How the brain sorts the world; Patient-specific cancer treatment; Genetic susceptibility to age-related macular degeneration and Glia contribute to neurodegeneration

Summaries of newsworthy papers Nature and the Nature Research Journals for papers that will be published online on 27 August 200


For papers that will be published online on 27 August 2006

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This press release contains:

* Summaries of newsworthy papers:
Neuroscience: How the brain sorts the world - Nature
Patient-specific cancer treatment - Nature Chemical Biology
Genetic susceptibility to age-related macular degeneration - Nature Genetics
Glia contribute to neurodegeneration - Nature Neuroscience

* Mention of papers to be published at the same time with the same embargo
* Geographical listing of authors

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[1] Neuroscience: How the brain sorts the world
DOI: 10.1038/nature05078

One way of assigning meaning and behavioural relevance to sensory stimuli is to categorize them - if our brains didn't do this, the world would be a pretty confusing place. For example, a continuous distribution of target speeds can be grouped into ‘fast’ or ‘slow’ categories. Neuroscientists have now characterized brain cells that seem to reflect this sorting process in monkey brains.

David Freedman and John Assad trained rhesus monkeys (Macaca mulatto) to divide dots moving on a screen into two categories, depending on their direction of movement. As they report, in a paper published online this week by Nature, the activity of neurons in a brain region called the lateral intraparietal (LIP) area strongly corresponded with the motion direction category viewed by the monkeys. When the monkeys were retrained to group the same stimuli into two new categories, the activity of neurons in the LIP changed to reflect the new rule.

This suggests that neurons in the LIP may play an important part in the process of transforming visual information into representative forms that allow us to attach meaning to stimuli.

Author contact:

David Freedman (Harvard Medical School, Boston, MA, USA)
Tel: +1 617 432 2805; [email protected] <mailto:[email protected]>

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

[2] AtSNX1 defines an endosome for auxin-carrier trafficking in Arabidopsis
DOI: 10.1038/nature05046

[3] Soma-germline interactions coordinate homeostasis and growth in the Drosophila gonad
DOI: 10.1038/nature05068

*******************NATURE CHEMICAL BIOLOGY *******************


[4] Patient-specific cancer treatment
DOI: 10.1038/nchembio814

Scientists have discovered a way to cause some cancerous cells to self-destruct. These findings, reported in the October issue of Nature Chemical Biology, describe the use of a small molecule to ‘wake up’ the key enzyme - caspase-3 - that causes cell death.

Caspase-3 normally exists as a proenzyme, meaning that further processing is required to make the final, active enzyme. This processing is normally performed by other caspases and serves as a signal that something has gone wrong with a cell; it signals that cell death or ‘apoptosis’ is desired. Paul Hergenrother and colleagues have now used the synthetic compound PAC-1 to trick procaspase-3 into processing itself, generating caspase-3 and causing cell death. They demonstrated, in a variety of cancer cell types, that cell death is correlated with the amount of procaspase-3 present in the cells, with more procaspase-3 resulting in cell death at lower concentrations of PAC-1, while healthy cells remain unaffected.

The variability of procaspase-3 levels in the cell lines tested means that some patients would be more responsive to this therapy than others. As such, this research potentially offers a novel opportunity for individualized cancer therapy.

Author contact:
Paul J Hergenrother (The University of Illinois, Urbana, IL, USA)
Tel: +1 217 333 0363; [email protected] <mailto:[email protected]>

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

[5] Kinetic flux profiling of nitrogen assimilation in Escherichia coli
DOI: 10.1038/nchembio816

*************************NATURE GENETICS *******************

[6] & [7] Genetic susceptibility to age-related macular degeneration

DOI: 10.1038/ng1873
DOI: 10.1038/ng1871

The genetic factors influencing susceptibility to a degenerative eye disorder are explored in two papers in the September issue of Nature Genetics. The scientists report that multiple genetic variants together explain a high proportion of inherited individual disease risk.

Age-related macular degeneration - AMD - is a degenerative disorder of the eye affecting the central retina, which gradually reduces vision and is one of the most common causes of vision loss in the elderly. The risk of developing AMD increases with age, and is influenced by environmental as well as genetic components. Previous studies showed that a common, variant form of a protein called complement factor H (CFH) is associated with increased susceptibility to AMD. These new studies show that additional variants within the CFH gene, which do not affect the function of the protein, also make an important contribution to disease risk.

In one study, Gonçalo Abecasis and colleagues examined variants within and surrounding the CFH gene, in AMD patients and healthy individuals from a single study population. They find that variants in the gene encoding CFH, which do not change the protein itself, strongly contribute to the risk of AMD. They also show that multiple variants together define a high proportion of risk. In an accompanying paper, Mark Daly and colleagues examine an independent set of AMD cases and similarly find that a common non-protein-coding variant in CFH influences disease risk. The authors also confirm previous associations between disease susceptibility and variation in two additional genes, and show that, together, the genetic variation in these three genes defines a broad spectrum of individual disease risk. It has been noted that siblings of individuals with AMD show a 3-6 fold higher incidence of disease compared to the general population. Daly and colleagues estimate that variation in the three genes they study explains roughly half of this increased risk seen among siblings.

Author contacts:
Gonçalo Abecasis (University of Michigan, Ann Arbor, MI, USA)
Tel: +1 734 763 4901; E-mail: [email protected] <mailto:[email protected]>

Mark Daly (Massachusetts General Hospital, Boston, MA, USA)
Tel: +1 617 726 5942; E-mail: [email protected] <mailto:[email protected]>

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

[8] Dual feedback loops in the GAL regulon suppress cellular heterogeneity in yeast
DOI: 10.1038/ng1869

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

[9] Glia contribute to neurodegeneration
DOI: 10.1038/nn1750

Glia - often called the ‘support cells’ of the brain - contribute to neurodegeneration in the progressive disease spinocerebellar ataxia type 7 (SCA7) because a mutation they express interferes with the transport of a neurotransmitter, reports a paper in the October issue of Nature Neuroscience. This suggests that the death of neurons may not result from their self-programmed ‘suicide’, a finding that could influence researchers’ approaches to treating this and other disorders.

Albert La Spada and colleagues created a mouse model of SCA7 that expressed a mutated protein - ataxin-7, which causes the disease - only in Bergmann glia of the cerebellum. The mice showed the characteristic gait impairment, or ataxia, that gives the disease its name, along with degeneration of Purkinje neurons in the cerebellum. A transporter molecule that normally removes the neurotransmitter glutamate was also found to be less abundant in the mice, which showed reduced glutamate transport function.

The authors conclude that reduced transport of glutamate into glial cells contributes to the degeneration of Purkinje neurons, as glutamate is known to be neurotoxic in large quantities. They speculate that this may be the process by which glial cells cause neuronal death in other neurodegenerative diseases, such as amyotrophic lateral sclerosis, Alzheimer disease, Huntington disease and prion disease, in which glia are implicated.

Author contact:
Albert R La Spada (University of Washington, Seattle, WA, USA)
Tel: +1 206 598 2138; E-mail: [email protected] <mailto:[email protected]>

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

[10] Arm immobilization causes cortical plastic changes and locally decreases sleep slow wave activity
DOI: 10.1038/nn1758

[11] Neutralizing the neurotoxic effects of exogenous and endogenous tPA
DOI: 10.1038/nn1757

[12] Meaningful interactions can enhance visual discrimination of human agents
DOI: 10.1038/nn1759


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

Nature PHYSICS ( <>)

[13] A coherent all-electrical interface between polar molecules and mesoscopic superconducting resonators
DOI: 10.1038/nphys386

[14] Exciton scattering and localization in branched dendrimeric structures
DOI: 10.1038/nphys389

[15] Cosmic-ray diffusion near the Bohm limit in the Cassiopeia A supernova remnant
DOI: 10.1038/nphys391

[16] Nonlinear optical signatures of the tensor order in Cd2Re2O7
DOI: 10.1038/nphys392

[17] First direct observation of Dirac fermions in graphite
DOI: 10.1038/nphys393

[18] Magnetic energy change available to superconducting condensation in optimally doped YBa2Cu3O6.95
DOI: 10.1038/nphys394

Nature MEDICINE (<>)

[19] Adoptive transfer of T-cell precursors enhances T-cell reconstitution after allogeneic hematopoietic stem cell transplantation
DOI: 10.1038/nm1463

Nature IMMUNOLOGY (<>)

[20] Transcription factors TFE3 and TFEB are critical for CD40 ligand expression and thymus-dependent humoral immunity
DOI: 10.1038/ni1378

[21] Regulation of T cell receptor-alpha gene recombination by transcription
DOI: 10.1038/ni1379


[22] A peptide motif in Raver1 mediates splicing repression by interaction with the PTB RRM2 domain
DOI: 10.1038/nsmb1137

[23] Involvement of AGO1 and AGO2 in mammalian transcriptional silencing
DOI: 10.1038/nsmb1140

[24] L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells
DOI: 10.1038/nsmb1141

[25] Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells
DOI: 10.1038/nsmb1142



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.

Innsbruck: 13

Sao Paulo: 17

Burnaby: 16
Toronto: 19

Lyon: 3

Dresden: 22
Frankfurt/Main: 9
Halle: 22
Tubingen: 18

Jerusalem: 11

Seoul: 4

Bristol: 18
Cambridge: 22
Didcot: 18
London: 22

Jefferson: 4
Berkeley: 12, 17
Duarte: 25
La Jolla: 25
Santa Barbara: 18
New Haven: 13
Urbana: 4
Amherst: 15
Boston: 1, 6
Cambridge: 6, 13, 15
Ann Arbor: 7
Detroit: 14
Rolla: 18
New Jersey
Princeton: 5
New Mexico
Los Alamos: 14
New York
Bronx: 22
New York: 2, 19, 20
North Carolina
Durham: 21
Philadelphia: 7, 11, 24
University Park: 17
South Carolina
Clemson: 16
Knoxville: 16, 18
Oak Ridge: 16, 18
Dallas: 23
Seattle: 8, 9
West Virginia
Morgantown: 7
Madison: 10


For media inquiries relating to embargo policy for all the Nature Research Journals:

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For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:

Nature Chemical Biology (Boston)
Andrea Garvey
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Nature Genetics (New York)
Orli Bahcall
Tel: +1 212 726 9311; E-mail: [email protected] <mailto:[email protected]>

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

Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected] <mailto:[email protected]>

Nature Neuroscience (New York)
Sandra Aamodt (based in California)
Tel: +1 530 795 3256; E-mail: [email protected] <mailto:[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] <mailto:[email protected]>

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Published: 27 Aug 2006

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