R tools for MicroRNA pathway analysis

In the early 2000s, microRNAs (miRNAs) were discovered as segments of a new class of highly conserved and small non-coding RNA molecules of 20-25 nucleotides that are transcribed from DNA.
They do not translation into proteins, rather they inhibit protein expression by binding to the 3’untranslated regions (3’ UTRs) of specific mRNA targets (that is/are complementary to them) and guiding their translational repression or complete degradation and gene silencing. With this, miRNAs provide a second level of regulation beyond primary gene expression. Integrative study of cellular pathways is pivotal to understanding the functions of individual genes and proteins in terms of systems and processes that contribute to normal physiology and to disease. "WikiPathways":http://wikipathways.org is an open, collaborative platform dedicated to the curation of biological pathways by and for the scientific community. The collection of pathways is publicly available to the researchers. The miRNA’s predicted by TargetScan in cardiomyocytes hypertrophy pathway has already been visualized on WikiPathways (WP1560). Since more studies investigate miRNAs using microarray technologies it would be desirable to be able to use information about miRNA’s in that analysis. One way to do that is to add the miRNA’s to all pathways. Therefore, we are integrating both validated and predicted miRNA information into biological pathways and making them available in WikiPathways. Initially, we focused on pathways related to the heart because miRNAs created a true revolution in the cardiovascular research field. The validated miRNAs have been downloaded from miRNA databases such as TarBase or miRTarbase. In order to link the validated miRNA targets to the genes in the pathways of our interest, we use "BridgeDb":http://www.bridgedb.org for identifier mapping. BridgeDb is a middleware between the relational databases, files and mapping services. BridgeDb is available in two forms. The first is a framework suitable for integration in Java applications. The other is based on Representational State Transfer (REST) webservices and is suitable for all other programming languages. The identifier mapping has been done in the R statistical environment as the connected Bioconductor repository has many pre-existing packages for microarray data analysis. For now we used the REST interface from R but we will also submit BridgeDb R package to Bioconductor.
Predicted miRNA targets by different prediction algorithms were verified by co evaluating miRNA and mRNA expression using microarray analysis. Quality control and normalization of the microarray datasets was done using the current functionality of the arrayanalysis.org web portal. Statistical analysis was done using Limma and the miRNAs were visualized in the pathways of interest using "PathVisio":http://www.pathvisio.org. Modules for statistical and pathway analysis have been developed which will be added to the "arrayanalysis.org":http://www.arrayanalysis.org portal. This also required connecting R to PathVisio, for which a new XMLRPC interface was developed. Through this PathVisio can be controlled by R scripts.
In conclusion, these R tools can help to integrate information about miRNAs with other knowledge about biological pathways and used for research purposes

Symmetry for a quasilinear elliptic equation in Hyperbolic space

In this article we establish the radial symmetry of positive solutions of a p- Laplace equation in the Hyperbolic space, which is the Euler Lagrange equation of the p- Poincare Sobolev inequality in the Hyperbolic space. We will also establish the sharp decay of solution and its gradient and also investigate the question of existence of solution

N7-(carboxymethyl)guanine-lithium crystalline complex: a bioinspired solid electrolyte

Electrochemical device with components having direct significance to biological life processes is a potent futuristic strategy for the realization of all-round green and sustainable development. We present here synthesis design, structural analysis and ion transport of a novel solid organic electrolyte (G7Li), a compound reminiscent of ion channels, derived from regioisomeric N7-guanine-carboxylate conjugate and Li-ions. G7Li, with it\u27s in-built supply of Li(+)-ions, exhibited remarkably high lithium-ion transference number (= 0.75) and tunable room temperature ionic conductivity spanning three decades (≈10(-7) to 10(-3) Ω(-1) cm(-1)) as a function of moisture content. The ionic conductivity show a distinct reversible transition around 80-100 °C, from a dual Li(+) and H(+) (<100 °C) to a pure Li(+) conductor (>100 °C). Systematic studies reveal a transition from water-assisted Li-ion transport to Li hopping-like mechanism involving guanine-Li coordination. While as-synthesized G7Li has potential in humidity sensors, the anhydrous G7Li is attractive for rechargeable batteries

The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins.

The long term side effects of any newly introduced drug is a subject of intense research, and often raging controversies. One such example is the dipeptidyl peptidase-IV (DPP4) inhibitor used for treating type 2 diabetes, which is inconclusively implicated in increased susceptibility to acute pancreatitis. Previously, based on a computational analysis of the spatial and electrostatic properties of active site residues, we have demonstrated that phosphoinositide-specific phospholipase C (PI-PLC) from Bacillus cereus is a prolyl peptidase using in vivo experiments. In the current work, we first report the inhibition of the native activity of PI-PLC by two DPP4 inhibitors - vildagliptin (LAF-237) and K-579. While vildagliptin inhibited PI-PLC at micromolar concentrations, K-579 was a potent inhibitor even at nanomolar concentrations. Subsequently, we queried a comprehensive, non-redundant set of 5000 human proteins (50% similarity cutoff) with known structures using serine protease (SPASE) motifs derived from trypsin and DPP4. A pancreatic lipase and a gastric lipase are among the proteins that are identified as proteins having promiscuous SPASE scaffolds that could interact with DPP4 inhibitors. The presence of such scaffolds in human lipases is expected since they share the same catalytic mechanism with PI-PLC. However our methodology also detects other proteins, often with a completely different enzymatic mechanism, that have significantly congruent domains with the SPASE motifs. The reported elevated levels of serum lipase, although contested, could be rationalized by inhibition of lipases reported here. In an effort to further our understanding of the spatial and electrostatic basis of DPP4 inhibitors, we have also done a comprehensive analysis of all 76 known DPP4 structures liganded to inhibitors till date. Also, the methodology presented here can be easily adopted for other drugs, and provide the first line of filtering in the identification of pathways that might be inadvertently affected due to promiscuous scaffolds in proteins