Inherited risk factors for common leukemia

Summaries of newsworthy papers include Geoscience: Rapid ancient sea level rise, Neuroscience: Why the brain makes new nerve cells, Nature: Telomerase structure revealed and Nature: Genetics of geography

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 31 August 2008

This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

Genetics: Inherited risk factors for common leukemia

Geoscience: Rapid ancient sea level rise

Neuroscience: Why the brain makes new nerve cells

Nature: Telomerase structure revealed

And finally…Nature: Genetics of geography

· 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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[1] Genetics: Inherited risk factors for common leukemia
DOI: 10.1038/ng.219

Scientists have produced the first unequivocal evidence for inherited factors that contribute to susceptibility to chronic lymphocytic leukemia (CLL), reports a paper online this week in Nature Genetics. Approximately 25% of all individuals with leukemia have this form of the disease.

CLL results from the abnormal proliferation of B cells – a type of white blood cell that originates in the bone marrow. While it is known that individuals with a family history of CLL are at higher risk, the genetic basis of this risk has not been defined.

Richard Houlston and colleagues carried out a genome-wide association study of individuals with CLL, followed up by replication attempts in two additional groups. They found six common variants that modestly increase risk of the disease. Three of these variants are in or near genes that are good candidates for involvement in CLL, based on their known functions in B cells. Individuals with all six variants are estimated to have an eightfold elevated risk of disease. The authors suggest that these variants may influence the risk of other disorders of B-cell proliferation as well.

Author contact:
Richard Houlston (Institute of Cancer Research, Sutton, UK)
Tel: +44 208 722 4175; E-mail: [email protected]

[2] Geoscience: Rapid ancient sea level rise
DOI: 10.1038/ngeo285

Rapid melting of North America’s Laurentide ice sheet 9,000 and 7,600 years ago caused sea level to rise by up to 1.3 cm per year, according to research published online this week in Nature Geoscience. The summer air temperature rise that led to these melt pulses is similar to that recently reported for Greenland, suggesting that predictions of future sea level rise may be too low.

Anders Carlson and colleagues used marine and terrestrial records to reconstruct the demise of the Laurentide ice sheet during the Holocene era, which started about 10,000 years ago. Their simulations of the most rapid melting episodes show that the driving factors for the thinning of the ice sheet were increased solar radiation and increasing summer temperatures. Although the radiation at present is much lower, similar temperature increases have been recorded in Greenland during the past decades.

In an accompanying News and Views, Mark Siddall writes ‘Carlson and colleagues…show that the decay of the Laurentide ice sheet in the early Holocene was extremely fast during the periods they consider…. Their work suggests that, in principle, future melt rates on the order of one metre per century are certainly not out of the question.’

Author contact:
Anders Carlson (University of Wisconsin, Madison, WI, USA)
Tel: +1 608 262 1921; E-mail: [email protected]

News and Views author:
Mark Siddall (Lamont Doherty Earth Observatory, Palisades, NY, USA)
Tel: +1 845 365 8561; E-mail: [email protected]

Alternative email (after September): [email protected]

[3] Neuroscience: Why the brain makes new nerve cells
DOI: 10.1038/nn.2185

The adult brain requires a continuous stream of new neurons for the maintenance of regions controlling smell and spatial navigation, suggests a paper online this week in Nature Neuroscience.

Until a few years ago, it was thought that the mature brain gradually loses nerve cells but cannot make any new ones. This dogma has since been overthrown, but whether the few newly generated nerve cells play any important roles is not known.

Ryoichiro Kageyama and colleagues tackled this question by genetically modifying mice to synthesize a fluorescent protein in all adult-born nerve cells, and recording the numbers of fluorescent neurons over the course of one year. Over this time, nearly all neurons in a certain layer of the olfactory bulb – crucial for smelling – were replaced with new ones. In the hippocampus, which is essential for spatial learning and memory, about 15% new cells were added.

The authors then investigated whether stopping neurogenesis would interfere with the mice’s ability to smell or learn. The team made another mouse line, producing a poisonous protein in all adult nerve cell precursors to kill them. With no new neurons available, the mice’s olfactory bulbs shrank – though their sense of smell surprisingly remained intact for at least four months, suggesting a lot of redundancy in the olfactory circuitry. In contrast, the mice’s ability to remember how to navigate a particular kind of maze was lost.

Author contact:
Ryoichiro Kageyama (Kyoto University, Japan)
Tel: +81 75 751 4011; E-mail: [email protected]

[4] Nature: Telomerase structure revealed
DOI: 10.1038/nature07283

Researchers have snuck a peak at the engine of telomerase, an important enzyme that aids chromosome stability.

In this week’s Nature, Emmanuel Skordalakes and colleagues present the high resolution, and long sought-after, structure of the catalytic subunit of telomerase. The enzyme adds DNA repeats to the ends of chromosomes, preventing them from becoming shorter with each cell division. Using modelling, it is possible to predict how single-stranded telomeric DNA and the RNA subunit of telomerase align and position the DNA primer at the active site.

Understanding the mechanism of telomerase activity will affect fields such as oncology, because telomerase is reactivated in many human cancers, and ageing, because the natural loss of telomerase activity with age causes cells to enter a state known as senescence, in which they can no longer divide.

Author contact:
Emmanuel Skordalakes (The Wistar Institute, Philadelphia, PA, USA)
Tel: +1 21 5495 8664; Tel: [email protected]

[5] And finally…Nature: Genetics of geography
DOI: 10.1038/nature07731

Our genes can give away where we are from, according to research published online this week in Nature. By analysing small areas of genetic variation known as single nucleotide polymorphisms, scientists have uncovered a surprising link between genes and geography.

John Novembre and colleagues examined the genetic fingerprints of over 3,000 Europeans, linking the data with information on their geographical origin. When they plotted their results on a two-dimensional grid, what emerged looked remarkably like a map of Europe. The authors say they were able to pinpoint a person’s origin to within a few hundred km in some cases.

As well as posing exciting prospects for testing genetic ancestry, the research has important implications for evaluating genome-wide association studies, which are commonly used to link genes with diseases.

Author contact:
John Novembre (University of California-Los Angeles, CA, USA)
Tel: +1 310 825 4065; E-mail: [email protected]

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Items from other Nature journals to be published online at the same time and with the same embargo:

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

[6] Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains
DOI: 10.1038/nature07254

[7] Structure of the 30S translation initiation complex
DOI: 10.1038/nature07192

NATURE BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)

[8] T-DNA–mediated transfer of Agrobacterium tumefaciens chromosomal DNA into plants
DOI: 10.1038/nbt.1491

[9] Pharmacological inhibitors of a new hepatitis C target discovered by microfluidic affinity analysis
DOI: 10.1038/nbt.1490

NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology)

[10] Spatial control of branching within dendritic arbors by dynein-dependent transport of Rab5-endosomes
DOI: 10.1038/ncb1776

[11] Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons
DOI: 10.1038/ncb1777

[12] The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner
DOI: 10.1038/ncb1780

NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)

[13] Mechanism of CuA assembly
DOI: 10.1038/nchembio.110

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

[14] Evidence for two independent prostate cancer risk–associated loci in the HNF1B gene at 17q12
DOI: 10.1038/ng.214

[15] Kras regulatory elements and exon 4A determine mutation specificity in lung cancer
DOI: 10.1038/ng.211

[16] Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease
DOI: 10.1038/ng.203

NATURE GEOSCIENCE (http://www.nature.com/ngeo)

[17] The isotopic signature of the global riverine molybdenum flux and anoxia in the ancient oceans
DOI: 10.1038/ngeo282

[18] Plant spore walls as a record of long-term changes in ultraviolet-B radiation
DOI: 10.1038/ngeo278

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

[19] Toll-like receptor–mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway
DOI: 10.1038/ni.1645

[20] The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells
DOI: 10.1038/ni.1648

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

[21] Breakdown of phonon glass paradigm in La- and Ce-filled Fe4Sb12 skutterudites
DOI: 10.1038/nmat2260

[22] Half-full glasses
DOI: 10.1038/nmat2271

[23] Avoided crossing of rattler modes in thermoelectric materials
DOI: 10.1038/nmat2273

[24] The donor–acceptor approach allows a black-to-transmissive switching polymeric electrochrome
DOI: 10.1038/nmat2272

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

[25] Attenuated Plasmodium yoelii lacking purine nucleoside phosphorylase confer protective immunity
DOI: 10.1038/nm.1867

[26] The Creb1 coactivator Crtc1 is required for energy balance and fertility
DOI: 10.1038/nm.1866

NATURE METHODS (http://www.nature.com/nmeth)

[27] Automated screening for mutants affecting dopaminergic neuron specification in C. elegans
DOI: 10.1038/nmeth.1250

Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)

[28] Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex
DOI: 10.1038/nn.2181

[29] miR-19, miR-101, and miR-130 co-regulate ataxin1 levels to potentially modulate SCA1 pathogenesis
DOI: 10.1038/nn.2183

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

[30] Linked and knotted beams of light
DOI: 10.1038/nphys1056

[31] Motion detection of a micromechanical resonator embedded in a d.c. SQUID
DOI: 10.1038/nphys1057

[32] Membrane-induced bundling of actin filaments
DOI: 10.1038/nphys1071

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

[33] Structural basis of enzyme encapsulation into a bacterial nanocompartment
DOI: 10.1038/nsmb.1473

[34] Primary microRNA transcripts are processed co-transcriptionally
DOI: 10.1038/nsmb.1475

[35] A regulatable switch mediates self-association in an immunoglobulin fold
DOI: 10.1038/nsmb.1483

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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.

ARGENTINA
Rosario: 13

CANADA:
Vancouver: 2

DENMARK
Aarhus: 23
Copenhagen: 23
Roskilde: 23

FRANCE
Caen: 20
Grenoble: 21
Illkirch: 7
Montpellier: 21
Paris: 20, 33
Strasbourg: 7

GERMANY
Bielefeld: 8
Bochum: 28
Cologne: 8
Freiburg: 8
Gatersleben: 8
Martinsried: 28
Regensburg: 33

GREECE
Patras: 13

ITALY
Ariano Irpino: 15
Camerino: 7
Florence: 13
Naples: 15
Rome: 16, 34
San Giovanni Rotondo: 16

JAPAN
Aichi: 3
Chiba: 6
Kanagawa: 31
Kyoto: 3, 10
Osaka: 6
Saitama: 3
Tokyo: 3, 6
Yokohama: 6

NETHERLANDS
Delft: 31
Leiden: 30

SWEDEN
Abisko: 18
Gothenburg: 23
Orebro: 14
Stockholm: 14
Umea: 14
Uppsala: 12

SWITZERLAND
Basel: 33
Geneva: 21
Lausanne: 5, 9
Villigen: 23
Zurich: 33

UNITED KINGDOM
Birmingham: 1
Bristol: 17
Cambridge: 18
Cardiff: 1
Durham: 8
Edinburgh: 10
Hull: 1
Leeds: 1
Leicester: 1
Liverpool: 1
London: 18, 28
Milton Keynes: 18
Newcastle: 1
Nottingham: 18
Oxford: 34
Sheffield: 18
Sutton: 1

UNITED STATES OF AMERICA

Alabama
Auburn: 22

Arizona
Phoenix: 14

California
Berkeley: 32
La Jolla: 26
Los Angeles: 5
Pasadena: 2
San Francisco: 11, 15
Santa Barbara: 30
Stanford: 9

Connecticut
New Haven: 35

Florida
Gainesville: 24
Jupiter: 26

Georgia
Atlanta: 16, 19

Illinois
Chicago: 5

Maryland
Baltimore: 14

Massachusetts
Boston: 14, 20
Danvers: 26
Woods Hole: 2

Minnesota
Minneapolis: 29

New Hampshire
Durham: 2

New York
Bronx: 25
Ithaca: 5
New York: 2, 25, 27, 30

North Carolina
Research Triangle: 5
Winston-Salem: 14

Ohio
Cincinnati: 16

Oregon
Eugene: 10

Pennsylvania
Philadelphia: 4, 16
University Park: 10

Texas
Houston: 29

Utah
Salt Lake City: 16

Wisconsin
Madison: 2
Milwaukee: 16

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Nature Geoscience (London)
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Nature Materials (London)
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Nature Medicine (New York)
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Nature Methods (New York)
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Nature Neuroscience (New York)
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Published: 31 Aug 2008

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