NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 12 August 2007
This press release is copyrighted to the Nature journals mentioned below.
This press release contains:
· Summaries of newsworthy papers:
Natural products in a flask – Nature Chemical Biology
How West Nile virus became dangerous – Nature Genetics
Prevention and treatment of craniosynostosis – Nature Genetics
Positive selection during human evolution – Nature Genetics
Signalling flies to sleep – Nature Neuroscience
A sponge to soak up regulatory RNAs – Nature Methods
· Mention of papers to be published at the same time with the same embargo
· Geographical listing of authors
PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of http://press.nature.com. Press contacts for the Nature journals are listed at the end of this release.
Warning: This document, and the Nature journal papers to which it refers, may contain information that is price sensitive (as legally defined, for example, in the UK Criminal Justice Act 1993 Part V) with respect to publicly quoted companies. Anyone dealing in securities using information contained in this document, or in advance copies of a Nature journal’s content, may be guilty of insider trading under the US Securities Exchange Act of 1934.
PICTURES: To obtain artwork from any of the journals, you must first obtain permission from the copyright holder (if named) or author of the research paper in question (if not).
NOTE: Once a paper is published, the digital object identifier (DOI) number can be used to retrieve the abstract and full text from the journal web site (abstracts are available to everyone, full text is available only to subscribers). To do this, add the DOI to the following URL: http://dx.doi.org/ (For example, http://dx.doi.org/10.1038/ng730). For more information about DOIs and Advance Online Publication, see http://www.nature.com/ng/aop/.
PLEASE CITE THE SPECIFIC NATURE JOURNAL AND WEBSITE AS THE SOURCE OF THE FOLLOWING ITEMS. IF PUBLISHING ONLINE, PLEASE CARRY A HYPERLINK TO THE APPROPRIATE JOURNAL’S WEBSITE.
*************************************NATURE CHEMICAL BIOLOGY ***********************************
(http://www.nature.com/nchembio)
[1] & [2] Natural products in a flask
DOI: 10.1038/nchembio.2007.22
DOI: 10.1038/nchembio.2007.20
Despite their complicated chemical structures, some potential drug leads can be created by mixing together enzymes in a flask, according to two papers in the September issue of Nature Chemical Biology. Chemicals that occur naturally, such as penicillin, have traditionally been very important sources of drugs. These ‘natural products’ often have very elaborate chemical structures that make them difficult to create by chemical synthesis.
Groups led by Bradley Moore and Christopher Walsh now independently show that two complex natural products, which have potential antibacterial and antitumour activity, can be made by taking the enzymes that normally create these chemicals inside cells and mixing them together outside of a cell. These studies have provided new insight into how these natural products are made and will help further efforts to turn these chemicals into drugs.
Author contacts:
Bradley Moore (University of California, San Diego, CA, USA) Author paper [1]
Tel: +1 858 822 6650; E-mail: [email protected]
Christopher Walsh (Harvard Medical School, Boston, MA, USA) Author paper [2]
Tel: +1 617 432 1715; E-mail: [email protected]
***********************************************NATURE GENETICS **************************************
(http://www.nature.com/naturegenetics)
[3] How West Nile virus became dangerous
DOI: 10.1038/ng2097
A single causative mutation has been identified in the virulent strain of West Nile virus that has been responsible for deadly outbreaks of human encephalitis in recent years, according to a paper online this week in Nature Genetics.
West Nile virus is a mosquito-borne virus that is transmitted between avian hosts and mosquitoes, and until the mid 1990s was associated with only mild infections of humans in Africa and the Middle East. More severe outbreaks of encephalitis were reported in Romania in 1996, and subsequently in Israel, Tunisia, Russia, and North America.
Aaron Brault and colleagues sequenced the genomes of West Nile virus strains that have been sampled globally in recent years, and found that a single mutation in a gene encoding an enzyme called a helicase arose independently on at least three separate occasions in strains associated with outbreaks of disease. When a poorly virulent strain from Kenya was engineered to contain the helicase mutation, it was found to replicate more rapidly and to cause death of inoculated American crows at a much higher rate than that of the original Kenyan virus. The authors also provide evidence that the helicase mutation was positively selected, which they say highlights the potential for viruses like West Nile to adapt rapidly to changing environments, with unpredictable consequences for human health.
Author contact:
Aaron Brault (University of California, Davis, CA, USA)
Tel: +1 530 754 8359; E-mail: [email protected]
[4] Prevention and treatment of craniosynostosis
DOI: 10.1038/ng2096
Two successful strategies for the prevention and treatment of craniosynostosis – premature fusion of the sutures in the skull – are reported online this week in Nature Genetics. At least one of the approaches may be testable in humans in the near term. Craniosynostosis is caused by the sutures of the skull closing too early in infancy, which affects normal brain and skull growth. It occurs in approximately 1 of every 2,500 live births. Apert syndrome, a rare but quite severe form of craniosynostosis, is caused in most cases by a specific mutation in a cell-surface receptor called FGFR2.
Chu-Xia Deng and colleagues created a mouse model of Apert syndrome that bears one of the most common FGFR2 mutations seen in humans. When these mice were crossed with mice expressing a ‘short hairpin’ RNA molecule specifically designed to block expression of the mutant form of FGFR2, the offspring that carry the FGFR2 mutation developed normally. The authors also report the involvement in the disease of an enzyme called ERK, which is regulated by FGFR2. When they injected a drug that inhibits ERK activity into pregnant mice carrying the FGFR2 mutation, the offspring showed no signs of Apert syndrome. Moreover, when the drug was injected at the onset of the disease during the early postnatal period, at least some of the treated mice maintained a normal appearance, although the treatment’s effectiveness was greater in male than in female mice.
Drugs similar to those used in this study are already being tested in clinical trials as anticancer drugs, and may now have additional applications in the prevention and treatment of birth defects such as craniosynostosis.
Author contact:
Chu-Xia Deng (National Institutes of Health, Bethesda, MD, USA)
Tel: +1 301 402 7225; E-mail: [email protected]
[5] Positive selection during human evolution
DOI: 10.1038/ng2104
Sequences in the human genome that have undergone positive selection are found in abundance in regions that regulate the expression of genes involved in neural or nutritional processes, suggests a paper online this week in Nature Genetics. The study provides some of the first large-scale evidence that the evolution of some human-specific traits can be traced to changes in gene regulatory (promoter) regions.
Cognitive, behavioural and dietary differences are among the most obvious differences between humans and the great apes. Although one might expect that genes involved in these processes would show evidence of positive natural selection in humans since the most recent common ancestor of humans and chimpanzees, there is little evidence to support this.
Ralph Haygood and colleagues compared probable promoter regions for more than 6,000 genes in the human, chimpanzee and macaque genomes. They generated statistics to identify those promoters that likely had undergone positive selection in the human genome. At least 250 such promoters were found. Although they represent several functional categories, prominent among them are promoters linked to genes involved in neural development and function, including axon guidance, synapse formation and neurotransmission in the brain. Nutrition-related genes include a large number involved in glucose metabolism.
Author contact:
Ralph Haygood (Duke University, Durham, NC, USA)
Tel: +1 919 668 6249; E-mail: [email protected]
Other papers from Nature Genetics to be published online at the same time and with the same embargo:
[6] Global diversity and evidence for coevolution of KIR and HLA
DOI: 10.1038/ng2077
[7] Unusual selection on the KIR3DL1/S1 natural killer receptors in Africans
DOI: 10.1038/ng2111
*******************************************NATURE NEUROSCIENCE ***********************************
(http://www.nature.com/natureneuroscience)
[8] Signalling flies to sleep
DOI: 10.1038/nn1957
A particular signalling pathway is shown to be important in regulation and maintenance of sleep, in a new study in the September issue of Nature Neuroscience. This work suggests that the fruit fly Drosophila may be a good model in which to identify the molecular pathways involved in sleep regulation.
Fruit flies (and other insects) undergo a process that is biologically similar to sleep in mammals, including immobility and additional ‘catch-up’ sleep following sleep deprivation. Ralph Greenspan and colleagues demonstrate that the activation of the epidermal growth factor receptor, which is known to be involved in natural 24 hour rhythms, led to an increase in sleep. Blocking activity in this signalling pathway led to a decrease in sleep and difficulty in catching up on sleep after deprivation. This regulation occurred in a region of the fly brain that is developmentally and functionally similar to the hypothalamus in mammals – the part of our brain that controls sleep.
Using this type of experimental approach may make it easier and faster for scientists to identify additional molecules required for the induction and/or maintenance of sleep. Drug companies might then be able to use this information to design better sleep aids.
Author contact:
Ralph Greenspan (The Neurosciences Institute, San Diego, CA, USA)
Tel: +1 858 626 2075; E-mail: [email protected]
Additional contact for comment on paper:
Christopher Colwell (University of California, Los Angeles, CA, USA)
Tel: +1 310 206 3973; E-mail: [email protected]
Other papers from Nature Neuroscience to be published online at the same time and with the same embargo:
[9] A stream of cells migrating from the caudal telencephalon reveals a link between the amygdala and neocortex
DOI: 10.1038/nn1955
[10] Daytime sleep condenses the time course of motor memory consolidation
DOI: 10.1038/nn1959
[11] Experience-dependent recovery of vision following chronic deprivation amblyopia
DOI: 10.1038/nn1965
********************************************NATURE METHODS******************************************
[12] A sponge to soak up regulatory RNAs
DOI: 10.1038/nmeth1079
Genetically encoded inhibitors that soak up microRNAs in mammalian cells are presented online this week in Nature Methods. Being able to incapacitate microRNAs provides valuable insights into their function during normal development and disease.
MicroRNAs, unlike longer messenger RNAs (mRNAs), do not contain information for making a protein, but their short, 21 nucleotide, sequences specifically regulate mRNA expression. MicroRNAs bind to partly complementary sequences on their target mRNAs and as a consequence the mRNA is either marked for decay or protein translation is inhibited. Overexpression of certain microRNAs has been linked to cancer and other diseases and a better understanding of their action is therefore important.
Philip Sharp and colleagues have developed a tool to specifically block microRNAs. The principle of their system is based on soaking up all the microRNAs with a complementary decoy sequence, so the mRNA can express its protein unhindered. In contrast to previously described chemically synthesized microRNA inhibitors, these microRNA sponges are genetically encoded. They are provided to the cell either in form of a plasmid or they are stably integrated into the genome of a cell. This provides a much higher level of control over the amount of microRNA sponges a cell produces and allows microRNA action in a specific cell or tissue type to be studied.
Author contact:
Philip Sharp (Massachusetts Institute of Technology, Cambridge, MA, USA)
Tel: +1 617 253 6421; E-mail: [email protected]
Other papers from Nature Methods to be published online at the same time and with the same embargo:
[13] Tomographic phase microscopy
DOI: 10.1038/nmeth1078
***************************************************************************************************************
Items from other Nature journals to be published online at the same time and with the same embargo:
Nature (http://www.nature.com/nature)
[14] The structural basis for activation of plant immunity by bacterial effector protein AvrPto
DOI: 10.1038/nature06109
[15] Loss of integrin alphavbeta8 on dendritic cells causes autoimmunity and colitis in mice
DOI: 10.1038/nature06110
Nature PHYSICS (http://www.nature.com/naturephysics)
[16] Two-dimensional transport and transfer of a single atomic qubit in optical tweezers
DOI: 10.1038/nphys698
[17] Charge-order-maximized momentum-dependent superconductivity
DOI: 10.1038/nphys699
NATURE MATERIALS (http://www.nature.com/naturematerials)
[18] Imbibition by polygonal spreading on microdecorated surfaces
DOI: 10.1038/nmat1978
[19] Coherent orbital waves in the photo-induced insulator–metal dynamics of a magnetoresistive manganite
DOI: 10.1038/nmat1979
[20] Phason dynamics in nonlinear photonic quasicrystals
DOI: 10.1038/nmat1981
NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)
[21] Hinged nanorods made using a chemical approach to flexible nanostructures
DOI: 10.1038/nnano.2007.250
Nature MEDICINE (http://www.nature.com/naturemedicine)
[22] Molecular imaging of Akt kinase activity
DOI: 10.1038/nm1608
[23] The E3 ligase HACE1 is a critical chromosome 6q21 tumor suppressor involved in multiple cancers
DOI: 10.1038/nm1621
[24] Clearance of amyloid-beta by circulating lipoprotein receptors
DOI: 10.1038/nm1635
Nature IMMUNOLOGY (http://www.nature.com/natureimmunology)
[25] Structural evidence of a germline-encoded T cell receptor–major histocompatibility complex interaction ‘codon’
DOI: 10.1038/ni1502
[26] Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3– precursor cells in the absence of interleukin 10
DOI: 10.1038/ni1504
NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology)
[27] A concentration-dependent switch in the bacterial response to temperature
DOI: 10.1038/ncb1632
Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
[28] Structural dynamics in the gating ring of cyclic nucleotide–gated ion channels
DOI: 10.1038/nsmb1281
[29] Lsm proteins bind and stabilize RNAs containing 5’ poly(A) tracts
DOI: 10.1038/nsmb1287
[30] MRE11-RAD50-NBS1 and ATM function as comediators of TRF1 in telomere length control
DOI: 10.1038/nsmb1286
***************************************************************************************************************
GEOGRAPHICAL LISTING OF AUTHORS
The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.
AUSTRIA
Vienna: 23
BRAZIL
Sao Jose dos Campos: 29
Sao Paulo: 6
CANADA:
Hamilton: 30
Montreal: 10
Toronto: 21, 23
Vancouver: 23
CHINA
Beijing: 14
FRANCE
Palaiseau: 16
Paris: 4, 18
GHANA
Legon: 7
GEORGIA
Tbilisi: 7
GERMANY
Goettingen: 9
INDIA
Gandhinagar: 17
Madurai: 7
Mumbai: 9
ISRAEL
Haifa: 10, 20
Tel Aviv: 10, 20
ITALY
Milan: 19
JAPAN
Chiba: 17
Hyogo: 17
Kobe: 9
Okayama: 17
Saitama: 9, 17
Tokyo: 9
Tsukuba: 19
KOREA
Seoul: 7
NETHERLANDS
Utrecht: 24
SERBIA
Belgrade: 29
SPAIN
Palma: 7
SWITZERLAND
Villigen: 29
TAIWAN
Taichung: 7
THAILAND
Bangkok: 7
TRINIDAD & TOBAGO
St Augustine: 7
TURKEY
Istanbul: 7
UNITED KINGDOM
Chilton: 19
London: 7
Manchester: 15
Oxford: 19
UNITED STATES OF AMERICA
Alabama
Birmingham: 26
Arizona
Tucson: 1
California
Berkeley: 19
Davis: 3
La Jolla: 1, 8
Palo Alto: 7
San Diego: 8
San Francisco: 15
Stanford: 7, 25
Colorado
Fort Collins: 3, 29
Connecticut
New Haven: 6
Maryland
Baltimore: 23
Bethesda: 3, 4
College Park: 11
Frederick: 6
Rockville: 6
Massachusetts
Boston: 2, 13
Cambridge: 12, 13, 18
Michigan
Ann Arbor: 22
Missouri
St Louis: 24
New Jersey
Princeton: 20
New York
Ithaca: 14, 22
New York: 15, 27, 29
Rochester: 24
North Carolina
Durham: 5
Pennsylvania
University Park: 3
Texas
Austin: 25
Vermont
Burlington: 6
Washington
Seattle: 9, 26, 28
VENEZUELA
Caracas: 7
PRESS CONTACTS…
For media inquiries relating to embargo policy for all the Nature Research Journals:
Katherine Anderson (Nature, London)
Tel: +44 20 7843 4502; E-mail: [email protected]
Ruth Francis (Senior Press Officer, Nature, London)
Tel: +44 20 7843 4562; E-mail: [email protected]
For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:
Nature Cell Biology (London)
Bernd Pulverer
Tel: +44 20 7843 4892; E-mail: [email protected]
Nature Chemical Biology (Boston)
Andrea Garvey
Tel: +1 617 475 9241, E-mail: [email protected]
Nature Genetics (New York)
Orli Bahcall
Tel: +1 212 726 9311; E-mail: [email protected]
Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]
Nature Materials (London)
Fabio Pulizzi
Tel: +44 20 7014 4024; E-mail: [email protected]
Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]
Nature Methods (New York)
Allison Doerr
Tel: +1 212 726 9393; E-mail: [email protected]
Nature Nanotechnology (London)
Peter Rodgers
Tel: +44 20 7014 4019; Email: [email protected]
Nature Neuroscience (New York)
Sandra Aamodt (based in California)
Tel: +1 530 795 3256; E-mail: [email protected]
Nature Physics (London)
Alison Wright
Tel: +44 20 7843 4555; E-mail: [email protected]
Nature Structural & Molecular Biology (New York)
Michelle Montoya
Tel: +1 212 726 9326; E-mail: [email protected]
About Nature Publishing Group
Nature Publishing Group (NPG) is a division of Macmillan Publishers Ltd, dedicated to serving the academic, professional scientific and medical communities. NPG's flagship title, Nature, was first published in 1869. Other publications include Nature research journals, Nature Reviews, Nature Clinical Practice and a range of prestigious academic journals including society-owned publications. NPG also provides news content through [email protected]. Scientific career information and free job postings are offered on Naturejobs.
NPG is a global company with headquarters in London and offices in New York, San Francisco, Washington DC, Boston, Tokyo, Paris, Munich, Hong Kong, Melbourne, Delhi, Mexico City and Basingstoke. For more information, please go to www.nature.com.
