An allylic ketyl radical intermediate in clostridial amino-acid fermentation

The human pathogenic bacterium Clostridium difficile thrives by the fermentation of l-leucine to ammonia, CO(2), 3-methylbutanoate and 4-methylpentanoate under anaerobic conditions. The reductive branch to 4-methylpentanoate proceeds by means of the dehydration of (R)-2-hydroxy-4-methylpentanoyl-CoA to 4-methylpent-2-enoyl-CoA, which is chemically the most demanding step. Ketyl radicals have been proposed to mediate this reaction catalysed by an iron-sulphur-cluster-containing dehydratase, which requires activation by ATP-dependent electron transfer from a second iron-sulphur protein functionally similar to the iron protein of nitrogenase. Here we identify a kinetically competent product-related allylic ketyl radical bound to the enzyme by electron paramagnetic resonance spectroscopy employing isotope-labelled (R)-2-hydroxy-4-methylpentanoyl-CoA species. We also found that the enzyme generated the stabilized pentadienoyl ketyl radical from the substrate analogue 2-hydroxypent-4-enoyl-CoA, supporting the proposed mechanism. Our results imply that also other 2-hydroxyacyl-CoA dehydratases and the related benzoyl-CoA reductases-present in anaerobically living bacteria-employ ketyl radical intermediates. The absence of radical generators such as coenzyme B12, S-adenosylmethionine or oxygen makes these enzymes unprecedented in biochemistry.     

Quantum teleportation between light and matter

Quantum teleportation is an important ingredient in distributed quantum networks, and can also serve as an elementary operation in quantum computers. Teleportation was first demonstrated as a transfer of a quantum state of light onto another light beam; later developments used optical relays and demonstrated entanglement swapping for continuous variables. The teleportation of a quantum state between two single material particles (trapped ions) has now also been achieved. Here we demonstrate teleportation between objects of a different nature--light and matter, which respectively represent 'flying' and 'stationary' media. A quantum state encoded in a light pulse is teleported onto a macroscopic object (an atomic ensemble containing 10 caesium atoms). Deterministic teleportation is achieved for sets of coherent states with mean photon number (n) up to a few hundred. The fidelities are 0.58 +/- 0.02 for n = 20 and 0.60 +/- 0.02 for n = 5--higher than any classical state transfer can possibly achieve. Besides being of fundamental interest, teleportation using a macroscopic atomic ensemble is relevant for the practical implementation of a quantum repeater. An important factor for the implementation of quantum networks is the teleportation distance between transmitter and receiver; this is 0.5 metres in the present experiment. As our experiment uses propagating light to achieve the entanglement of light and atoms required for teleportation, the present approach should be scalable to longer distances.     

Transforming growth factor-beta induces development of the T(H)17 lineage

A new lineage of effector CD4+ T cells characterized by production of interleukin (IL)-17, the T-helper-17 (T(H)17) lineage, was recently described based on developmental and functional features distinct from those of classical T(H)1 and T(H)2 lineages. Like T(H)1 and T(H)2, T(H)17 cells almost certainly evolved to provide adaptive immunity tailored to specific classes of pathogens, such as extracellular bacteria. Aberrant T(H)17 responses have been implicated in a growing list of autoimmune disorders. T(H)17 development has been linked to IL-23, an IL-12 cytokine family member that shares with IL-12 a common subunit, IL-12p40 (ref. 8). The IL-23 and IL-12 receptors also share a subunit, IL-12Rbeta1, that pairs with unique, inducible components, IL-23R and IL-12Rbeta2, to confer receptor responsiveness. Here we identify transforming growth factor-beta (TGF-beta) as a cytokine critical for commitment to T(H)17 development. TGF-beta acts to upregulate IL-23R expression, thereby conferring responsiveness to IL-23. Although dispensable for the development of IL-17-producing T cells in vitro and in vivo, IL-23 is required for host protection against a bacterial pathogen, Citrobacter rodentium. The action of TGF-beta on naive T cells is antagonized by interferon-gamma and IL-4, thus providing a mechanism for divergence of the T(H)1, T(H)2 and T(H)17 lineages.     

DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage

Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.