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

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

Signal Processing during Developmental Multicellular Patterning

Developing design strategies for tissue engineering and regenerative medicine is limited by our nascent understanding of how cell populations self-organize into multicellular structures on synthetic scaffolds. Mechanistic insights can be gleaned from the quantitative analysis of biomolecular signals that drive multicellular patterning during the natural processes of embryonic and adult development. This review describes three critical layers of signal processing that govern multicellular patterning: spatiotemporal presentation of extracellular cues, intracellular signaling networks that mediate crosstalk among extracellular cues, and finally, intranuclear signal integration at the level of transcriptional regulation. At every level in this hierarchy, the quantitative attributes of signals have a profound impact on patterning. We discuss how experiments and mathematical models are being used to uncover these quantitative features and their impact on multicellular phenotype

Sodium Benzoate is Associated with Salmonella Typhi Resistant to Chloramphenicol

Background: There are many factors that govern growth and resistant of Salmonella typhi. A study had reported that the use of sodium benzoate caused antibiotic resistant. However, no study has directly evaluated the effect of sodium benzoate exposure on S. typhi sensitivity to chloramphenicol. The aim of this study was to evaluate the resistance or sensitivity of S. typhi to chloramphenicol after sodium benzoate exposure. Methods: The study was conducted in seven groups: three treatment groups (sodium benzoate insensitive S. typhi+8 µg/mL, 16 µg/mL, and 32 µg/mL of chloramphenicol), three positive control groups (sodium benzoate sensitive S. typhi+8 µg/mL, 16 µg/mL, and 32 µg/mL of chloramphenicol), and one negative control groups (sodium benzoate sensitive S. typhi+0 µg/mL of chloramphenicol). The effect of sodium benzoate exposure to S. typhi sensitivity to chloramphenicol was measured after 24 hours. Spearman test was used to analyzed this association. Results: In this study, we found that the average S. typhi growth in the treatment groups (A, B, C) was 445 CFU/mL, 385 CFU/mL, and 171 CFU/mL, respectively. While in the positive control group (D, E, F) was not obtained any S. typhi growth. Average S. typhi growth in the negative control group was 430 CFU/mL. Discussion: We found that sodium benzoate exposure inhibited S. typhi growth and affected S. typhi sensitivity to chloramphenicol (p<0.05). In addition, we found that 32 µg/mL chloramphenicol had the highest mean difference value, so this showed that the dose 32 µg/mL of chloramphenicol had the best effectiveness of various treatment groups (p<0.05). Conclusions: Sodium benzoate exposure can inhibit S. typhi growth and cause S. typhi resistant to chloramphenicol.&nbsp

Oxygen isotopic and petrological constraints on the origin and relationship of IIE iron meteorites and H chondrites

New oxygen isotopic measurements of IIEs and H chondrites are indistinguishable — strengthening a possible common origin for these groups. Combining oxygen results with mineralogy, the nature of their parent body or bodies can be explored

The prospects for mathematical logic in the twenty-first century

The four authors present their speculations about the future developments of mathematical logic in the twenty-first century. The areas of recursion theory, proof theory and logic for computer science, model theory, and set theory are discussed independently.Comment: Association for Symbolic Logi

How organizational performance influences managerial search? - Towards 'informating search' theory

Although we expect managers to use the capabilities of business analytics systems to search for solutions and improve firm performance, we do not have a good understanding of the factors that motivate managers to undertake such search. Drawing on attribution and control theories, we propose a theory that explicates the performance conditions under which managers undertake search activities. Specifically, we theorize that managers are motivated to search for knowledge when both, operational performance and overall organizational performance, are declining. Further, we propose that managers' search response to sustained organizational performance failure is faster (low search latency) when the magnitude of sustained failure is larger. We tested our hypotheses with longitudinal data collected monthly over a period of four years from seven hospitals. Distributed lag model analysis of the data supports our hypotheses. We conclude with implications for research and practice, and plans for future research

Superconductivity and Physical Properties of CaPd2Ge2 Single Crystals

We present the superconducting and normal state properties of CaPd2Ge2 single crystal investigated by magnetic susceptibility \chi, isothermal magnetization M, heat capacity C_p, in-plane electrical resistivity \rho and London penetration depth \lambda versus temperature T and magnetic field H measurements. Bulk superconductivity is inferred from the \rho(T) and C_p(T) data. The \rho(T) data exhibit metallic behavior and undergoes a superconducting transition with T_c onset = 1.98 K and zero resistivity state at T_c 0 = 1.67 K. The \chi(T) reveal the onset of superconductivity at 2.0 K. For T>2.0 K, the \chi(T) and M(H) are weakly anisotropic paramagnetic with \chi_ab > \chi_c. The C_p(T) confirm the bulk superconductivity below T_c = 1.69(3) K. The superconducting state electronic heat capacity is analyzed within the framework of a single-band \alpha-model of BCS superconductivity and various normal and superconducting state parameters are estimated. Within the \alpha-model, the C_p(T) data and the ab plane \lambda(T) data consistently indicate a moderately anisotropic s-wave gap with \Delta(0)/k_B T_c ~ 1.6, somewhat smaller than the BCS value of 1.764. The relationship of the heat capacity jump at T_c and the penetration depth measurement to the anisotropy in the s-wave gap is discussed.Comment: 12 pages, 9 figures, 2 Tables; Submitted to PR