NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 13 August 2006
This press release is copyrighted to the Nature journals mentioned below.
This press release contains:
* Summaries of newsworthy papers:
Neurobiology: Survival of the well-connected - Nature
Neuroscience: Protein folding lost in translation - Nature
Development: How neurons sprout like trees - Nature
Antiviral protein linked to healthier lungs - Nature Medicine
One recurrent cause of mental retardation found - Nature Genetics
Fighting flies - Nature Genetics
A potential new target for antidepressants - Nature Neuroscience
Blocking autoimmune brain inflammation - Nature Immunology
* 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.
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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************************************
(<http://www.nature.com/nature>)
[1] Neurobiology: Survival of the well-connected
DOI: 10.1038/nature05028
The survival of newly formed brain cells in the adult mouse depends on the input activity they receive, according to a study published online in Nature this week. It suggests that new neurons in an area of the mammalian brain thought to be involved in learning and memory compete for survival through the activity of neurotransmitter receptors on their surface.
Fred Gage and colleagues studied newly formed neurons in a region known as the dentate gyrus. Using an original technical development, they were able to show that new neurons are much less likely to survive if they do not possess a particular receptor called NMDAR - the N-methyl-d-aspartate-type glutamate receptor. This receptor mediates excitatory signals from connected neurons, without which the researchers believe new neurons do not survive.
The authors report that the specific, activity-dependent establishment of new neuronal circuits occurs during a crucial period soon after the new neurons are 'born', and propose that it may enable these brain cells to play an important part in learning and memory.
Author contact:
Fred H gage (The Salk Institute, La Jolla, CA, USA)
Tel: +1 858 453 4100 x1012; E-mail: [email protected]
[2] Neuroscience: Protein folding lost in translation
DOI: 10.1038/nature05096
A new mechanism that could underlie certain neurodegenerative diseases is published online this week by Nature. The researchers reveal that upsetting the accuracy of translation, the process by which messenger RNAs are coded into proteins, can lead to the accumulation of misfolded proteins.
Susan Ackerman and colleagues studied mice with the so-called 'sticky' mutation, which develop tremors, movement problems and cellular death of cerebellar neurons. The results of the study implicate the faulty manufacture of transfer RNAs (tRNAs) - the molecules that insert amino acids into their appropriate position during translation - as the reason behind the neurodegeneration seen in sticky mice. The team showed that the sticky mutation disrupts an enzyme called alanyl-tRNA synthetase, which attaches a specific amino acid to tRNA molecules. The mutation causes the production of proteins containing aberrant amino acids, and these proteins cannot fold correctly and so accumulate within neurons, killing them. The researchers propose that some heritable diseases could be caused by mild mutations that disrupt tRNA synthetase enzymes.
Author contact:
Susan L Ackerman (Howard Hughes Medical Institute, Jackson Laboratory, Bar Harbor, ME, USA)
Tel: +1 207 288 6494; E-mail: [email protected]
[3] Development: How neurons sprout like trees
DOI: 10.1038/nature05090
A paper to be published online by Nature this week reveals how some neurons establish and maintain a precise tree-like pattern of dendrites, the slim projections that carry electrical signals to and from neighbouring cells.
Certain neurons in the fruitfly Drosophila have a very precise arrangement in which the spreading dendrites of one overlap little with another, like tiles on a floor. Yuh-Nung Jan and colleagues show that a pathway of molecules already implicated in cell proliferation and cancer is also vital for this patterning. In fruitflies with mutations in a gene called warts, neurons are initially able to tile dendrites across the body wall correctly but then progressively lose branches. A gene called hippo appears to be essential for both the establishment and maintenance of dendritic tiling.
Author contact:
Yuh-Nung Jan (University of California & Howard Hughes Medical Institute, San Francisco, CA, USA)
Tel: +1 415 476 8747; E-mail: [email protected]
Other papers from Nature to be published online at the same time and with the same embargo:
[4] Highly ordered arrangement of single neurons in orientation pinwheels
DOI: 10.1038/nature05019
[5] Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo
DOI: 10.1038/nature05112
*********************************Nature MEDICINE*****************************
(<http://www.nature.com/naturemedicine>)
[6] Antiviral protein linked to healthier lungs
DOI: 10.038/nm1462
Failure to produce enough of an antiviral protein called interferon-lambda may be linked to increased susceptibility to infection with rhinovirus - a common trigger for asthma exacerbations - according to a study by Sebastian Johnston and colleagues in the September issue of Nature Medicine.
The authors infected volunteers with rhinovirus, a virus that normally causes common colds. They found that clinical markers of lung function impairment were inversely correlated with the amount of interferon-lambda produced by the volunteers’ lung cells; volunteers with lower levels of the antiviral protein tended to have worse lung function in response to the viral infection. In parallel studies done on cells directly infected in the lab, the authors also showed that virus replication was linked with the amount of interferon-lambda produced by the cells, and that supplying more interferon-lambda could block virus replication.
The work does not show that a deficiency in interferon-lambda causes asthma - it is possible that not producing enough interferon could be a consequence, not a cause of the asthma in humans - but it does indicate that interferon therapy might be a viable approach to treat asthma exacerbations, particularly those caused by rhinovirus infection.
Author contact:
Sebastian Johnston (Imperial College London, UK)
Tel: +44 207 594 3764; E-mail: [email protected] <mailto:[email protected]>
Other papers from Nature Medicine to be published online at the same time and with the same embargo:
[7] Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid
DOI: 10.1038/nm1466
[8] Loss of the tumor suppressor Vhlh leads to upregulation of Cxcr4 and rapidly progressive glomerulonephritis in mice
DOI: 10.1038/nm1460
[9] NR4A orphan nuclear receptors are transcriptional regulators of hepatic glucose metabolism
DOI: 10.1038/nm1471
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(<http://www.nature.com/naturegenetics>)
[10] [11] & [12] One recurrent cause of mental retardation found
DOI: 10.1038/ng1853
DOI: 10.1038/ng1858
DOI: 10.1038/ng1862
Three papers to be published in the September issue of Nature Genetics describe a recurrent cause of mental retardation, which results from the deletion of a large segment of DNA from chromosome 17. The deletion, encompassing several genes, is associated with a region of DNA that is commonly carried in an inverted orientation by a large portion of the human population.
The deletion arises recurrently, and is reported to account for roughly 1% of cases of mental retardation among the populations screened in the three studies. It seems to be found preferentially among children of individuals who carry one particular form of the inversion, which is common among Europeans. Individuals carrying the deletion also show characteristic facial, behavioral and other clinical features, which should aid clinicians in diagnosing similar cases.
One of the deleted genes, MAPT, has been previously implicated as having a causal role in neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Loss of this gene is therefore a prime candidate for explaining some of the characteristic features associated with mental retardation.
Author contacts:
Bert de Vries (University Medical Center Nijmegen, The Netherlands) Author paper [10]
Tel: +31 24 3613946; E-mail: [email protected]
Please note this author is traveling and it may be easier to reach
David Koolen Tel: +31 24 366 86 24; E-mail: [email protected]
Charles Shaw-Smith (University of Cambridge, UK) Author paper [11]
Tel: +44 1223 216 446; E-mail: [email protected]
Evan Eichler (University of Washington, Seattle, USA) Author [12]
Tel: +1 206 543 9526; E-mail: [email protected]
[13] Fighting flies
DOI: 10.1038/ng1864
The first comprehensive molecular analysis of aggressive behavior in any laboratory species is reported in a study to be published in the September issue of Nature Genetics. Herman Dierick and Ralph Greenspan developed an original set of assays to record and quantify aggression in the fruit fly Drosophila melanogaster.
Most laboratory strains of D. melanogaster rapidly lose the aggressiveness that is common to strains in the wild, suggesting that aggressive behavior might be recoverable in laboratory strains by deliberately selecting for it. Dierick and Greenspan devised a new ‘two-male arena assay’, in which twenty pairs of males were placed in a chamber containing separate arenas, and assessed for several parameters related to aggression, including the frequency, intensity, and total amount of time spent fighting (see video and still image). More aggressive males were then selected and mated to random females, a procedure which was repeated for more than twenty generations. Flies in the final generation were thirty times as aggressive as those in the first generation.
The authors report that approximately eighty genes were significantly differentially expressed between the more aggressive and less aggressive flies. One of the genes, Cyp6a20, when mutated, alone had a significant effect on aggressive behavior. Although it is not yet possible to generalize from these preliminary data, the assay and approach used should set a new standard for the genetic analysis of aggressive behavior.
Author contact:
Ralph Greenspan (The Neurosciences Institute, San Diego, USA)
Tel: +1 858 626 2075; E-mail: [email protected]
******************************NATURE NEUROSCIENCE *************************
(<http://www.nature.com/natureneuroscience>)
[14] A potential new target for antidepressants
DOI: 10.1038/nn1749
A potassium channel called TREK1 may represent a new target for antidepressant drugs, according to research to be published in the September issue of Nature Neuroscience. The channel may exert its effects through a signaling pathway in the brain different to that normally targeted by most conventional antidepressants, which are thought to work by increasing the level of the neurotransmitter serotonin.
Michel Lazdunski and colleagues studied mice lacking the gene for the TREK1 channel, which normally contributes to the background currents that set the resting membrane potential of neurons. In several behavioral tests used to model depression, the mice behaved as if they had been treated with an antidepressant. In addition, they had increased serotonergic activity, and did not release as much of the stress hormone corticosterone as normal mice in response to mild stress. Moreover, the authors report that the TREK1 channel was also directly inhibited by conventional antidepressants.
The finding that mice lacking the gene for TREK1 behave as if they have been given an antidepressant suggests that small molecule ‘blockers’ of the potassium channel might be effective therapeutically. If TREK1 is found to exert its antidepressant effects through a pathway independent of serotonin, it is possible that future therapies targeting TREK1 channels may be faster acting and may have fewer side effects than conventional antidepressants.
Author contact:
Michel Lazdunski (Institut de Pharmacologie Moleculaire et Cellulaire, Sophia Antipolis, France)
Tel: +33 4 93 95 77 02/03; E-mail: [email protected]
Other papers from Nature Neuroscience to be published online at the same time and with the same embargo:
[15] Dynamic shifts of visual receptive fields in cortical area MT by spatial attention
DOI: 10.1038/nn1748
*****************************NATURE IMMUNOLOGY **********************
(<http://www.nature.com/natureimmunology>)
[16] & [17] Blocking autoimmune brain inflammation
DOI: 10.1038/ni1375
DOI: 10.1038/ni1376
A key factor that controls the development of brain inflammation is reported in two studies in the September issue of Nature Immunology. Identification of this factor - called interleukin 27 - may provide a new target for treating inflammatory diseases of the central nervous system.
Nico Ghilardi and Christopher A. Hunter and colleagues studied two different mouse models of brain inflammation that resemble human diseases such as multiple sclerosis. Both groups show that brain inflammation is worse in mice that cannot respond to interleukin 27, a factor that communicates messages to immune cells. This more severe brain inflammation is associated with an influx of T cells that produce a molecule known to promote inflammation - interleukin 17 - into the brain. The treatment of T cells with interleukin 27 blocks the development of cells that produce interleukin 17. By preventing harmful interleukin 17-producing cells from developing, interleukin 27 could represent a potential therapeutic target for treating autoimmune diseases.
Author contacts:
Nico Ghilardi (Genentech, Inc., South San Francisco, CA, USA) Author paper [16]
Tel: +1 650 225 6907; E-mail: [email protected]
Christopher A Hunter (University of Pennsylvania, Philadelphia, PA, USA) Author paper [17]
Tel: +1 215 573 7772; E-mail: [email protected]
Please note this author is traveling and it may be easier to reach
Jason Stumhofer E-mail: [email protected]
Other papers from Nature Immunology to be published online at the same time and with the same embargo:
[18] Interleukin 18-independent engagement of interleukin 18 receptor-a is required for autoimmune inflammation
DOI: 10.1038/ni1377
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Items from other Nature journals to be published online at the same time and with the same embargo:
NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio <http://www.nature.com/natureneuroscience>)
[19] Ceruloplasmin is an NO oxidase and nitrite synthase that determines endocrine NO homeostasis
DOI: 10.1038/nchembio813
[20] Biosynthesis of Dictyostelium discoideum differentiation inducing factor by a hybrid type I fatty acid-type III polyketide synthase
DOI: 10.1038/nchembio811
NATURE MATERIALS (<http://www.nature.com/naturematerials>)
[21] Electrochemical lithiation synthesis of nanoporous materials with superior catalytic and capacitive activity
DOI: 10.1038/nmat1709
[22] Time-resolved electrostatic force microscopy of polymer solar cells
DOI: 10.1038/nmat1712
[23] Enhanced magnetic field sensitivity of spin-dependent transport in cluster-assembled metallic nanostructures
DOI: 10.1038/nmat1713
[24] A new view of the onset of plasticity during the nanoindentation of aluminium
DOI: 10.1038/nmat1714
NATURE CELL BIOLOGY (<http://www.nature.com/naturecellbiology>)
[25] Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1
DOI: 10.1038/ncb1460
[26] STIM1 carboxyl-terminus activates native SOC, Icrac and TRPC1 channels
DOI: 10.1038/ncb1454
[27] Plus end-specific depolymerase activity of Kip3, a kinesin-8 protein, explains its role in positioning the yeast mitotic spindle
DOI: 10.1038/ncb1457
[28] Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner
DOI: 10.1038/ncb1462
[29] PIASy mediates NEMO sumoylation and NF-kappaB activation in response to genotoxic stress
DOI: 10.1038/ncb1458
[30] The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor
DOI: 10.1038/ncb1463
[31] Essential CDK1-inhibitory role for separase during meiosis I in vertebrate oocytes
DOI: 10.1038/ncb1467
Nature STRUCTURAL & MOLECULAR BIOLOGY (<http://www.nature.com/natstructmolbiol>)
[32] Dynamically driven protein allostery
DOI: 10.1038/nsmb1132
[33] Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1
DOI: 10.1038/nsmb1133
[34] Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes
DOI: 10.1038/nsmb1134
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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.
AUSTRALIA
Parkville: 17
BELGIUM
Antwerp: 10
Brussels: 34
Louvain: 16
BRAZIL
Sao Paolo: 11
CANADA
Montreal: 14, 34
Toronto: 8
CHINA
Ningxia: 14
FRANCE
Montpellier: 7
Paris: 14
Rouen: 14
Sophia-Antipolis: 14
Toulouse: 34
GERMANY
Dresden: 28
Gottingen: 15, 18
Munich-Martinsried: 4, 31
Munich: 8
Stuttgart: 21
ITALY
Ferrera: 6
Milan: 8
Troina: 10
JAPAN
Fukuoka: 17
Handayama: 19
Mishima: 3
Sapporo: 20
Takatsuku: 30
KOREA
Chungnam: 2
NETHERLANDS
Amsterdam: 12
Nijmegen: 10, 15
NORWAY
Trondheim: 1
SOUTH KOREA
Seoul: 4
SWEDEN
Stockholm: 10
SWITZERLAND
Lausanne: 23
Zurich: 10, 18
UNITED KINGDOM
Cambridge: 11, 20
Dundee: 28
London: 6, 11, 12
Newcastle: 31
Oxford: 10, 12
Southampton: 6
UNITED STATES OF AMERICA
California
Berkeley: 24
La Jolla: 1, 2, 20
Los Angeles: 9
San Diego: 13, 17
San Francisco: 3, 12, 16, 27
Thousand Oaks: 17
Connecticut
New Haven: 30
Illinois
Chicago: 12
Indiana
West Lafayette: 24
Iowa
Iowa City: 25, 33
Maine
Bar Harbor: 2
Maryland
Baltimore: 5, 19, 25, 26
Bethesda: 5, 17, 19, 33
Frederick: 5
Massachusetts
Boston: 4, 27
Worcester: 30
Michigan
Ann Arbor: 8
Minnesota
Minneapolis: 24
Missouri
Kansas City: 25
New Jersey
Newark: 6, 7, 32
Piscataway: 32
New York
Bronx: 7
Stony Brook: 9
Pennsylvania
Philadelphia: 8, 17, 27
South Carolina
Charleston: 4
Texas
College Station: 7
Dallas: 25, 26
Washington
Seattle: 8, 12, 22
Wisconsin
Madison: 25, 29
Milwaukee: 19
PRESS CONTACTS…
For media inquiries relating to embargo policy for all the Nature Research Journals:
Helen Jamison (Nature London)
Tel: +44 20 7843 4658; 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)
Maria Bellantone
Tel: +44 20 7843 4556; E-mail: [email protected]
Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]
Nature Neuroscience (New York)
Sandra Aamodt (based in California)
Tel: +1 530 795 3256; E-mail: [email protected]
Nature Structural & Molecular Biology (New York)
Michelle Montoya
Tel: +1 212 726 9326; E-mail: [email protected]
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