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  • It has been a goal in applied physics to construct devices in which superconductivity can be switched on and off with an electric field. Recently, it was shown that the conducting interface between LaAlO3 and SrTiO3 (both in bulk form are insulators) can produce a two-dimensional superconducting condensate. This paper now uses the electric field effect, which tunes the charge carrier density, to explore the phase diagram of the system.

    • A. D. Caviglia
    • S. Gariglio
    • J.-M. Triscone
    Letter
  • Early hypotheses suggested that the digits of tetrapods (land vertebrates) were homologues of fin radials, but this idea fell out of favour on the basis of developmental studies and also on the fin of Panderichthys, a fish closely related to land vertebrates, which appeared to lack distal digit-like fin radials. A new CT study of a classic specimen of Panderichthys shows that the old interpretation was in error. Panderichthys did indeed have digit-like radials: nothing stands in the way of the era of fish fingers.

    • Catherine A. Boisvert
    • Elga Mark-Kurik
    • Per E. Ahlberg
    Letter
  • Brain–machine interfaces are a promising approach for treating spinal cord injury-caused paralysis by rerouting control signals from the brain directly to the muscles. This paper demonstrates that monkeys can directly control stimulation of muscles using the activity of neurons in motor cortex, restoring goal-directed movement to a transiently paralysed arm. In addition, monkeys learned to use these artificial connections so that single neurons previously not associated with the movement could be used to control functional stimulation.

    • Chet T. Moritz
    • Steve I. Perlmutter
    • Eberhard E. Fetz
    Letter
  • Tamoxifen is commonly used for breast cancer therapy. This paper shows that the transcriptional repression of the ERBB2 oncogene by tamoxifen in breast cancer cells is affected by an antagonistic interaction between the transcriptional regulators PAX2 and AIB-1. This affects the ability of tamoxifen to inhibit cancer cell proliferation. The relative levels of PAX2 and AIP1 in breast cancer patients treated with tamoxifen correlates with relapse-free survival.

    • Antoni Hurtado
    • Kelly A. Holmes
    • Jason S. Carroll
    Letter
  • A role for Sox18 transcription factor has been suggested by lymphatic dysfunction in the human syndrome hypotrichosis-lymphedema-telangiectasia (HLT), which is caused by mutations in Sox18. This paper shows that Sox18 directly activates Prox1 transcription. Sox18-null embryos show a complete absence of Prox1-positive lymphatic endothelial cells emanating from the cardinal vein.

    • Mathias François
    • Andrea Caprini
    • Peter Koopman
    Letter
  • Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. This paper shows that changes in stem cell orientation within the niche during ageing contribute to the decline in spermatogenesis in Drosophila male germ line.

    • Jun Cheng
    • Nezaket Türkel
    • Yukiko M. Yamashita
    Article
  • Cancer stem cells in human tumours have been defined as cells that are tumourigenic and self-renew when transplanted into immunocompromised mice. It has been shown in a number of tumour types that such cancer stem cells exist at relatively low frequencies. This paper now shows that in human melanomas at least, there is a high proportion of tumourigenic cells when the conditions for such transplanation experiments are modified, casting doubt on the generality of the cancer stem cell model.

    • Elsa Quintana
    • Mark Shackleton
    • Sean J. Morrison
    Article
  • It is shown that a mitochondrial protein, mitofusin 2, is enriched at the mitochondrial–endoplasmic reticulum interface and mediates tethering of both organelles. Ablation of mitofusin 2 results in disruption of endoplasmic reticulum morphology and loss of calcium transfer between the two organelles. Thus, mitofusin-2 mediates tethering mitochondria to the endoplasmic reticulum.

    • Olga Martins de Brito
    • Luca Scorrano
    Article
  • Shiga toxigenic Escherichia coli causes severe gastrointestinal disease, which is in part mediated by subtilase cytotoxin. The B subunit of this toxin is now shown to have high affinity to glycans containing N-glycolylneuraminic acid, a saccharide that is not synthesized by humans. Instead it is ingested by dietary intake of red meat and dairy products and subsequently incorporated into intestinal and kidney tissue.

    • Emma Byres
    • Adrienne W. Paton
    • Travis Beddoe
    Letter
  • This paper identifies a gene, kintoun (ktu), which is important for dynein arm formation resulting in the formation of motile cilia. It is conserved from ciliated unicellular organisms to higher mammals. Mutations in the homologous gene of two human primary ciliary dyskinesia families are also identified.

    • Heymut Omran
    • Daisuke Kobayashi
    • Hiroyuki Takeda
    Article
  • Suppressing the homologous recombination of repetitive DNA sequences is important for maintaining genome stability, and packaging of repeat DNA into silent chromatin was generally thought to protect it from recombination. Yeast ribosomal DNA (rDNA) repetitive sequences are shown to associate with the nuclear periphery via inner nuclear membrane proteins, and this tethering is required for rDNA stability. Sir2-dependent silencing is not sufficient to inhibit rDNA recombination.

    • Karim Mekhail
    • Jan Seebacher
    • Danesh Moazed
    Letter
  • Species-specific recognition between the egg extracellular matrix (zona pellucida) and sperm is the first step of mammalian fertilization. This paper reports the 2.3 Å resolution structure of the 'zona pellucida filament' of the egg, which act as sperm receptors. The structure supports the presence of ZP–N repeats within the amino-terminal region of ZP2 and other vertebrate zona pellucida/vitelline proteins, and has implications for egg coat architecture and the post-fertilization block to polyspermy and speciation.

    • Magnus Monné
    • Ling Han
    • Luca Jovine
    Letter
  • This paper documents the evolutionary interaction between the innate immunity gene protein kinase R (PKR), its substrate elF2α, and its poxvirus mimic K3L. It is concluded that the rapid evolution of the PKR gene may be due to viral mimicry.

    • Nels C. Elde
    • Stephanie J. Child
    • Harmit S. Malik
    Letter
  • In teleosts, proper balance and hearing depend on mechanical sensors in the inner ear. These sensors include actin-based microvilli and microtubule-based cilia that extend from the surface of sensory hair cells and attach to biomineralized 'ear stones', orotoliths. This paper show that in zebra fish, fluid flow generated by cilia influences the number, growth and localization of otoliths, as well as their mineralization during development.

    • Jessica R. Colantonio
    • Julien Vermot
    • Kent L. Hill
    Letter
  • The human microbiota has been implicated in many health-related issues. In this study, the microbiota composition of monozygotic and dizygotic twins and their mothers is examined. Although a core microbiome could not be defined on a phylogenetic level, the data suggests that core functions are conserved.

    • Peter J. Turnbaugh
    • Micah Hamady
    • Jeffrey I. Gordon
    Letter
  • MicroRNAs are expressed in a type of heart cell known as cardiomyocytes and their aberrant regulation was correlated with heart disease. This study looks at how miRNAs in other heart cells may contribute to disease. It is found that in cardiac fibroblasts, miR-21 is upregulated in diseased heart. This activates a signalling pathway that exacerbates cardiac disease. By using an RNA molecule directed against miR-21, it was possible to reverse these effects, demonstrating that therapeutic treatment to downregulate a microRNA can be effective in vivo.

    • Thomas Thum
    • Carina Gross
    • Stefan Engelhardt
    Letter
  • 220-million-year-old fossils from southwestern China represent the most primitive turtle known, and shed light on intermediate steps in the acquisition of the unique and highly specialized turtle body-plan.

    • Chun Li
    • Xiao-Chun Wu
    • Li-Jun Zhao
    Letter
  • The ideal in organic synthesis is to prepare complex molecules using the smallest possible number of steps. Also important is atom economy, limiting waste by ensuring that most of atoms present in the reactants end up in the product. This paper demonstrates both of these principles to great effect in the synthesis of bryostatin 16, a biologically active, naturally occurring compound. The synthesis uses nearly half the number of steps of previously reported routes to bryostatins.

    • Barry M. Trost
    • Guangbin Dong
    Letter