Religious destinations today are visited by a large number of tourists, whose travel motives may vary from purely religious to purely secular. Diverse motives and on-site experiences are, in turn, causing a shift in the identity perception of these destinations. However, research is still limited regarding the dynamic relationship between travelers’ motivation and the perceived identity of a religious space. Using a theoretical–thematic analysis, this study analyzes the online written accounts of visitors to Camino de Santiago (a route-based pilgrimage site) to understand (i) the motivational and experiential differences among religious versus non-religious travelers, and (ii) the perceived identity of Camino with respect to Smith’s “pilgrimage–tourism continuum”. Despite the increase in secular motives, the majority of travelers showed some form of spiritual connection with Camino. Concurrent with the contemporary shifts in the idea of “religion”, Camino continues to be a religious place driven by inner goals, albeit in a more personal, interpretive, and “spiritual” way.
The occurrence of harmful algal blooms in nutrient-rich freshwater bodies has increased world-wide, including in the Pacific Northwest. Some cyanobacterial genera have the potential to produce secondary metabolites that are highly toxic to humans, livestock and wildlife. Reliable methods for the detection of cyanobacterial toxins with high specificity and low limits of detection are in high demand. Here we test a relatively new hybrid high resolution accurate mass quadrupole time-of-flight mass spectrometry platform (TripleTOF) for the analysis of cyanobacterial toxins in freshwater samples. We developed a new method that allows the quantitative analysis of four commonly observed microcystin congeners (LR, LA, YR, and RR) and anatoxin-a in a 6-min LC run without solid-phase enrichment. Limits of detection for the microcystin congeners (LR, LA, YR, and RR) and anatoxin-a were <5 ng/L (200-fold lower than the guideline value of 1 μg/L as maximum allowable concentration of MC-LR in drinking water). The method was applied for screening freshwaters in the Pacific Northwest during the bloom and post-bloom periods. The use of high resolution mass spectrometry and concomitant high sensitivity detection of specific fragment ions with high mass accuracy provides an integrated approach for the simultaneous identification and quantification of cyanobacterial toxins. The method is sensitive enough for detecting the toxins in single Microcystis colonies.
Supplementary Materials from Induction of Retinoid X Receptor Activity and Consequent Upregulation of p21<sup>WAF1/CIP1</sup> by Indenoisoquinolines in MCF7 Cells
High level of plasma TGF-β is significantly correlated with poor outcomes with approved immune-oncology therapeutics. Poor clinical results for ALK5 inhibitors and bifunctional fusion protein targeting TGF-β and PD-L1 are also being reported in several clinical trials. Therefore, a novel therapeutic with superior efficacy differentiated from previous TGF-β modulators will demonstrate significant clinical outcomes in combination with immuno-oncology therapeutics. In TME, TGF-β and VEGF synergistically induce eradication of immunogenic tumors. Therefore, a dual-inhibitor targeting both ALK5 and VEGFR2 has high potential to demonstrate effective clinical efficacy against TGF-β- and VEGF-enriched tumors as a single or combination treatment. TU2218 is a highly potent, orally available inhibitor against ALK5 and VEGFR2 with an IC50 of 1.2 nM and 4.9 nM respectively. In a human PBMC assay, 0.5-1 μM TU2218 treatment significantly enhanced IFN-γ production or IFN-γ-producing T lymphocytes number by TGF-β-driven immunosuppression, but vactosertib, galunisertib and TGF-β neutralizing antibody did not have significant effects. In a human regulatory T cells assay, CD4+CD25+ Tregs suppressed the proliferation of naïve CD4+CD25- T cells after TCR triggering. In contrast, 0.5 μM TU2218 treated Tregs completely reversed the TCR-mediated proliferation of CD4+CD25- T cells. In addition, the immunomodulatory activity of TU2218 was analyzed on the co-culture system of cancer cells with human PBMC. In this assay, MCF-7 and HT-1080 displayed strong inhibitory effects on IFN-γ secretion of human PBMC, but TU2218 completely restored IFN-γ production compared with the poor effect of either vactosertib or TGF-β neutralizing antibody. In an NK assay, TGF-β reduced the level of surface proteins of NKG2D and NKp30 on CD56dim and CD56bright human primary NK cells and NK92 cell lines. TU2218 treatment completely reversed not only the inhibitory effect of TGF-β on the expression of NKG2D but also TGF-β-driven impairment of NK cytolytic activity for K562 cell lines on the co-culture system. Results show TU2218 possesses potent anti-cancer immune activities through boosting T and NK immunity as well as blocking Treg activity, implicating the mechanism of overcoming immune tolerance and reversing immunosuppression in TME. These effects of TU2218 in human immune cells would be a basis for novel combination options to develop promising therapeutics for patients with advanced cancer. Citation Format: Nam-Hoon Kim, Seong-Ho Kang, Jihyun Lee, Seung-Hyun Kim, Chan-Hee Yu, Jae Won Choi, Soyoun Ahn, Jeongmin Seo, Hun-Taek Kim. Functional characterization of TU2218, ALK5 and VEGFR2 dual inhibitor, on in vitro tumor immunity-mimetic systems [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5538.
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