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

Property A and exactness of the uniform Roe algebra

In this short note, prepared for the volume of conjectures to celebrate Guido Mislin's retirement, we outline the conjecture that a uniformly discrete bounded geometry metric space X has property A if and only if the uniform Roe algebra C^?(X ) is exact

The role of renal transporters and novel regulatory interactions in the TAL that control blood pressure

Hypertension (HTN), a major public health issue is currently the leading factor in the global burden of disease, where associated complications account for 9.4 million deaths worldwide every year (98). Excessive dietary salt intake is among the environmental factors that contribute to HTN, known as salt sensitivity. The heterogeneity of salt sensitivity and the multiple mechanisms that link high salt intake to increases in blood pressure are of upmost importance for therapeutic application. A continual increase in the kidney's reabsorption of sodium (Na+) relies on sequential actions at various segments along the nephron. When the distal segments of the nephron fail to regulate Na+, the effects on Na+ homeostasis are unfavourable. We propose that the specific nephron region where increased active uptake occurs as a result of variations in Na+ reabsorption is at the thick ascending limb of the loop of Henle (TAL). The purpose of this review is to urge the consideration of the TAL that contributes to the pathophysiology of salt sensitive HTN. Further research in this area will enable development of a therapeutic application for targeted treatment

Optimum take-off angle in the long jump

In this study, we found that the optimum take-off angle for a long jumper may be predicted by combining the equation for the range of a projectile in free flight with the measured relations between take-off speed, take-off height and take-off angle for the athlete. The prediction method was evaluated using video measurements of three experienced male long jumpers who performed maximum-effort jumps over a wide range of take-off angles. To produce low take-off angles the athletes used a long and fast run-up, whereas higher take-off angles were produced using a progressively shorter and slower run-up. For all three athletes, the take-off speed decreased and the take-off height increased as the athlete jumped with a higher take-off angle. The calculated optimum take-off angles were in good agreement with the athletes' competition take-off angles

Origin and significance of 'dispersed facies' basal ice: Svínafellsjökull, Iceland

Dispersed facies basal ice - massive (i.e. structureless) ice with dispersed debris aggregates - is present at the margins of many glaciers and, as a product of internal glacial processes, has the potential to provide important information about the mechanisms of glacier flow and the nature of the subglacial environment. The origin of dispersed facies is poorly understood, with several hypotheses having been advanced for its formation, and there is disagreement as to whether it is largely a sedimentary or a tectonic feature. We test these established hypotheses at the temperate glacier Svfnafellsjokull, Iceland, and find that none fully account for dispersed facies characteristics at this location. Instead, dispersed facies physical, sedimentological and stable-isotope (5180, 8D) characteristics favour a predominantly tectonic origin that we suggest comprises the regelation and straininduced metamorphism of debris-rich basal ice that has been entrained into an englacial position by tectonic processes operating at the base of an icefall. Further thickening of the resultant dispersed facies may also occur tectonically as a result of ice flow against the reverse bed slope of a terminal overdeepening. Lack of efficient subglacial drainage in the region of the overdeepening may limit basal melting and thus favour basal ice preservation, including the preservation of dispersed facies. Despite the relatively low sediment content of dispersed facies (~1.6% by volume), its thickness (up to 25 m) and ubiquity at Svfnafellsjokull results in a significant contribution to annual sediment discharge (1635-3270 m3 a"1) that is ~6.5 times that contributed by debris-rich stratified facies basal ice

A method for the direct measurement of electronic site populations in a molecular aggregate using two-dimensional electronic-vibrational spectroscopy

Two dimensional electronic spectroscopy has proved to be a valuable experimental technique to reveal electronic excitation dynamics in photosynthetic pigment-protein complexes, nanoscale semiconductors, organic photovoltaic materials, and many other types of systems. It does not, however, provide direct information concerning the spatial structure and dynamics of excitons. 2D infrared spectroscopy has become a widely used tool for studying structural dynamics but is incapable of directly providing information concerning electronic excited states. 2D electronic-vibrational (2DEV) spectroscopy provides a link between these domains, directly connecting the electronic excitation with the vibrational structure of the system under study. In this work, we derive response functions for the 2DEV spectrum of a molecular dimer and propose a method by which 2DEV spectra could be used to directly measure the electronic site populations as a function of time following the initial electronic excitation. We present results from the response function simulations which show that our proposed approach is substantially valid. This method provides, to our knowledge, the first direct experimental method for measuring the electronic excited state dynamics in the spatial domain, on the molecular scale

Perceptions of trends in Seychelles artisanal trap fisheries: comparing catch monitoring, underwater visual census and fishers' knowledge

Fisheries scientists and managers are increasingly engaging with fishers' knowledge (FK) to provide novel information and improve the legitimacy of fisheries governance. Disputes between the perceptions of fishers and scientists can generate conflicts for governance, but can also be a source of new perspectives or understandings. This paper compares artisanal trap fishers' reported current catch rates with landings data and underwater visual census (UVC). Fishers' reports of contemporary 'normal' catch per day tended to be higher than recent median landings records. However, fishers' reports of 'normal' catch per trap were not significantly different from the median CPUE calculated from landings data, and reports of 'good' and 'poor' catch rates were indicative of variability observed in landings data. FK, landings and UVC data all gave different perspectives of trends over a ten-year period. Fishers' perceptions indicated greater declines than statistical models fitted to landings data, while UVC evidence for trends varied between sites and according to the fish assemblage considered. Divergence in trend perceptions may have resulted from differences in the spatial, temporal or taxonomic focus of each dataset. Fishers may have experienced and understood behavioural changes and increased fishing power, which may have obscured declines from landings data. Various psychological factors affect memory and recall, and may have affected these memory-based estimates of trends, while different assumptions underlying the analysis of both interview data and conventional scientific data could also have led to qualitatively different trend perceptions. Differing perspectives from these three data sources illustrate both the potential for 'cognitive conflicts' between stakeholders who do not rely on the same data sources, as well as the importance of multiple information sources to understand dynamics of fisheries. Collaborative investigation of such divergence may facilitate learning and improve fisheries governance