A large geometric distortion in the first photointermediate of rhodopsin, determined by double-quantum solid-state NMR

Double-quantum magic-angle-spinning NMR experiments were performed on 11,12-C-13(2)-retinylidene-rhodopsin under illumination at low temperature, in order to characterize torsional angle changes at the C11-C12 photoisomerization site. The sample was illuminated in the NMR rotor at low temperature (similar to 120 K) in order to trap the primary photointermediate, bathorhodopsin. The NMR data are consistent with a strong torsional twist of the HCCH moiety at the isomerization site. Although the HCCH torsional twist was determined to be at least 40A degrees, it was not possible to quantify it more closely. The presence of a strong twist is in agreement with previous Raman observations. The energetic implications of this geometric distortion are discussed

Contrasting environmental drivers of adult and juvenile growth in a marine fish: implications for the effects of climate change

Many marine fishes have life history strategies that involve ontogenetic changes in the use of coastal habitats. Such ontogenetic shifts may place these species at particular risk from climate change, because the successive environments they inhabit can differ in the type, frequency and severity of changes related to global warming. We used a dendrochronology approach to examine the physical and biological drivers of growth of adult and juvenile mangrove jack (Lutjanus argentimaculatus) from tropical north-western Australia. Juveniles of this species inhabit estuarine environments and adults reside on coastal reefs. The Niño-4 index, a measure of the status of the El Niño-Southern Oscillation (ENSO) had the highest correlation with adult growth chronologies, with La Niña years (characterised by warmer temperatures and lower salinities) having positive impacts on growth. Atmospheric and oceanographic phenomena operating at ocean-basin scales seem to be important correlates of the processes driving growth in local coastal habitats. Conversely, terrestrial factors influencing precipitation and river runoff were positively correlated with the growth of juveniles in estuaries. Our results show that the impacts of climate change on these two life history stages are likely to be different, with implications for resilience and management of populations

Influence of temperature and applied potential on the permeability of polyphenol films prepared on vitreous carbon in acid and alkaline media

The electrochemical polymerization of phenol is known to rapidly produce a thin insulating film at the anode surface. This film generally blocks further polymerization. The objective of this study is to show that, depending on the operating conditions, polymeric films resulting from phenol oxidation present different properties and that certain films can be so porous that they allow the oxidation of phenol to continue. The deposition of polyphenol films with improved permeability could be attractive in the removal of phenol from polluted solutions. Polyphenol films were prepared in aqueous solution on a vitreous carbon anode either by cyclic voltammetry or by electro-oxidation at constant potential. The apparent permeability P (%) of the films prepared by these techniques was evaluated by monitoring changes in the electrode response towards phenol and potassium ferricyanide at 25 and 85°C and as a function of the potential applied during electropolymerization performed either in acidic (1 mol L-¹H₂SO₄) or in alkaline (1 mol L-¹ NaOH) aqueous solution. It was shown that: (1) the polyphenol film electrosynthesized in alkaline medium was more permeable than that prepared in acidic medium, (2) the apparent permeability was higher when the polyphenol film was electrosynthesized with simultaneous oxygen evolution and (3) the use of a high temperature in the polyphenol film preparation, especially in the presence of a concomitant oxygen evolution, significantly enhanced its apparent permeability (P ≥ 100 %). These results are interpreted in terms of a mixed-transport mechanism involving both pore and membrane diffusion. The effect of the permeability of the polymeric film on the removal of phenol from aqueous solution by electropolymerization is discussed

Influence of temperature and applied potential on the permeability of polyphenol films prepared on vitreous carbon in acid and alkaline media

The electrochemical polymerization of phenol is known to rapidly produce a thin insulating film at the anode surface. This film generally blocks further polymerization. The objective of this study is to show that, depending on the operating conditions, polymeric films resulting from phenol oxidation present different properties and that certain films can be so porous that they allow the oxidation of phenol to continue. The deposition of polyphenol films with improved permeability could be attractive in the removal of phenol from polluted solutions. Polyphenol films were prepared in aqueous solution on a vitreous carbon anode either by cyclic voltammetry or by electro-oxidation at constant potential. The apparent permeability P (%) of the films prepared by these techniques was evaluated by monitoring changes in the electrode response towards phenol and potassium ferricyanide at 25 and 85°C and as a function of the potential applied during electropolymerization performed either in acidic (1 mol L-¹H₂SO₄) or in alkaline (1 mol L-¹ NaOH) aqueous solution. It was shown that: (1) the polyphenol film electrosynthesized in alkaline medium was more permeable than that prepared in acidic medium, (2) the apparent permeability was higher when the polyphenol film was electrosynthesized with simultaneous oxygen evolution and (3) the use of a high temperature in the polyphenol film preparation, especially in the presence of a concomitant oxygen evolution, significantly enhanced its apparent permeability (P ≥ 100 %). These results are interpreted in terms of a mixed-transport mechanism involving both pore and membrane diffusion. The effect of the permeability of the polymeric film on the removal of phenol from aqueous solution by electropolymerization is discussed

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

Feasibility Study of Dual Energy Radiographic Imaging for Target Localization in Radiotherapy for Lung Tumors

Purpose Dual-energy (DE) radiographic imaging improves tissue discrimination by separating soft from hard tissues in the acquired images. This study was to establish a mathematic model of DE imaging based on intrinsic properties of tissues and quantitatively evaluate the feasibility of applying the DE imaging technique to tumor localization in radiotherapy. Methods We investigated the dependence of DE image quality on the radiological equivalent path length (EPL) of tissues with two phantoms using a stereoscopic x-ray imaging unit. 10 lung cancer patients who underwent radiotherapy each with gold markers implanted in the tumor were enrolled in the study approved by the hospital's Ethics Committee. The displacements of the centroids of the delineated gross tumor volumes (GTVs) in the digitally reconstructed radiograph (DRR) and in the bone-canceled DE image were compared with the averaged displacements of the centroids of gold markers to evaluate the feasibility of using DE imaging for tumor localization. Results The results of the phantom study indicated that the contrast-to-noise ratio (CNR) was linearly dependent on the difference of EPL and a mathematical model was established. The objects and backgrounds corresponding to ΔEPL less than 0.08 are visually indistinguishable in the bone-canceled DE image. The analysis of patient data showed that the tumor contrast in the bone-canceled images was improved significantly as compared with that in the original radiographic images and the accuracy of tumor localization using the DE imaging technique was comparable with that of using fiducial makers. Conclusion It is feasible to apply the technique for tumor localization in radiotherapy

Sample size calculation for microarray experiments with blocked one-way design

<p>Abstract</p> <p>Background</p> <p>One of the main objectives of microarray analysis is to identify differentially expressed genes for different types of cells or treatments. Many statistical methods have been proposed to assess the treatment effects in microarray experiments.</p> <p>Results</p> <p>In this paper, we consider discovery of the genes that are differentially expressed among <it>K </it>(> 2) treatments when each set of <it>K </it>arrays consists of a block. In this case, the array data among <it>K </it>treatments tend to be correlated because of block effect. We propose to use the blocked one-way ANOVA <it>F</it>-statistic to test if each gene is differentially expressed among <it>K </it>treatments. The marginal p-values are calculated using a permutation method accounting for the block effect, adjusting for the multiplicity of the testing procedure by controlling the false discovery rate (FDR). We propose a sample size calculation method for microarray experiments with a blocked one-way design. With FDR level and effect sizes of genes specified, our formula provides a sample size for a given number of true discoveries.</p> <p>Conclusion</p> <p>The calculated sample size is shown via simulations to provide an accurate number of true discoveries while controlling the FDR at the desired level.</p

PIF Genes Mediate the Effect of Sucrose on Seedling Growth Dynamics

As photoautotrophs, plants can use both the form and amount of fixed carbon as a measure of the light environment. In this study, we used a variety of approaches to elucidate the role of exogenous sucrose in modifying seedling growth dynamics. In addition to its known effects on germination, high-resolution temporal analysis revealed that sucrose could extend the number of days plants exhibited rapid hypocotyl elongation, leading to dramatic increases in ultimate seedling height. In addition, sucrose changed the timing of daily growth maxima, demonstrating that diel growth dynamics are more plastic than previously suspected. Sucrose-dependent growth promotion required function of multiple phytochrome-interacting factors (PIFs), and overexpression of PIF5 led to growth dynamics similar to plants exposed to sucrose. Consistent with this result, sucrose was found to increase levels of PIF5 protein. PIFs have well-established roles as integrators of response to light levels, time of day and phytohormone signaling. Our findings strongly suggest that carbon availability can modify the known photomorphogenetic signaling network