histone modifications around the UGT1A1 locus. In particular, we demonstrated that by recruiting HNF1A, the cofactors mixed-lineage leukemia 1, the transcriptional co-activator p300, and nuclear receptor coactivator 6 aggregate at the UGT1A1 promoter, thereby regulating histone modifications and subsequent UGT1A1 expression. In this study, we proposed new ideas for the developmental regulation of metabolic enzymes via histone modifications, and our findings will potentially contribute to the development of age-specific therapies.

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#29025423   2017/10/13 Save this To Up

Downregulation of NMI promotes tumor growth and predicts poor prognosis in human lung adenocarcinomas.

N-myc (and STAT) interactor (NMI) plays vital roles in tumor growth, progression, and metastasis. In this study, we identified NMI as a potential tumor suppressor in lung cancer and explored its molecular mechanism involved in lung cancer progression.

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#29024794   2017/10/12 Save this To Up

Brain computer interface with the P300 speller: usability for disabled people with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, restricts patients' communication capacity a few years after onset. A proof-of-concept of brain-computer interface (BCI) has shown promise in ALS and "locked-in" patients, mostly in pre-clinical studies or with only a few patients, but performance was estimated not high enough to support adoption by people with physical limitation of speech. Here, we evaluated a visual BCI device in a clinical study to determine whether disabled people with multiple deficiencies related to ALS would be able to use BCI to communicate in a daily environment.

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#29024407   2017/10/12 Save this To Up

Ghrelin deletion protects against age-associated hepatic steatosis by downregulating the C/EBPα-p300/DGAT1 pathway.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. NAFLD usually begins as low-grade hepatic steatosis which further progresses in an age-dependent manner to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma in some patients. Ghrelin is a hormone known to promote adiposity in rodents and humans, but its potential role in hepatic steatosis is unknown. We hypothesized that genetic ghrelin deletion will protect against the development of age-related hepatic steatosis. To examine this hypothesis, we utilized ghrelin knockout (KO) mice. Although no different in young animals (3 months old), we found that at 20 months of age, ghrelin KO mice have significantly reduced hepatic steatosis compared to aged-matched wild-type (WT) mice. Examination of molecular pathways by which deletion of ghrelin reduces steatosis showed that the increase in expression of diacylglycerol O-acyltransferase-1 (DGAT1), one of the key enzymes of triglyceride (TG) synthesis, seen with age in WT mice, is not present in KO mice. This was due to the lack of activation of CCAAT/enhancer binding protein-alpha (C/EBPα) protein and subsequent reduction of C/EBPα-p300 complexes. These complexes were abundant in livers of old WT mice and were bound to and activated the DGAT1 promoter. However, the C/EBPα-p300 complexes were not detected on the DGAT1 promoter in livers of old KO mice resulting in lower levels of the enzyme. In conclusion, these studies demonstrate the mechanism by which ghrelin deletion prevents age-associated hepatic steatosis and suggest that targeting this pathway may offer therapeutic benefit for NAFLD.

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#29023501   2017/10/12 Save this To Up

Cognitive processing of orientation discrimination in anisometropic amblyopia.

Cognition is very important in our daily life. However, amblyopia has abnormal visual cognition. Physiological changes of the brain during processes of cognition could be reflected with ERPs. So the purpose of this study was to investigate the speed and the capacity of resource allocation in visual cognitive processing in orientation discrimination task during monocular and binocular viewing conditions of amblyopia and normal control as well as the corresponding eyes of the two groups with ERPs. We also sought to investigate whether the speed and the capacity of resource allocation in visual cognitive processing vary with target stimuli at different spatial frequencies (3, 6 and 9 cpd) in amblyopia and normal control as well as between the corresponding eyes of the two groups. Fifteen mild to moderate anisometropic amblyopes and ten normal controls were recruited. Three-stimulus oddball paradigms of three different spatial frequency orientation discrimination tasks were used in monocular and binocular conditions in amblyopes and normal controls to elicit event-related potentials (ERPs). Accuracy (ACC), reaction time (RT), the latency of novelty P300 and P3b, and the amplitude of novelty P300 and P3b were measured. Results showed that RT was longer in the amblyopic eye than in both eyes of amblyopia and non-dominant eye in control. Novelty P300 amplitude was largest in the amblyopic eye, followed by the fellow eye, and smallest in both eyes of amblyopia. Novelty P300 amplitude was larger in the amblyopic eye than non-dominant eye and was larger in fellow eye than dominant eye. P3b latency was longer in the amblyopic eye than in the fellow eye, both eyes of amblyopia and non-dominant eye of control. P3b latency was not associated with RT in amblyopia. Neural responses of the amblyopic eye are abnormal at the middle and late stages of cognitive processing, indicating that the amblyopic eye needs to spend more time or integrate more resources to process the same visual task. Fellow eye and both eyes in amblyopia are slightly different from the dominant eye and both eyes in normal control at the middle and late stages of cognitive processing. Meanwhile, abnormal extents of amblyopic eye do not vary with three different spatial frequencies used in our study.

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#29021763   2017/10/12 Save this To Up

The Functional Role of Individual-Alpha Based Frontal Asymmetry in the Evaluation of Emotional Pictures: Evidence from Event-Related Potentials.

The perceptual processing of emotional stimuli is subject to the regulation of brain function. This study investigated whether frontal electroencephalography (EEG) alpha asymmetry at resting conditions predicted the evaluation of emotional picture stimuli by event-related potentials (ERPs). In this study, participants first completed a 2-min resting task, and then passively viewed emotional pictures. The results showed that left active individuals had smaller frontal EEG alpha asymmetry scores to negative pictures than to positive and neutral pictures, whereas right active individuals had similar frontal EEG alpha asymmetry scores to negative, positive, and neutral pictures. Furthermore, the study showed a larger P300 to negative pictures than to positive and neutral pictures for left active individuals; however, there were no significant ERP differences to negative, positive, and neutral pictures for right active individuals. These findings suggest that frontal EEG alpha asymmetry at resting conditions can reflect interindividual differences in emotional perception tendencies to emotional picture stimuli.

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