Humor development in children

Studying children's humor development can be a window into children's social and cognitive development. According to McGhee (1974, 1976), both children and adults find jokes maximally funny when they are cognitively demanding and present an "incongruency" - that is, a violation of your expectations about how the world works. In order for an incongruency to be perceived as funny, you must have a sophisticated enough grasp of the concepts that the joke is about so that you perceive the incongruency, but at the same time, the joke must be "cognitively demanding" - that is, it can't be too obvious. This "Cognitive Congruency Principle" (McGhee, 1974, 1976; Zigler et al., 1966) has been demonstrated by showing that children in elementary school find jokes most funny when they are about concepts that children have recently mastered. Humor also contains a social component, requiring the ability to read and produce social cues to indicate that you are joking (McGhee, 1974, Hoicka & Akhtar, 2012). Hoicka and Akhtar (2012) suggested that humor was a socio-cognitive phenomenon and were curious to know if toddlers could produce novel humor, or if it all consists of copied humor patterns from their parents. They found that even children under 12 months of age "produce" humor through hide-and-seek and peekaboo games, and that many children begin to produce novel verbal and conceptual jokes around 2 years of age. Questions remain regarding the development of humor, more specifically the types of jokes/humor young children/babies use and how they differ across developmental stages. By evaluating children’s use of humor in the context of the "jokes" they engage in, we can more deeply understand why and how they use humor to communicate at their given age. (Author abstract)Hardiman, N., O'Connor, M., Carlson, J., & Magee, N. (2021). Humor development in children. Retrieved from http://academicarchive.snhu.ed

Pten cell autonomously modulates the hematopoietic stem cell response to inflammatory cytokines

Summary: Pten negatively regulates the phosphatidylinositol 3-kinase (PI3K) pathway and is required to maintain quiescent adult hematopoietic stem cells (HSCs). Pten has been proposed to regulate HSCs cell autonomously and non-cell autonomously, but the relative importance of each mechanism has not been directly tested. Furthermore, the cytokines that activate the PI3K pathway upstream of Pten are not well defined. We sought to clarify whether Pten cell autonomously or non-cell autonomously regulates HSC mobilization. We also tested whether Pten deficiency affects the HSC response to granulocyte colony-stimulating factor (G-CSF) and interferon-α (IFNα) since these cytokines induce HSC mobilization or proliferation, respectively. We show that Pten regulates HSC mobilization and expansion in the spleen primarily via cell-autonomous mechanisms. Pten-deficient HSCs do not require G-CSF to mobilize, although they are hyper-sensitized to even low doses of exogenous G-CSF. Pten-deficient HSCs are similarly sensitized to IFNα. Pten therefore modulates the HSC response to inflammatory cytokines. : Magee and colleagues show that Pten suppresses HSC mobilization and extramedullary expansion primarily through cell-autonomous mechanisms. The authors also show that Pten-deficient HSCs are hyper-sensitive to mobilizing effects of G-CSF and interferon-α, even at low-cytokine concentrations. These findings suggest that a key function of Pten in HSCs is to blunt signal transduction downstream of inflammatory cytokines

A frontal attention mechanism in the visual mismatch negativity

Automatic detection of environmental change is a core component of attention. The mismatch negativity (MMN), an electrophysiological marker of this mechanism, has been studied prominently in the auditory domain, with cortical generators identified in temporal and frontal regions. Here, we combined electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to assess whether the underlying frontal regions associated with auditory change detection also play a role in visual change detection. Twenty healthy young adults completed a visual MMN task in separate EEG and fMRI sessions. Region of interest analyses were conducted on left and right middle frontal (MFG) and inferior frontal (IFG) gyri, i.e., the frontal areas identified as potential auditory MMN generators. A significant increase in activation was observed in the left IFG and MFG in response to blocks containing deviant stimuli. These findings suggest that a frontal mechanism is involved in the detection of change in the visual MMN. Our results support the notion that frontal mechanisms underlie attention switching, as measured via MMN, across multiple modalities

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Pten Cell Autonomously Modulates the Hematopoietic Stem Cell Response to Inflammatory Cytokines.

Pten negatively regulates the phosphatidylinositol 3-kinase (PI3K) pathway and is required to maintain quiescent adult hematopoietic stem cells (HSCs). Pten has been proposed to regulate HSCs cell autonomously and non-cell autonomously, but the relative importance of each mechanism has not been directly tested. Furthermore, the cytokines that activate the PI3K pathway upstream of Pten are not well defined. We sought to clarify whether Pten cell autonomously or non-cell autonomously regulates HSC mobilization. We also tested whether Pten deficiency affects the HSC response to granulocyte colony-stimulating factor (G-CSF) and interferon-α (IFNα) since these cytokines induce HSC mobilization or proliferation, respectively. We show that Pten regulates HSC mobilization and expansion in the spleen primarily via cell-autonomous mechanisms. Pten-deficient HSCs do not require G-CSF to mobilize, although they are hyper-sensitized to even low doses of exogenous G-CSF. Pten-deficient HSCs are similarly sensitized to IFNα. Pten therefore modulates the HSC response to inflammatory cytokines

Oocyte cryopreservation in a transgender man on long-term testosterone therapy: a case report

Objective: To report a case of ovarian stimulation for the purposes of oocyte cryopreservation in a transgender man without cessation of long-term testosterone therapy. Design: Report of a unique case of fertility preservation through ovarian stimulation and oocyte cryopreservation in a transgender man who had been on testosterone therapy for 18 months before treatment. The patient elected to continue testosterone therapy throughout ovarian stimulation and oocyte retrieval. To our knowledge, there have not been any published reports of patients undergoing oocyte cryopreservation while continuing long-term testosterone therapy. Setting: Private fertility clinic with university affiliation. Patient(s): A 20-year-old transgender man undergoing oocyte cryopreservation before gonadectomy. Intervention(s): Fertility preservation through oocyte cryopreservation. Main Outcome Measure(s): This patient had a robust response to ovarian gonadotropin stimulation. Leuprolide acetate was used for final oocyte maturation to minimize ovarian hyperstimulation syndrome risk. Result(s): Cryopreservation of 22 mature oocytes. Conclusion(s): Cryopreservation of mature oocytes is possible for patients on continued long-term testosterone therapy. The impact of long-term testosterone therapy on markers of ovarian reserve, reproductive potential, and long-term reproductive outcomes have yet to be elucidated and further studies are needed in this area