Automated analysis of atrial late gadolinium enhancement imaging that correlates with endocardial voltage and clinical outcomes: A 2-center study

This work was supported by the British Heart Foundation PG/10/37/28347, RG/10/11/28457, NIHR Biomedical Research Centre funding, and the ElectroCardioMaths Programme of the Imperial BHF Centre of Research Excellence

Sensory determinants of stated liking for vegetable names and actual liking for canned vegetables: A cross-country study among European adolescents.

Sensory properties are reported as one of the main factors hindering an appropriate vegetable intake by the young. In the present work the sensory determinants of likings for vegetables were explored in adolescents of four European countries (Denmark, n = 88; France, n = 206; Italy, n = 110 and United Kingdom, n = 93). A questionnaire was designed to study cross country differences in stated liking for and familiarity with a list of vegetables popular among European markets (between-vegetable approach). A within-vegetable comparison approach with actual tasting was used to analyze differences and similarities in liking for canned pea and sweet corn samples across the countries. A close positive relationship between stated liking and familiarity was found. Irrespective of the country, one group of highly liked vegetables (carrots, tomatoes, green salad) was identified, characterized by innately liked tastes (sweet, umami), delicate flavour and bright appealing colour. A second group of highly disliked vegetables consists of cauliflowers and broccoli, characterized by disliked sensations such as bitter taste and objectionable flavour. Internal Preference Maps from actual liking scores indicate that the generally disliked tastes (bitter, sour), are clearly correlated with a negative hedonic response for both peas and sweet corn. The hedonic valence of a generally well accepted taste such as salty and texture descriptors depends on the type of vegetable. Internal preference maps from actual liking data indicate that flavour and appearance descriptors of the distinct sensory properties of each type of vegetable positively affect liking, while the intensity of unusual flavours is related to sample disliking

The interaction between caveolin-1 and Rho-GTPases promotes metastasis by controlling the expression of alpha5-integrin and the activation of Src, Ras and Erk

Proteins containing a caveolin-binding domain (CBD), such as the Rho-GTPases, can interact with caveolin-1 (Cav1) through its caveolin scaffold domain. Rho-GTPases are important regulators of p130Cas, which is crucial for both normal cell migration and Src kinase-mediated metastasis of cancer cells. However, although Rho-GTPases (particularly RhoC) and Cav1 have been linked to cancer progression and metastasis, the underlying molecular mechanisms are largely unknown. To investigate the function of Cav1–Rho-GTPase interaction in metastasis, we disrupted Cav1–Rho-GTPase binding in melanoma and mammary epithelial tumor cells by overexpressing CBD, and examined the loss-of-function of RhoC in metastatic cancer cells. Cancer cells overexpressing CBD or lacking RhoC had reduced p130Cas phosphorylation and Rac1 activation, resulting in an inhibition of migration and invasion in vitro. The activity of Src and the activation of its downstream targets FAK, Pyk2, Ras and extracellular signal-regulated kinase (Erk)1/2 were also impaired. A reduction in α5-integrin expression, which is required for binding to fibronectin and thus cell migration and survival, was observed in CBD-expressing cells and cells lacking RhoC. As a result of these defects, CBD-expressing melanoma cells had a reduced ability to metastasize in recipient mice, and impaired extravasation and survival in secondary sites in chicken embryos. Our data indicate that interaction between Cav1 and Rho-GTPases (most likely RhoC but not RhoA) promotes metastasis by stimulating α5-integrin expression and regulating the Src-dependent activation of p130Cas/Rac1, FAK/Pyk2 and Ras/Erk1/2 signaling cascades

Caveolin-1–mediated Suppression of Cyclooxygenase-2 via a β-catenin-Tcf/Lef–dependent Transcriptional Mechanism Reduced Prostaglandin E2 Production and Survivin Expression

Augmented expression of cyclooxygenase-2 (COX-2) and enhanced production of prostaglandin E2 (PGE2) are associated with increased tumor cell survival and malignancy. Caveolin-1 is a scaffold protein that has been proposed to function as a tumor suppressor in human cancer cells, although mechanisms underlying this ability remain controversial. Intriguingly, the possibility that caveolin-1 regulates the expression of COX-2 has not been explored. Here we show that augmented caveolin-1 expression in cells with low basal levels of this protein, such as human colon cancer (HT29, DLD-1), breast cancer (ZR75), and embryonic kidney (HEK293T) cells reduced COX-2 mRNA and protein levels and β-catenin-Tcf/Lef and COX-2 gene reporter activity, as well as the production of PGE2 and cell proliferation. Moreover, COX-2 overexpression or PGE2 supplementation increased levels of the inhibitor of apoptosis protein survivin by a transcriptional mechanism, as determined by PCR analysis, survivin gene reporter assays and Western blotting. Furthermore, addition of PGE2 to the medium prevented effects attributed to caveolin-1–mediated inhibition of β-catenin-Tcf/Lef–dependent transcription. Finally, PGE2 reduced the coimmunoprecipitation of caveolin-1 with β-catenin and their colocalization at the plasma membrane. Thus, by reducing COX-2 expression, caveolin-1 interrupts a feedback amplification loop involving PGE2-induced signaling events linked to β-catenin/Tcf/Lef–dependent transcription of tumor survival genes including cox-2 itself and survivin