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However, the variance learned was much broader than the one presented, consistent with less informative priors in children irrespective of autism diagnosis. These findings have important implications for Bayesian accounts of perception throughout development, and Bayesian accounts of autism specifically. LAY SUMMARY Recent theories about the underlying cognitive mechanisms of autism propose that the way autistic individuals estimate variability or uncertainty in their perceptual environment may differ from how typical individuals do so. Children had to search an oddly tilted line in a set of lines pointing in different directions, and based on their response times we examined how they learned about the variability in a set of objects. We found that autistic children learn variability as well as typical children, but both groups learn with less precision than typical adults do on the same task.
Tumor hypoxia is a characteristic of paramount importance due to low oxygenation levels in tissue negatively correlating with resistance to traditional therapies. The ability to noninvasively identify such could provide for personalized treatment(s) and enhance survival rates. Accordingly, we recently developed an NIR fluorescent hypoxia-sensitive smart probe (NO
-Rosol) for identifying hypoxia via selectively imaging nitroreductase (NTR) activity, which could correlate to oxygen deprivation levels in cells, thereby serving as a proxy. We demonstrated proof of concept by subjecting a glioblastoma (GBM) cell line to extreme stress by evaluating such under radiobiological hypoxic (pO
≤ ~0.5%) conditions, which is a far cry from representative levels for hypoxia for brain glioma (pO
= ~1.7%) which fluctuate little from physiological hypoxic (pO
= 1.0-3.0%) conditions.
We aimed to evaluate the robustness, suitability, and feasibility of NO
-Rosol for imaging hypoxia in vitro and in vivo via assessiimaging in vivo via it demonstrating a tumor-to-background of 5 upon (i) diffusion throughout, (ii) bioreductive activation by NTR activity in, and (iii) retention within, GBM39 tumor tissue.
We established the robustness, suitability, and feasibility of NO
-Rosol for imaging hypoxia under relevant oxygenation levels in vitro and in vivo via assessing NTR activity in GBM39 models.
We established the robustness, suitability, and feasibility of NO2 -Rosol for imaging hypoxia under relevant oxygenation levels in vitro and in vivo via assessing NTR activity in GBM39 models.
Women are more vulnerable to stress-related disorders than men, which is counterintuitive as female sex hormones, especially estrogen, have been shown to be protective against stress disorders.
In this study, we investigated whether two different models of stress act differently on ovariectomized (OVX) rats and the impact of estrogen on physical or psychological stress-induced impairments in cognitive-behaviors. PI3K inhibitor Adult female Wistar rats at 21-22weeks of age were utilized for this investigation. Sham and OVX rats were subjected to physical and psychological stress for 1hr/day for 7days, and cognitive performance was assessed using morris water maze (MWM) and passive avoidance (PA) tests. The open field and elevated plus maze tests (EPM) evaluated exploratory and anxiety-like behaviors.
In sham and OVX rats, both physical and psychological stressors were associated with an increase in EPM-determined anxiety-like behavior. OVX rats exhibited decreased explorative behavior in comparison with nonstressed sham rats (p<.05). Both physical stress and psychological stress resulted in disrupted spatial cognition as assayed in the MWM (p<.05) and impaired learning and memory as determined by the PA test when the OVX and sham groups were compared with the nonstressed sham group. Estrogen increased explorative behavior, learning and memory (p<.05), and decreased anxiety-like behavior compared with vehicle in OVX rats exposed to either type of stressor.
When taken together, estrogen and both stressors had opposite effects on memory, anxiety, and PA performance in a rat model of menopause, which has important implications for potential protective effects of estrogen in postmenopausal women exposed to chronic stress.
When taken together, estrogen and both stressors had opposite effects on memory, anxiety, and PA performance in a rat model of menopause, which has important implications for potential protective effects of estrogen in postmenopausal women exposed to chronic stress.
Chimeric antigen receptor (CAR) T-cell therapy of pediatric sarcomas is challenged by the paucity of targetable cell surface antigens. A candidate target in osteosarcoma (OS) is the ganglioside G
, but heterogeneous expression of G
limits its value.
We aimed to identify mechanisms that upregulate G
target expression in OS.
G
surface expression in OS cells, studied by flow cytometry, was found to vary both among and within individual OS cell lines. Pharmacological approaches, including inhibition of the histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2) and modulation of the protein kinase C, failed to increase G
expression. Instead, cell confluency was found to be associated with higher G
expression levels both in monolayer cultures and in tumor spheroids. The sensitivity of OS cells to targeting by G
-specific CAR T cells was compared in an in vitro cytotoxicity assay. Higher cell confluencies enhanced the sensitivity of OS cells to G
-antigen specific, CAR T-cell-mediated in vitro cytolysis. Mechanistic studies revealed that confluency-dependent upregulation of G
expression in OS cells is mediated by increased de novo biosynthesis, through a yet unknown mechanism.
Expression of G
in OS cell lines is highly variable and associated with increasing cell confluency in vitro. Strategies for selective upregulation of GD2 are needed to enable effective therapeutic targeting of this antigen in OS.
Expression of GD2 in OS cell lines is highly variable and associated with increasing cell confluency in vitro. Strategies for selective upregulation of GD2 are needed to enable effective therapeutic targeting of this antigen in OS.
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