Epidermal growth factor-mediated T-cell factor/lymphoid enhancer factor transcriptional activity is essential but not sufficient for cell cycle progression in nontransformed mammary epithelial cells

Because beta-catenin target genes such as cyclin D1 are involved in cell cycle progression, we examined whether beta-catenin has a more pervasive role in normal cell proliferation, even upon stimulation by non-Wnt ligands. Here, we demonstrate that epidermal growth factor (EGF) stimulates T-cell factor/lymphoid enhancer factor (Tcf/Lef) transcriptional activity in nontransformed mammary epithelial cells (MCF-10A) and that its transcriptional activity is essential for EGF-mediated progression through G(1)/S phase. Thus, expression of dominant-negative Tcf4 blocks EGF-mediated Tcf/Lef transcriptional activity and bromodeoxyuridine uptake. In fact, the importance of EGF-mediated Tcf/Lef transcriptional activity for cell cycle progression may lie further upstream at the G(1)/S phase transition. We demonstrate that dominant-negative Tcf4 inhibits a reporter of cyclin D1 promoter activity in a dose-dependent manner. Importantly, dominant-negative Tcf4 suppresses EGF- mediated cell cycle activity specifically by thwarting EGF- mediated Tcf/Lef transcriptional activity, not by broader effects on EGF signaling. Thus, although expression of dominant-negative Tcf4 blocks EGF- mediated TOPFLASH activation, it has no effect on either EGF receptor or ERK phosphorylation, further underscoring the fact that Tcf/ Lef-mediated transcription is essential for cell cycle progression, even when other pro-mitogenic signals are at normal levels. Yet, despite its essential role, Tcf/Lef transcriptional activity alone is not sufficient for cell cycle progression. Serum also stimulates Tcf/ Lef transcriptional activation in MCF-10A cells but is unable to promote DNA synthesis. Taken together, our data support a model wherein EGF promotes Tcf/ Lef transcriptional activity, and this signal is essential but not sufficient for cell cycle activity

Systematic co-occurrence of tail correlation functions among max-stable processes

The tail correlation function (TCF) is one of the most popular bivariate extremal dependence measures that has entered the literature under various names. We study to what extent the TCF can distinguish between different classes of well-known max-stable processes and identify essentially different processes sharing the same TCF.Comment: 31 pages, 4 Tables, 5 Figure

The informativeness of the technical conversion factor for the price ratio of processing livestock

The technical conversion factor (TCF) is a survey-based estimate of the percentage of carcass weight obtained per unit of live weight. Practitioners and researchers have used it to predict the corresponding price ratio (PR). We use both in-sample regressions and out-of-sample forecasting analysis to test the validity of this approach in case of predicting the price effects of processing livestock in Europe. By regressing the PR on the inverse value of the corresponding TCF for a large panel of European countries and animal types, we find a significant positive relation between these variables, which also has economic value in terms of improving out-of-sample forecasting precision. This result is shown to be robust to animal type, year, and country fixed effects. The TCF therefore has predictive value about the corresponding PR.(3

APC-β-catenin-TCF signaling silences the intestinal guanylin-GUCY2C tumor suppressor axis.

Sporadic colorectal cancer initiates with mutations in APC or its degradation target β-catenin, producing TCF-dependent nuclear transcription driving tumorigenesis. The intestinal epithelial receptor, GUCY2C, with its canonical paracrine hormone guanylin, regulates homeostatic signaling along the crypt-surface axis opposing tumorigenesis. Here, we reveal that expression of the guanylin hormone, but not the GUCY2C receptor, is lost at the earliest stages of transformation in APC-dependent tumors in humans and mice. Hormone loss, which silences GUCY2C signaling, reflects transcriptional repression mediated by mutant APC-β-catenin-TCF programs in the nucleus. These studies support a pathophysiological model of intestinal tumorigenesis in which mutant APC-β-catenin-TCF transcriptional regulation eliminates guanylin expression at tumor initiation, silencing GUCY2C signaling which, in turn, dysregulates intestinal homeostatic mechanisms contributing to tumor progression. They expand the mechanistic paradigm for colorectal cancer from a disease of irreversible mutations in APC and β-catenin to one of guanylin hormone loss whose replacement, and reconstitution of GUCY2C signaling, could prevent tumorigenesis

Trade Policy Reform and the Textile, Clothing and Footwear Industry, Australia: 1993-97

Textiles, clothing and footwear (TCF) industries in Australia experienced extensive trade reforms in the 1990s, which were expected to promote a competitive TCF activities. This paper examines two hypotheses (1) trade reforms have had a positive impact on TCF industries and (2) trade reforms have had an adverse impact on Small and Medium Enterprises (SMEs). Selected growth performance variables were intensively analysed. The results of the study are consistent with hypothesis (1) but are inconclusive with hypothesis (2). It was found that the positive productivity effect of SMEs does not appear to have been translated into export gain. The needs for further research to identify and focus upon the barriers inhibiting the export performance of SMEs is suggested.trade reforms, manufacturing performance, Australia

Critical Role of TCF-1 in Repression of the IL-17 Gene

Overwhelming activation of IL-17, a gene involved in inflammation, leads to exaggerated Th17 responses associated with numerous autoimmune conditions, such as experimental autoimmune encephalomyelitis (EAE). Here we show that TCF-1 is a critical factor to repress IL-17 gene locus by chromatin modifications during T cell development. Deletion of TCF-1 resulted in increased IL-17 gene expression both in thymus and peripheral T cells, which led to enhanced Th17 differentiation. As a result, TCF-1-/- mice were susceptible to Th17-dependent EAE induction. Rag1-/- mice reconstituted with TCF-1-/- T cells were also susceptible to EAE, indicating TCF-1 is intrinsically required to repress IL-17. However, expression of wild-type TCF-1 or dominant negative TCF-1 did not interfere with Th17 differentiation in mature T cells. Furthermore, expression of TCF-1 in TCF-1-/- T cells could not restore Th17 differentiation to wild-type levels, indicating that TCF-1 cannot affect IL-17 production at the mature T cell stage. This is also supported by the normal up-regulation or activation in mature TCF-1-/- T cells of factors known to regulate Th17 differentiation, including RORγt and Stat3. We observed hyperacetylation together with trimethylation of Lys-4 at the IL-17 locus in TCF-1-/- thymocytes, two epigenetic modifications indicating an open active state of the gene. Such epigenetic modifications were preserved even when TCF-1-/- T cells migrated out of thymus. Therefore, TCF-1 mediates an active process to repress IL-17 gene expression via epigenetic modifications during T cell development. This TCF-1-mediated repression of IL-17 is critical for peripheral T cells to generate balanced immune responses

Random raman fiber laser based on a twin-core fiber with FBGs inscribed by femtosecond radiation

Narrowband Raman lasing in a polarization-maintaining two-core fiber (TCF) is demonstrated. Femtosecond point-by-point inscription of fiber Bragg gratings (FBGs) in individual cores produces a half-open cavity with random distributed feedback. The laser linewidth in the cavity with a single FBG inscribed in one core of the TCF reduced by ∼2 times with respect to the cavity with a fiber loop mirror. It is shown that the inscription of two FBGs in different cores leads to the formation of a Michelson-type interferometer, leading to the modulation of generation spectra near threshold. This technique offers new possibilities for spectral filtering or multi-wavelength generation