NFAT promotes carcinoma invasive migration through glypican-6

Invasive migration of carcinoma cells is a prerequisite for the metastatic dissemination of solid tumours. Numerous mechanisms control the ability of cancer cells to acquire a motile and invasive phenotype, and subsequently degrade and invade the basement membrane. Several genes that are up-regulated in breast carcinoma are responsible for mediating the metastatic cascade. Recent studies have revealed that the NFAT (nuclear factor of activated T-cells) is a transcription factor that is highly expressed in aggressive breast cancer cells and tissues, and mediates invasion through transcriptional induction of pro-invasion and migration genes. In the present paper we demonstrate that NFAT promotes breast carcinoma invasion through induction of GPC (glypican) 6, a cell-surface glycoprotein. NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype. The mechanism by which GPC6 promotes invasive migration involves inhibition of canonical β-catenin and Wnt signalling, and up-regulation of non-canonical Wnt5A signalling leading to the activation of JNK (c-Jun N-terminal kinase) and p38 MAPK (mitogen-activated protein kinase). Thus GPC6 is a novel NFAT target gene in breast cancer cells that promotes invasive migration through Wnt5A signalling

An acceptance model for sports technologies: the effects of sports motivation, sports type and context-aware characteristics

Purpose This study explores the drivers behind sports technology use and identifies the need for a new conceptualization of sports technology adoption. To address this issue, the authors create a new construct, “context-awareness,” with four dimensions: tracking, coaching, sharing and gamification. Design/methodology/approach The paper uses a mixed-method approach, including in-depth interviews and partial least squares structural equation modeling. The proposed model combines technology acceptance frameworks with the Sports Motivation Scale and a novel context-awareness scale. It is empirically tested with a diverse sample of 600 respondents to identify use-intention differences according to sports motivation and sport types. Findings The paper reveals group differences in sports type (dynamic vs nondynamic) and sports motivation (intrinsic vs extrinsic) regarding sports technology use. It also suggests that perceived technology characteristics mediate the relationship between context-aware features and intention to use. Originality/value This research introduces a new construct of “context-awareness” into the literature on new technology acceptance. The proposed model combines insights from information systems, sports science, sports marketing and sports medicine to explain the adoption of complex technology

Action spectroscopy of chlorophyll and other coordination complexes

Action spectroscopy provides key insights into the nature of electronic transitions of coordination complexes such as porhyrin-containing biochromophores like chlorophyll or transition metal complexes such as tris(bipyridine)ruthenium

Segregated tunneling-percolation model for transport nonuniversality

We propose a theory of the origin of transport nonuniversality in disordered insulating-conducting compounds based on the interplay between microstructure and tunneling processes between metallic grains dispersed in the insulating host. We show that if the metallic phase is arranged in quasi-one dimensional chains of conducting grains, then the distribution function of the chain conductivities g has a power-law divergence for g -> 0 leading to nonuniversal values of the transport critical exponent t. We evaluate the critical exponent t by Monte Carlo calculations on a cubic lattice and show that our model can describe universal as well nonuniversal behavior of transport depending on the value of few microstructural parameters. Such segregated tunneling-percolation model can describe the microstructure of a quite vast class of materials known as thick-film resistors which display universal or nonuniversal values of t depending on the composition.Comment: 8 pages, 5 figures (Phys. Rev. B - 1 August 2003)(fig1 replaced

Full Connectivity: Corners, edges and faces

We develop a cluster expansion for the probability of full connectivity of high density random networks in confined geometries. In contrast to percolation phenomena at lower densities, boundary effects, which have previously been largely neglected, are not only relevant but dominant. We derive general analytical formulas that show a persistence of universality in a different form to percolation theory, and provide numerical confirmation. We also demonstrate the simplicity of our approach in three simple but instructive examples and discuss the practical benefits of its application to different models.Comment: 28 pages, 8 figure

Pentraxin-3 is a PI3K signaling target that promotes stem cell–like traits in basal-like breast cancers

Basal-like breast cancers (BLBCs) exhibit hyperactivation of the phosphoinositide 3-kinase (PI3K) signaling pathway because of the frequent mutational activation of the PIK3CA catalytic subunit and the genetic loss of its negative regulators PTEN (phosphatase and tensin homolog) and INPP4B (inositol polyphosphate-4-phosphatase type II). However, PI3K inhibitors have had limited clinical efficacy in BLBC management because of compensatory amplification of PI3K downstream signaling loops. Therefore, identification of critical PI3K mediators is paramount to the development of effective BLBC therapeutics. Using transcriptomic analysis of activated PIK3CA-expressing BLBC cells, we identified the gene encoding the humoral pattern recognition molecule pentraxin-3 (PTX3) as a critical target of oncogenic PI3K signaling. We found that PTX3 abundance is stimulated, in part, through AKT- and nuclear factor κB (NF-κB)-dependent pathways and that presence of PTX3 is necessary for PI3K-induced stem cell-like traits. We further showed that PTX3 expression is greater in tumor samples from patients with BLBC and that it is prognostic of poor patient survival. Our results thus reveal PTX3 as a newly identified PI3K-regulated biomarker and a potential therapeutic target in BLBC

Ancient DNA SNP-panel data suggests stability in bluefin tuna genetic diversity despite centuries of fluctuating catches in the eastern Atlantic and Mediterranean

Atlantic bluefin tuna (Thunnus thynnus; BFT) abundance was depleted in the late 20th and early 21st century due to overfishing. Historical catch records further indicate that the abundance of BFT in the Mediterranean has been fluctuating since at least the 16th century. Here we build upon previous work on ancient DNA of BFT in the Mediterranean by comparing contemporary (2009–2012) specimens with archival (1911–1926) and archaeological (2nd century BCE–15th century CE) specimens that represent population states prior to these two major periods of exploitation, respectively. We successfully genotyped and analysed 259 contemporary and 123 historical (91 archival and 32 archaeological) specimens at 92 SNP loci that were selected for their ability to differentiate contemporary populations or their association with core biological functions. We found no evidence of genetic bottlenecks, inbreeding or population restructuring between temporal sample groups that might explain what has driven catch fluctuations since the 16th century. We also detected a putative adaptive response, involving the cytoskeletal protein synemin which may be related to muscle stress. However, these results require further investigation with more extensive genome-wide data to rule out demographic changes due to overfishing, and other natural and anthropogenic factors, in addition to elucidating the adaptive drivers related to these

Chiral unitary theory: application to nuclear problems

In this talk we briefly describe some basic elements of chiral perturbation theory, $\chi PT$, and how the implementation of unitarity and other novel elements lead to a better expansion of the $T$ matrix for meson meson and meson baryon interactions. Applications are then done to the $\pi \pi$ interaction in nuclear matter in the scalar and vector channels, antikaons in nuclei and $K^-$ atoms, and how the $\phi$ meson properties are changed in a nuclear medium.Comment: 15 pages, 9 figures, Invited talk in the International Symposium on Nuclear Physics, Bombay, december 200