Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c

The forkhead box (FOX) transcription factor FOXM1 is ubiquitously expressed in proliferating cells. FOXM1 expression peaks at the G2/M phase of the cell cycle and its functional deficiency in mice leads to defects in mitosis. To investigate the role of FOXM1 in the cell cycle, we used synchronized hTERT-BJ1 fibroblasts to examine the cell cycle-dependent regulation of FOXM1 function. We observed that FOXM1 is localized mainly in the cytoplasm in cells at late-G1 and S phases. Nuclear translocation occurs just before entry into the G2/M phase and is associated with phosphorylation of FOXM1. Consistent with the dependency of FOXM1 function on mitogenic signals, nuclear translocation of FOXM1 requires activity of the Raf/MEK/MAPK signaling pathway and is enhanced by the MAPK activator aurintricarboxylic acid. This activating effect was suppressed by the MEK1/2 inhibitor U0126. In transient reporter assays, constitutively active MEK1 enhances the transactivating effect of FOXM1c, but not FOXM1b, on the cyclin B1 promoter. RT-PCR analysis confirmed that different cell lines and tissues predominantly express the FOXM1c transcript. Mutations of two ERK1/2 target sequences within FOXM1c completely abolish the MEK1 enhancing effect, suggesting a direct link between Raf/MEK/MAPK signaling and FOXM1 function. Importantly, inhibition of Raf/MEK/MAPK signaling by U0126 led to suppression of FOXM1 target gene expression and delayed progression through G2/M, verifying the functional relevance of FOXM1 activation by MEK1. In summary, we provide the first evidence that Raf/MEK/MAPK signaling exerts its G2/M regulatory effect via FOXM1c.published_or_final_versio

Lower bounds for several online variants of bin packing

We consider several previously studied online variants of bin packing and prove new and improved lower bounds on the asymptotic competitive ratios for them. For that, we use a method of fully adaptive constructions. In particular, we improve the lower bound for the asymptotic competitive ratio of online square packing significantly, raising it from roughly 1.68 to above 1.75.Comment: WAOA 201

The restorative role of annexin A1 at the blood–brain barrier

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood–brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood–brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood–brain barrier damage in disease and aging

Over-expression of FoxM1 facilitates progression through G2/M phase and stimulates expression of cyclin B1

The method presented to detect and quantify the porosity value content of composite materials is part of a development effort to establish an integrated ultrasonic evaluation system 1. The overall research effort aims to automate the NDE process and predict mechanical and structural properties of composite materials using NDE techniques. The ultrasonic NDE technique used herein is based on digitized waveforms obtained from pulse-echo scans. For the fast integration of new algorithms into the system, a software framework was created with compatability between the signal and image processing modules. The porosity volume content of the test specimens is related to statistical properties of the ultrasonic data rather than to the ultrasonic attenuation with respect to frequency2

The transcription factor WIN alters cell cycle kinetics through modulation of cyclin expression

Conference Theme: Signalling for Life and Death: Cytometry in the Analysis and Modelling of Cell Signallin