Oncogenes: Pinpointing lymphoblastic leukaemia lesions

Summaries of newsworthy papers including: Freezing the Eocene greenhouse, Frequency-tunable terahertz metamaterials, Decisions occur before awareness, ‘What’ and ‘where’ in auditory cortex, Arsenic action on leukaemia, Surgery on a microchip


For papers that will be published online on 13 April 2008
This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:
Oncogenes: Pinpointing lymphoblastic leukaemia lesions - Nature
Freezing the Eocene greenhouse - Nature Geoscience
Frequency-tunable terahertz metamaterials - Nature Photonics
Decisions occur before awareness - Nature Neuroscience
‘What’ and ‘where’ in auditory cortex - Nature Neuroscience
Arsenic action on leukaemia - Nature Cell Biology
Surgery on a microchip - 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.

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/.


************************************* NATURE ****************************************


[1] Oncogenes: Pinpointing lymphoblastic leukaemia lesions
DOI: 10.1038/nature06866

A rogue chromosome - dubbed the Philadelphia chromosome - is responsible for a type of leukaemia known clinically as chronic myelogenous leukaemia, or CML, and for a subset of another type of leukaemia called acute lymphoblastic leukaemia, or ALL. This abnormal chromosome produces a version of a signalling protein that causes bone marrow cells to multiply uncontrollably. A paper in this week’s Nature identifies another mutant protein that contributes to this catastrophic process in ALL patients.

James Downing and colleagues examined the genetic material of 304 ALL patients and found that over 80% of those carrying the lesion associated with the Philadelphia chromosome also lacked a gene known as IKZF1. The protein encoded by this gene, called Ikaros, is a transcription factor, normally responsible for mediating DNA read-out via an RNA intermediate.

The authors conclude that genetic lesions resulting in the loss of Ikaros activity cause a crucial malfunctioning that can contribute to the development of ALL in people carrying the Philadelphia lesion.

Author contact:
James Downing (St Jude Children's Research Hospital, Memphis, TN, USA)
Tel: +1 901 495 3510; E-mail: [email protected]

Other papers from Nature to be published online at the same time and with the same embargo:

[2] Functional genomic screen reveals genes involved in lipid-droplet formation and utilization
DOI: 10.1038/nature06928

[3] Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes
DOI: 10.1038/nature06904

[4] Nucleosome organization in the Drosophila genome
DOI: 10.1038/nature06929

[5] Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes
DOI: 10.1038/nature06908

[6] Insect olfactory receptors are heteromeric ligand-gated ion channels
DOI: 10.1038/nature06850

[7] Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels
DOI: 10.1038/nature06861

***************************** NATURE GEOSCIENCE ***********************************


[8] Freezing the Eocene greenhouse
DOI: 10.1038/ngeo179

About 34 million years ago, the Earth’s climate abruptly cooled from warm greenhouse conditions to an icehouse climate - a time known as the Eocene-Oligocene transition. A study published online this week in Nature Geoscience suggests that this transition happened in three geologically rapid steps, each lasting for only several thousand years, culminating in a two degree cooling of the deep oceans and producing Antarctic ice sheets that were 25% larger than exist today.

Miriam Katz used marine sediments to reconstruct ocean temperature and sea level changes for the Eocene-Oligocene transition. Shell records indicated two intervals of bottom water cooling, providing previously elusive evidence that the deep oceans followed suit when the climate became cooler. Sea level decreased by up to 100 metres during the transition because water was stored in the Antarctic Ice Sheet.

Author contact:
Miriam Katz (Rensselaer Polytechnic Institute, Troy, NY, USA)
Tel: +1 518 276 8521, E-mail: [email protected]

Other papers from Nature Geoscience to be published online at the same time and with the same embargo:

[9] Partitioning of palladium at high pressures and temperatures during core formation
DOI: 10.1038/ngeo180

****************************** NATURE PHOTONICS ********************************


[10] Frequency-tunable terahertz metamaterials
DOI: 10.1038/nphoton.2008.52

The ability to use light to tune the frequency at which a material has a resonant response to terahertz waves - waves that can pass through non-conducting objects opaque to visible light - is reported online this week in Nature Photonics. The result overcomes the limitations of designs demonstrated so far and could lead to a new breed of active, frequency-agile terahertz devices that are controlled by light.

Terahertz waves, rays of electromagnetic radiation that lie in the frequency range of from 300 GHz to 3 THz, bridge the worlds of electronics and photonics and are useful for performing unique tasks in the fields of imaging, spectroscopy and telecommunications. Despite the recent progress in terahertz generation and detection, the techniques for controlling and manipulating terahertz waves are still lagging behind.

Terahertz metamaterials - composed of a two-dimensional array of resonators that interact with electromagnetic radiation in different ways to natural materials - can help. Unfortunately, they usually have a response that is fixed by their geometry. The response cannot be adjusted or tuned, and a new sample has to be redesigned and fabricated if effects at other frequencies are desired

Hou-Tong Chen and co-workers report that by incorporating two strips of silicon into each metallic split-ring resonator, they can tune the frequency resonance of a metamaterial from 1.06 THz to 850 GHz - a tuning range of 20% - when the array is illuminated with pulses of near-infrared laser light.

The achievement is anticipated to aid the development of a new host of frequency-agile devices for use in this exciting region of the electromagnetic spectrum.

Author contact:
Hou-Tong Chen (Los Alamos National Laboratory, Los Alamos, NM, USA)
Tel: +1 505 665 7365; E-mail: [email protected]

Other papers from Nature Photonics to be published online at the same time and with the same embargo:

[11] Superconducting nanowire photon-number-resolving detector at telecommunication wavelengths
DOI: 10.1038/nphoton.2008.51

******************************* NATURE NEUROSCIENCE *****************************


[12] Decisions occur before awareness
DOI: 10.1038/nn.2112

Activity in certain areas of the brain signals what choice people are going to make up to ten seconds before they become consciously aware of their decision, reports a study published online this week in Nature Neuroscience.

John-Dylan Haynes and colleagues used functional magnetic resonance imaging (fMRI) to track activity in the brain while people viewed a stream of letters on screen, and then pressed a button. Each subject was asked to decide freely which of two buttons to press and when to press it.

The authors used a sophisticated statistical technique, called pattern recognition, to look at brain activity associated with each choice. Activity in prefrontal and parietal cortex predicted which button the person was going to press. This activity occurred up to ten seconds before subjects were consciously aware of having made a decision. These areas have previously shown to be involved in executive control, self-reflection and selection amongst different choices. These results suggest that high-level control areas begin to prepare an upcoming decision long before it enters conscious awareness.

Author contact:
John-Dylan Haynes (Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany)
Tel: +49 3552 1722; E-mail: [email protected]

[13] ‘What’ and ‘where’ in auditory cortex
DOI: 10.1038/nn.2108

Auditory areas in the brain are split into two pathways for recognizing what a sound is and where it is coming from, which are similar to those used in visual processing.

A study published online this week in Nature Neuroscience reports conclusive evidence for auditory brain areas being segregated by whether they contribute to recognizing an object - the ‘what’ pathway - or processing where an object is located - the ‘where’ pathway.

Previous work had suggested that such segregation might exist for auditory brain areas, but the idea has been controversial. Stephen Lomber and Shveta Malhotra used cooling coils laid on the surface of the brain to reversibly deactivate specific brain areas in cats. They found that when a part of the brain, known as the posterior auditory field, was deactivated by cooling, the cats were unable to indicate where a sound was coming from. However, they could still distinguish between different types of sound patterns, indicating that the ‘what’ auditory pathway was intact. Conversely, when another nearby part of the brain, the anterior auditory field was deactivated instead, the cats now lost the ability to tell apart different sound patterns, but they could still correctly indicate where a sound was coming from. This suggests that the ‘where’ pathway was still intact with the anterior auditory field was deactivated. This shows that the posterior auditory field is involved in working out where an auditory object is, and the anterior auditory field is involved in working out what an auditory object is.

The existence of similar segregation in visual and auditory processing suggests that this could be a general organization principle in the brain.

Author contact:
Stephen Lomber (University of Western Ontario, Canada)
Tel: +1 519 663 5777 x34110; E-mail: [email protected]

Additional contact for comment on paper:

David Moore (MRC Institute of Hearing Research, Nottingham, UK)
Tel: +44 115 922 3431; E-mail: [email protected]

Other papers from Nature Neuroscience to be published online at the same time and with the same embargo:

[14] Reduction of stimulus visibility compresses apparent time intervals
DOI: 10.1038/nn.2111

*******************************************NATURE CELL BIOLOGY ************************************


[15] & [16] Arsenic action on leukaemia

DOI: 10.1038/ncb1716
DOI: 10.1038/ncb1717

Scientists have identified the mechanism by which compounds of arsenic can actually have therapeutic properties when used to treat certain types of cancer.

Therapeutic use of the poison arsenic to treat acute promyelocytic leukaemia leads to modification of the oncoprotein PML-RARalpha, causing its degradation. Two studies published online this week in Nature Cell Biology identify an enzyme that modifies proteins for destruction, known as ubiquitin ligase RNF4, as being responsible for recognizing PML-RARalpha and targeting it for degradation.

Originally identified in 1992 as the active ingredient in a traditional Chinese medicine, arsenic trioxide (ATO) has since been used to treat acute promyelocytic leukemia - a cancer of the blood and bone marrow. However, the mechanism of ATO action had remained unknown. Previous studies have shown that ATO treatment causes modification of PML-RARalpha by addition of several copies of the signalling molecule SUMO. How this modification correlates with the observed loss of PML-RARalpha was unclear.

Two studies from Ronald T. Hay and Hugues de Thé show that RNF4 specifically recognizes the SUMO chains attached to PML-RARalpha. RNF4 can then add further ubiquitin modifications to target the oncoprotein for degradation by the proteasome. Interestingly, PML-RARalpha represents the first cellular substrate of RNF4 to be identified.

This work adds vital information into how arsenic and arsenic-related compounds can be used as therapeutic agents to treat haematological cancers and could aid the development of improved treatments.

Author contacts:
Ronald T. Hay (University of Dundee, UK) Author paper 15
Tel: +44 1382 386 309; E-mail: [email protected]

Hugues de Thé (Université de Paris, France) Author paper 16
Tel: +33 1 57 27 67 70; E-mail: [email protected]

************************************ NATURE METHODS *************************************


[17] Surgery on a microchip
DOI: 10.1038/nmeth.1203

A microfluidic chip to immobilize the small worm C. elegans and perform laser nanosurgery to sever individual nerves and study their regeneration is reported in a study published online in Nature Methods this week.

C. elegans is a genetically tractable, transparent and easy to maintain model organism for laboratory study. Its basic nervous system and simple movement behaviours make it an ideal model for studying the fine function of the nervous system. Its high mobility however, is a challenge for microscopic manipulation and observation.

Adela Ben-Yakar and colleagues designed a microfluidic chip with two compartments separated by a pressure deformable membrane that holds a worm perfectly still during surgery and imaging. The worm can be released to a holding compartment and recaptured at will. This meant that the authors could successfully cut individual nerves and imaged the regeneration.

To date researchers have used chemical anesthetics, cold or embedding in a gelatinous substance to immobilize worms but this is time consuming and may alter biological functions. There have been attempts at using microfluidic devices to study worms but none have immobilized them well enough to perform laser nanosurgery.

Author contact:
Adela Ben-Yakar (University of Texas, TX, USA)
Tel: +1 512 475 9280; E-mail: [email protected]

Other papers from Nature Methods to be published online at the same time and with the same embargo:

[18] Suspended drop electroporation for high-throughput delivery of biomolecules into cells
DOI: 10.1038/nmeth.1201

[19] Live-cell photoactivated localization microscopy of nanoscale adhesion dynamics
DOI: 10.1038/nmeth.1202


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)

[20] Structural and biochemical evidence for a boat-like transition state in beta-mannosidases
DOI: 10.1038/nchembio.81

[21] Identification of RIP1 kinase as a specific cellular target of necrostatins
DOI: 10.1038/nchembio.83

Nature PHYSICS (http://www.nature.com/naturephysics)

[22] Nonlinear spectroscopy of photons bound to one atom
DOI: 10.1038/nphys940

[23] Probing vortex-core dynamics using current-induced resonant excitation of a trapped domain wall
DOI: 10.1038/nphys936

[24] Charged-impurity scattering in graphene
DOI: 10.1038/nphys935

[25] Resolved-sideband cooling of a micromechanical oscillator
DOI: 10.1038/nphys939

NATURE MATERIALS (http://www.nature.com/naturematerials)

[26] A zeolite family with chiral and achiral structures built from the same building layer
DOI: 10.1038/nmat2169

[27] Simultaneous optimization of charge-carrier mobility and optical gain in semiconducting polymer films
DOI: 10.1038/nmat2165

NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)

[28] Bit storage and bit flip operations in an electromechanical oscillator
DOI: 10.1038/nnano.2008.84

Nature MEDICINE (http://www.nature.com/naturemedicine)

[29] Replacing PCR with COLD-PCR enriches variant DNA sequences and redefines the sensitivity of genetic testing
DOI: 10.1038/nm1708

NATURE GENETICS (http://www.nature.com/naturegenetics)

[30] Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal gd T cells
DOI: 10.1038/ng.108

[31] No evidence of clonal somatic genetic alterations in cancer-associated fibroblasts from human breast and ovarian carcinomas
DOI: 10.1038/ng.117

[32] Exposing the fitness contribution of duplicated genes
DOI: 10.1038/ng.123

[33] Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)
DOI: 10.1038/ng.130

NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)

[34] The proline-rich sequence of CD3e controls T cell antigen receptor expression on and signaling potency in preselection CD4+CD8+ thymocytes
DOI: 10.1038/ni.1608

Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)

[35] The HSA domain binds nuclear actin-related proteins to regulate chromatin-remodeling ATPases
DOI: 10.1038/nsmb.1403

[36] DNA apurinic-apyrimidinic site binding and excision by endonuclease IV
DOI: 10.1038/nsmb.1414

[37] ATP-dependent chromatin remodeling shapes the DNA replication landscape
DOI: 10.1038/nsmb.1419



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.

Adelaide: 1
Brisbane: 17
Crawley: 20
Fitzroy: 31
Melbourne: 31

Ghent: 12

London: 13
Toronto: 16

Hebei: 27
Shanghai: 16, 21

Kuopio: 15

Gif-sur-Yvette: 20
Marseille: 34
Paris: 16, 20

Berlin: 12
Garching: 22, 25
Jena: 7
Leipzig: 12
Magdeburg: 12
Martinsried: 2

Budapest: 26
Veszprem: 26

Rome: 11

Chiba: 6
Hyogo: 14
Kanagawa: 14, 28
Mishima: 5
Nagoya: 2
Tokyo: 5
Tsukuba: 5
Yokohama: 5

Eindhoven: 11

Oslo: 36

Moscow: 11

Cadiz: 34

Stockholm: 26

Lausanne: 11
Zurich: 20

Izmir: 33

Cambridge: 5
Dundee: 15
London: 26, 27, 30
Newcastle: 20
Oxford: 3
York: 20

Berkeley: 4
La Jolla: 36
San Diego: 21, 36
San Jose: 23
San Francisco: 2, 34
Stanford: 18
New Haven: 30, 33
Orlando: 24
Tallahassee: 9
Chicago: 1
Baltimore: 33
Bethesda: 19, 33
College Park: 24
Rockville: 36
Boston: 10, 21, 29, 31, 32, 33
Cambridge: 21, 32
Chestnut Hill: 10
Ann Arbor: 17
St Louis: 33
New Hampshire
Hanover: 21
New Jersey
New Brunswick: 8
Piscataway: 8
New Mexico
Los Alamos: 10
New York
Albany: 4, 36
Cold Spring Harbor: 3
New York: 6, 35
Plainview: 33
Troy: 8
North Carolina
Durham: 33
Cleveland: 21
Columbus: 4
Eugene: 8
Philadelphia: 3
University Park: 4
South Carolina
Columbia: 23
Memphis: 1
Austin: 17
College Station: 8
Houston: 9
Richardson: 13
Salt Lake City: 35
Ashburn: 19
Seattle: 37


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 Geoscience (London)
Heike Langenberg
Tel: +44 20 7843 4042; E-mail: [email protected]

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)
Alison Stoddart
Tel: +44 20 7843 4593; 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 Photonics (Tokyo))
Oliver Graydon
Tel: +81 3 3267 8776; 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.

Published: 13 Apr 2008

Contact details:

The Macmillan Building, 4 Crinan Street
N1 9XW
United Kingdom

+44 20 7833 4000
News topics: 
Content type: 

Nature and Nature Research Journals