No abstract

Hypoxic‐ischaemic encephalopathy is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy and cognitive disabilities. Hypoxia‐ischaemia (HI) strongly up‐regulates Signal Transducer and Activator of Transcription 3 (STAT3) in the immature brain. Our aim was to establish whether STAT3 up‐regulation is associated with neonatal HI‐brain damage and evaluate the phosphorylated STAT3‐contribution from different cell types in eliciting damage. We subjected postnatal day seven mice to unilateral carotid artery ligation followed by 60 min hypoxia. Neuronal STAT3‐deletion reduced cell death, tissue loss, microglial and astroglial activation in all brain regions. Astroglia‐specific STAT3‐deletion also reduced cell death, tissue loss and microglial activation, although not as strongly as the deletion in neurons. Systemic pre‐insult STAT3‐blockade at tyrosine 705 (Y705) with JAK2‐inhibitor WP1066 reduced microglial and astroglial activation to a more moderate degree, but in a pattern similar to the one produced by the cell‐specific deletions. Our results suggest that STAT3 is a crucial factor in neonatal HI‐brain damage and its removal in neurons or astrocytes, and, to some extent, inhibition of its phosphorylation via JAK2‐blockade reduces inflammation and tissue loss. Overall, the protective effects of STAT3 inactivation make it a possible target for a therapeutic strategy in neonatal HI. Current data show that neuronal and astroglial STAT3 molecules are involved in the pathways underlying cell death, tissue loss and gliosis following neonatal hypoxia‐ischaemia, but differ with respect to the target of their effect. Y705‐phosphorylation contributes to hypoxic‐ischaemic histopathology. Protective effects of STAT3 inactivation make it a possible target for a therapeutic strategy in neonatal hypoxia‐ischaemia.

For several decades, electroencephalography (EEG) has featured as one of the most commonly used tools in emotional state recognition via monitoring of distinctive brain activities. An array of datasets have been generated with the use of diverse emotion-eliciting stimuli and the resulting brainwave responses conventionally captured with high-end EEG devices. However, the applicability of these devices is to some extent limited by practical constraints and may prove difficult to be deployed in highly mobile context omnipresent in everyday happenings. In this study, we evaluate the potential of OpenBCI to bridge this gap by first comparing its performance to research grade EEG system, employing the same algorithms that were applied on benchmark datasets. Moreover, for the purpose of emotion classification, we propose a novel method to facilitate the selection of audio-visual stimuli of high/low valence and arousal. Our setup entailed recruiting 200 healthy volunteers of varying years of age to identify the top 60 affective video clips from a total of 120 candidates through standardized self assessment, genre tags, and unsupervised machine learning. Additional 43 participants were enrolled to watch the pre-selected clips during which emotional EEG brainwaves and peripheral physiological signals were collected. These recordings were analyzed and extracted features fed into a classification model to predict whether the elicited signals were associated with a high or low level of valence and arousal. As it turned out, our prediction accuracies were decidedly comparable to those of previous studies that utilized more costly EEG amplifiers for data acquisition.

Voltage-gated sodium channel (Na v ) expression in non-excitable cells has raised questions regarding their non-canonical roles. Interestingly, a growing body of evidence also points towards the prevalence of aberrant Na v expression in malignant tumors, potentially opening a new therapeutic window. In this study, the transcriptional consequences of channel inhibition were investigated in non-small cell lung carcinoma H460 and neuroblastoma SH-SYSY cell lines, that both express Na v 1.7. Channel activity was blocked by the application of both selective, ProTx-II, and non-selective, tetrodotoxin, inhibitors. Global gene expression profiling did not point to any statistically significant inhibition-associated perturbation of the transcriptome. A small subset of genes that showed relatively consistent changes across multiple treatments were further assayed in the context of a multiplex bead expression array which failed to recapitulate the changes seen in the global array. We conclude that there is no robust transcriptional signature associated with the inhibition of two sodium channel expressing cancer cell lines and consequently sodium channel inhibition will not lend itself to therapeutic approaches such as transcription-based drug repurposing.