Accelerating exhaustive pairwise metagenomic comparisons

In this manuscript, we present an optimized and parallel version of our previous work IMSAME, an exhaustive gapped aligner for the pairwise and accurate comparison of metagenomes. Parallelization strategies are applied to take advantage of modern multiprocessor architectures. In addition, sequential optimizations in CPU time and memory consumption are provided. These algorithmic and computational enhancements enable IMSAME to calculate near optimal alignments which are used to directly assess similarity between metagenomes without requiring reference databases. We show that the overall efficiency of the parallel implementation is superior to 80% while retaining scalability as the number of parallel cores used increases. Moreover, we also show thats equential optimizations yield up to 8x speedup for scenarios with larger data.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds

Animals are frequently used as model systems for determination of safety and efficacy in pharmaceutical research and development. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this cross-species methodology by investigating species specific differences of the peroxisome proliferatoractivator receptor (PPAR) a response in rat and human

Testing CPT- and Lorentz-odd electrodynamics with waveguides

We study CPT- and Lorentz-odd electrodynamics described by the Standard Model Extension. Its radiation is confined to the geometry of hollow conductor waveguide, open along $z$. In a special class of reference frames, with vanishing both 0-th and $z$ components of the background field, $(k_{\rm AF})^\mu$, we realize a number of {\em huge and macroscopically detectable} effects on the confined waves spectra, compared to standard results. Particularly, if $(k_{\rm AF})^\mu$ points along $x$ (or $y$) direction only transverse electric modes, with $E_z=0$, should be observed propagating throughout the guide, while all the transverse magnetic, $B_z=0$, are absent. Such a strong mode suppression makes waveguides quite suitable to probe these symmetry violations using a simple and easily reproducible apparatus.Comment: 11pages, double-spacing, tex forma

Glycine-rich RNA binding protein of Oryza sativa inhibits growth of M15 E. coli cells

<p>Abstract</p> <p>Background</p> <p>Plant glycine-rich RNA binding proteins have been implicated to have roles in diverse abiotic stresses.</p> <p>Findings</p> <p><it>E. coli </it>M15 cells transformed with full-length rice glycine-rich RNA binding protein4 (OsGR-RBP4), truncated rice glycine-rich RNA binding protein4 (OsGR-RBP4ΔC) and rice FK506 binding protein (OsFKBP20) were analyzed for growth profiles using both broth and solid media. Expression of OsGR-RBP4 and OsGR-RBP4ΔC proteins caused specific, inhibitory effect on growth of recombinant M15 <it>E. coli </it>cells. The bacterial inhibition was shown to be time and incubation temperature dependent. Removal of the inducer, IPTG, resulted in re-growth of the cells, indicating that effect of the foreign proteins was of reversible nature. Although noted at different levels of dilution factors, addition of purified Os-GR-RBP4 and OsGR-RBP4ΔC showed a similar inhibitory effect as seen with expression inside the bacterial cells.</p> <p>Conclusions</p> <p>Expression of eukaryotic, stress-associated OsGR-RBP4 protein in prokaryotic <it>E. coli </it>M15 cells proves injurious to the growth of the bacterial cells. <it>E. coli </it>genome does not appear to encode for any protein that has significant homology to OsGR-RBP4 protein. Therefore, the mechanism of inhibition appears to be due to some illegitimate interactions of the OsGR-RBP4 with possibly the RNA species of the trans-host bacterial cells. The detailed mechanism underlying this inhibition remains to be worked out.</p

Molecular diversity of phospholipase D in angiosperms

BACKGROUND: The phospholipase D (PLD) family has been identified in plants by recent molecular studies, fostered by the emerging importance of plant PLDs in stress physiology and signal transduction. However, the presence of multiple isoforms limits the power of conventional biochemical and pharmacological approaches, and calls for a wider application of genetic methodology. RESULTS: Taking advantage of sequence data available in public databases, we attempted to provide a prerequisite for such an approach. We made a complete inventory of the Arabidopsis thaliana PLD family, which was found to comprise 12 distinct genes. The current nomenclature of Arabidopsis PLDs was refined and expanded to include five newly described genes. To assess the degree of plant PLD diversity beyond Arabidopsis we explored data from rice (including the genome draft by Monsanto) as well as cDNA and EST sequences from several other plants. Our analysis revealed two major PLD subfamilies in plants. The first, designated C2-PLD, is characterised by presence of the C2 domain and comprises previously known plant PLDs as well as new isoforms with possibly unusual features-catalytically inactive or independent on Ca(2+). The second subfamily (denoted PXPH-PLD) is novel in plants but is related to animal and fungal enzymes possessing the PX and PH domains. CONCLUSIONS: The evolutionary dynamics, and inter-specific diversity, of plant PLDs inferred from our phylogenetic analysis, call for more plant species to be employed in PLD research. This will enable us to obtain generally valid conclusions

Limited Genetic Diversity Preceded Extinction of the Tasmanian Tiger

The Tasmanian tiger or thylacine was the largest carnivorous marsupial when Europeans first reached Australia. Sadly, the last known thylacine died in captivity in 1936. A recent analysis of the genome of the closely related and extant Tasmanian devil demonstrated limited genetic diversity between individuals. While a similar lack of diversity has been reported for the thylacine, this analysis was based on just two individuals. Here we report the sequencing of an additional 12 museum-archived specimens collected between 102 and 159 years ago. We examined a portion of the mitochondrial DNA hyper-variable control region and determined that all sequences were on average 99.5% identical at the nucleotide level. As a measure of accuracy we also sequenced mitochondrial DNA from a mother and two offspring. As expected, these samples were found to be 100% identical, validating our methods. We also used 454 sequencing to reconstruct 2.1 kilobases of the mitochondrial genome, which shared 99.91% identity with the two complete thylacine mitochondrial genomes published previously. Our thylacine genomic data also contained three highly divergent putative nuclear mitochondrial sequences, which grouped phylogenetically with the published thylacine mitochondrial homologs but contained 100-fold more polymorphisms than the conserved fragments. Together, our data suggest that the thylacine population in Tasmania had limited genetic diversity prior to its extinction, possibly as a result of their geographic isolation from mainland Australia approximately 10,000 years ago

Domain-Domain Interactions Underlying Herpesvirus-Human Protein-Protein Interaction Networks

Protein-domains play an important role in mediating protein-protein interactions. Furthermore, the same domain-pairs mediate different interactions in different contexts and in various organisms, and therefore domain-pairs are considered as the building blocks of interactome networks. Here we extend these principles to the host-virus interface and find the domain-pairs that potentially mediate human-herpesvirus interactions. Notably, we find that the same domain-pairs used by other organisms for mediating their interactions underlie statistically significant fractions of human-virus protein inter-interaction networks. Our analysis shows that viral domains tend to interact with human domains that are hubs in the human domain-domain interaction network. This may enable the virus to easily interfere with a variety of mechanisms and processes involving various and different human proteins carrying the relevant hub domain. Comparative genomics analysis provides hints at a molecular mechanism by which the virus acquired some of its interacting domains from its human host

Structure-Function Analysis of Diacylglycerol Acyltransferase Sequences from 70 Organisms

<p>Abstract</p> <p>Background</p> <p>Diacylglycerol acyltransferase families (DGATs) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Understanding the roles of DGATs will help to create transgenic plants with value-added properties and provide clues for therapeutic intervention for obesity and related diseases. The objective of this analysis was to identify conserved sequence motifs and amino acid residues for better understanding of the structure-function relationship of these important enzymes.</p> <p>Results</p> <p>117 DGAT sequences from 70 organisms including plants, animals, fungi and human are obtained from database search using tung tree DGATs. Phylogenetic analysis separates these proteins into DGAT1 and DGAT2 subfamilies. These DGATs are integral membrane proteins with more than 40% of the total amino acid residues being hydrophobic. They have similar properties and amino acid composition except that DGAT1s are approximately 20 kDa larger than DGAT2s. DGAT1s and DGAT2s have 41 and 16 completely conserved amino acid residues, respectively, although only two of them are shared by all DGATs. These residues are distributed in 7 and 6 sequence blocks for DGAT1s and DGAT2s, respectively, and located at the carboxyl termini, suggesting the location of the catalytic domains. These conserved sequence blocks do not contain the putative neutral lipid-binding domain, mitochondrial targeting signal, or ER retrieval motif. The importance of conserved residues has been demonstrated by site-directed and natural mutants.</p> <p>Conclusions</p> <p>This study has identified conserved sequence motifs and amino acid residues in all 117 DGATs and the two subfamilies. None of the completely conserved residues in DGAT1s and DGAT2s is present in recently reported isoforms in the multiple sequences alignment, raising an important question how proteins with completely different amino acid sequences could perform the same biochemical reaction. The sequence analysis should facilitate studying the structure-function relationship of DGATs with the ultimate goal to identify critical amino acid residues for engineering superb enzymes in metabolic engineering and selecting enzyme inhibitors in therapeutic application for obesity and related diseases.</p

Crosstalk between Virulence Loci: Regulation of Salmonella enterica Pathogenicity Island 1 (SPI-1) by Products of the std Fimbrial Operon

Invasion of intestinal epithelial cells is a critical step in Salmonella infection and requires the expression of genes located in Salmonella pathogenicity island 1 (SPI-1). A key factor for SPI-1 expression is DNA adenine (Dam) methylation, which activates synthesis of the SPI-1 transcriptional activator HilD. Dam-dependent regulation of hilD is postranscriptional (and therefore indirect), indicating the involvement of unknown cell functions under Dam methylation control. A genetic screen has identified the std fimbrial operon as the missing link between Dam methylation and SPI-1. We show that all genes in the std operon are part of a single transcriptional unit, and describe three previously uncharacterized ORFs (renamed stdD, stdE, and stdF). We present evidence that two such loci (stdE and stdF) are involved in Dam-dependent control of Salmonella SPI-1: in a Dam− background, deletion of stdE or stdF suppresses SPI-1 repression; in a Dam+ background, constitutive expression of StdE and/or StdF represses SPI-1. Repression of SPI-1 by products of std operon explains the invasion defect of Salmonella Dam− mutants, which constitutively express the std operon. Dam-dependent repression of std in the ileum may be required to permit invasion, as indicated by two observations: constitutive expression of StdE and StdF reduces invasion of epithelial cells in vitro (1,000 fold) and attenuates Salmonella virulence in the mouse model (>60 fold). In turn, crosstalk between std and SPI-1 may play a role in intestinal infections by preventing expression of SPI-1 in the caecum, an intestinal compartment in which the std operon is known to be expressed

Comparison of bacterial microbiota of the predatory mite Neoseiulus cucumeris (Acari: Phytoseiidae) and its factitious prey Tyrophagus putrescentiae (Acari: Acaridae)

Neoseiulus cucumeris is a predatory mite used for biological control of arthropod pests. Mass-reared predators are fed with factitious prey mites such as Tyrophagus putrescentiae. Although some information on certain endosymbionts of N. cucumeris and T. putrescentiae exists, it is unclear whether both species share bacterial communities. The bacterial communities in populations of predator and prey mites, as well as the occurence of potential acaropathogenic bacteria were analyzed. The comparisons were based on the following groups: (i) N. cucumeris mass-production; (ii) N. cucumeris laboratory population with disease symptoms; (iii) T. putrescentiae pure populations and; (iv) T. putrescentiae from rearing units of N. cucumeris. Only 15% of OTUs were present in all samples from predatory and prey mite populations (core OTUs): the intracellular symbionts Wolbachia, Cardinium, plus other Blattabacterium-like, Solitalea-like, and Bartonella-like symbionts. Environmental bacteria were more abundant in predatory mites, while symbiotic bacteria prevailed in prey mites. Relative numbers of certain bacterial taxa were significantly different between the microbiota of prey mites reared with and without N. cucumeris. No significant differences were found in the bacterial communities of healthy N. cucumeris compared to N. cucumeris showing disease symptoms. We did not identify any confirmed acaropathogenic bacteria among microbiota