Mutations in dynamin 2 cause dominant centronuclear myopathy

Autosomal dominant centronuclear myopathy is a rare congenital myopathy characterized by delayed motor milestones and muscular weakness. In 11 families affected by centronuclear myopathy, we identified recurrent and de novo missense mutations in the gene dynamin 2 (DNM2, 19p13.2), which encodes a protein involved in endocytosis and membrane trafficking, actin assembly and centrosome cohesion. The transfected mutants showed reduced labeling in the centrosome, suggesting that DNM2 mutations might cause centronuclear myopathy by interfering with centrosome function.     

Nosiheptide,a sulfur-containing peptide antibiotic isolated fromStreptomyces actuosus 40037

Summary Nosiheptide (9671 R.P.) isolated fromStreptomyces actuosus 40037 (NRRL 2954) is a sulfur-containing polypeptidic antibiotic, quite different from all the other members of this family. Very active in vitro against gram-positive bacteria, it is inactive in vivo in experimentally infected mice. Not toxic, even at high dose, it may be used as a feed additive for chickens and pigs and it shows a favourable effect on the growth and conversion index.     

Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli

The recognition and phagocytosis of microbes by macrophages is a principal aspect of innate immunity that is conserved from insects to humans. Drosophila melanogaster has circulating macrophages that phagocytose microbes similarly to mammalian macrophages, suggesting that insect macrophages can be used as a model to study cell-mediated innate immunity. We devised a double-stranded RNA interference-based screen in macrophage-like Drosophila S2 cells, and have defined 34 gene products involved in phagocytosis. These include proteins that participate in haemocyte development, vesicle transport, actin cytoskeleton regulation and a cell surface receptor. This receptor, Peptidoglycan recognition protein LC (PGRP-LC), is involved in phagocytosis of Gram-negative but not Gram-positive bacteria. Drosophila humoral immunity also distinguishes between Gram-negative and Gram-positive bacteria through the Imd and Toll pathways, respectively; however, a receptor for the Imd pathway has not been identified. Here we show that PGRP-LC is important for antibacterial peptide synthesis induced by Escherichia coli both in vitro and in vivo. Furthermore, totem mutants, which fail to express PGRP-LC, are susceptible to Gram-negative (E. coli), but not Gram-positive, bacterial infection. Our results demonstrate that PGRP-LC is an essential component for recognition and signalling of Gram-negative bacteria. Furthermore, this functional genomic approach is likely to have applications beyond phagocytosis.     

High-speed linear optics quantum computing using active feed-forward

As information carriers in quantum computing, photonic qubits have the advantage of undergoing negligible decoherence. However, the absence of any significant photon-photon interaction is problematic for the realization of non-trivial two-qubit gates. One solution is to introduce an effective nonlinearity by measurements resulting in probabilistic gate operations. In one-way quantum computation, the random quantum measurement error can be overcome by applying a feed-forward technique, such that the future measurement basis depends on earlier measurement results. This technique is crucial for achieving deterministic quantum computation once a cluster state (the highly entangled multiparticle state on which one-way quantum computation is based) is prepared. Here we realize a concatenated scheme of measurement and active feed-forward in a one-way quantum computing experiment. We demonstrate that, for a perfect cluster state and no photon loss, our quantum computation scheme would operate with good fidelity and that our feed-forward components function with very high speed and low error for detected photons. With present technology, the individual computational step (in our case the individual feed-forward cycle) can be operated in less than 150 ns using electro-optical modulators. This is an important result for the future development of one-way quantum computers, whose large-scale implementation will depend on advances in the production and detection of the required highly entangled cluster states.     

A transglutaminase homologue as a condensation catalyst in antibiotic assembly lines

The unrelenting emergence of antibiotic-resistant bacterial pathogens demands the investigation of antibiotics with new modes of action. The pseudopeptide antibiotic andrimid is a nanomolar inhibitor of the bacterial acetyl-CoA carboxylase that catalyses the first committed step in prokaryotic fatty acid biosynthesis. Recently, the andrimid (adm) biosynthetic gene cluster was isolated and heterologously expressed in Escherichia coli. This establishes a heterologous biological host in which to rapidly probe features of andrimid formation and to use biosynthetic engineering to make unnatural variants of this important and promising new class of antibiotics. Bioinformatic analysis of the adm cluster revealed a dissociated biosynthetic assembly system lacking canonical amide synthases between the first three carrier protein domains. Here we report that AdmF, a transglutaminase (TGase) homologue, catalyses the formation of the first amide bond, an N-acyl-beta-peptide link, in andrimid biosynthesis. Hence, AdmF is a newly discovered biosynthetic enzyme that acts as a stand-alone amide synthase between protein-bound, thiotemplated substrates in an antibiotic enzymatic assembly line. TGases (enzyme class (EC) 2.3.2.13) normally catalyse the cross-linking of (poly)peptides by creating isopeptidic bonds between the gamma-carboxamide group of a glutamine side chain of one protein and various amine donors, including lysine side chains. To the best of our knowledge, the present study constitutes the first report of a TGase-like enzyme recruited for the assembly of an antibiotic. Moreover, genome mining using the AdmF sequence yielded additional TGases in unassigned natural product biosynthetic pathways. With many more microbial genomes being sequenced, such a strategy could potentially unearth biosynthetic pathways producing new classes of antibiotics.