in silico analyses of metabolic pathway and protein interaction network for identification of next gen therapeutic targets in Chlamydophila pneumoniae

Chlamydophila pneumoniae, the causative agent of chronic obstructive pulmonary disease (COPD), is presently the fifth mortality causing chronic disease in the world. The understanding of disease and treatment options are limited represents a severe concern and a need for better therapeutics. With the advancements in the field of complete genome sequencing and computational approaches development have lead to metabolic pathway analysis and protein-protein interaction network which provides vital evidence to the protein function and has been appropriate to the fields such as systems biology and drug discovery. Protein interaction network analysis allows us to predict the most potential drug targets among large number of the non-homologous proteins involved in the unique metabolic pathway. A computational comparative metabolic pathway analysis of the host H. sapiens and the pathogen C pneumoniae AR39 has been carried out at three level analyses. Firstly, metabolic pathway analysis was performed to identify unique metabolic pathways and non-homologous proteins were identified. Secondly, essentiality of the proteins was checked, where these proteins contribute to the growth and survival of the organism. Finally these proteins were further subjected to predict protein interaction networks. Among the total 65 pathways in the C pneumoniae AR39 genome 10 were identified as the unique metabolic pathways which were not found in the human host, 32 enzymes were predicted as essential and these proteins were considered for protein interaction analysis, later using various criteria''s we have narrowed down to prioritize ribonucleotide-diphosphate reductase subunit beta as a potential drug target which facilitate for the successful entry into drug designing.     

Insights into the molecular regulatory network of pathomechanisms in osteochondroma

Osteochondroma is a benign autosomal dominant hereditary disease characterized by abnormal proliferation of cartilage in the long bone. It is divided into solitary osteochondroma and hereditary multiple exostoses (HMEs). The exostosin-1 (EXT-1) and exostosin-2 (EXT-2) gene mutations are well-defined molecular mechanisms in the pathogenesis of HME. EXT-1 and EXT-2 encode glycosyltransferases that are necessary for the synthesis of heparin sulfate. Accumulating evidence suggests that mutations in the EXT family induce changes in isolated hypogonadotropic hypogonadism-parathyroid hormone-related protein, bone morphogenetic protein, and fibroblast growth factor signaling pathways. Studies have also found that a large number of microRNAs (miRNAs) are abnormally expressed in osteochondroma tissues, and some of them also participate in several major signaling pathways. The regulation of miRNA expression could be another breakthrough in the treatment of osteochondroma. Although the pathogenesis of osteochondroma is very complicated, significant progress has been made in recent years. It is hoped that the pathogenesis of osteochondroma will be clearly understood and the most effective methods for the prevention and treatment of osteochondroma will be determined. This review provides an update on the recent progress in the interpretation of the underlying molecular mechanisms of osteochondroma.     

Developmental sequence of bone-resorbing cells induced by intramuscular implantation of mineral-containing bone particles into rainbow trout,Oncorhynchus mykiss

Mineral-containing bone particles (BPs) were implanted intramuscularly into rainbow trout (Oncorhynchus mykiss) to investigate the sequence of appearance of bone-resorbing cells. A fibrous substance first surrounded the implanted BPs and was gradually replaced by connective tissue containing capillaries. Two weeks after BP implantation, relatively small multinucleated cells (type-1 cells), whose cytoplasm stained deeply with hematoxylin, appeared along the surfaces of the BPs. At later stages (after 4–8 weeks), the majority of cells which appeared to be resorbing the BPs were multinucleated cells whose cytoplasm stained deeply with eosin (type-2 cells). Type-2 cells contained more nuclei than type-1 cells. Electron-microscopical observations revealed that type-2 cells had the characteristic features of osteoclasts: the presence of numerous mitochondria, vacuoles and granules, and a differentiation of the cell membrane and cytoplasm into a ruffled border and clear zone, respectively. A tartrate-resistant acid phosphatase activity, which is an established characteristic of osteoclasts in terrestrial vertebrates, but which had not previously been examined in teleosts, was demonstrated histochemically in the type-2 cells. Development of type-2 cells was closely correlated with the development of connective tissue. These findings suggest that the development of a capillary network around the implanted BPs enables circulating osteoclast-progenitors to reach the surface of the BPs.     

The Short-chain Dehydrogenase/Reductase Engineering Database (SDRED): A classification and analysis system for a highly diverse enzyme family

The Short-chain Dehydrogenases/Reductases Engineering Database (SDRED) covers one of the largest known protein families (168 150 proteins). Assignment to the superfamilies of Classical and Extended SDRs was achieved by global sequence similarity and by identification of family-specific sequence motifs. Two standard numbering schemes were established for Classical and Extended SDRs that allow for the determination of conserved amino acid residues, such as cofactor specificity determining positions or superfamily specific sequence motifs. The comprehensive sequence dataset of the SDRED facilitates the refinement of family-specific sequence motifs. The glycine-rich motifs for Classical and Extended SDRs were refined to improve the precision of superfamily classification. In each superfamily, the majority of sequences formed a tightly connected sequence network and belonged to a large homologous family. Despite their different sequence motifs and their different sequence length, the two sequence networks of Classical and Extended SDRs are not separate, but connected by edges at a threshold of 40% sequence similarity, indicating that all SDRs belong to a large, connected network. The SDRED is accessible at https://sdred.biocatnet.de/.     

Cytokine array analysis of peritoneal fluid between women with endometriosis of different stages and those without endometriosis

Cytokines are key mediators of intercellular communication and are likely to promote the development and progression of endometriosis. Previous studies provided evidence that endometriosis develops as a result of the pathogenetic factors in the peritoneal environment, especially the peritoneal fluid (PF). We determined different cytokine expression in peritoneal fluid between women with minimal/mild and moderate/severe endometriosis and those without endometriosis using the cytokine array. As a result, 78 cytokines were found to have a threefold change, including 74 increases and four decreases in endometriosis compared with the control group; 96 cytokines had a threefold change including 91 increases and five decreases in minimal and mild endometriosis compared with the control group; 83 cytokines had a threefold change including 14 increases and 69 decreases in moderate and severe endometriosis compared with minimal and mild endometriosis. The cytokine networks were produced by Pathway Studio software and revealed that most cytokines are involved in cell binding, interaction and protein synthesis and transportation regulation. Among them activin A, Smad7 and β-nerve growth factor are the most interesting as they may be involved in the pathogenesis of endometriosis. These results suggest that cytokines are very important factors in the development of endometriosis. The findings of differentially expressed cytokines improves our knowledge of the pathogenesis and development of endometriosis and these findings warrant further studies to develop potential targets for the diagnosis and treatment of endometriosis.     

Internodons as equivalence classes in genealogical networks: building-blocks for a rigorous species concept

Among the options suggested in phylogenetic systematics to solve the species problem is the Hennigian or internodal species concept. This concept interprets species as parts of the genealogical network of individual organisms between two successive permanent splits or between a permanent split and an extinction event. Though this option is at present not favoured by phylogeneticists, we believe that, to solve the species problem, there is no alternative to finding a satisfactory partition of the genealogical network. In previous work a formal definition has been developed of Hennigian or internodal species (called internodons here), based on a logical relation between individual organisms. In this paper, we prove that this definition indeed partitions genealogical networks exhaustively into mutually exclusive entities, by showing that the defining relation is an equivalence relation. Although internodons should not themselves be seen as species, they are essential building-blocks for any satisfying species concept.     

Identification of novel therapeutic targets for neuropathic pain based on gene expression patterns

Neuropathic pain (NP) caused by nerve injury or dysfunction is one of the most challenging neurological diseases. In-depth study of disease signatures contributes to the development of novel target treatment for NP. In this study, we analyzed expression profiles of qualified NP datasets (GSE24982 and GSE63442) deposited at Gene Expression Omnibus database by systematic bioinformatics approaches. We analyzed the differentially expressed genes of high and low pain compared with normal control group, and between spinal nerve ligation (SNL) injury model and sham-operation group. A total of 1,243 upregulated and 1,533 downregulated genes were identified in GSE24982, 380 upregulated and 355 downregulated genes were identified in GSE63442. By comparing low-pain samples with the corresponding sham-operation group, we identified 457 upregulated and 409 downregulated genes. Overlapping genes were screened out and signaling pathway and expression regulation model analyses were performed. SCN10A and SST were identified as biomarkers for NP. In conclusion, our study showed the expression pattern of gene about NP. These identified biomarkers could serve as potential therapeutic targets for treating NP.