Genetics: Variants associated with Hodgkin’s lymphoma

Summaries of newsworthy papers include: A habitable microenvironment on Mars? Unfolding the story of an anthrax toxin; Autophagy defect in muscle disease; Brain control of insulin sensitivity; Selective inhibition of immune responses; Geoscience: Million-year-old sand in the Namib

This press release contains:

• Summaries of newsworthy papers:

Geoscience: A habitable microenvironment on Mars?

Structural & Molecular Biology: Unfolding the story of an anthrax toxin

Medicine: Autophagy defect in muscle disease

Genetics: Variants associated with Hodgkin’s lymphoma

Neuroscience: Brain control of insulin sensitivity

Immunology: Selective inhibition of immune responses

And finally…Geoscience: Million-year-old sand in the Namib

• 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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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/.

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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.

[1] Geoscience: A habitable microenvironment on Mars?
DOI: 10.1038/ngeo990

Hydrated silica deposits in the Syrtis Major volcanic complex on Mars could indicate a relatively recent habitable environment, suggests a study online this week in Nature Geoscience. The shape of the deposits, and their location in and around a volcanic cone, point to an origin in a hydrothermal system, which could have both harboured life and preserved its remains.

John Skok and colleagues analysed data obtained with the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM). They detected spectroscopic signatures that are consistent with hydrated silica near the Nili Patera volcanic cone a relatively young volcanic feature on Mars. The researchers interpret the data as indicative of a recent hydrothermal system. On Earth, hydrothermal environments with silica formation are considered to have a significant potential for preserving
microbial fossils.

Author contact:
John Skok (Brown University, Providence, RI, USA)
Tel: +1 607 972 1131
E-mail: [email protected]

[2] Structural & Molecular Biology: Unfolding the story of an anthrax toxin
DOI: 10.1038/nsmb.1923

How the anthrax toxin gets into cells is visualized in a paper published online this week in Nature Structural & Molecular Biology. Understanding the machinery underlying such a basic process in the anthrax lifecycle allows researchers to look for weak spots to target such pathogens.

Bacillus anthracis, the bacterium that causes anthrax, produces the toxin lethal factor (LF), which, once it enters cells, leads to fatality for patients. But injecting these proteins into host cells is akin to getting a ship into a bottle, in that they have to be unfolded to get them through a narrow channel into the cell where they are refolded into their active shape.

The anthrax lethal toxin injection system itself consists of protective antigen (PA) and lethal factor (LF), with LF unfolding for translocation into the host cell. Structural and functional analyses indicate how each of four LF molecules unfolds and binds on the surface of eight PA molecules in clefts that help stabilize the unfolded state. This indicates how the bacterium can control the shape of the molecule and ensure it remains functional.

Author contact:
Bryan Krantz (University of California, Berkeley, CA, USA)
Tel: +1 510 666 2788
E-mail: [email protected]

[3] Medicine: Autophagy defect in muscle disease
DOI: 10.1038/nm.2247

Defects in autophagy—the degradation of damaged cellular organelles—are linked to muscular dystrophy, which is a disease in which muscle degenerates, according an article published this week in Nature Medicine.

Autophagy is crucial in the turnover of cell components and clearance of damaged organelles. Defects of this system have a role in various diseases, but little was known about autophagy in muscular dystrophy. Previous results had shown that some forms of muscular dystrophy are linked to abnormal mitochondria and spontaneous cell death, leading to muscle degeneration.

Using mice with a genetic form of muscular dystrophy, Paolo Bonaldo and his group show that the persistence of abnormal mitochondria and cell death are caused by defective autophagy in the muscle cell. Importantly, forced activation of autophagy in these cells restored muscle-cell survival in the mice, pointing to what could be a new therapeutic strategy against this disease.

Author contact:
Paolo Bonaldo (University of Padova, Italy)
Tel: +39 49 8276084
E-mail: [email protected]

[4] Genetics: Variants associated with Hodgkin’s lymphoma
DOI: 10.1038/ng.696

Genetic variants associated with classical Hodgkin’s lymphoma (cHL) are reported this week in Nature Genetics. cHL is a lymph node cancer, and is one of the most common cancers among young adults in developed countries.

Richard Houlston and colleagues report a genome-wide association study for cHL in 589 cases and 5,199 healthy controls from the UK, with replication of these results in an additional four cohorts.
They identify three genomic regions newly associated with cHL, and based on this, suggest the involvement of the MYC, GATA3 and the NFkB pathways in the disease. The authors also replicate earlier associations to the human leukocyte antigen (HLA) class II region, which
shows the most significant association to cHL susceptibility.

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

[5] Neuroscience: Brain control of insulin sensitivity
DOI: 10.1038/nn.2664

Serotonin receptors expressed in a specific type of neuron in the brain regulate insulin sensitivity in the liver, reports a study published online this week in Nature Neuroscience.

Previous work has implicated brain serotonin receptors, specifically the 2C subtype, in the regulation of whole body energy balance and glucose homeostasis. Joel Elmquist and colleagues took advantage of genetically-modified mice lacking the serotonin 2C receptor to delve further into the identity of the neurons mediating these effects. They find that mice lacking the serotonin 2C receptor displayed insulin resistance in the liver. This resistance was ameliorated when the expression of the serotonin 2C receptor was restored in a specific group of neurons, the pro-opiomelanocortin (POMC)-expressing neurons, in the arcuate nucleus of the hypothalamus—a brain region critical for regulation of feeding and glucose homeostasis.

The authors also found that serotonin 2C receptor expression in POMC neurons was sufficient to mediate the anti-diabetic effects of a drug that targets these receptors. These findings in mice provide potential insight into blood glucose control in humans.

Author contact:
Joel Elmquist (The University of Texas Southwestern Medical Center, Dallas, TX, USA)
Tel: +1 214 648 2911
E-mail: [email protected]

[6] Immunology: Selective inhibition of immune responses
DOI: 10.1038/ni.1955

A discriminating inhibitor for Zap70, a molecule important to propagate activation signals upon antigen recognition by immune T cells, reveals new insights about immune cell signaling and regulation according to a report in this week’s online edition of Nature Immunology. This work points to a new target for immune cell intervention that might prove beneficial in settings where immune tolerance is desired, such as T cell-mediated autoimmunity or organ transplantation.

Zap70 is known to activate a pathway that triggers proliferation and function of effector T cells. Loss of Zap70 function leads to defective T cell development, hence how Zap70 functions in
mature T cells was left unknown.

Art Weiss and colleagues generated small molecule inhibitors targeting a modified version of Zap70. They show an unexpected new function of Zap70 in regulatory T cells, which act to prevent autoimmune responses and restrains effector T cells. While the new inhibitors block the catalytic activity of modified Zap70 kinases and thereby blocked effector cell functions, which are important for combating infections, the suppressive activity of regulatory T cells remains intact. These
findings point to a kinase-independent role for Zap70 in regulatory T cells.

Author contact:
Art Weiss (University of California, San Francisco, CA, USA)
Tel: +1 415 476 1291
E-mail: [email protected]

[7] And finally…Geoscience: Million-year-old sand in the Namib
DOI: 10.1038/ngeo985

The sands of the Namib Sand Sea have been there for at least a million years reports a paper published online this week in Nature Geoscience. This suggests that, despite large-scale climate changes in the region over the past million years, at no time was the area completely cleared of sand.

Pieter Vermeesch and colleagues used geochemical tracers to track the movement of sand across the 400-km sand sea. They also measured radioactive isotopes produced by cosmic rays, which allowed them to estimate the amount of time that the sand had been present in the region. They conclude that it takes a minimum of one million years for winds to blow sands across the sand sea, although the sand dunes may not have been active for the entire time span.

Author contact:
Pieter Vermeesch (Birkbeck College, London, UK)
Tel: +44 20 7679 2418
E-mail: [email protected]

***********************************************************

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

NATURE

[8] The structural basis for membrane binding and pore formation by lymphocyte perforin
DOI: 10.1038/nature09518

NATURE BIOTECHNOLOGY

[9] Programmable in situ amplification for multiplexed imaging of Mrna expression
DOI: 10.1038/nbt.1692

NATURE CELL BIOLOGY

[10] A kinase cascade leading to Rab11-FIP5 controls transcytosis of the polymeric immunoglobulin receptor
DOI: 10.1038/ncb2118

NATURE CHEMICAL BIOLOGY

[11] Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteins
DOI: 10.1038/nchembio.467

[12] Ultra-sensitive in situ visualization of active glucocerebrosidase molecules
DOI: 10.1038/nchembio.466

NATURE CHEMISTRY

[13] Synergistic self-assembly of RNA and DNA molecules
DOI: 10.1038/nchem.890

[14] Reversing the direction in a light-driven rotary molecular motor
DOI: 10.1038/nchem.872

[15] The effect of isotopic substitution on the chirality of a self-assembled helix
DOI: 10.1038/nchem.889

NATURE GENETICS

[16] The developmental dynamics of the maize leaf transcriptome
DOI: 10.1038/ng.703

[17] Natural variation at Strubbelig Receptor Kinase 3 drives immune-triggered incompatibilities between Arabidopsis thaliana accessions

DOI: 10.1038/ng.704

[18] /Yersinia pestis/ genome sequencing identifies patterns of global
phylogenetic diversity
DOI: 10.1038/ng.705

NATURE GEOSCIENCE

[19] Photolysis of sulphuric acid as the source of sulphur oxides in the mesosphere of Venus
DOI: 10.1038/ngeo989

NATURE IMMUNOLOGY

[20] Plasma cells negatively regulate the follicular helper T cell program
DOI:10.1038/ni.1954

[21] CD1a-autoreactive T cells are a normal component of the human alpha beta T cell repertoire
DOI:10.1038/ni.1956

NATURE MATERIALS

[22] Design of selective catalysts for hydrogen oxidation and oxygen reduction reactions by molecular patterning of platinum with calix[4]arene molecules
DOI: 10.1038/nmat2883

NATURE MEDICINE

[23] A reductionist cell-free major histocompatibility complex class II antigen processing system identifies immunodominant epitopes
DOI: 10.1038/nm.2248

[24] CX3CR1 is required for airway inflammation by promoting T helper cell survival and maintenance in inflamed lung
DOI: 10.1038/nm.2253

NATURE METHODS

[25] Rapid blue light induction of protein interactions in living cells
DOI: 10.1038/nmeth.1524

[26] Maltose–neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins
DOI: 10.1038/nmeth.1526

NATURE NANOTECHNOLOGY

[27] Nanomechanical recognition measurements of individual DNA molecules reveal epigenetic methylation patterns
DOI: 10.1038/nnano.2010.212

[28] Magnetoelectric coupling at metal surfaces
DOI: 10.1038/nnano.2010.214

[29] Ultrasensitive detection and characterization of biomolecules using superchiral fields
DOI: 10.1038/nnano.2010.209

NATURE NEUROSCIENCE

[30] Toll-like receptor-7 mediates pruritus
DOI: 10.1038/nn.2683

[31] GRLD-1 regulates cell-wide abundance of glutamate receptor through post-transcriptional regulation
DOI: 10.1038/nn.2667

[32] Microsaccades precisely relocate gaze in a high visual acuity task
DOI: 10.1038/nn.2663

[33] Kinesin 3 and cytoplasmic dynein mediate interkinetic nuclear migration in neural stem cells
DOI: 10.1038/nn.2665

[34] Tuning arousal with optogenetic modulation of locus coeruleus neurons
DOI: 10.1038/nn.2682

NATURE PHYSICS

[35] Multiple-length-scale elastic instability mimics parametric resonance of nonlinear oscillators
DOI: 10.1038/nphys1806

[36] Gate-controlled ionization and screening of cobalt adatoms on a graphene surface
DOI: 10.1038/nphys1807

[37] Optimal control of vortex core polarity by resonant microwave pulses
DOI: 10.1038/nphys1810

NATURE STRUCTURAL & MOLECULAR BIOLOGY

[38] Structural basis of open channel block in a prokaryotic pentameric ligand-gated ion channel
DOI: 10.1038/nsmb.1933

*****************************************************

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
Carlton: 8
Melbourne: 8
Parkville: 8

AUSTRIA
Linz: 27

BELGIUM
Mons: 35

CANADA
Toronto: 14, 16

CHINA
Beijing: 18
DENMARK
Aarhus: 4
Copenhagen: 4, 26

FRANCE
Evry: 17
Gif-sur-Yvette: 37
Guyancourt: 19
Lille: 24
Montpellier: 18
Nantes: 24
Paris: 18, 19, 24, 26, 35
Sophia-Antipolis: 10
Toulouse: 20
Valbonne: 24
Versailles: 17

GERMANY
Berlin: 18
Cologne: 4, 17
Halle: 28, 37
Heidelberg: 4
Karlsruhe: 28
Munich: 38
Neuherberg: 18
Wurzburg: 37

IRELAND
Cork: 18

ITALY
Bologna: 3
Ferrara: 3
Padova: 3

JAPAN
Chiba: 28
Tokushima: 34

MADAGASCER
Antananarivo: 18

NETHERLANDS
Amsterdam: 4, 12
Eindhoven: 15
Groningen: 4, 14
Leiden: 4, 12
Utrecht: 21

ROMANIA
Cluj-Napoca: 28

SLOVENIA
Ljubljana: 22

SPAIN
Girona: 10

SWEDEN
Malmo: 4
Stockholm: 4
Uppsala: 4

SWITZERLAND
Basel: 20
Zurich: 7, 38

TAIWAN
Taipei: 19
Zhongli: 19

UNITED KINGDOM
Cambridge: 18
East Kilbride: 7
Exeter: 29
Glasgow: 4, 29
London: 4, 7, 8, 18, 26, 27
Manchester: 4
Oxford: 7
Sutton: 4
York: 4

UNITED STATES OF AMERICA
Arizona
Flagstaff: 18
Phoenix: 18

California
Berkeley: 2, 24, 36
Fremont: 4
La Jolla: 20
Pasadena: 9, 19
San Francisco: 6, 10, 33
Stanford: 4, 26, 31, 34

Colorado
Aurora: 10
Fort Collins: 18

Connecticut
Groton: 25
New Haven: 16

Delaware

Illinois
Argonne: 22

Indiana
Notre Dame: 1
West Lafayette: 13

Iowa
Ames: 16

Maryland
Baltimore: 18, 23
Laurel: 1
Silver Spring: 23

Massachusetts
Boston: 4, 5, 21, 30, 32
Medford: 6

Michigan
Ann Arbor: 19, 31

New York
Ithaca: 10, 16
New York: 11, 33

North Carolina
Durham: 11, 25

Oregon
Portland: 38

Tennessee
Oak Ridge: 28

Texas
Dallas: 5, 23
Houston: 5
Lubbock: 26

Wisconsin

Madison: 26

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Published: 31 Oct 2010

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