Extracellular BMP-antagonist regulation in development and disease: tied up in knots

Developmental processes are regulated by the bone morphogenetic protein (BMP) family of secreted molecules. BMPs bind to serine/threonine kinase receptors and signal through the canonical Smad pathway and other intracellular effectors. Integral to the control of BMPs is a diverse group of secreted BMP antagonists that bind to BMPs and prevent engagement with their cognate receptors. Tight temporospatial regulation of both BMP and BMP-antagonist expression provides an exquisite control system for developing tissues. Additional facets of BMP-antagonist biology, such as crosstalk with Wnt and Sonic hedgehog signaling during development, have been revealed in recent years. In addition, previously unappreciated roles for the BMP antagonists in kidney fibrosis and cancer have been elucidated. This review provides a description of BMP-antagonist biology, together with highlights of recent novel insights into the role of these antagonists in development, signal transduction and human disease.

Low power field programmable gate array implementation of fast digital signal processing algorithms: characterisation and manipulation of data locality

Dynamic power consumption is very dependent on interconnect, so clever mapping of digital signal processing algorithms to parallelised realisations with data locality is vital. This is a particular problem for fast algorithm implementations where typically, designers will have sacrificed circuit structure for efficiency in software implementation. This study outlines an approach for reducing the dynamic power consumption of a class of fast algorithms by minimising the index space separation; this allows the generation of field programmable gate array (FPGA) implementations with reduced power consumption. It is shown how a 50% reduction in relative index space separation results in a measured power gain of 36 and 37% over a Cooley-Tukey Fast Fourier Transform (FFT)-based solution for both actual power measurements for a Xilinx Virtex-II FPGA implementation and circuit measurements for a Xilinx Virtex-5 implementation. The authors show the generality of the approach by applying it to a number of other fast algorithms namely the discrete cosine, the discrete Hartley and the Walsh-Hadamard transforms.

Prognostic Significance of TRAIL Signaling Molecules in Stage II and III Colorectal Cancer

Purpose: We previously found that cellular FLICE-inhibitory protein (c-FLIP), caspase 8, and tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptor 2 (DR5) are major regulators of cell viability and chemotherapy-induced apoptosis in colorectal cancer. In this study, we determined the prognostic significance of c-FLIP, caspase 8, TRAIL and DR5 expression in tissues from patients with stage II and III colorectal cancer.

Experimental Design: Tissue microarrays were constructed from matched normal and tumor tissue derived from patients (n = 253) enrolled in a phase III trial of adjuvant 5-fluorouracil–based chemotherapy versus postoperative observation alone. TRAIL, DR5, caspase 8, and c-FLIP expression levels were determined by immunohistochemistry.

Results: Colorectal tumors displayed significantly higher expression levels of c-FLIP (P < 0.001), caspase 8 (P = 0.01), and DR5 (P < 0.001), but lower levels of TRAIL (P < 0.001) compared with matched normal tissue. In univariate analysis, higher TRAIL expression in the tumor was associated with worse overall survival (P = 0.026), with a trend to decreased relapse-free survival (RFS; P = 0.06), and higher tumor c-FLIP expression was associated with a significantly decreased RFS (P = 0.015). Using multivariate predictive modeling for RFS in all patients and including all biomarkers, age, treatment, and stage, we found that the model was significant when the mean tumor c-FLIP expression score and disease stage were included (P < 0.001). As regards overall survival, the overall model was predictive when both TRAIL expression and disease stage were included (P < 0.001).

Conclusions: High c-FLIP and TRAIL expression may be independent adverse prognostic markers in stage II and III colorectal cancer and might identify patients most at risk of relapse.

Developments in the production of biological and synthetic binders for immunoassay and sensor-based detection of small molecules

The need for chemical and biological entities of predetermined selectivity and affinity towards target analytes is greater than ever, in applications such as environmental monitoring, bioterrorism detection and analysis of natural toxin contaminants in the food chain.

Thermal and quantum fluctuations in chains of ultracold polar molecules

Ultracold polar molecules, in highly anisotropic traps and interacting via a repulsive dipolar potential, may form one-dimensional chains at high densities. According to classical theory, at low temperatures there exists a critical value of the density at which a second-order phase transition from a linear to a zigzag chain occurs. We study the effect of thermal and quantum fluctuations on these self-organized structures using classical and quantum Monte Carlo methods, by means of which we evaluate the pair correlation function and the static structure factor. Depending on the parameters, these functions exhibit properties typical of a crystalline or of a liquid system. We compare the thermal and the quantum results, identifying analogies and differences. Finally, we discuss experimental parameter regimes where the effects of quantum fluctuations on the linear-zigzag transition can be observed.

Modification of Ag nanoparticles with mixed thiols for improved SERS detection of poorly adsorbing target molecules: detection of MDMA

Here we report an example of a mixed thiol monolayer on the surface of Ag nanoparticles which promotes adsorption and quantitative SERS detection of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”); the thiols in the mixed monolayers act synergistically since MDMA does not adsorb onto colloids modified with either of the thiols separately.

TIME-RESOLVED RESONANCE RAMAN-SPECTROSCOPY OF TRIPLET-STATE METALATED AND FREE-BASE TETRAARYLPORPHYRINS

Resonance Raman spectra of the T-1 excited states of Zn and free-base tetra-4-sulfonatophenylporphyrin (TPPS) have been recorded at room temperature in aqueous solution using two-colour time-resolved methods. The spectra of both sulfonated molecules are very similar to their tetraphenylporphyrin (TPP) analogues, which have been recorded in THF solution using the same pump-probe conditions, but they have higher signal-to-noise ratios because interference from strong solvent bands is reduced. Although two different T-1 spectra of Zn(TPP) have been reported these spectra differ slightly from each other and from the spectrum reported here, which has band positions very close (+/-6 cm(-1)) to those of Zn(TPPS). The high S/N ratios obtainable for the water-soluble porphyrins have allowed reliable polarization data to be recorded for their S-0 and T-1 states. This data set allows a realistic comparison of the changes in bonding associated with excitation of both free-base and Zn tetraarylporphyrins to the T-1 state.

Echolocation signal structure in the Megachiropteran bat Rousettus aegyptiacus Geoffroy 1810

Rousettus aegyptiacus Geoffroy 1810 is a member of the only genus of Megachiropteran bats to use vocal echolocation, but the structure of its brief, click-like signal is poorly described. Although thought to have a simple echolocation system compared to that of Microchiroptera, R. aegyptiacus is capable of good obstacle avoidance using its impulse sonar. The energy content of the signal was at least an order of magnitude smaller than in Microchiropteran bats and dolphins (approximately 4 X 10(-8) J m(-2)). Measurement of the duration, amplitude and peak frequency demonstrate that the signals of this animal are broadly similar in structure and duration to those of dolphins. Gabor functions were used to model signals and to estimate signal parameters, and the quality of the Gabor function fit to the early part of the signal demonstrates that the echolocation signals of R. aegyptiacus match the minimum spectral spread for their duration and amplitude and are thus well matched to its best hearing sensitivity. However, the low energy content of the signals and short duration should make returning echoes difficult to detect. The performance of R. aegyptincus in obstacle avoidance experiments using echolocation therefore remains something of a conundrum.