A possible model of benzimidazole binding to beta-tubulin disclosed by invoking an inter-domain movement.

Although it is well established that benzimidazole (BZMs) compounds exert their therapeutic effects through binding to helminth beta-tubulin and thus disrupting microtubule-based processes in the parasites, the precise location of the benzimidazole-binding site on the beta-tubulin molecule has yet to be determined. In the present study, we have used previous experimental data as cues to help identify this site. Firstly, benzimidazole resistance has been correlated with a phenylalanine-to-tyrosine substitution at position 200 of Haemonchus contortus beta-tubulin isotype-I. Secondly, site-directed mutagenesis studies, using fungi, have shown that other residues in this region of the protein can influence the interaction of benzimidazoles with beta-tubulin. However, the atomic structure of the alphabeta-tubulin dimer shows that residue 200 and the other implicated residues are buried within the protein. This poses the question: how might benzimidazoles interact with these apparently inaccessible residues? In the present study, we present a mechanism by which those residues generally believed to interact with benzimidazoles may become accessible to the drugs. Furthermore, by docking albendazole-sulphoxide into a modelled H. contortus beta-tubulin molecule we offer a structural explanation for how the mutation conferring benzimidazole resistance in nematodes may act, as well as a possible explanation for the species-specificity of benzimidazole anthelmintics.

Novel Analysis of Oceanic Surface Water Metagenomes Suggests Importance of Polyphosphate Metabolism in Oligotrophic Environments

Polyphosphate is a ubiquitous linear homopolymer of phosphate residues linked by high-energy bonds similar to those found in ATP. It has been associated with many processes including pathogenicity, DNA uptake and multiple stress responses across all domains. Bacteria have also been shown to use polyphosphate as a way to store phosphate when transferred from phosphate-limited to phosphate-rich media - a process exploited in wastewater treatment and other environmental contaminant remediation. Despite this, there has, to date, been little research into the role of polyphosphate in the survival of marine bacterioplankton in oligotrophic environments. The three main proteins involved in polyphosphate metabolism, Ppk1, Ppk2 and Ppx are multi-domain and have differential inter-domain and inter-gene conservation, making unbiased analysis of relative abundance in metagenomic datasets difficult. This paper describes the development of a novel Isofunctional Homolog Annotation Tool (IHAT) to detect homologs of genes with a broad range of conservation without bias of traditional expect-value cutoffs. IHAT analysis of the Global Ocean Sampling (GOS) dataset revealed that genes associated with polyphosphate metabolism are more abundant in environments where available phosphate is limited, suggesting an important role for polyphosphate metabolism in marine oligotrophs.

Characterization of Inter-Body Interference in Context Aware Body Area Networking (CABAN)

The characterization and understanding of body to body communication channels is a pivotal step in the development of emerging wireless applications such as ad-hoc personnel localisation and context aware body area networks (CABAN). The latter is a recent innovation where the inherent mobility of body area networks can be used to improve the coexistence of multiple co-located BAN users. Rather than simply accepting reductions in communication performance, sensed changes in inter-network co-channel interference levels may facilitate intelligent inter-networking; for example merging or splitting with other BANs that remain in the same domain. This paper investigates the inter-body interference using controlled measurements of the full mesh interconnectivity between two ambulatory BANs operating in the same environment at 2.45 GHz. Each of the twelve network nodes reported received signal strength to allow for the creation of carrier to interference ratio time series with an overall entire mesh sampling period of 54 ms. The results indicate that even with two mobile networks, it is possible to identify the onset of co-channel interference as the BAN users move towards each other and, similarly, the transition to more favourable physical layer channel conditions as they move apart. © 2011 IEEE.

Implementation of Content Centric Networks Through Domain Name System

Content Centric Network (CCN) is a proposed future internet architecture that is based on the concept of contents name instead of the hosts name followed in the traditional internet architecture. CCN architecture might do changes in the existing internet architecture or might replace it completely. In this paper, we present modifications to the existing Domain Name System (DNS) based on the CCN architecture requirements without changing the existing routing architecture. Hence the proposed solution achieves the benefits of both CCN and existing network infrastructure (i.e. content based routing, independent of host location, caching and content delivery protocols).