NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 18 February 2007
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This press release contains:
• Summaries of newsworthy papers:
Consortium tackles the genetic basis of autism – Nature Genetics
Making room for others – Nature Immunology
Abnormal cell migration – Nature Structural & Molecular Biology
Splicing out of control – Nature Structural & Molecular Biology
• Mention of papers to be published at the same time with the same embargo
• Geographical listing of authors
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************************* NATURE GENETICS *******************
 Consortium tackles the genetic basis of autism
The genomes of the largest collection of families with multiple cases of autism ever assembled have been scanned in a new study. The results provide new insights into the genetic basis of autism, according to a report published online this week in Nature Genetics.
Autism spectrum disorders (ASD) influence social interaction and communication and affect 6 out of every 1,000 children. The Autism Genome Project Consortium – comprising 50 centres in North America and Europe – collected DNA samples from nearly 1,500 families, each of which has more than two members with ASD.
The team carried out a two-fold analysis. First they assessed the frequency of alterations in copy number of different segments of the genome, finding an unexpectedly high percentage of the families – 7 to 12%, depending on how the analysis was done – in which all affected individuals share possibly detrimental chromosomal abnormalities. Two female siblings had deletions of the gene encoding the protein neurexin 1, which interacts with neuroligins – a family of proteins that have been implicated in some cases of autism. Finally, the authors carried out a ‘linkage’ analysis of these families, searching for regions of the genome that might be shared by the individuals with ASD. One particular region on chromosome 11 was identified, which has not previously been reported to harbour genes that affect risk of developing autism.
Bernie Devlin (University of Pittsburgh, PA, USA)
Tel: +1 412 246 6642; E-mail: [email protected]
Stephen Scherer (The Hospital for Sick Children and University of Toronto, ON, Canada)
Tel: +1 416 813 7613; E-mail: [email protected]
Other papers from Nature Genetics to be published online at the same time and with the same embargo:
 Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum
 Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes
 Complete inactivation of DNMT1 leads to mitotic catastrophe in human cancer cells
**********************NATURE IMMUNOLOGY **********************
 Making room for others
Newly activated antibody-producing immune cells can displace older antibody-synthesizing residents in the bone marrow, according to a report to be published online this week in Nature Immunology. These findings help explain how individuals, as they age, develop ‘immunologic memory’ to newly encountered pathogens.
Kenneth Smith and colleagues show plasma cells – which make antibodies tailored for specific pathogens – express a protein called FcgammaRIIb on their surface; and that older plasma cells express more of it than newly generated ones. The group shows that when FcgammaRIIb binds onto the older cells it triggers some of these cells to self destruct and thereby make space for the newly made plasma cells to take up residence in the bone marrow. Here they can produce antibodies against recently encountered pathogens.
The authors suggest that plasma cell expression of this protein provides a feedback mechanism to limit the number of antibody-producing cells in the body, which matches previous correlations showing patients with mutations in FcgammaRIIb have higher risk for antibody-mediated autoimmune diseases. Importantly, Smith’s group also show human myeloma cells – which are a form of cancerous cells arising from plasma cells – are also sensitive to FcgammaRIIb-induced self destruction. Thus, it might be possible to use FcgammaRIIb-targeted therapies to target both pathogenic autoantibody producing cells and myeloma.
Kenneth Smith (University of Cambridge, UK)
Tel: +44 1223 762 645; E-mail: [email protected]
Additional contact information for comment:
Jeffrey V. Ravetch (Rockefeller University, New York, NY, USA)
Tel: +1 212 327 7321; E-mail: [email protected]
*********NATURE STRUCTURAL & MOLECULAR BIOLOGY**********
 Abnormal cell migration
Mutations in a certain type of oncogene and tumour suppressor can collaborate to send cancerous cells into a malignant state, according to a study to be published online this week in Nature Structural & Molecular Biology. Mingxuan Xia and Hartmut Land examine the consequences of mutations in the oncogene Ras and the tumour suppressor p53.
Tumours are generally thought to arise due to the interaction of multiple mutations that alter protein function. Oncogenes, such as Ras, promote tumour formation when aberrantly activated through mutations. On the other hand, tumour suppressors, such as p53, have the opposite effect, in that they normally guard against aberrant cell growth.
A key event in the progression of cells to a malignant state during cancer progression is the abnormal acquisition of movement, which allows tumour cells to spread from their original location. A major regulator of cell movement is a factor called Rho. The team finds that when they experimentally activate Ras, Rho moves to its site of function at the cell membrane but is unable to trigger cell migration. However, when activated Ras is present with a p53 mutation that causes decreased p53 activity, membrane-localized Rho is now activated and cells acquire movement.
Hartmut Land (University of Rochester Medical Center, NY, USA)
Tel: +1 585 273 1442; E-mail: [email protected]
 Splicing out of control
A factor that regulates gene function by splicing messenger RNA may be involved in tumour formation, according to research to be published in the March issue of Nature Structural & Molecular Biology. Adrian Krainer and colleagues report that SF2/ASF is present at abnormally high levels in human tumour cells.
Splicing is one form of messenger RNA regulation and, rather like editing a reel of film, involves cutting out segments and pasting the message back together again. Splicing factors, such as SF2/ASF, can regulate which parts of the original message end up in the final edit, and can profoundly alter the function of the final gene product depending on which segments are kept in the message.
The authors find that deliberately increasing SF2/ASF expression alters the splicing status of a number of genes that have previously been implicated in promoting tumour formation when misregulated. This, they suggest, might lead to unchecked cell growth and the loss of the cell death safety net that would usually eliminate such out of control cells.
Adrian Krainer (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA)
Tel: +1 516 367 8417; E-mail: [email protected]
Other papers from Nature Structural & Molecular Biology to be published online at the same time and with the same embargo:
 Demethlyation of trimethylated histone H3 Lys4 in vivo by members of the JARID1 family of JmjC proteins
 Yeast Jhd2p is a histone H3 Lys4 trimethyl methylase
Items from other Nature journals to be published online at the same time and with the same embargo:
 MAPK-mediated bimodal gene expression and adaptive gradient sensing in yeast
 A ubiquitin ligase transfers preformed polyubiquitin chains from a conjugating enzyme to a substrate
Nature PHYSICS (http://www.nature.com/naturephysics)
 A local metallic state in globally insulating La1.24Sr1.76Mn2O7 well above the metal–insulator transition
 Kinks in the dispersion of strongly correlated electrons
 Two new vortex liquids
 Fluctuating Cu–O–Cu bond model of high-temperature superconductivity
 Spin qubits in graphene quantum dots
 Two energy scales in the spin excitations of the high-temperature superconductor La2−xSrxCuO4
 Valley filter and valley valve in graphene
NATURE MATERIALS (http://www.nature.com/naturematerials)
 Polyamorphism in a metallic glass
 Trends in electrocatalysis on extended and nanoscale Pt-bimetallic alloy surfaces
 Microscopic annealing process and its impact on superconductivity in T ¢–structure electron-doped copper oxides
NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)
 Carbon nanotube guided formation of silicon oxide nanotrenches
 Coerced mechanical coarsening of nanoparticle assemblies
Nature MEDICINE (http://www.nature.com/naturemedicine)
 Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3beta activity
 Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment
 Adrenal GRK2 upregulation mediates sympathetic overdrive in heart failure
Nature BIOTECHNOLOGY (http://www.nature.com/naturebiotechnolgy)
 Female-specific insect lethality engineered using alternative splicing
 Improving catalytic function by ProSAR-driven enzyme evolution
Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)
 Glutamate exocytosis from astrocytes controls synaptic strength
 Neural representation of transparent overlay
 GDNF and GFRalpha1 promote formation of neuronal synapses by ligand-induced cell adhesion
 Dual functions of mammalian olfactory sensory neurons as odor detectors and mechanical sensors
 Grb4 and GIT1 transduce ephrinB reverse signals modulating spine morphogenesis and synapse formation
NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology)
 Constitutive RelA activation mediated by Nkx3.2 controls chondrocyte viability
 CIPC is a mammalian circadian clock protein without invertebrate homologues
 Myosin IIA regulates cell motility and actomyosin–microtubule crosstalk
 Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate
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.
Toronto: 1, 37
Turku : 25
Paris: 1, 2
Berlin: 5, 19, 26, 37
Heidelberg: 1, 39
Osaka: 10, 11
Warsaw: 15, 20
Santa Maria de Feira: 2
Cape Town: 5
Stockholm: 5, 11, 33
Liverpool: 22, 25
London: 1, 19
Newcastle upon Tyne: 1
Oxford: 1, 29
UNITED STATES OF AMERICA
Berkeley: 14, 22
La Jolla: 12, 37
Los Angeles: 1
Redwood City: 30
Stanford: 1, 13
New Haven: 1
District of Columbia
Argonne: 14, 21, 22, 23
Iowa City: 1
Baltimore: 1, 12, 21, 32
Bethesda: 13, 38
College Park: 23
Boston: 1, 37
Cambridge: 4, 26
Ann Arbor: 1
St Louis: 1
Cold Spring Harbor: 7
New York: 1
Rochester: 1, 6
Staten Island: 1
Yorktown Heights: 17
Chapel Hill: 1, 9
Philadelphia: 1, 26, 28, 34
Oak Ridge: 23
Nashville: 1, 3
Salt Lake City: 1
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For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:
Nature Biotechnology (New York)
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Nature Cell Biology (London)
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Nature Genetics (New York)
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Nature Immunology (New York)
Tel: +1 212 726 9372; E-mail: [email protected]
Nature Materials (London)
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 Methods (New York)
Tel: +1 212 726 9393; E-mail: [email protected]
Nature Nanotechnology (London)
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)
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