Nature

Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all branches of science and how science impacts upon all aspects of society and life.
  • Conditional tolerance of temperate phages via transcription-dependent CRISPR-Cas targeting
    [Aug 2014]

    Conditional tolerance of temperate phages via transcription-dependent CRISPR-Cas targeting

    Nature 514, 7524 (2014). doi:10.1038/nature13637

    Authors: Gregory W. Goldberg, Wenyan Jiang, David Bikard & Luciano A. Marraffini

    A fundamental feature of immune systems is the ability to distinguish pathogenic from self and commensal elements, and to attack the former but tolerate the latter. Prokaryotic CRISPR-Cas immune systems defend against phage infection by using Cas nucleases and small RNA guides that specify one or more target sites for cleavage of the viral genome. Temperate phages include viruses that can integrate into the bacterial chromosome, and they can carry genes that provide a fitness advantage to the lysogenic host. However, CRISPR-Cas targeting that relies strictly on DNA sequence recognition provides indiscriminate immunity both to lytic and lysogenic infection by temperate phages—compromising the genetic stability of these potentially beneficial elements altogether. Here we show that the Staphylococcus epidermidis CRISPR-Cas system can prevent lytic infection but tolerate lysogenization by temperate phages. Conditional tolerance is achieved through transcription-dependent DNA targeting, and ensures that targeting is resumed upon induction of the prophage lytic cycle. Our results provide evidence for the functional divergence of CRISPR-Cas systems and highlight the importance of targeting mechanism diversity. In addition, they extend the concept of ‘tolerance to non-self’ to the prokaryotic branch of adaptive immunity.

    Categories: Journal Articles
  • Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C
    [Aug 2014]

    Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C

    Nature 514, 7524 (2014). doi:10.1038/nature13660

    Authors: Katharine L. Sackton, Nevena Dimova, Xing Zeng, Wei Tian, Mengmeng Zhang, Timothy B. Sackton, Johnathan Meaders, Kathleen L. Pfaff, Frederic Sigoillot, Hongtao Yu, Xuelian Luo & Randall W. King

    Protein machines are multi-subunit protein complexes that orchestrate highly regulated biochemical tasks. An example is the anaphase-promoting complex/cyclosome (APC/C), a 13-subunit ubiquitin ligase that initiates the metaphase–anaphase transition and mitotic exit by targeting proteins such as securin and cyclin B1 for ubiquitin-dependent destruction by the proteasome. Because blocking mitotic exit is an effective approach for inducing tumour cell death, the APC/C represents a potential novel target for cancer therapy. APC/C activation in mitosis requires binding of Cdc20 (ref. 5), which forms a co-receptor with the APC/C to recognize substrates containing a destruction box (D-box). Here we demonstrate that we can synergistically inhibit APC/C-dependent proteolysis and mitotic exit by simultaneously disrupting two protein–protein interactions within the APC/C–Cdc20–substrate ternary complex. We identify a small molecule, called apcin (APC inhibitor), which binds to Cdc20 and competitively inhibits the ubiquitylation of D-box-containing substrates. Analysis of the crystal structure of the apcin–Cdc20 complex suggests that apcin occupies the D-box-binding pocket on the side face of the WD40-domain. The ability of apcin to block mitotic exit is synergistically amplified by co-addition of tosyl-l-arginine methyl ester, a small molecule that blocks the APC/C–Cdc20 interaction. This work suggests that simultaneous disruption of multiple, weak protein–protein interactions is an effective approach for inactivating a protein machine.

    Categories: Journal Articles
  • HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia
    [Aug 2014]

    HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia

    Nature 514, 7521 (2014). doi:10.1038/nature13614

    Authors: Jean-Benoît Arlet, Jean-Antoine Ribeil, Flavia Guillem, Olivier Negre, Adonis Hazoume, Guillaume Marcion, Yves Beuzard, Michaël Dussiot, Ivan Cruz Moura, Samuel Demarest, Isaure Chauvot de Beauchêne, Zakia Belaid-Choucair, Margaux Sevin, Thiago Trovati Maciel, Christian Auclair, Philippe Leboulch, Stany Chretien, Luba Tchertanov, Véronique Baudin-Creuza, Renaud Seigneuric, Michaela Fontenay, Carmen Garrido, Olivier Hermine & Geneviève Courtois

    β-Thalassaemia major (β-TM) is an inherited haemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of haemoglobin, leading to the accumulation of free α-globin chains that form toxic aggregates. Despite extensive knowledge of the molecular defects causing β-TM, little is known of the mechanisms responsible for the ineffective erythropoiesis observed in the condition, which is characterized by accelerated erythroid differentiation, maturation arrest and apoptosis at the polychromatophilic stage. We have previously demonstrated that normal human erythroid maturation requires a transient activation of caspase-3 at the later stages of maturation. Although erythroid transcription factor GATA-1, the master transcriptional factor of erythropoiesis, is a caspase-3 target, it is not cleaved during erythroid differentiation. We have shown that, in human erythroblasts, the chaperone heat shock protein70 (HSP70) is constitutively expressed and, at later stages of maturation, translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. The primary role of this ubiquitous chaperone is to participate in the refolding of proteins denatured by cytoplasmic stress, thus preventing their aggregation. Here we show in vitro that during the maturation of human β-TM erythroblasts, HSP70 interacts directly with free α-globin chains. As a consequence, HSP70 is sequestrated in the cytoplasm and GATA-1 is no longer protected, resulting in end-stage maturation arrest and apoptosis. Transduction of a nuclear-targeted HSP70 mutant or a caspase-3-uncleavable GATA-1 mutant restores terminal maturation of β-TM erythroblasts, which may provide a rationale for new targeted therapies of β-TM.

    Categories: Journal Articles
  • Scale up the supply of experimental Ebola drugs
    [Aug 2014]

    Scale up the supply of experimental Ebola drugs

    Nature 512, 7514 (2014). http://www.nature.com/doifinder/10.1038/512233a

    Author: Oliver Brady

    Estimates of the probable impact of the outbreak show that existing stocks of potentially useful medicines are insufficient, says Oliver Brady.

    Categories: Journal Articles
  • Ocean sciences: Farmed salmon swim to freedom
    [Aug 2014]

    Ocean sciences: Farmed salmon swim to freedom

    Nature 512, 7514 (2014). doi:10.1038/512234a

    Vastly more salmon could be escaping from aquaculture farms (pictured) than is officially reported, say Ove Skilbrei and his colleagues at the Institute of Marine Research in Bergen, Norway.Farmed salmon that escape could mate with wild populations and make them less fit for survival.

    Categories: Journal Articles
  • HIV: Antibody–drug mix stops relapse
    [Aug 2014]

    HIV: Antibody–drug mix stops relapse

    Nature 512, 7514 (2014). doi:10.1038/512234b

    A combination of antibodies and multiple virus-activating drugs can keep HIV from resurging in infected mice, even after treatment ends.During drug treatment, HIV enters a dormant state and stays hidden inside infected cells; afterwards, it bounces back. A team led by Michel Nussenzweig at

    Categories: Journal Articles
  • Materials: Soft machines made like Lego
    [Aug 2014]

    Materials: Soft machines made like Lego

    Nature 512, 7514 (2014). doi:10.1038/512234c

    Soft, stretchy, Lego-style bricks offer a way to make three-dimensional (3D) prototypes of elastic structures, according to researchers at Harvard University in Cambridge, Massachusetts.'Click-e-bricks', which were developed by George Whitesides and his colleagues, can be used to build stretchy devices, such as hollow ones

    Categories: Journal Articles
  • Astronomy: Comets forge organic molecules
    [Aug 2014]

    Astronomy: Comets forge organic molecules

    Nature 512, 7514 (2014). doi:10.1038/512234d

    Astronomers have captured three-dimensional images of organic compounds streaming from two comets.Comets contain some of the oldest materials in the Solar System. Using the Atacama Large Millimeter/submillimeter Array (ALMA) in Chile, Martin Cordiner of the NASA Goddard Space Flight Center in Greenbelt, Maryland, and

    Categories: Journal Articles
  • Microbiology: How Salmonella bounces back
    [Aug 2014]

    Microbiology: How Salmonella bounces back

    Nature 512, 7514 (2014). doi:10.1038/512235a

    Two groups have shown how Salmonella bacteria can resist antibiotics.Dirk Bumann of the University of Basel in Switzerland and his colleagues infected mice with modified Salmonella strains that glow green when they divide. They found varying rates of division in different tissues,

    Categories: Journal Articles
  • Astronomy: Dusty visitors from interstellar space
    [Aug 2014]

    Astronomy: Dusty visitors from interstellar space

    Nature 512, 7514 (2014). doi:10.1038/512235b

    Seven particles captured by NASA's Stardust spacecraft may be the first sample of dust from beyond the Solar System that has been brought back to Earth.Andrew Westphal at the University of California, Berkeley, and his colleagues — with the help of 30,714 citizen scientists

    Categories: Journal Articles
  • Conservation biology: Poaching leads to elephant decline
    [Aug 2014]

    Conservation biology: Poaching leads to elephant decline

    Nature 512, 7514 (2014). doi:10.1038/512235c

    The illegal killing of elephants in Africa to supply the ivory trade has reached unsustainable rates.George Wittemyer at Colorado State University in Fort Collins and his colleagues used data from elephant carcass surveys in 45 sites across Africa to model broader trends in elephant

    Categories: Journal Articles
  • Virology: Secret to Ebola's success
    [Aug 2014]

    Virology: Secret to Ebola's success

    Nature 512, 7514 (2014). doi:10.1038/512235d

    The Ebola virus might elude immune responses by stopping a key protein in infected cells from activating defence genes.Ebola, which kills up to 90% of people it infects, is known to disrupt the activity of interferon, a crucial antiviral protein. Gaya Amarasinghe at Washington

    Categories: Journal Articles
  • Engineering: Robot swarms take shape
    [Aug 2014]

    Engineering: Robot swarms take shape

    Nature 512, 7514 (2014). doi:10.1038/512235e

    A thousand-strong army of coin-sized robots (pictured) can arrange itself into various configurations.Michael Rubenstein and his co-workers at Harvard University in Cambridge, Massachusetts, programmed 1,024 robots with a simple set of rules and an image of a shape to be formed. Four

    Categories: Journal Articles
  • Strong words over a 'Hobbit'
    [Aug 2014]

    Strong words over a 'Hobbit'

    Nature 512, 7514 (2014). doi:10.1038/512235f

    Author: Chris Woolston

    Nature's roundup of the papers and issues gaining traction on social media.Ancient hominin bones made good fodder for debate on social media of late, when researchers suggested a theory about the identity of the Indonesian 'Hobbit'. Scientists also took note of a fast,

    Categories: Journal Articles
  • Clarification
    [Aug 2014]

    Clarification

    Nature 512, 7514 (2014). doi:10.1038/512235g

    The Research Highlight 'Brain scans predict TV hits' (Nature512, 8;10.1038/512008c2014) notes that Jacek Dmochowski is at Stanford University; however, the research described was done at the City College of New York.

    Categories: Journal Articles
  • Seven days: 15–21 August 2014
    [Aug 2014]

    Seven days: 15–21 August 2014

    Nature 512, 7514 (2014). http://www.nature.com/doifinder/10.1038/512236a

    The week in science: Africa’s Ebola problem continues to worsen, the true cost of scientific misconduct in the United States, and Maryam Mirzakhani is first woman to win a Fields Medal.

    Categories: Journal Articles
  • Bone technique redrafts prehistory
    [Aug 2014]

    Bone technique redrafts prehistory

    Nature 512, 7514 (2014). http://www.nature.com/doifinder/10.1038/512242a

    Author: Ewen Callaway

    Carbon-dating improvements show that Neanderthals disappeared from Europe much earlier than thought.

    Categories: Journal Articles
  • Lakes under the ice: Antarctica’s secret garden
    [Aug 2014]

    Lakes under the ice: Antarctica’s secret garden

    Nature 512, 7514 (2014). http://www.nature.com/doifinder/10.1038/512244a

    Author: Douglas Fox

    Samples from a lake hidden under 800 metres of ice contain thousands of microbes and hint at vast ecosystems yet to be discovered.

    Categories: Journal Articles
  • Microbiology: Microbiome science needs a healthy dose of scepticism
    [Aug 2014]

    Microbiology: Microbiome science needs a healthy dose of scepticism

    Nature 512, 7514 (2014). doi:10.1038/512247a

    Author: William P. Hanage

    To guard against hype, those interpreting research on the body's microscopic communities should ask five questions, says William P. Hanage.

    Categories: Journal Articles
  • History of science: The first scientist
    [Aug 2014]

    History of science: The first scientist

    Nature 512, 7514 (2014). doi:10.1038/512250a

    Author: Roberto Lo Presti

    Roberto Lo Presti applauds a brilliant reappraisal of Aristotle as the father of observational biology.

    Categories: Journal Articles