Cancer cell reprogramming based on treatment with G-quadruplex, having antiproliferative power, along with small molecules able to develop iPSCs into neurons, could create a novel approach to diminish the chance of glioblastoma recurrence and circumvent tumor resistance to conventional therapy. In this research, we have tested several combinations of factors to affect both total cell cultures, derived from tumor tissue of patients after surgical resection and two subfractions of this cell culture after dividing them into CD133-enriched and CD133-depleted populations (assuming CD133 to be a marker of glioblastoma stem-like cells). CD133+ and CD133- cells exhibit different responses to the same combinations of factors; CD133+ cells have stem-like properties and are more resistant. Therefore, the ability to affect CD133+ cells provides a possibility to circumvent resistance to conventional therapy and to build a promising strategy for translation to improve the treatment of patients with glioblastoma.
Spelling errors are ubiquitous in all writing systems. Most studies exploring spelling errors focused on the phonological plausibility of errors. However, unlike typical pseudohomophones, spelling errors occur in naturally produced written language. We investigated the time course of recognition of the most frequent orthographic errors in Russian (error in an unstressed vowel in the root) and the effect of word frequency on this process. During event-related potentials (ERP) recording, 26 native Russian speakers silently read high-frequency correctly spelled words, low-frequency correctly spelled words, high-frequency words with errors, and low-frequency words with errors. The amplitude of P200 was more positive for correctly spelled words than for misspelled words and did not depend on the frequency of the words. In addition, in the 350–500-ms time window, we found a more negative response for misspelled words than for correctly spelled words in parietal–temporal-occipital regions regardless of word frequency. Considering our results in the context of a dual-route model, we concluded that recognizing misspelled high-frequency and low-frequency words involves common orthographic and phonological processes associated with P200 and N400 components such as whole word orthography processing and activation of phonological representations correspondingly. However, at the 500–700 ms stage (associated with lexical-semantic access in our study), error recognition depends on the word frequency. One possible explanation for these differences could be that at the 500–700 ms stage recognition of high-frequency misspelled and correctly spelled words shifts from phonological to orthographic processes, while low-frequency misspelled words are accompanied by more prolonged phonological activation. We believe these processes may be associated with different ERP components P300 and N400, reflecting a temporal overlap between categorization processes based on orthographic properties for high-frequency words and phonological processes for low-frequency words. Therefore, our results complement existing reading models and demonstrate that the neuronal underpinnings of spelling error recognition during reading may depend on word frequency.
Hippocampal damage after traumatic brain injury (TBI) is associated with late posttraumatic conditions, such as depression, cognitive decline and epilepsy. Mechanisms of selective hippocampal damage after TBI are not well understood. In this study, using rat TBI model (lateral fluid percussion cortical injury), we assessed potential association of immediate posttraumatic seizures and changes in corticosterone (CS) levels with neuroinflammation and neuronal cell loss in the hippocampus. Indices of distant hippocampal damage (neurodegeneration and neuroinflammation) were assessed using histological analysis (Nissl staining, Iba-1 immunohistochemical staining) and ELISA (IL-1β and CS) 1, 3, 7 and 14 days after TBI or sham operation in male Wistar rats (n = 146). IL-1β was elevated only in the ipsilateral hippocampus on day 1 after trauma. CS peak was detected on day 3 in blood, the ipsilateral and contralateral hippocampus. Neuronal cell loss in the hippocampus was demonstrated bilaterally; in the ipsilateral hippocampus it started earlier than in the contralateral. Microglial activation was evident in the hippocampus bilaterally on day 7 after TBI. The duration of immediate seizures correlated with CS elevation, levels of IL-1β and neuronal loss in the hippocampus. The data suggest potential association of immediate post-traumatic seizures with CS-dependent neuroinflammation-mediated distant hippocampal damage.
This study aimed to examine the behavioral and neural correlates of facial emotion recognition in young women with subsyndromal panic disorder (SPD). In the experiment 15 non-medicated women with SPD and 17 matched healthy controls were tasked with recognizing angry, fearful, happy, and neutral facial expressions, and accuracy, reaction time (RT), and event-related potentials (ERPs) were recorded. Significant between-group differences in behavioral characteristics (accuracy of emotion recognition and RT) were not found, however, the SPD subjects demonstrated a slower response to fearful expressions compared to neutral and happy expressions. More distinct between-group differences were observed for the EPRs. The SPD subjects demonstrated increased amplitudes of the P100 ERP component in the occipital area and the P200 component over the occipital and temporal regions. In the frontal regions the SPD group showed a greater amplitude of the N200 component and also an increased negativity 350−450 ms after stimulus presentation. According to the dipole source modeling data, the SPD subjects showed enhanced activation in the extra-striate cortex which increased in intensity when angry and fearful faces were presented. Thus, young women with SPD which manifested in infrequent panic attacks showed significant alterations in ERP characteristics of emotional processing, which may be considered as a more sensitive indicator of early-stage panic disorder than the observed behavioral measures.