In normal colon, claudin-7 is one of the highly expressed claudin proteins and its knockdown in mice results in altered epithelial cell homeostasis and neonatal death. Notably, dysregulation of the ...epithelial homeostasis potentiates oncogenic transformation and growth. However, the role of claudin-7 in the regulation of colon tumorigenesis remains poorly understood. Using a large colorectal cancer (CRC) patient database and mouse models of colon cancer, we found claudin-7 expression to be significantly downregulated in cancer samples. Most notably, forced claudin-7 expression in poorly differentiated and highly metastatic SW620 colon cancer cells induced epithelial characteristics and inhibited their growth in soft agar and tumor growth in vivo. By contrast, knockdown of claudin-7 in HT-29 or DLD-1 cells induced epithelial-to-mesenchymal transition (EMT), colony formation, xenograft-tumor growth in athymic mice and invasion. Importantly, a claudin-7 signature gene profile generated by overlapping the DEGs (differentially expressed genes in a high-throughput transcriptome analysis using claudin-7-manipulated cells) with human claudin-7 signature genes identified high-risk CRC patients. Furthermore, Rab25, a colon cancer suppressor and regulator of the polarized cell trafficking constituted one of the highly upregulated DEGs in claudin-7 overexpressing cells. Notably, silencing of Rab25 expression counteracted the effects of claudin-7 expression and not only increased proliferation and cell invasion but also increased the expression of p-Src and mitogen-activated protein kinase-extracellular signal-regulated kinase 1/2 that were suppressed upon claudin-7 overexpression. Of interest, CRC cell lines, which exhibited decreased claudin-7 expression, also exhibited promoter DNA hypermethylation, a modification associated with transcriptional silencing. Taken together, our data demonstrate a previously undescribed role of claudin-7 as a colon cancer suppressor and suggest that loss of claudin-7 potentiates EMT to promote colon cancer, in a manner dependent on Rab25.
Six novel uranyl terpyridine aromatic carboxylate coordination polymers, UO(2)(C(6)H(2)O(4)S)(C(15)H(11)N(3)) (1), UO(2)(C(6)H(2)O(4)S)(C(15)H(10)N(3)Cl)·H(2)O (2), ...UO(2)(C(8)H(4)O(4))(C(15)H(11)N(3)) (3), UO(2)(C(8)H(4)O(4))(C(15)H(10)N(3)Cl) (4), UO(2)(C(12)H(6)O(4))(C(15)H(11)N(3)) (5), and UO(2)(C(12)H(6)O(4))(C(15)H(10)N(3)Cl) (6), were synthesized under solvothermal conditions and characterized by single-crystal and powder X-ray diffraction and luminescence and UV-vis spectroscopy. Compounds 1, 2, and 5 crystallize as molecular uranyl dimers, whereas compounds 3, 4, and 6 contain ladder motifs of uranyl centers. Fluorescence spectra of 1-4 show characteristic UO(2)(2+) emission, wherein bathochromic and hypsochromic shifts are noted as a function of organic species. In contrast, uranyl emission from 5 and 6 is quenched by the naphthalene dicarboxylic acid linker molecules.
We report the discovery of a repeating photometric signal from a low-mass member of the Praesepe open cluster that we interpret as a Neptune-sized transiting planet. The star is JS 183 (HSHJ 163, ...EPIC 211916756), with Teff = 3325 100 K, M* = 0.44 0.04 M , R* = 0.44 0.03 R , and . The planet has an orbital period of 10.134588 days and a radius of RP = 0.32 0.02 RJ. Since the star is faint at V = 16.5 and J = 13.3, we are unable to obtain a measured radial velocity orbit, but we can constrain the companion mass to below about 1.7 MJ, and thus well below the planetary boundary. JS 183b (since designated as K2-95b) is the second transiting planet found with K2 that resides in a several-hundred-megayear open cluster; both planets orbit mid-M dwarf stars and are approximately Neptune sized. With a well-determined stellar density from the planetary transit, and with an independently known metallicity from its cluster membership, JS 183 provides a particularly valuable test of stellar models at the fully convective boundary. We find that JS 183 is the lowest-density transit host known at the fully convective boundary, and that its very low density is consistent with current models of stars just above the fully convective boundary but in tension with the models just below the fully convective boundary.
A range of fluorescent alkynyl-naphthalimide fluorophores has been synthesized and their photophysical properties examined. The fluorescent ligands are based upon a 4-substituted 1,8-naphthalimide ...core and incorporate structural variations (at the 4-position) to tune the amphiphilic character: chloro (L1), 4-2-(2-aminoethoxy)ethanol (L2), 4-2-(2-methoxyethoxy)ethylamino (L3), piperidine (L4), morpholine (L5), 4-methylpiperidine (L6), and 4-piperidone ethylene ketal (L7) variants. The amino-substituted species (L2-L7) are fluorescent in the visible region at around 517-535 nm through a naphthalimide-localized intramolecular charge transfer (ICT), with appreciable Stokes' shifts of ca. 6500 cm(-1) and lifetimes up to 10.4 ns. Corresponding two-coordinate Au(I) complexes Au(L)(PPh3) were isolated, with X-ray structural studies revealing the expected coordination mode via the alkyne donor. The Au(I) complexes retain the visible fluorescence associated with the coordinated alkynyl-naphthalimide ligand. The ligands and complexes were investigated for their cytotoxicity across a range of cell lines (LOVO, MCF-7, A549, PC3, HEK) and their potential as cell imaging agents for HEK (human embryonic kidney) cells and Spironucleus vortens using confocal fluorescence microscopy. The images reveal that these fluorophores are highly compatible with fluorescence microscopy and show some clear intracellular localization patterns that are dependent upon the specific nature of the naphthalimide substituent.
Purpose: Drawing from self-determination theory (SDT), the present study examined the relationship between motivation and eudaimonic well-being in the sport context. Method: The association between ...motivation and eudaimonic well-being was assessed using a latent variable model through Structural Equation Modeling (SEM). Three hundred ninety-nine athletes (M
age
= 25.08, SD = 7.35) from 15 different individual and team sports completed a questionnaire package. Results: Results indicated that integrated and identified regulations positively predicted athletes' eudaimonic well-being. External regulation was also a positive predictor of eudaimonic well-being, while introjected regulation and amotivation negatively predicted athletes' eudaimonic well-being. Finally, athletes' intrinsic motivation did not significantly predict their eudaimonic well-being. Conclusions: Results highlight the complex link between different types of sport motivation and athletes' well-being.
Abstract Directly observing exoplanets with coronagraphs is impeded by the presence of speckles from aberrations in the optical path, which can be mitigated in hardware with wave front control, as ...well as in post-processing. This work explores using an instrument model in post-processing to separate astrophysical signals from residual aberrations in coronagraphic data. The effect of wave front error (WFE) on the coronagraphic intensity consists of a linear contribution and a quadratic contribution. When either of the terms is much larger than the other, the instrument response can be approximated by a transfer matrix mapping WFE to detector plane intensity. From this transfer matrix, a useful projection onto instrumental modes that removes the dominant error modes can be derived. We apply this approach to synthetically generated Roman Space Telescope hybrid Lyot coronagraph data to extract “robust observables,” which can be used instead of raw data for applications such as detection testing. The projection improves planet flux ratio detection limits by about 28% in the linear regime and by over a factor of 2 in the quadratic regime, illustrating that robust observables can increase sensitivity to astrophysical signals and improve the scientific yield from coronagraphic data. While this approach does not require additional information such as observations of reference stars or modulations of a deformable mirror, it can and should be combined with these other techniques, acting as a model-informed prior in an overall post-processing strategy.
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