The Relationship between Autistic Tendencies, Social Anxiety and Reinforcement Learning

This item is only available electronically.Humans learn the probabilities of socially rewarding and punishing stimuli (such as facial expressions of basic emotions) to coordinate appropriate responses to their environment, and subsequently navigate social interaction. Many cases of autistic tendencies, a neurodevelopmental condition hallmarked by deficits in social communication and reduced responsiveness to socially rewarding faces, are comorbid with social anxiety, characterised by severe distress and a tendency to avoid socially punishing faces. Both conditions affect the rate of social reinforcement learning patterns. Therefore, it is unclear how much autistic tendencies or co-occurring social anxiety symptoms predict aberrant learning patterns. Thus, we aimed to explore whether social anxiety mediates or moderates this relationship. Participants were recruited from the general population and completed a learning task that assessed their selection of which facial expressions (happy and angry) were followed by a positive or negative outcome. Additionally, questionnaires were administered to measure autistic tendencies and social anxiety symptoms. Regression analyses demonstrated no significant relationships between the predictors and social reward learning (approaching happy faces). However, consistent with the literature, an interaction between autistic tendencies and social anxiety predicted aberrant social punishment learning (avoiding angry faces). Therefore, the level of social anxiety is an important moderator in understanding the broad expression of social deficit symptoms in comorbid diagnoses. Although further research is needed for reward learning, our results implicate that certain individual differences are associated with increased social avoidance tendencies, therapists could tailor treating this bias based on the severity of autistic tendencies and social anxiety in an individual.Thesis (B.PsychSc(Hons)) -- University of Adelaide, School of Psychology, 202

Methanol Extract of Myelophycus caespitosus Inhibits the Inflammatory Response in Lipopolysaccharidestimulated BV2 Microglial Cells by Downregulating NF-kB via Inhibition of the Akt Signaling Pathway

Purpose: To determine whether the methanol extract of Myelophycus caespitosus (MEMC) downregulates the expression of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated BV2 microglial cells.Methods: Reverse transcription-polymerase chain reaction (RT-PCR) together with Western blot analysis was used to evaluate the expression of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin E2(PGE2) as well as their regulatory genes such as inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), in LPS-stimulated BV2 microglial cells. The level of NO production was analyzed using Griess reaction.The release of PGE2 was determined using sandwich enzyme-linked immunosorbent assay. The DNA-binding activity of nuclear factor-êB (NF-êB) was measured by electrophoretic mobility shift assay.Results: MEMC inhibited LPS-induced pro-inflammatory mediators, NO and PGE2, as well as their respective genes, iNOS and COX-2, at both protein and mRNA levels, without any significant cytotoxicity. Treatment withMEMC also substantially reduced the LPS-induced DNA-binding activity of NF-êB and nuclear translocation of NF-êB subunits p65 and p50 via the inhibition of IêBá phosphorylation and degradation. MEMC promoteddephosphorylation of Akt that subsequently suppressed the DNA-binding activity of NF-êB in LPS-stimulated BV2 microglial cells.Conclusion: Collectively, these data suggest that MEMC attenuates expression of pro-inflammatory mediators such as NO and PGE2 by suppression of their regulatory genes through the inhibition of Aktmediated NF-êB activity.Keywords: Myelophycus caespitosus, Nitric oxide, Prostaglandin E2, Nuclear factor-êB

Inhibition of Nitric Oxide and Prostaglandin E2 Expression by Methanol Extract of Polyopes affinis in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway

Purpose: To determine whether the methanol extract of Polyopes affinis (MEPA) down-regulates the expression of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated BV2 microglial cells.Methods: The production of nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Griess reagents and enzyme-linked immunosorbent assay (ELISA), respectively. Expression levels of mRNA and protein in LPS-stimulated BV2 microglial cells were assessed by reverse transcription-polymerase (RT-PCR) and Western blot analysis. Activation of nuclear factor-êB (NF-êB) was detected by electrophoretic mobility shift assay (EMSA).Results: MEPA inhibited the expression of LPS-induced pro-inflammatory mediators, NO and PGE2, as well as their respective genes, iNOS and COX-2, at both protein and mRNA levels, without any accompanying cytotoxicity. Moreover, treatment with MEPA significantly suppressed the LPS-induced DNA-binding activity of NF-êB, which is known as a main transcription factor for the regulation of proinflammatory genes, as well as the nuclear translocation of its subunit p65 and p50, by degrading IêBá.MEPA increased Akt dephosphorylation which leads to suppression of the DNA-binding activity of NF-kB in LPS-stimulated BV2 microglial cells and suppressed phosphorylation of ERK and JNK, which are involved in the mitogen-activated protein kinase (MAPK) signaling pathway for regulating proinflammatory genes.Conclusion: Our results indicate that MEPA down-regulates  pro-inflammatory mediators such as NO and PGE2 by suppressing Akt-dependent NF-êB activity as well as phosphorylation of ERK and JNK inLPS-stimulated BV2 microglial cells.Keywords: Polyopes affinis, Nitric oxide, Prostaglandin E2, Nuclear factor-k

p53-Mediated Oxidative Stress Enhances Indirubin-3′-Monoxime-Induced Apoptosis in HCT116 Colon Cancer Cells by Upregulating Death Receptor 5 and TNF-Related Apoptosis-Inducing Ligand Expression

Indirubin-3′-monoxime (I3M) exhibits anti-proliferative activity in various cancer cells; however, its anti-cancer mechanism remains incompletely elucidated. This study revealed that I3M promotes the expression of death receptor 5 (DR5) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in HCT116 p53+/+ cells, resulting in caspase-mediated apoptosis. However, this study demonstrated that HCT116 p53−/− cells were insensitive to I3M-mediated apoptosis, indicating that I3M-induced apoptosis depends on the p53 status of HCT116 cells. Additionally, in HCT116 p53-/- cells, I3M significantly increased Ras expression, while in HCT116 p53+/+ cells, it reduced Ras expression. Furthermore, I3M remarkably increased the production of reactive oxygen species (ROS), which were reduced in transient p53 knockdown, indicating that I3M-mediated apoptosis was promoted by p53-mediated ROS production. Our results also showed that I3M enhanced transcription factor C/EBP homologous protein (CHOP) expression, resulted in endoplasmic reticulum (ER) stress-mediated DR5 expression, which was upregulated by ROS production in HCT116 p53+/+ cells. Moreover, co-treatment with I3M and TRAIL enhanced DR5 expression, thereby triggering TRAIL-induced apoptosis of HCT116 p53+/+ cells, which was interfered by a DR5-specific blocking chimeric antibody. In summary, I3M potently enhances TRAIL-induced apoptosis by upregulating DR5 expression via p53-mediated ROS production in HCT116 p53+/+ cells. However, HCT116 p53−/− cells were less sensitive to I3M-mediated apoptosis, suggesting that I3M could be a promising anti-cancer candidate against TRAIL-resistant p53+/+ cancer cells. Additionally, this study also revealed that I3M sensitizes colorectal cancer cells such as HT29 and SW480 to TRAIL-mediated apoptosis

Passing the baton

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Glutamine Cooperatively Upregulates Lipopolysaccharide-Induced Nitric Oxide Production in BV2 Microglial Cells through the ERK and Nrf-2/HO-1 Signaling Pathway

Glutamine (Gln) is a nonessential α-amino acid for protein biosynthesis. However, the mechanism through which Gln regulates NO production in microglial cells is still unclear. In this study, we investigated whether the presence or absence of Gln affects NO production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Our data revealed that Gln depletion decreased cell viability accompanied by mild cytotoxicity, and blocked LPS-induced NO production concomitant with a significant decrease in inducible NO synthase (iNOS) expression. Additionally, Gln depletion for 24 h blocked the restoration of LPS-mediated NO production in the presence of Gln, suggesting that Gln depletion caused long-term immune deprivation. In particular, sodium-coupled amino acid transporter 1 and 2 (SNAT1 and SNAT2), which are the main Gln transporters, were highly upregulated in LPS-stimulated BV2 microglial cells, in the presence of Gln accompanied by NO production. Regardless of the presence of Gln, LPS positively stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, and transient Nrf2 knockdown and HO-1 inhibition stimulated LPS-induced NO production and iNOS expression; however, transient Nrf2 knockdown did not affect SNAT1 and SNAT2 expression, indicating that Gln transporters, SNAT1 and SNAT2, were not regulated by Nrf2, which downregulated the HO-1-mediated NO production. Moreover, Gln depletion significantly reduced LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation; furthermore, a specific ERK inhibitor, PD98059, and transient ERK knockdown attenuated LPS-stimulated NO production and iNOS expression, in the presence of Gln, accompanied by downregulation of SNAT1 and SNAT2, suggesting that the ERK signaling pathway was related to LPS-mediated NO production via SNAT1 and SNAT2. Altogether, our data indicated that extracellular Gln is vital for NO production from microglia in inflammatory conditions

Personality traits empower entrepreneurial intention of generation Z in Sri Lanka

Abstract Entrepreneurship has a critical role in making society more creative and conscience. Entrepreneurial Intention (EI) guided and supported to build job creators, innovations, and entrepreneurial mindset to foster both men and women entrepreneurial spirit. Youth generation also plays a significant role in  economic growth of country. The research predominantly aimed to identify and measure the influence of personality traits on the EI of generation Z in Sri Lanka. The primary cause for concern is the rising demand for entrepreneurs who can spur economic growth by developing fresh concepts and turning them into successful ventures. The present study investigates the impact of the big five personality traits on EI. The study used both quantitative and qualitative approaches. In the qualitative survey, the data collected from eight semi-structured interviews were analyzed using the thematic analysis and NVivo tool. The quantitative survey used a cluster sample of generation Z in the Colombo district, Sri Lanka. A total of 384 valid questionnaires were received and examined. To test the hypotheses, the researchers used Smart PLS software (version 4.0) and the Structure Equation Model technique. The result showed that Conscientiousness, and Neuroticism significantly impact on the EI of generation Z. Further, Extraversion, Agreeableness and Openness to Experience have an insignificant impact on EI. The study gives policymakers and the government advice on how to understand the characteristics of generation Z, which are likely to become future entrepreneurs, and how to support new businesses by providing various incentives