OST-HTH: a novel predicted RNA-binding domain

BACKGROUND: The mechanism by which the arthropod Oskar and vertebrate TDRD5/TDRD7 proteins nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. Using sequence profile searches we identify a novel domain in these proteins that is widely conserved across eukaryotes and bacteria. RESULTS: Using contextual information from domain architectures, sequence-structure superpositions and available functional information we predict that this domain is likely to adopt the winged helix-turn-helix fold and bind RNA with a potential specificity for dsRNA. We show that in eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. CONCLUSIONS: Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized domain (DUF88). We present evidence that it is an RNAse belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains and might be recruited to degrade certain RNAs. REVIEWERS: This article was reviewed by Sandor Pongor and Arcady Mushegian

Using Generalized Procrustes Analysis (GPA) for normalization of cDNA microarray data

<p>Abstract</p> <p>Background</p> <p>Normalization is essential in dual-labelled microarray data analysis to remove non-biological variations and systematic biases. Many normalization methods have been used to remove such biases within slides (Global, Lowess) and across slides (Scale, Quantile and VSN). However, all these popular approaches have critical assumptions about data distribution, which is often not valid in practice.</p> <p>Results</p> <p>In this study, we propose a novel assumption-free normalization method based on the Generalized Procrustes Analysis (GPA) algorithm. Using experimental and simulated normal microarray data and boutique array data, we systemically evaluate the ability of the GPA method in normalization compared with six other popular normalization methods including Global, Lowess, Scale, Quantile, VSN, and one boutique array-specific housekeeping gene method. The assessment of these methods is based on three different empirical criteria: across-slide variability, the Kolmogorov-Smirnov (K-S) statistic and the mean square error (MSE). Compared with other methods, the GPA method performs effectively and consistently better in reducing across-slide variability and removing systematic bias.</p> <p>Conclusion</p> <p>The GPA method is an effective normalization approach for microarray data analysis. In particular, it is free from the statistical and biological assumptions inherent in other normalization methods that are often difficult to validate. Therefore, the GPA method has a major advantage in that it can be applied to diverse types of array sets, especially to the boutique array where the majority of genes may be differentially expressed.</p

The impact of computed high b-value images on the diagnostic accuracy of DWI for prostate cancer: A receiver operating characteristics analysis.

To evaluate the performance of computed high b value diffusion-weighted images (DWI) in prostate cancer detection. 97 consecutive patients who had undergone multiparametric MRI of the prostate followed by biopsy were reviewed. Five radiologists independently scored 138 lesions on native high b-value images (b = 1200 s/mm2), apparent diffusion coefficient (ADC) maps, and computed high b-value images (contrast equivalent to b = 2000 s/mm2) to compare their diagnostic accuracy. Receiver operating characteristic (ROC) analysis and McNemar's test were performed to assess the relative performance of computed high b value DWI, native high b-value DWI and ADC maps. No significant difference existed in the area under the curve (AUC) for ROCs comparing B1200 (b = 1200 s/mm2) to computed B2000 (c-B2000) in 5 readers. In 4 of 5 readers c-B2000 had significantly increased sensitivity and/or decreased specificity compared to B1200 (McNemar's p &lt; 0.05), at selected thresholds of interpretation. ADC maps were less accurate than B1200 or c-B2000 for 2 of 5 readers (P &lt; 0.05). This study detected no consistent improvement in overall diagnostic accuracy using c-B2000, compared with B1200 images. Readers detected more cancer with c-B2000 images (increased sensitivity) but also more false positive findings (decreased specificity)

The catalytic core of DEMETER guides active DNA demethylation in Arabidopsis.

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the maternal genome in the central cell prior to fertilization and is essential for seed viability. DME preferentially targets small transposons that flank coding genes, influencing their expression and initiating plant gene imprinting. DME also targets intergenic and heterochromatic regions, but how it is recruited to these differing chromatin landscapes is unknown. The C-terminal half of DME consists of 3 conserved regions required for catalysis in vitro. We show that this catalytic core guides active demethylation at endogenous targets, rescuing dme developmental and genomic hypermethylation phenotypes. However, without the N terminus, heterochromatin demethylation is significantly impeded, and abundant CG-methylated genic sequences are ectopically demethylated. Comparative analysis revealed that the conserved DME N-terminal domains are present only in flowering plants, whereas the domain architecture of DME-like proteins in nonvascular plants mainly resembles the catalytic core, suggesting that it might represent the ancestral form of the 5mC DNA glycosylase found in plant lineages. We propose a bipartite model for DME protein action and suggest that the DME N terminus was acquired late during land plant evolution to improve specificity and facilitate demethylation at heterochromatin targets

Partial Regularity of solutions to the Four-dimensional Navier-Stokes equations at the first blow-up time

The solutions of incompressible Navier-Stokes equations in four spatial dimensions are considered. We prove that the two-dimensional Hausdorff measure of the set of singular points at the first blow-up time is equal to zero.Comment: 19 pages, a comment regarding five or higher dimensional case is added in Remark 1.3. accepted by Comm. Math. Phy

Developing an effective 2-D urban flood inundation model for city emergency management based on cellular automata

Flash floods have occurred frequently in the urban areas of southern China. An effective process-oriented urban flood inundation model is urgently needed for urban storm-water and emergency management. This study develops an efficient and flexible cellular automaton (CA) model to simulate storm-water runoff and the flood inundation process during extreme storm events. The process of infiltration, inlets discharge and flow dynamics can be simulated with little preprocessing on commonly available basic urban geographic data. In this model, a set of gravitational diverging rules are implemented to govern the water flow in a rectangular template of three cells by three cells of a raster layer. The model is calibrated by one storm event and validated by another in a small urban catchment in Guangzhou of southern China. The depth of accumulated water at the catchment outlet is interpreted from street-monitoring closed-circuit television (CCTV) videos and verified by on-site survey. A good level of agreement between the simulated process and the reality is reached for both storm events. The model reproduces the changing extent and depth of flooded areas at the catchment outlet with an accuracy of 4 cm in water depth. Comparisons with a physically based 2-D model (FloodMap) show that the model is capable of effectively simulating flow dynamics. The high computational efficiency of the CA model can meet the needs of city emergency management