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

Dust from collisions: mid-infrared absorbance spectroscopy of Martian meteorites

Mid-infrared transmission/absorbance spectra of a representative range of martian meteorites are presented. The data is used for mineralogical bulk studies, but also for the comparison with astronomical dust spectra

Model-independent WIMP Scattering Responses and Event Rates: A Mathematica Package for Experimental Analysis

The community's reliance on simplified descriptions of WIMP-nucleus interactions reflects the absence of analysis tools that integrate general theories of dark matter with standard treatments of nuclear response functions. To bridge this gap, we have constructed a public-domain Mathematica package for WIMP analyses based on our effective theory formulation. Script inputs are 1) the coefficients of the effective theory, through which one can characterize the low-energy consequences of arbitrary ultraviolet theories of WIMP interactions; and 2) one-body density matrices for commonly used targets, the most compact description of the relevant nuclear physics. The generality of the effective theory expansion guarantees that the script will remain relevant as new ultraviolet theories are explored; the use of density matrices to factor the nuclear physics from the particle physics will allow nuclear structure theorists to update the script as new calculations become available, independent of specific particle-physics contexts. The Mathematica package outputs the resulting response functions (and associated form factors) and also the differential event rate, once a galactic WIMP velocity profile is specified, and thus in its present form provides a complete framework for experimental analysis. The Mathematica script requires no a priori knowledge of the details of the non-relativistic effective field theory or nuclear physics, though the core concepts are reviewed here and in arXiv:1203.3542.Comment: 30+6 page

Bioengineering models of cell signaling

Strategies for rationally manipulating cell behavior in cell-based technologies and molecular therapeutics and understanding effects of environmental agents on physiological systems may be derived from a mechanistic understanding of underlying signaling mechanisms that regulate cell functions. Three crucial attributes of signal transduction necessitate modeling approaches for analyzing these systems: an ever-expanding plethora of signaling molecules and interactions, a highly interconnected biochemical scheme, and concurrent biophysical regulation. Because signal flow is tightly regulated with positive and negative feedbacks and is bidirectional with commands traveling both from outside-in and inside-out, dynamic models that couple biophysical and biochemical elements are required to consider information processing both during transient and steady-state conditions. Unique mathematical frameworks will be needed to obtain an integrated perspective on these complex systems, which operate over wide length and time scales. These may involve a two-level hierarchical approach wherein the overall signaling network is modeled in terms of effective "circuit" or "algorithm" modules, and then each module is correspondingly modeled with more detailed incorporation of its actual underlying biochemical/biophysical molecular interactions