Heparan sulfate 3-O-sulfotransferase isoform 5 generates both an antithrombin-binding site and an entry receptor for herpes simplex virus,type 1

Heparan sulfate 3-O-sulfotransferase transfers sulfate to the 3-OH position of a glucosamine residue of heparan sulfate (HS) to form 3-O-sulfated HS. The 3-O-sulfated glucosamine residue contributes to two important biological functions of HS: binding to antithrombin and thereby carrying anticoagulant activity, and binding to herpes simplex viral envelope glycoprotein D to serve as an entry receptor for herpes simplex virus 1. A total of five HS 3-O-sulfotransferase isoforms were reported previously. Here we report the isolation and characterization of a novel HS 3-O-sulfotransferase isoform, designated as HS 3-O-sulfotransferase isoform 5 (3-OST-5). 3-OST-5 cDNA was isolated from a human placenta cDNA library and expressed in COS-7 cells. The disaccharide analysis of 3-OST-5-modified HS revealed that 3-OST-5 generated at least three 3-O-sulfated disaccharides as follows: IdoUA2S-AnMan3S, GlcUA-AnMan3S6S, and IdoUA2S-AnMan3S6S. Transfection of the plasmid expressing 3-OST-5 rendered wild type Chinese hamster ovary cells susceptible to the infection by herpes simplex virus 1, suggesting that 3-OST-5-modified HS serves as an entry receptor for herpes simplex virus 1. In addition, 3-OST-5-modified HS bound to herpes simplex viral envelope protein glycoprotein D. Furthermore, we found that 3-OST-5-modified HS also bound to antithrombin, suggesting that 3-OST-5 also produces anticoagulant HS. In summary, our results indicate that a new member of 3-OST family generates both anticoagulant HS and an entry receptor for herpes simplex virus 1. These results provide a new insight regarding the mechanism for the biosynthesis of biologically active HS.     

Structure-affinity relationships of 5'-aromatic ethers and 5'-aromatic sulfides as partial A1 adenosine agonists, potential supraventricular anti-arrhythmic agents

Atrial fibrillation (AF) is the most commonly encountered sustained clinical arrhythmia with an estimated 2.3 million cases in the US (2001). A(1) adenosine receptor agonists can slow the electrical impulse propagation through the atrioventricular (AV) node (i.e., negative dromotropic effect) resulting in prolongation of the stimulus-to-His bundle (S-H) interval to potentially reduce ventricular rate. Compounds that are full agonists of the A(1) adenosine receptor can cause high grade AV block. Therefore, it is envisioned that a compound that is a partial agonist of the A(1) adenosine receptor could avoid this deleterious effect. 5(') Phenyl sulfides (e.g., 17, EC(50)=1.26 microM) and phenyl ethers (e.g., 28, EC(50)=0.2 microM) are partial agonists with respect to their AV nodal effects in guinea pig isolated hearts. Additional affinity, GTPgammaS binding data suggesting partial activity of the A(1) adenosine receptor, and PK results for 5(') modified adenosine derivatives are shown.     

RAmiRNA: Software suite for generation of SVMbased prediction models of mature miRNAs

MicroRNAs (miRNAs) are short endogenous non-coding RNA molecules that regulate protein coding gene expression in animals, plants, fungi, algae and viruses through the RNA interference pathway. By virtue of their base complementarity, mature miRNAs stop the process of translation, thus acting as one of the important molecules in vivo. Attempts to predict precursor-miRNAs and mature miRNAs have been achieved in a significant number of model organisms but development of prediction models aiming at relatively less studied organisms are rare. In this work, we provide a suite of standalone softwares called RAmiRNA (RAdicalmiRNA detector), to solve the problem of custom development of prediction models for mature miRNAs using support vector machine (SVM) learning. RAmiRNA could be used to develop SVM based model for prediction of mature miRNAs in an organism or a group of organisms in a UNIX based local machine. Additionally RAmiRNA generates training accuracy for a quick estimation of prediction ability of generated model. AVAILABILITY: The database is available for free at http://ircb.iiita.ac.in.     

ZNF471 modulates EMT and functions as methylation regulated tumor suppressor with diagnostic and prognostic significance in cervical cancer

Cell Biology and Toxicology - Cervical cancer (CC) is a leading cause of cancer-related death among women in developing countries. However, the underlying mechanisms and molecular targets for...     

‘Proof of concept’ of how tube-net diameter affects growth and agar content in industrially important farmed red seaweed Gracilaria dura

Journal of Applied Phycology - Several emerging therapeutic applications of agar and its derivatives make it one of the sought-after hydrocolloids, commanding the highest price in global markets....     

APP: an Automated Proteomics Pipeline for the analysis of mass spectrometry data based on multiple open access tools

Background

Mass spectrometry analyses of complex protein samples yield large amounts of data and specific expertise is needed for data analysis, in addition to a dedicated computer infrastructure. Furthermore, the identification of proteins and their specific properties require the use of multiple independent bioinformatics tools and several database search algorithms to process the same datasets. In order to facilitate and increase the speed of data analysis, there is a need for an integrated platform that would allow a comprehensive profiling of thousands of peptides and proteins in a single process through the simultaneous exploitation of multiple complementary algorithms.

Results

We have established a new proteomics pipeline designated as APP that fulfills these objectives using a complete series of tools freely available from open sources. APP automates the processing of proteomics tasks such as peptide identification, validation and quantitation from LC-MS/MS data and allows easy integration of many separate proteomics tools. Distributed processing is at the core of APP, allowing the processing of very large datasets using any combination of Windows/Linux physical or virtual computing resources.

Conclusions

APP provides distributed computing nodes that are simple to set up, greatly relieving the need for separate IT competence when handling large datasets. The modular nature of APP allows complex workflows to be managed and distributed, speeding up throughput and setup. Additionally, APP logs execution information on all executed tasks and generated results, simplifying information management and validation.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-014-0441-8) contains supplementary material, which is available to authorized users.     

Glucotoxic and diabetic conditions induce caspase 6-mediated degradation of nuclear lamin A in human islets,rodent islets and INS-1 832/13 cells

Nuclear lamins form the lamina on the interior surface of the nuclear envelope, and regulate nuclear metabolic events, including DNA replication and organization of chromatin. The current study is aimed at understanding the role of executioner caspase 6 on lamin A integrity in islet β-cells under duress of glucotoxic (20 mM glucose; 24 h) and diabetic conditions. Under glucotoxic conditions, glucose-stimulated insulin secretion and metabolic cell viability were significantly attenuated in INS-1 832/13 cells. Further, exposure of normal human islets, rat islets and INS-1 832/13 cells to glucotoxic conditions leads to caspase 6 activation and lamin A degradation, which is also observed in islets from the Zucker diabetic fatty rat, a model for type 2 diabetes (T2D), and in islets from a human donor with T2D. Z-Val-Glu-Ile-Asp-fluoromethylketone, a specific inhibitor of caspase 6, markedly attenuated high glucose-induced caspase 6 activation and lamin A degradation, confirming that caspase 6 mediates lamin A degradation under high glucose exposure conditions. Moreover, Z-Asp-Glu-Val-Asp-fluoromethylketone, a known caspase 3 inhibitor, significantly inhibited high glucose-induced caspase 6 activation and lamin A degradation, suggesting that activation of caspase 3 might be upstream to caspase 6 activation in the islet β-cell under glucotoxic conditions. Lastly, we report expression of ZMPSTE24, a zinc metallopeptidase involved in the processing of prelamin A to mature lamin A, in INS-1 832/13 cells and human islets; was unaffected by high glucose. We conclude that caspases 3 and 6 could contribute to alterations in the integrity of nuclear lamins leading to metabolic dysregulation and failure of the islet β-cell.     

Studies on the epoxidation of mahua oil (Madhumica indica) by hydrogen peroxide

Mahua oil (Madhumica indica) with an iodine value of 88 g/100 g, and containing 46% oleic acid and 12.74% linoleic acid, was epoxidised in situ with hydrogen peroxide as oxygen donor and glacial acetic acid as active oxygen carrier in presence of catalytic amount of an inorganic acid. Catalytic loading of two different acids, i.e., H2SO4 and HNO3 were studied, and H2SO4 was found to be more effective in terms of conversion to oxirane. The effects of various parameters, such as temperature, hydrogen peroxide-to-ethylenic unsaturation mole ratio, acetic acid-to-ethylenic unsaturation mole ratio, and stirring speed, on the epoxidation rate as well as on the oxirane ring stability and iodine value of the epoxidised mahua oil (EMO) were studied. The effects of these parameters on the conversion to the epoxidised oil were studied and the optimum conditions were established. The rate constant and activation energy for epoxidation of MO was found to be of the order of 10(-6) l mol(-1) s(-1) and 14.5 kcal mol(-1), respectively. Thermodynamic parameters such as enthalpy, entropy and free energy of activation were found to be of 13.8 kcal mol(-1), -51.1 cal mol(-1) K(-1) and 30.6 kcal mol(-1), respectively. Relative conversion data showed that it was possible to develop epoxides from locally available natural renewable resources such as mahua oil.