Self-reported vs. self-rated pronunciation in a non-native language

The study investigates how their own accent in English is self-perceived by Polish learners. More specifically, we compare how, and to what extent, self-reported pronunciation differs from self-rated pronunciation prior to and after the exposure to one’s recorded speech. Previous research on non-native accent rating has concentrated on scores obtained from native speakers or other proficient speakers of English. In the current study, we concentrate on how learners evaluate their own accent in English for parameters such as pronunciation, articulation, and fluency. We also introduce an independent variable of proficiency to see if it interacts with the perception of learners’ pronunciation. Both quantitative and qualitative analyses were conducted and the result showed that there are no major differences between how learners report their accent in English and how they rate it from the recording of their own speech. It indicates that the general self-image of one’s accent is fairly stable and exposure to the sample of one’s speech does not change the overall self-perceptio

Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain

OBJECTIVE: The brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression. METHODS: We assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction. RESULTS: Chronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum. CONCLUSIONS: This stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications

Covid-19, leukemia, and secondary malignancies of the skin – is there a connection: a case report and literature analysis

We report the case of a patient who was diagnosed with two melanomas and one skin cancer within two years. Of particular interest was the fact, that at the time these tumors were diagnosed, the patient was already suffering from chronic myeloid leukemia, which developed three months after recovering from Covid-19. From the time of leukemia occurrence, the patient has been taking the tyrosine kinase inhibitor (TKI) - Gleevec. Thus, we took into the account the possibile effect of Gleevec administration on the risk of skin tumor appearance. It was also important to analyze the impact of the SARS-CoV-2 virus and chronic myeloid leukemia on the risk of secondary malignancies. According to so far published data, the direct relationship between Gleevec treatment and the occurrence of skin cancers cannot be proved. However, literature data indicate a direct and indirect relationship between SARS-CoV-2 infection and an increased incidence of carcinogenesis

Extended neuroleptic administration modulates NMDA-R subunit immunoexpression in the rat neocortex and diencephalon

Background This study aimed to evaluate the effect of extended olanzapine, clozapine and haloperidol administration on NMDA-R subunit immunoexpression in the rat neocortex and diencephalon. Methods To explore NR1, NR2A and NR2B subunit protein expression, densytometric analysis of immunohistochemically stained brain slices was performed. Results Interestingly, all neuroleptics caused a downregulation of NMDA-R subunit expression in the thalamus but increased the level of NR1 in the hypothalamus. Olanzapine upregulated hypothalamic NR2A expression, while clozapine and haloperidol decreased hypothalamic levels. We observed no significant changes in NR2B immunoreactivity. None of the studied medications had significant influence on NMDA-R subunit expression in the neocortex. Conclusions Neuroleptic-induced reduction in the expression of thalamic NMDA-R subunits may play an important role in the regulation of glutamatergic transmission disorders in cortico–striato–thalamo–cortical loop in schizophrenia. A decrease in NMDA signaling in this region after long-term neuroleptic administration may also cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances

Escitalopram affects spexin expression in the rat hypothalamus, hippocampus and striatum

Background Spexin (SPX) is a recently discovered neuropeptide that exhibits a large spectrum of central and peripheral regulatory activity, especially when considered as a potent anorexigenic factor. It has already been proven that antidepressants, including selective serotonin reuptake inhibitors (SSRI), can modulate peptidergic signaling in various brain structures. Despite these findings, there is so far no information regarding the influence of treatment with the SSRI antidepressant escitalopram on brain SPX expression. Methods In this current study we measured SPX mRNA and protein expression in the selected brain structures (hypothalamus, hippocampus and striatum) of rats chronically treated with a 10 mg/kg dose of escitalopram using quantitative Real-Time PCR and immunohistochemistry. Results Strikingly, long-term (4 week) drug treatment led to the downregulation of SPX expression in the rat hypothalamus. This supports the hypothesis that SPX may be involved in the hypothalamic serotonin-dependent actions of SSRI antidepressants and possibly also in the central mechanism of body mass increase. Conversely, SPX expression increased in the hippocampus and striatum. Conclusions This is the first report of the effects of a neuropsychiatric medication on SPX expression in animal brain. Our findings shed a new light on the pharmacology of antidepressants and may contribute to a better understanding of the alternative mechanisms responsible for antidepressant action

Long-term treatment with olanzapine increases the number of Sox2 and doublecortin expressing cells in the adult subventricular zone

Continuously active neurogenic regions in the adult brain are located in the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of the hippocampal dentate gyrus. Neurogenesis is modulated by many factors such as growth factors, neurotransmitters and hormones. Neuropsychiatric drugs, especially antidepressants, mood stabilizers and antipsychotics may also affect the origin of neuronal cells. The purpose of this study was to determine the effects of chronic olanzapine treatment on adult rat neurogenesis at the level of the SVZ. The number of neuroblasts was evaluated using immunohistochemical and fluorescent detection of sex determining region Y-box 2 (Sox-2) and doublecortin (DCX) expressing cells. The results indicate that olanzapine has proneurogenic effects in the adult rat SVZ, as the mean number of sex determining region Y-box 2 (Sox-2) and doublecortin-positive cells increased significantly, while there was a similar tendency in the subgranular zone SGZ. Collectively, these results suggest that long-term treatment with olanzapine may stimulate neurogenic stem cell formation in the SVZ which supports adult neurogenesis

Oleanolic acid derivatives as modulators of Nrf2 and other transcription factors connected with oxidative stress –the influence on target gene expression

Ostatnie badania wykazały, że triterpenoidy (duża grupa naturalnych substancji syntezowanych w roślinach) mogą wykazywać funkcje cytoprotekcyjne. Kwas oleanowy (ang. oleanolic acid, OA), triterpenoid wytwarzany przez Phytolacca americana, Syzygium spp i Allium sativum, posiada słabe właściwości hepatoprotekcyjne i przeciwnowotworowe. Bazując na strukturze kwasu oleanowego otrzymano wiele pochodnych zwanych syntetycznymi triterpenoidami oleanowymi (ang. synthetic oleanane triterpenoids, SO) posiadających ulepszone właściwości przeciwzapalne i cytoprotekcyjne. Mechanizm ich działania jest oparty na modulacji czynników transkrypcyjnych, na przykład aktywacji Nrf2 (ang. nuclear factor erythroid 2-related factor 2) i hamowaniu NF-κB (ang. nuclear factor kappa-light-chain-enhancer of activated B cells).Głównym celem badań było określenie efektu 32 nowych pochodnych OA na aktywację Nrf2 w mysich fibroblastach (NIH3T3) i ludzkich keratynocytach (HaCaT). Badania z wykorzystaniem transfekcji przejściowej plazmidem reporterowym zawierającym gen reporterowy pod kontrolą sekwencji wiążącej Nrf2 (antioxidant response element, ARE) pozwoliły na wybranie czterech najlepiej działających związków. Ponadto, sprawdzono ich wpływ na aktywność czynników transkrypcyjnych NF-κB i AP-1 oraz na ekspresję genów docelowych za pomocą PCR w czasie rzeczywistym i testu ELISA. Na koniec użyto technik western blotting i barwienia immunocytochemicznego aby określić lokalizację jądrową Nrf2.Otrzymane wyniki wskazują, że niektóre pochodne kwasu oleanowego powodują aktywację Nrf2, co znalazło potwierdzenie w wykrytej jego translokacji z cytoplazmy do jądra komórkowego. Prowadzi to do zwiększenia ekspresji enzymów antyutleniających regulowanych przez Nrf2 np. oksygenaza hemowej -1 (HO-1) i oksydoreduktaza NADPH-chinonowa (NQO-1). Wybrane substancje mają również zdolność hamowania aktywności NF-κB i AP-1 oraz związanego z nim zmniejszenia produkcji cytokin prozapalnych, np. TNF-α, IL-1β i IL-12. Zaprezentowane wyniki pokazujące przeciwzapalne i cytoprotekcyjne działanie pochodnych kwasu oleanowego mają duże znaczenie kliniczne. Związki takie mogą znaleźć potencjalne zastosowanie w terapiach schorzeń związanych ze stresem oksydacyjnym.Recent studies indicate that triterpenoids (a large family of natural compounds synthesized in plants) may exert cytoprotective functions. Oleanolic acid (OA), triterpenoid produced by Phytolacca americana, Syzygium spp and Allium sativum has been shown to have weak hepatoprotective and antitumour activities. However, based on structure of OA, many derivatives called synthetic oleanane triterpenoids (SO), with improved anti-inflammatory and cytoprotective properties have been obtained. Their mechanism of action is based on modulation of activity of transcription factors, for example activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and suppression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The primary goal of the study was to determine the effect of 32 newly synthesized OA derivatives on Nrf2 activation in murine fibroblasts (NIH3T3) and human keratinocytes (HaCat). Reporter plasmid containing luciferase gene under the control of antioxidant responsive element (ARE) sequence to which Nrf2 binds was used. As a result of this screening, four most potent Nrf2 activators were chosen. Additionally it was found that the selected compounds caused translocation of Nrf2 from the cytoplasm to the nucleus as shown by western blotting and immunostaining. Moreover, the effect of these compounds on NF-κB and activator protein-1 (AP-1) transcription factors activities were tested followed by evaluation of target genes expression by real-time PCR, ELISA and western blotting. The obtained results indicate that some derivatives of OA cause Nrf2 activation, which has a reflection in induction of Nrf2 target genes expression, namely heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1). On the other hand, decrease of NF-κB and AP-1 activities as well as downregulation of pro-inflammatory cytokines production (for example TNFα, IL-1 and IL-12) after OA derivatives delivery have been noted. Interestingly, observed effects of OA derivatives were greater than effects caused by OA. Consequently, some of examined OA derivatives have anti-inflammatory and cytoprotective effects which could be potentially used in therapies of diseases connected with oxidative stress and inflammation

The novel neuropeptide phoenixin is highly co-expressed with nesfatin-1 in the rat hypothalamus, an immunohistochemical study

The hypothalamus regulates a number of autonomic functions essential for homeostasis; therefore, investigations concerning hypothalamic neuropeptides and their functions and distribution are of great importance in contemporary neuroscience. Recently, novel regulatory factors expressed in the hypothalamus have been discovered, of which nesfatin-1 and phoenixin (PNX), show intriguing similarities in their brain distributions. There are currently few studies characterizing PNX expression, so it is imperative to accurately trace its localization, with particular attention to the hypothalamic nuclei and nesfatin-1 co-expression. Using fluorescence and classical immunohistochemical stainings on adult rat brain, we visualized the potential co-expression of nesfatin-1 and PNX immunoreactive cells. We have demonstrated a distinct PNX-immunoreactivity in 21-32% of cells in the arcuate nucleus, paraventricular nucleus, ventromedial and lateral hypothalamus. Nesfatin-1 expression reached 45-68% of all neurons in the same sites, while co-expression was strikingly seen in the vast majority (70-86%) of PNX-immunoreactive neurons in the rat hypothalamic nuclei. Our results demonstrate for the first time, a wide distribution of PNX in the hypothalamus which could implicate a potential functional relationship with nesfatin-1, possibly in the regulation of the hypothalamic-pituitary-gonadal axis or other autonomic functions, which require further study

Neurolight -astonishing advances in brain imaging

In recent years, significant advances in basic neuroanatomical studies have taken place. Moreover, such classical, clinically-oriented human brain imaging methods such as MRI, PET and DTI have been applied to small laboratory animals allowing improvement in current experimental neuroscience. Contemporary structural neurobiology also uses various technologies based on fluorescent proteins. One of these is optogenetics, which integrates physics, genetics and bioengineering to enable temporal precise control of electrical activity of specific neurons. Another important challenge in the field is the accurate imaging of complicated neural networks. To address this problem, three-dimensional reconstruction techniques and retrograde labeling with modified viruses has been developed. However, a revolutionary step was the invention of the "Brainbow" system, utilizing gene constructs including the sequences of fluorescent proteins and the usage of Cre recombinase to create dozens of colour combinations, enabling visualization of neurons and their connections in extremely high resolution. Furthermore, the newly- introduced CLARITY method should make it possible to visualize three-dimensionally the structure of translucent brain tissue using the hydrogel polymeric network. This original technique is a big advance in neuroscience creating novel viewpoints completely different than standard glass slide immunostaining