Dopamine and anxiety

Summaries of newsworthy papers include Fighting neuroblastoma, Don’t stop the beat, Bacterial gangs cause clots, Anaemic soils, Widespread alternative splicing, Subverting host immunity to intracellular pathogens and A rose by any other name

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 02 November 2008

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

This press release contains:

· Summaries of newsworthy papers:

Neuroscience: Dopamine and anxiety

Medicine: Fighting neuroblastoma

Materials: Don’t stop the beat

Chemical Biology: Bacterial gangs cause clots

Geoscience: Anaemic soils

Nature: Widespread alternative splicing

Immunology: Subverting host immunity to intracellular pathogens

And finally… Neuroscience: A rose by any other name

· Mention of papers to be published at the same time with the same embargo

· Geographical listing of authors

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[1] Neuroscience: Dopamine and anxiety
DOI: 10.1038/nn.2222

Individual differences in reactions to negative emotional cues are based on how much dopamine can be stored in our brain, according to a study published online this week in Nature Neuroscience. This could help to explain why different people deal with stressful or emotional events in different ways.

Andreas Heinz and colleagues measure the storage capacity of the neurotransmitter dopamine in the amygdala, an area of the brain that is involved in emotional processing, and find an association between individual differences in dopamine storage capacity and emotional processing. The team shows that people with a higher storage capacity of dopamine have a greater activation of the amygdala and anterior cingulate cortex when viewing unhappy pictures. Moreover, the functional coupling between the amygdala and anterior cingulate cortex correlated inversely with their subjects’ score on a standard test of trait anxiety.

This work provides a possible explanation for how individual differences in dopamine storage capacity can explain differences in individual temperament, particularly as they relate to how people cope with stressful or emotional events.

Author contact:
Andreas Heinz (Charite-University Medicine Berlin, Germany)
Tel: +49 30 450 517002; E-mail: [email protected]

Thorsten Kienast (Charite-University Medicine Berlin, Germany) Co-author
E-mail: [email protected]

[2] Medicine: Fighting neuroblastoma
DOI: 10.1038/nm.1882

A strategy to treat neuroblastoma using the patient’s immune cells is published online this week in Nature Medicine.

Cytotoxic T lymphocytes (CTLs), a type of immune cell that can be directed to fight cancer cells, do not survive long term and have limited antitumour activity within the body. This is partly because the target tumour cells typically lack appropriate co-stimulatory molecules that enhance the effectiveness of the CTLs. Malcolm Brenner and his colleagues have now overcome this limitation by engineering CTLs to express an antigen receptor directed to GD2, a tumor-associated molecule expressed by human neuroblastoma cells. The authors reasoned that these CTLs would receive optimal co-stimulation, enhancing their survival and antitumour activity mediated through the GD2 receptors.

Studying patients with neuroblastoma, the authors find that CTLs expressing the GD2-specific receptor indeed survived longer than control T lymphocytes. Infusion of these engineered cells had no adverse effects and was associated with tumour regression in half of the subjects tested. This leads to the conclusion that CTLs could be a powerful weapon for combating neuroblastoma, and perhaps other tumors, in people.

Author contact:
Malcolm Brenner (Baylor College of Medicine, Houston, TX, USA)
Tel. +1 832 824 4663; E-mail: [email protected]

[3] Materials: Don’t stop the beat
DOI: 10.1038/nmat2316

A new type of scaffold for the engineering of rat heart tissue is published in Nature Materials this week. Researchers show that the ‘accordion-like’ three-dimensional structure allows the heart cells to grow and orient in certain directions and, although preliminary, may overcome many of the structural–mechanical limitations experienced in previous cardiac tissue engineering models.

The heart is a complex organ comprising multi-layered tissue, with the ability to pump blood around the body. The creation of materials to engineer heart muscle tissue has proven challenging. Lisa Freed and colleagues’ scaffold closely matches the mechanical properties of rat heart tissue, and allows the induction of heart-cell contractility following stimulation with an electric field. Their scaffold is engineered from bilaminar scaffolds with three-dimensional interconnected pore networks, creating an accordion-like honeycomb structure. Although they have not demonstrated their materials in vivo, the team argues that these accordion-like structural scaffolds pave the way towards further integration of tissue-specialized scaffolds into tissue engineering strategies.

Author contact
Lisa Freed (Massachusetts Institute of Technology, Cambridge, MA, USA)
Tel: +1 617 253 3858; E-mail: [email protected]

[4] Chemical Biology: Bacterial gangs cause clots
DOI: 10.1038/nchembio.124

Scientists have discovered a new way that blood clots can form, which could lead to new methods for treating serious health problems such as bacterial infections and sepsis.

Bacterial infections and blood clotting often occur at the same time, but it was thought that the clotting was caused by the host response to the bacteria, rather than by the bacteria itself.

Online in Nature Chemical Biology, Rustem Ismagilov and colleagues demonstrate that bacteria can directly initiate the blood clot causing process, known as coagulation, if they are present in a high local density. Considering the location of bacterial cells, instead of just their presence or absence, could therefore significantly change our understanding of coagulation.

Author contact:
Rustem Ismagilov (University of Chicago, IL, USA)
Tel: +1 773 702 5816, E-mail: [email protected]

[5] Geoscience: Anaemic soils
DOI: 10.1038/ngeo339

Increasing levels of nitrogen deposition will push soils to a toxic level of acidification in which iron becomes more soluble, and plant growth is reduced, according to a study published online in Nature Geoscience.

A long history of human-influenced nitrogen deposition associated with industry and agriculture has left soils in the western Tatra Mountains of Slovakia highly acidic. William Bowman and colleagues reveal that increasing the nitrogen load in the region triggers the release of soluble iron into alpine grassland soils. This iron release is indicative of extreme soil acidification, analogous to conditions seen in soils after acid mine drainage.

On the basis of these results, the authors warn that high levels of nitrogen deposition in Europe and North America over the past half century may have rendered many soils susceptible to a new stage of acidification where iron, rather than calcium or aluminum, is the main buffer.

Author contact:
William Bowman (University of Colorado, Boulder, CO, USA)
Tel: +1 303 492 2557; Email: [email protected]

[6] Nature: Widespread alternative splicing
DOI: 10.1038/nature07509

Over 90% of human genes undergo alternative splicing, a form of messenger RNA processing that yields multiple proteins from a single gene, a paper published online in this week’s Nature suggests.

When the human genome was decoded there was a lower than expected number of genes, prompting renewed interest in alternative splicing. Therefore, Christopher Burge and colleagues analysed the entire mRNA content of 15 different tissue types or cancer cell lines to produce a comprehensive catalogue of gene and alternative mRNA expression. Almost all genes that have interruptions in their coding regions are alternatively spliced, they find — a mechanism that permits greater phenotypic complexity than indicated by gene number alone.

Alternative splicing also seems to be linked to polyadenylation, a process whereby non-templated adenines are added to the ends of messenger RNA to help stabilize it. The study suggests that both processes are regulated by a common mechanism.

Author contact:
Christopher Burge (Massachusetts Institute of Technology, Cambridge, MA, USA)
Tel: +1 617 258 5997; E-mail: [email protected]

[7] Immunology: Subverting host immunity to intracellular pathogens
DOI: 10.1038/ni.1671

Scientists have identified a mechanism that allows infections such as Mycobacterium tuberculosis to avoid effective immune responses. The work provides a possible new target for treating diseases caused by many types of pathogens.

Activated immune cells called macrophages are important in combating infections. A key anti-microbial molecule produced by the macrophages is nitric oxide (NO), a noxious gas required for control of infections caused by Mycobacterium tuberculosis, Leishmania cruzi and other infectious agents.

Online in Nature Immunology this week, Peter Murray and colleagues report that such illness causing agents activate the expression of an enzyme in macrophages called arginase 1 that reduces the amount of NO activity in the macrophages. By inducing arginase 1, these agents avoid a natural and otherwise effective response to infection. When arginase 1 is eliminated from macrophages, for example, lung bacterial load during tuberculosis infection is significantly reduced.

By pinpointing how these intracellular pathogens evade the immune system, the study highlights a unique ‘loophole’ in the normal immune response to these infectious agents.

Author contact:
Peter Murray (St. Jude Children's Research Hospital, Memphis, TN, USA)
Tel: +1 901 495 3219; E-mail: [email protected]

[8] And finally… Neuroscience: A rose by any other name
DOI: 10.1038/nn.2217

Neurons in the olfactory cortex can adjust their firing patterns so that similar smells evoke similar neural responses, reports a study published online in Nature Neuroscience this week. This suggests an explanation for why we can perceive a single scent such as “rose”, even though no two roses smell exactly alike.

Donald Wilson and colleagues recorded from neurons in the rat olfactory bulb in response to mixtures of up to 10 odours. They found that responses of groups of neurons to the mixtures depended on the composition of the mixture, even when they differed by only one component. However, responses of groups of neurons in the olfactory cortex – which receive projections from the olfactory bulb – showed a form of pattern completion, grouping similar odors together. The odour mixtures that evoked similar patterns of neural activity in the olfactory cortex were more likely to be judged as similar-smelling by the rats.

This mechanism for pattern completion suggests a way in which we maintain perceptual stability despite minor variations in odour.

Author contact:
Donald Wilson (Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA)
Tel: +1 845 398 2178; Email: [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)

[9] A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity
DOI: 10.1038/nature07537

[10] Temporal identity in axonal target layer recognition
DOI: 10.1038/nature07407

[11] Coordinate control of synaptic-layer specificity and rhodopsins in photoreceptor neurons
DOI: 10.1038/nature07419

[12] A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex
DOI: 10.1038/nature07422

[13] HITS-CLIP yields genome-wide insights into brain alternative RNA processing
DOI: 10.1038/nature07488

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

[14] An integrated software system for analyzing ChIP-chip and ChIP-seq data
DOI: 10.1038/nbt.1505

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

[15] Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis
DOI: 10.1038/ncb1798

[16] Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic beta cells
DOI: 10.1038/ncb1801

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

[17] Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci
DOI: 10.1038/ng.249

[18] Lung cancer susceptibility locus at 5p15.33
DOI: 10.1038/ng.254

[19] Common 5p15.33 and 6p21.33 variants influence lung cancer risk
DOI 10.1038/ng.273

[20] Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing
DOI: 10.1038/ng.259

[21] Differential expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines
DOI: 10.1038/ng.264

[22] Embryonic stem cell-specific microRNA regulate the G1-S transition and promote rapid proliferation
DOI: 10.1038/ng.250

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

[23] Strong transport and mixing of deep water through the Southwest Indian Ridge
DOI: 10.1038/ngeo340

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

[24] Tonic B cell antigen receptor signals supply an NF-kappaB substrate for prosurvival BLyS signaling
DOI: 10.1038/ni.1666

[25] Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation
DOI: 10.1038/ni.1667

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

[26] 5′-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma
DOI: 10.1038/nm.1887

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

[27] High-resolution statistical mapping reveals yeast gene territories in vivo
DOI: 10.1038/nmeth.1266

[28] Detecting microRNA binding and siRNA off-target effects from expression data
DOI: 10.1038/nmeth.1267

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

[29] Nanomechanical detection of itinerant electron spin flip
DOI: 10.1038/nnano.2008.311

[30] Wideband-tuneable, nanotube mode-locked, fibre laser
DOI: 10.1038/nnano.2008.312

[31] Carbon nanotubes as templates for polymerized lipid assemblies
DOI: 10.1038/nnano.2008.318

[32] Time-domain control of ultrahigh-frequency nanomechanical systems
DOI: 10.1038/nnano.2008.319

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

[33] Feedback of visual object information to foveal retinotopic cortex
DOI: 10.1038/nn.2218

[34] Real-time chemical responses in the nucleus accumbens differentiate rewarding and aversive stimuli
DOI: 10.1038/nn.2219

NATURE PHOTONICS (http://www.nature.com/nphoton)

[35] Drift-free femtosecond timing synchronization of remote optical and microwave sources
DOI: 10.1038/nphoton.2008.225

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

[36] Experimental entanglement distillation of mesoscopic quantum states
DOI: 10.1038/nphys1112

[37] Preparation of distilled and purified continuous-variable entangled states
DOI: 10.1038/nphys1110

[38] Linear-temperature resistivity and change in the Fermi surface at the pseudogap critical point of a high-Tc superconductor
DOI: 10.1038/nphys1109

***************************************************************************************************************
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
Sydney: 33

BELGIUM
Leuven: 33

CANADA:
Edmonton: 32
Montreal: 18
Quebec: 38
Toronto: 18, 20, 38

CZECH REPUBLIC
Brno: 18
Olomouc: 18, 36, 37
Prague: 18

DENMARK
Aarhus: 81
Copenhagen: 18
Lyngby: 36

FRANCE
Evry: 18
Illkirch: 31
Lyon: 18, 29
Marseille: 15
Paris: 4, 18, 27
Toulouse: 27
Villejuif: 18

GERMANY
Aachen: 1
Berlin: 1
Bonn: 26
Bremen: 29
Cologne: 12
Dresen: 1
Erlangen: 7, 36
Freiburg: 7, 26
Goettingen: 12
Hamburg: 16
Hannover: 37
Heidelberg: 18
Karlsruhe: 30
Langen: 26
Leipzig: 16
Mainz: 1
Munich: 1, 26
Munster: 10
Potsdam-Rehbrucke: 18
Tubingen: 16

GREECE
Athens: 18

HUNGARY
Budapest: 18

ITALY
Brescia: 9
Florence: 18
Milan: 18
Naples: 18
Ragusa: 18
Turin: 18

JAPAN
Osaka: 26
Tokyo: 1

NETHERLANDS
Bilthoven: 18
Utrecht: 18

NORWAY
Tromso: 18
Trondheim: 18

POLAND
Lodz: 18
Szczecin: 18
Warsaw: 18

PORTUGAL
Lisbon: 27

RUSSIA
Moscow: 18

SLOVAKIA
Banska Bystrica: 18
Nitra: 5

SOUTH KOREA
Gyeongbuk: 29
Seoul: 27

SPAIN
Barcelona: 11, 18
Granada: 18
Murcia: 18
Oviedo: 18
Pamplona: 18
San Sebastian: 18

SWEDEN
Stockholm: 6
Umea: 18
Uppsala: 18

UNITED KINGDOM
Cambridge: 12, 13, 17, 18, 19, 28, 30
Liverpool: 18
London: 1, 18
Oxford: 18
Sutton: 19

UNITED STATES OF AMERICA

Alabama
Huntsville: 14

California
Hayward: 6
La Jolla: 23, 25
Los Angeles: 11
San Francisco: 14, 22
Santa Clara: 13
Stanford: 14

Colorado
Denver: 7
Fort Collins: 5, 7
Lafayette: 22

Florida
Tallahassee: 28

Hawaii
Honolulu: 16

Illinois
Chicago: 4, 34

Maryland
Baltimore: 14, 24
Bethesda: 4, 7, 33

Massachusetts
Boston: 17, 25, 29
Cambridge: 3, 6, 26, 33, 35
Worcester: 7

Missouri
St Louis: 9

Montana
Missoula: 5

New Jersey
Newark: 7

New Mexico
Santa Fe: 6

New York
Cold Spring Harbor: 21
New York: 8, 13
Orangeburg: 8

North Carolina
Chapel Hill: 34

Oklahoma
Norman: 8

Oregon
Eugene: 11

Pennsylvania
Philadelphia: 24
Pittsburgh: 1

Tennessee
Memphis: 7

Texas
Austin: 38
Dallas: 25
Houston: 2, 19, 21

Virginia
Charlottesville: 17

Washington
Seattle: 18

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Nature Chemical Biology (Boston)
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Nature Genetics (New York)
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Nature Medicine (New York)
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Published: 02 Nov 2008

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