Grid warehousing of molecular dynamics protein unfolding data

With the increasing awareness of protein folding disorders, the explosion of genomic information, and the need for efficient ways to predict protein structure, protein folding and unfolding has become a central issue in molecular sciences research. Molecular dynamics computer simulations are increasingly employed to understand the folding and unfolding of proteins. Running protein unfolding simulations is computationally expensive and finding ways to enhance performance is a grid issue on its own. However, more and more groups run such simulations and generate a myriad of data, which raises new challenges in managing and analyzing these data. Because the vast range of proteins researchers want to study and simulate, the computational effort needed to generate data, the large data volumes involved, and the different types of analyses scientists need to perform, it is desirable to provide a public repository allowing researchers to pool and share protein unfolding data. This paper describes efforts to provide a grid-enabled data warehouse for protein unfolding data. We outline the challenge and present first results in the design and implementation of the data warehouse.

On the use of a time sequence of surface pressures in four-dimensional data assimilation

The possibility of using a time sequence of surface pressure observations in four-dimensional data assimilation is being investigated. It is shown that a linear multilevel quasi-geostrophic model can be updated successfully with surface data alone, provided the number of time levels are at least as many as the number of vertical levels. It is further demonstrated that current statistical analysis procedures are very inefficient to assimilate surface observations, and it is shown by numerical experiments that the vertical interpolation must be carried out using the structure of the most dominating baroclinic mode in order to obtain a satisfactory updating. Different possible ways towards finding a practical solution are being discussed.

The BioDICE Taverna plugin for clustering and visualization of biological data: a workflow for molecular compounds exploration

Background: In many experimental pipelines, clustering of multidimensional biological datasets is used to detect hidden structures in unlabelled input data. Taverna is a popular workflow management system that is used to design and execute scientific workflows and aid in silico experimentation. The availability of fast unsupervised methods for clustering and visualization in the Taverna platform is important to support a data-driven scientific discovery in complex and explorative bioinformatics applications. Results: This work presents a Taverna plugin, the Biological Data Interactive Clustering Explorer (BioDICE), that performs clustering of high-dimensional biological data and provides a nonlinear, topology preserving projection for the visualization of the input data and their similarities. The core algorithm in the BioDICE plugin is Fast Learning Self Organizing Map (FLSOM), which is an improved variant of the Self Organizing Map (SOM) algorithm. The plugin generates an interactive 2D map that allows the visual exploration of multidimensional data and the identification of groups of similar objects. The effectiveness of the plugin is demonstrated on a case study related to chemical compounds. Conclusions: The number and variety of available tools and its extensibility have made Taverna a popular choice for the development of scientific data workflows. This work presents a novel plugin, BioDICE, which adds a data-driven knowledge discovery component to Taverna. BioDICE provides an effective and powerful clustering tool, which can be adopted for the explorative analysis of biological datasets.

Supra-molecular assembly of a lumican-derived peptide amphiphile enhances its collagen-stimulating activity

C16-YEALRVANEVTLN, a peptide amphiphile (PA) incorporating a biologically active amino acid sequence found in lumican, has been examined for its influence upon collagen synthesis by human corneal fibroblasts in vitro, and the roles of supra-molecular assembly and activin receptor-like kinase ALK receptor signaling in this effect were assessed. Cell viability was monitored using the Alamar blue assay, and collagen synthesis was assessed using Sirius red. The role of ALK signaling was studied by receptor inhibition. Cultured human corneal fibroblasts synthesized significantly greater amounts of collagen in the presence of the PA over both 7-day and 21-day periods. The aggregation of the PA to form nanotapes resulted in a notable enhancement in this activity, with an approximately two-fold increase in collagen production per cell. This increase was reduced by the addition of an ALK inhibitor. The data presented reveal a stimulatory effect upon collagen synthesis by the primary cells of the corneal stroma, and demonstrate a direct influence of supra-molecular assembly of the PA upon the cellular response observed. The effects of PA upon fibroblasts were dependent upon ALK receptor function. These findings elucidate the role of self-assembled nanostructures in the biological activity of peptide amphiphiles, and support the potential use of a self-assembling lumican derived PA as a novel biomaterial, intended to promote collagen deposition for wound repair and tissue engineering purposes

The occurrence of Laurencia marilzae (Ceramiales, Rhodophyta) in Brazil based on morphological and molecular data

Laurencia marilzae is recorded for the first time from the western Atlantic Ocean; it was found in Laje de Santos Marine State Park, Sao Paulo, southeastern Brazil. The specimens were collected in the rocky subtidal zone from 7 to 15 m depth. The most distinctive characteristic of this species is the presence of corps en cerise in all cells of the thallus, including cortex, medulla, and trichoblasts. The phylogenetic position of the species was inferred by analysis of the chloroplast-encoded rbcL gene sequences from 43 taxa, using two other rhodomelacean taxa and two members of the Ceramiaceae as outgroups. Within the Laurencia assemblage, L. marilzae from Brazil and from the Canary Islands ( type locality) formed a distinctive lineage sister to all other Laurencia species analyzed. Male plants are described for the first time. This study expands the geographical distribution of L. marilzae to the western Atlantic Ocean.

The timing of Neotropical speciation dynamics: A reconstruction of Myiopagis flycatcher diversification using phylogenetic and paleogeographic data

Neotropical forests have brought forth a large proportion of the world`s terrestrial biodiversity, but the underlying evolutionary mechanisms and their timing require further elucidation. Despite insights gained from phylogenetic studies, uncertainties about molecular clock rates have hindered efforts to determine the timing of diversification processes. Moreover, most molecular research has been detached from the extensive body of data on Neotropical geology and paleogeography. We here examine phylogenetic relationships and the timing of speciation events in a Neotropical flycatcher genus (Myiopagis) by using calibrations from modern geologic data in conjunction with a number of recently developed DNA sequence dating algorithms and by comparing these estimates with those based on a range of previously proposed molecular clock rates. We present a well-supported hypothesis of systematic relationships within the genus. Our age estimates of Myiopagis speciation events based on paleogeographic data are in close agreement with nodal ages derived from a ""traditional"" avian mitochondrial 2%/My clock, while contradicting other clock rates. Our comparative approach corroborates the consistency of the traditional avian mitochondrial clock rate of 2%/My for tyrant-flycatchers. Nevertheless, our results argue against the indiscriminate use of molecular clock rates in evolutionary research and advocate the verification of the appropriateness of the traditional clock rate by means of independent calibrations in individual studies. (C) 2009 Elsevier Inc. All rights reserved.

Sequence and function of lysosomal and digestive cathepsin D-like proteinases of Musca domestica midgut

Musca domestica larvae display in anterior and middle midgut contents, a proteolytic activity with pH optimum of 3.0-3.5 and kinetic properties like cathepsin D. Three cDNAs coding for preprocathepsin D-like proteinases (ppCAD 1, ppCAD 2, ppCAD 3) were cloned from a M. domestica midgut cDNA library. The coded protein sequences included the signal peptide, propeptide and mature enzyme that has all conserved catalytic and substrate binding residues found in bovine lysosomal cathepsin D. Nevertheless, ppCAD 2 and ppCAD 3 lack the characteristic proline loop and glycosylation sites. A comparison among the sequences of cathepsin D-like enzymes from some vertebrates and those found in M. domestica and in the genomes of Aedes aegypti, Drosophila melanogaster, Tribolium castaneum, and Bombyx mori showed that only flies have enzymes lacking the proline loop (as defined by the motif: DxPxPx(G/A)P), thus resembling vertebrate pepsin. ppCAD 3 should correspond to the digestive cathepsin D-like proteinase (CAD) found in enzyme assays because: (1) it seems to be the most expressed CAD, based on the frequency of ESTs found. (2) The mRNA for CAD 3 is expressed only in the anterior and proximal middle midgut. (3) Recombinant procathepsin D-like proteinase (pCAD 3), after auto-activation has a pH optimum of 2.5-3.0 that is close to the luminal pH of M. domestica midgut. (4) Immunoblots of proteins from different tissues revealed with anti-pCAD 3 serum were positive only in samples of anterior and middle midgut tissue and contents. (5) CAD 3 is localized with immunogold inside secretory vesicles and around microvilli in anterior and middle midguit cells. The data support the view that on adapting to deal with a bacteria-rich food in an acid midgut region, M. domestica digestive CAD resulted from the same archetypical gene as the intracellular cathepsin D, paralleling what happened with vertebrates. The lack of the proline loop may be somehow associated with the extracellular role of both pepsin and digestive CAD 3. (C) 2009 Elsevier Ltd. All rights reserved.

Coding behavioural data for cladistic analysis: using dynamic homology without parsimony

Many of the controversies around the concept of homology rest on the subjectivity inherent to primary homology propositions. Dynamic homology partially solves this problem, but there has been up to now scant application of it outside of the molecular domain. This is probably because morphological and behavioural characters are rich in properties, connections and qualities, so that there is less space for conflicting character delimitations. Here we present a new method for the direct optimization of behavioural data, a method that relies on the richness of this database to delimit the characters, and on dynamic procedures to establish character state identity. We use between-species congruence in the data matrix and topological stability to choose the best cladogram. We test the methodology using sequences of predatory behaviour in a group of spiders that evolved the highly modified predatory technique of spitting glue onto prey. The cladogram recovered is fully compatible with previous analyses in the literature, and thus the method seems consistent. Besides the advantage of enhanced objectivity in character proposition, the new procedure allows the use of complex, context-dependent behavioural characters in an evolutionary framework, an important step towards the practical integration of the evolutionary and ecological perspectives on diversity. (C) The Willi Hennig Society 2010.

Sequence-specific reconstruction from fragmentary databases using seed sequences: implementation and validation on SAGE, proteome and generic sequencing data

Motivation: DNA assembly programs classically perform an all-against-all comparison of reads to identify overlaps, followed by a multiple sequence alignment and generation of a consensus sequence. If the aim is to assemble a particular segment, instead of a whole genome or transcriptome, a target-specific assembly is a more sensible approach. GenSeed is a Perl program that implements a seed-driven recursive assembly consisting of cycles comprising a similarity search, read selection and assembly. The iterative process results in a progressive extension of the original seed sequence. GenSeed was tested and validated on many applications, including the reconstruction of nuclear genes or segments, full-length transcripts, and extrachromosomal genomes. The robustness of the method was confirmed through the use of a variety of DNA and protein seeds, including short sequences derived from SAGE and proteome projects.

Fast Acquisition of (13)C NMR Spectra using the Steady-state Free Precession Sequence

In this paper, we show that the steady-state free precession sequence can be used to acquire (13)C high-resolution nuclear magnetic resonance spectra and applied to qualitative analysis. The analysis of brucine sample using this sequence with 60 degrees flip angle and time interval between pulses equal to 300 ms (acquisition time, 299.7 ms; recycle delay, 300 ms) resulted in spectrum with twofold enhancement in signal-to-noise ratio, when compared to standard (13)C sequence. This gain was better when a much shorter time interval between pulses (100 ms) was applied. The result obtained was more than fivefold enhancement in signal-to-noise ratio, equivalent to more than 20-fold reduction in total data recording time. However, this short time interval between pulses produces a spectrum with severe phase and truncation anomalies. We demonstrated that these anomalies can be minimized by applying an appropriate apodization function and plotting the spectrum in the magnitude mode.