Analysis of binding properties and specificity through identification of the interface forming residues (IFR) for serine proteases <Emphasis Type=Italic>in silico</Emphasis> docked to different inhibitors

Background  

Enzymes belonging to the same super family of proteins in general operate on variety of substrates and are inhibited by wide selection of inhibitors. In this work our main objective was to expand the scope of studies that consider only the catalytic and binding pocket amino acids while analyzing enzyme specificity and instead, include a wider category which we have named the Interface Forming Residues (IFR). We were motivated to identify those amino acids with decreased accessibility to solvent after docking of different types of inhibitors to sub classes of serine proteases and then create a table (matrix) of all amino acid positions at the interface as well as their respective occupancies. Our goal is to establish a platform for analysis of the relationship between IFR characteristics and binding properties/specificity for bi-molecular complexes.     

The co-distribution of Plasmodium falciparum and hookworm among African schoolchildren

Background

On the island of Bioko (Equatorial Guinea), insecticide-treated nets (ITNs) have been the main tool used to control malaria over the last 13 years. In 2004, started an indoor residual spraying (IRS) campaign to control malaria. The purpose of this study is to asses the impact of the two control strategies on the island of Bioko (Equatorial Guinea), with regards to Plasmodium infection and anaemia in the children under five years of age.

Methods

Two transversal studies, the first one prior to the start of the IRS campaign and the second one year later. Sampling was carried out by stratified clusters. Malaria infection was measured by means of thick and thin film, and the packed cell volume (PCV) percentage. Data related to ITN use and information regarding IRS were collected. The Pearson's chi-square and logistic regression statistical tests were used to calculate odds ratios (OR)

Results

In the first survey, 168 children were sampled and 433 children in the second one. The prevalence of infection was 40% in 2004, and significantly lower at 21.7% in 2005. PCV was 41% and 39%, respectively. 58% of the children surveyed in 2004 and 44.3% in 2005 had slept under an ITN. 78% of the dwellings studied in 2005 had been sprayed. In the 2005 survey, sleeping without a mosquito net meant a risk of infection 3 times greater than sleeping protected with a net hanged correctly and with no holes (p < 0.05).

Conclusion

IRS and ITNs have proven to be effective control strategies on the island of Bioko. The choice of one or other strategy is, above all, a question of operational feasibility and availability of local resources.     

Spectral behavior of vegetation in Harmony Point,Nelson Island,Antarctica

Biodiversity and Conservation - The present article aims to identify the spectral pattern of several species of mosses, lichens, and of an alga found in Maritime Antarctica from hyperspectral data...     

Network analysis of temporal functionalities of the gut induced by perturbations in new-born piglets

Background

Evidence is accumulating that perturbation of early life microbial colonization of the gut induces long-lasting adverse health effects in individuals. Understanding the mechanisms behind these effects will facilitate modulation of intestinal health. The objective of this study was to identify biological processes involved in these long lasting effects and the (molecular) factors that regulate them. We used an antibiotic and the same antibiotic in combination with stress on piglets as an early life perturbation. Then we used host gene expression data from the gut (jejunum) tissue and community-scale analysis of gut microbiota from the same location of the gut, at three different time-points to gauge the reaction to the perturbation. We analysed the data by a new combination of existing tools. First, we analysed the data in two dimensions, treatment and time, with quadratic regression analysis. Then we applied network-based data integration approaches to find correlations between host gene expression and the resident microbial species.

Results

The use of a new combination of data analysis tools allowed us to identify significant long-lasting differences in jejunal gene expression patterns resulting from the early life perturbations. In addition, we were able to identify potential key gene regulators (hubs) for these long-lasting effects. Furthermore, data integration also showed that there are a handful of bacterial groups that were associated with temporal changes in gene expression.

Conclusion

The applied systems-biology approach allowed us to take the first steps in unravelling biological processes involved in long lasting effects in the gut due to early life perturbations. The observed data are consistent with the hypothesis that these long lasting effects are due to differences in the programming of the gut immune system as induced by the temporary early life changes in the composition and/or diversity of microbiota in the gut.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1733-8) contains supplementary material, which is available to authorized users.     

Genomics and proteomics approaches to the study of cancer-stroma interactions

Background

The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression.

Methods

The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells.

Results

We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR.

Conclusions

A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.

     

Evolving DNA motifs to predict GeneChip probe performance

Background  

Affymetrix High Density Oligonuclotide Arrays (HDONA) simultaneously measure expression of thousands of genes using millions of probes. We use correlations between measurements for the same gene across 6685 human tissue samples from NCBI's GEO database to indicated the quality of individual HG-U133A probes. Low correlation indicates a poor probe.