High-quality draft genome sequence of Bifidobacterium longum E18, isolated from a healthy adult

Bifidobacteria are important gastrointestinal commensals of a number of animals, including humans, and various beneficial effects on host health have been attributed to them. Here, we announce the noncontiguous finished genome sequence of Bifidobacterium longum E18, isolated from a healthy adult, which reveals traits involved in its interaction with the host

Symmetric dimeric adamantanes for exploring the structure of two viroporins: influenza virus M2 and hepatitis C virus p7

Yasmine M Mandour,1 Ulrike Breitinger,2 Chunlong Ma,3 Jun Wang,3 Frank M Boeckler,4 Hans-Georg Breitinger,2 Darius P Zlotos1 1Department of Pharmaceutical Chemistry, German University in Cairo, 2Department of Biochemistry, The German University in Cairo, Cairo, Egypt; 3Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, USA; 4Department of Pharmaceutical and Medicinal Chemistry, Eberhard Karls University of Tübingen, Tübingen, Germany Background: Adamantane-based compounds have been identified to interfere with the ion-channel activity of viroporins and thereby inhibit viral infection. To better understand the difference in the inhibition mechanism of viroporins, we synthesized symmetric dimeric adamantane analogs of various alkyl-spacer lengths.Methods: Symmetric dimeric adamantane derivatives were synthesized where two amantadine or rimantadine molecules were linked by various alkyl-spacers. The inhibitory activity of the compounds was studied on two viroporins: the influenza virus M2 protein, expressed in Xenopus oocytes, using the two-electrode voltage-clamp technique, and the hepatitis C virus (HCV) p7 channels for five different genotypes (1a, 1b, 2a, 3a, and 4a) expressed in HEK293 cells using whole-cell patch-clamp recording techniques.Results: Upon testing on M2 protein, dimeric compounds showed significantly lower inhibitory activity relative to the monomeric amantadine. The lack of channel blockage of the dimeric amantadine and rimantadine analogs against M2 wild type and M2-S31N mutant was consistent with previously proposed drug-binding mechanisms and further confirmed that the pore-binding model is the pharmacologically relevant drug-binding model. On the other hand, these dimers showed similar potency to their respective monomeric analogs when tested on p7 protein in HCV genotypes 1a, 1b, and 4a while being 700-fold and 150-fold more potent than amantadine in genotypes 2a and 3a, respectively. An amino group appears to be important for inhibiting the ion-channel activity of p7 protein in genotype 2a, while its importance was minimal in all other genotypes.Conclusion: Symmetric dimeric adamantanes can be considered a prospective class of p7 inhibitors that are able to address the differences in adamantane sensitivity among the various genotypes of HCV. Keywords: adamantane, dimers, viroporins, p7, M2, HC

Molecular dynamics simulation links conformation of a pore-flanking region to hyperekplexia-related dysfunction of the inhibitory glycine receptor.

AbstractInhibitory glycine receptors mediate rapid synaptic inhibition in mammalian spinal cord and brainstem. The previously identified hyperekplexia mutation GLRA1(P250T), located within the intracellular TM1-2 loop of the GlyR α1 subunit, results in altered receptor activation and desensitization. Here, elementary steps of ion channel function of α1(250) mutants were resolved and shown to correlate with hydropathy and molar volume of residue α1(250). Single-channel recordings and rapid activation kinetic studies using laser pulse photolysis showed reduced conductance but similar open probability of α1(P250T) mutant channels. Molecular dynamics simulation of a helix-turn-helix motif representing the intracellular TM1-2 domain revealed alterations in backbone conformation, indicating an increased flexibility in these mutants that paralleled changes in elementary steps of channel function. Thus, the architecture of the TM1-2 loop is a critical determinant of ion channel conductance and receptor desensitization

High-level Process Control in Eden

High-level control of parallel process behaviour simplifies the development of parallel software substantially by freeing the programmer from low-level process management and coordination details. The latter are handled by a sophisticated runtime system which controls program execution. In this paper we look behind the scenes and show how the enormous gap between high-level parallel language constructs and their low-level implementation has been bridged in the implementation of the parallel functional language Eden. The main idea has been to specify the process control in a functional language and to restrict the extensions of the low-level runtime system to a few selected primitive operations

Eden -- Parallel Functional Programming with Haskell

Eden is a parallel functional programming language which extends Haskell with constructs for the definition and instantiation of parallel processes. Processes evaluate function applications remotely in parallel. The programmer has control over process granularity, data distribution, communication topology, and evaluation site, but need not manage synchronisation and data exchange between processes. The latter are performed by the parallel runtime system through implicit communication channels, transparent to the programmer. Common and sophisticated parallel communication patterns and topologies, so-called algorithmic skeletons, are provided as higher-order functions in a user-extensible skeleton library written in Eden. Eden is geared toward distributed settings, i.e. processes do not share any data, but can equally well be used on multicore systems. This tutorial gives an up-to-date introduction into Eden’s programming methodology based on algorithmic skeletons, its language constructs, and its layered implementation on top of the Glasgo