A novel harmony search-K means hybrid algorithm for clustering gene expression data

Recent progress in bioinformatics research has led to the accumulation of huge quantities of biological data at various data sources. The DNA microarray technology makes it possible to simultaneously analyze large number of genes across different samples. Clustering of microarray data can reveal the hidden gene expression patterns from large quantities of expression data that in turn offers tremendous possibilities in functional genomics, comparative genomics, disease diagnosis and drug development. The k- ¬means clustering algorithm is widely used for many practical applications. But the original k-¬means algorithm has several drawbacks. It is computationally expensive and generates locally optimal solutions based on the random choice of the initial centroids. Several methods have been proposed in the literature for improving the performance of the k-¬means algorithm. A meta-heuristic optimization algorithm named harmony search helps find out near-global optimal solutions by searching the entire solution space. Low clustering accuracy of the existing algorithms limits their use in many crucial applications of life sciences. In this paper we propose a novel Harmony Search-K means Hybrid (HSKH) algorithm for clustering the gene expression data. Experimental results show that the proposed algorithm produces clusters with better accuracy in comparison with the existing algorithms.     

Application of magnetic techniques in the field of drug discovery and biomedicine

Magnetic separation technology, using magnetic particles, is quick and easy method for sensitive and reliable capture of specific proteins, genetic material and other biomolecules. The technique offers an advantage in terms of subjecting the analyte to very little mechanical stress compared to other methods. Secondly, these methods are non-laborious, cheap and often highly scalable. Moreover, techniques employing magnetism are more amenable to automation and miniaturization. Now that the human genome is sequenced and about 30,000 genes are annotated, the next step is to identify the function of these individual genes, carrying out genotyping studies for allelic variation and SNP analysis, ultimately leading to identification of novel drug targets. In this post-genomic era, technologies based on magnetic separation are becoming an integral part of todays biology laboratory. This article briefly reviews the selected applications of magnetic separation techniques in the field of biotechnology, biomedicine and drug discovery.     

Restoring the Narrative of American Environmentalism

The conventional narrative of American environmentalism is no longer very helpful for conservationists and restorationists seeking philosophical justification and guidance for their work. The tradition has often been cropped into a narrower and simplified account of the battle between the philosophies of wise use and preservation, a move bolstered by the turn to historical images of President Teddy Roosevelt and John Muir visiting California's Yosemite National Park in the early years of the twentieth century. This cropped conservation picture needs to be restored and widened to engage the pragmatism that has always been a part of the U.S. environmental tradition, but that became eclipsed by preservationist ideology with the rise of the fields of environmental history and environmental philosophy in the late twentieth century. Restoring this lost pragmatism to the environmental tradition will prove vital to recovering the value of environmental history and philosophy for conservation and restoration practice and to reclaiming a more holistic and useful narrative of people, culture, and environment.     

Following Nature: Bioinspired Mediation Strategy for Gram‐Positive Bacterial Cells

Employment of redox polymers as mediators is a promising concept to facilitate electron transfer (ET) and improve operational performance of bioelectrochemical systems. Materials science offers a broad range of mediation possibilities; however, their employment so far relies on a trial‐and‐error approach, since there is no comprehensive understanding of the nature of the ET between bacterial cells and redox polymers. In the current work, the polymer–cell interaction is investigated in detail and clear experimental evidence that a redox polymer containing quinone moieties mimicking the natural bacterial charge carriers can be incorporated into the respiratory chain of Gram‐positive Enterococcus faecalis cells and outperform monomeric mediator in ET features is reported. The presented findings disclose the main principles to overcome incompatibilities between abiotic charge carriers and microbial metabolism and provide essential knowledge for further development of mediated microbial bioelectrocatalysis.     

Short chain oligogalacturonides induce ethylene production and expression of the gene encoding aminocyclopropane 1-carboxylic acid oxidase in tomato plants

Oligogalacturonic acids (OGAs), derived from plant cell wall pectin, have been implicated in a number of signal transduction pathways involved in growth, development and defense responses of higher plants. This study investigates the size range of OGAs capable of inducing ethylene synthesis in tomato plants, and demonstrates that in contrast with many other effects, only short chain OGAs are active. Oligomers across a range of DP from 2-15 were separated and purified to homogeneity by QAE-Sephadex anion exchange chromatography using a novel elution system. The OGAs were applied to tomato plants and assayed for their ability to induce ethylene gas release and changes in steady state levels of mRNA encoding the ethylene forming enzyme aminocyclopropane-1-carboxylic acid oxidase (ACO). The study demonstrated that only OGAs in the size range of DP4-6 were active both in eliciting ACO expression and in the production of ethylene.      

Historical trends in frog populations in New Zealand based on public perceptions

Surveys were distributed to New Zealand land users in 1998 and 2008 to acquire information about New Zealand frogs with the aim of compiling and mapping their distribution and inferred population trends without costly and time-consuming field surveys. The overall frog population trend was reported as declining, with possible causes reported as an increase in agriculture, an increase in the distribution of predatory fish and disease. The resultant maps could be used for four main purposes: 1) to identify regions where Litoria populations are known to occur, which can be eliminated when considering suitable regions for translocation of Leiopelma; 2) to identify growing or stable populations of Litoria species, which may assist future disease surveys, population monitoring and to identify sources of genetic material that may serve as an Ark for declining Australian populations; 3) to highlight populations that are in decline to enable effective targeting of detailed disease studies; and 4) to approximate the stability of amphibian populations in the absence of more accurate, but costly, scientific monitoring.     

Isothermal titration calorimetry uncovers substrate promiscuity of bicupin oxalate oxidase from Ceriporiopsis subvermispora

Isothermal titration calorimetry (ITC) may be used to determine the kinetic parameters of enzyme-catalyzed reactions when neither products nor reactants are spectrophotometrically visible and when the reaction products are unknown. We report here the use of the multiple injection method of ITC to characterize the catalytic properties of oxalate oxidase (OxOx) from Ceriporiopsis subvermispora (CsOxOx), a manganese dependent enzyme that catalyzes the oxygen-dependent oxidation of oxalate to carbon dioxide in a reaction coupled with the formation of hydrogen peroxide. CsOxOx is the first bicupin enzyme identified that catalyzes this reaction. The multiple injection ITC method of measuring OxOx activity involves continuous, real-time detection of the amount of heat generated (dQ) during catalysis, which is equal to the number of moles of product produced times the enthalpy of the reaction (ΔH_app). Steady-state kinetic constants using oxalate as the substrate determined by multiple injection ITC are comparable to those obtained by a continuous spectrophotometric assay in which H₂O₂ production is coupled to the horseradish peroxidase-catalyzed oxidation of 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) and by membrane inlet mass spectrometry. Additionally, we used multiple injection ITC to identify mesoxalate as a substrate for the CsOxOx-catalyzed reaction, with a kinetic parameters comparable to that of oxalate, and to identify a number of small molecule carboxylic acid compounds that also serve as substrates for the enzyme.     

Hydrophobic salt-modified Nafion for enzyme immobilization and stabilization

Over the last decade, there has been a wealth of application for immobilized and stabilized enzymes including biocatalysis, biosensors, and biofuel cells. In most bioelectrochemical applications, enzymes or organelles are immobilized onto an electrode surface with the use of some type of polymer matrix. This polymer scaffold should keep the enzymes stable and allow for the facile diffusion of molecules and ions in and out of the matrix. Most polymers used for this type of immobilization are based on polyamines or polyalcohols - polymers that mimic the natural environment of the enzymes that they encapsulate and stabilize the enzyme through hydrogen or ionic bonding. Another method for stabilizing enzymes involves the use of micelles, which contain hydrophobic regions that can encapsulate and stabilize enzymes. In particular, the Minteer group has developed a micellar polymer based on commercially available Nafion. Nafion itself is a micellar polymer that allows for the channel-assisted diffusion of protons and other small cations, but the micelles and channels are extremely small and the polymer is very acidic due to sulfonic acid side chains, which is unfavorable for enzyme immobilization. However, when Nafion is mixed with an excess of hydrophobic alkyl ammonium salts such as tetrabutylammonium bromide (TBAB), the quaternary ammonium cations replace the protons and become the counter ions to the sulfonate groups on the polymer side chains (Figure 1). This results in larger micelles and channels within the polymer that allow for the diffusion of large substrates and ions that are necessary for enzymatic function such as nicotinamide adenine dinucleotide (NAD). This modified Nafion polymer has been used to immobilize many different types of enzymes as well as mitochondria for use in biosensors and biofuel cells. This paper describes a novel procedure for making this micellar polymer enzyme immobilization membrane that can stabilize enzymes. The synthesis of the micellar enzyme immobilization membrane, the procedure for immobilizing enzymes within the membrane, and the assays for studying enzymatic specific activity of the immobilized enzyme are detailed below.     

Fabrication of macroporous chitosan scaffolds doped with carbon nanotubes and their characterization in microbial fuel cell operation

Chitosan (CHIT) scaffolds doped with multi-walled carbon nanotubes (CNT) were fabricated and evaluated for their utility as a microbial fuel cell (MFC) anodic material. High resolution microscopy verified the ability of Shewanella oneidensis MR-1 to directly colonize CHIT-CNT scaffolds. Cross-linking agents 1-ethyl-3-[3-dimethylaminopropyl] carbodimide hydrochloride (EDC), glutaraldehyde and glyoxal were independently studied for their ability to strengthen the CHIT-CNT matrix without disrupting the final pore structure. 2.5 vol% glyoxal was found to be the optimal cross-linker in terms of porosity (BET surface area=30.2 m(2) g(-1)) and structural stability. Glyoxyl and EDC cross-linked CHIT-CNT scaffolds were then studied for their ability to transfer electrons to underlying glassy carbon. Results showed an open circuit cell voltage of 600 mV and a maximum power density of 4.75 W/m(3) at a current density of 16 A/m(3) was achieved in non stirred batch mode, which compares well with published data using carbon felt electrodes where a power density of 3.5 W/m(3) at a current density of 7 A/m(3) have been reported. Additionally, CHIT-CNT scaffolds were impregnated into carbon felt electrodes and these results suggest that CHIT-CNT scaffolds can be successfully integrated with multiple support materials to create hybrid electrode materials. Further, preliminary tests indicate that the integrated scaffolds offer a robust macroporous electrode material that can be used in flow-through configurations.     

On the origin of the stereoselective affinity of Nutlin-3 geometrical isomers for the MDM2 protein

The stereoselective affinity of small-molecule binding to proteins is typically broadly explained in terms of the thermodynamics of the final bound complex. Using Brownian dynamics simulations, we show that the preferential binding of the MDM2 protein to the geometrical isomers of Nutlin-3, an effective anticancer lead that works by inhibiting the interaction between the proteins p53 and MDM2, can be explained by kinetic arguments related to the formation of the MDM2:Nutlin-3 encounter complex. This is a diffusively bound state that forms prior to the final bound complex. We find that the MDM2 protein stereoselectivity for the Nutlin-3a enantiomer stems largely from the destabilization of the encounter complex of its mirror image enantiomer Nutlin-3b, by the K70 residue that is located away from the binding site. On the other hand, the trans-Nutlin-3a diastereoisomer exhibits a shorter residence time in the vicinity of MDM2 compared with Nutlin-3a due to destabilization of its encounter complex by the collective interaction of pairs of charged residues on either side of the binding site: Glu25 and Lys51 on one side, and Lys94 and Arg97 on the other side. This destabilization is largely due to the electrostatic potential of the trans-Nutlin-3a isomer being largely positive over extended continuous regions around its structure, which are otherwise well-identified into positive and negative regions in the case of the Nutlin-3a isomer. Such rich insight into the binding processes underlying biological selectivity complements the static view derived from the traditional thermodynamic analysis of the final bound complex. This approach, based on an explicit consideration of the dynamics of molecular association, suggests new avenues for kinetics-based anticancer drug development and discovery.