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.     

Coupling efficiency of rhodopsin and transducin in bicelles

G protein coupled receptors (GPCRs) can be activated by various extracellular stimuli, including hormones, peptides, odorants, neurotransmitters, nucleotides, or light. After activation, receptors interact with heterotrimeric G proteins and catalyze GDP release from the Gα subunit, the rate limiting step in G protein activation, to form a high affinity nucleotide-free GPCR-G protein complex. In vivo, subsequent GTP binding reduces affinity of the Gα protein for the activated receptor. In this study, we investigated the biochemical and structural characteristics of the prototypical GPCR, rhodopsin, and its signaling partner, transducin (G(t)), in bicelles to better understand the effects of membrane composition on high affinity complex formation, stability, and receptor mediated nucleotide release. Our results demonstrate that the high-affinity complex (rhodopsin-G(t)(empty)) forms more readily and has dramatically increased stability when rhodopsin is integrated into bicelles of a defined composition. We increased the half-life of functional complex to 1 week in the presence of negatively charged phospholipids. These data suggest that a membrane-like structure is an important contributor to the formation and stability of functional receptor-G protein complexes and can extend the range of studies that investigate properties of these complexes.     

Influence of gibberellic acid on auxin biosynthesis and their effects on coleoptile elongation in garlic

To demonstrate the effect of auxin on intact coleoptile growth, garlic (Allium sativum L.) cloves were inoculated in agar supplemented with DW (control), GA₃ and GA₃+tryptophan (a precursor of IAA, GA₃+T). The coleoptiles were harvested at 24 h intervals to measure growth in terms of length, activities of IAAld DH (which convert tryptophan to IAA) and peroxidase (that oxidizes IAA). Contents of endogenous IAA and PAA were also measured by indirect ELISA. Peroxidase activity was suppressed by GA₃ treatment and increased by GA₃+T treatment. Although endogenous contents of IAA were increased by the addition of GA₃ and even more by GA₃+T in the media, there was no further increase in coleoptile length, suggesting that garlic coleoptiles are sufficient in their production of IAA.     

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.     

Differential Metabolic Reprogramming by Zika Virus Promotes Cell Death in Human versus Mosquito Cells

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Phenotypic and Genetic Diversity of Aeromonas Species Isolated from Fresh Water Lakes in Malaysia

Gram-negative bacilli of the genus Aeromonas are primarily inhabitants of the aquatic environment. Humans acquire this organism from a wide range of food and water sources as well as during aquatic recreational activities. In the present study, the diversity and distribution of Aeromonas species from freshwater lakes in Malaysia was investigated using glycerophospholipid-cholesterol acyltransferase (GCAT) and RNA polymerase sigma-factor (rpoD) genes for speciation. A total of 122 possible Aeromonas strains were isolated and confirmed to genus level using the API20E system. The clonality of the isolates was investigated using ERIC-PCR and 20 duplicate isolates were excluded from the study. The specific GCAT-PCR identified all isolates as belonging to the genus Aeromonas, in agreement with the biochemical identification. A phylogenetic tree was constructed using the rpoD gene sequence and all 102 isolates were identified as: A. veronii 43%, A. jandaei 37%, A. hydrophila 6%, A. caviae 4%, A. salmonicida 2%, A. media 2%, A. allosaccharophila 1%, A. dhakensis 1% and Aeromonas spp. 4%. Twelve virulence genes were present in the following proportions—exu 96%, ser 93%, aer 87%, fla 83%, enolase 70%, ela 62%, act 54%, aexT 33%, lip 16%, dam 16%, alt 8% and ast 4%, and at least 2 of these genes were present in all 102 strains. The ascV, aexU and hlyA genes were not detected among the isolates. A. hydrophila was the main species containing virulence genes alt and ast either present alone or in combination. It is possible that different mechanisms may be used by each genospecies to demonstrate virulence. In summary, with the use of GCAT and rpoD genes, unambiguous identification of Aeromonas species is possible and provides valuable data on the phylogenetic diversity of the organism.     

Change in Mesoherbivore Browsing Is Mediated by Elephant and Hillslope Position

Elephant are considered major drivers of ecosystems, but their effects within small-scale landscape features and on other herbivores still remain unclear. Elephant impact on vegetation has been widely studied in areas where elephant have been present for many years. We therefore examined the combined effect of short-term elephant presence (< 4 years) and hillslope position on tree species assemblages, resource availability, browsing intensity and soil properties. Short-term elephant presence did not affect woody species assemblages, but did affect height distribution, with greater sapling densities in elephant access areas. Overall tree and stem densities were also not affected by elephant. By contrast, slope position affected woody species assemblages, but not height distributions and densities. Variation in species assemblages was statistically best explained by levels of total cations, Zinc, sand and clay. Although elephant and mesoherbivore browsing intensities were unaffected by slope position, we found lower mesoherbivore browsing intensity on crests with high elephant browsing intensity. Thus, elephant appear to indirectly facilitate the survival of saplings, via the displacement of mesoherbivores, providing a window of opportunity for saplings to grow into taller trees. In the short-term, effects of elephant can be minor and in the opposite direction of expectation. In addition, such behavioural displacement promotes recruitment of saplings into larger height classes. The interaction between slope position and elephant effect found here is in contrast with other studies, and illustrates the importance of examining ecosystem complexity as a function of variation in species presence and topography. The absence of a direct effect of elephant on vegetation, but the presence of an effect on mesoherbivore browsing, is relevant for conservation areas especially where both herbivore groups are actively managed.     

Physiological and biochemical changes associated with cotton fibre development

The relationship between growth and some enzymes of carbohydrate metabolism in developing cotton fibre were studied. Two respiratory pathways of glucose oxidation i.e. oxidative pentose phosphate pathway (OPPP) and glycolysis operates in the elongating cotton fibres and the extent of their operation varies with the demand for respiratory products. In this respect, hexokinase, G-6-PDH, 6PGDH, and MDH show increased activities during the period of rapid cell elongation and decreased activities when rate slows down. The conversion of PEP to malate and/or via a transhydrogenase system consisting of enzymes PEPC, MDH and NADP-MDH(d) may play a significant role in carbohydrate compartmentation of developing cotton fibre. As the rate of fibre growth slows down, a decline in enzyme activities, points to a shift in metabolic priorities.     

Biocomplexity in large tree mortality: interactions between elephant,fire and landscape in an African savanna

The vegetation dynamics of the savanna ecosystem are driven by complex interactions between biotic and abiotic factors, and thus are expected to exhibit emergent properties of biocomplexity. We explore the relative importance of static and dynamic drivers in explaining the patterns of mortality of large trees in the Kruger National Park, South Africa. Data on large trees were collected from 22 transects in April 2006, and these transects were re‐sampled in November 2008. Of the 2546 individually‐identified trees that were re‐sampled, 290 (11.4%) died in the interim. We tested several competing hypotheses with varying levels of complexity, and found that mortality of large trees was affected mainly by both static (geophysical and landscape characteristics) and dynamic (elephant damage and fire) factors that were either additive or interactive in their effects. Elephant damage was the main predictor of tree mortality, but fire also played an important role depending on the landscape type. Other static variables such as position‐on‐slope, height below canopy, and altitude had weak effects in explaining tree mortality. These results indicate that keystone features such as large trees, show differential vulnerability to mortality that is landscape‐specific. For conservation managers, this implies that the dynamic drivers (elephant and fire) of tree mortality have to be managed at the specific landscape‐level. We suggest that this emergent biocomplexity in the spatial and temporal patterns of large tree mortality is not unique to the African savannas, but is likely widespread across heterogeneous landscapes.     

A CHRNA5 allele related to nicotine addiction and schizophrenia

Schizophrenia and nicotine addiction are both highly heritable phenotypes. Because individuals with schizophrenia have a higher rate of smoking than those in the general population, one could hypothesize that genes associated with smoking might be overrepresented in schizophrenia and thus help explain their increased smoking incidence. Although a number of genes have been proposed to explain the increased smoking risk in schizophrenia, none of them have been consistently linked to smoking and schizophrenia, and thus difficult to explain the increased smoking in schizophrenia. A functional smoking-related nicotinic acetylcholine receptor α5 subunit gene (CHRNA5) nonsynonymous single nucleotide polymorphism (SNP) rs16969968 (Asp398Asn) has recently been discovered and replicated. As such, we tested whether this variant contributes to smoking in schizophrenia in a sample of 313 schizophrenia patients and 525 controls. The Asp398Asn risk allele is significantly associated with smoking severity independently in schizophrenia patient smokers (P = 0.001) and control smokers (P = 0.029). Furthermore, the same risk allele is significantly associated with schizophrenia in both Caucasian (P = 0.022) and African-American (P = 0.006) nonsmoker schizophrenia patients compared with control nonsmokers. Intriguingly, this SNP was not significantly associated with smoking status (smokers vs. nonsmokers) in either schizophrenia patients or controls. Therefore, our study identifies a genetic variant that is simultaneously linked to smoking and schizophrenia in the same cohort, but whether this SNP contributes to the increased smoking prevalence in schizophrenia patients requires additional studies.