Genome sequencing provides insights into dysentery epidemics and more of the latest news from Nature

Genome sequencing of a global collection of Shigella sonnei or baciliary dysentery, in developing countries is reported in a study published in Nature Genetics. Their study provides insights into the course of recent shigellosis epidemics. S. sonnei are human-adapted E. coli responsible for approximately 150 million cases of dysentery each year.

This press release contains:

· Summaries of newsworthy papers:

Immunology: Protecting baby

Neuroscience: Hindering responses to antipsychotic drugs

Genetics: Sequencing of malaria parasite genomes

Medicine: Cancer chemotherapy backfires

Geoscience: Volcanic sulphur on early Earth

Genetics: Genome sequencing provides insights into dysentery epidemics

Methods: How genes team up to induce cancer

Geoscience: Early and pulsed growth of eastern Tibet

And finally…Neuroscience: Learning from others’ mistakes

· Geographical listing of authors

[1] Immunology: Protecting baby

DOI:10.1038/ni.2388

A reason for why infants are less able to fend off viral infections is explained in a mouse study published online this week in Nature Immunology.

Natural killer (NK) cells are a class of white blood cells that help combat viral infections. These cells are especially important early in infection to limit viral replication.

Yasmina Laouar and colleagues find that young mice, like human infants, are more susceptible to viruses because they lack mature NK cells. Exploring why this might be, the authors find that a molecule called TGF-beta limits the proliferation of immature NK precursors and blocks their maturation to fully armed effector cells. Neonatal and infant mice whose blood cells cannot respond to TGF-beta are able to generate functional NK cells and are able to fend off viral infections. Although TGF-beta is typically thought to protect individuals by preventing deleterious inflammation, in young mice it prevents robust immune responses that would protect them from viral challenge. Further investigation is needed to see if this is also true in humans.

Author contact:

Yasmina Laouar (University of Michigan, Ann Arbor, MI, USA)

Tel +1 734 615 2248; E-mail: [email protected]

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[2] Neuroscience: Modifying responses to antipsychotic drugs

DOI: 10.1038/nn.3181

Chronic treatment with antipsychotic drugs induces modifications to histones, the proteins around which DNA wraps, which may hinder the responses to these drugs. These findings from this mouse study, reported online this week in Nature Neuroscience, suggest that inhibiting the modification of histones may improve their efficacy.

Javier Gonzalez-Maeso and colleagues report that mice treated chronically with antipsychotic drugs have modifications to histones that reduced the expression of glutamate receptors in the frontal cortex of mice. This reduction in glutamate receptors was also associated with increased schizophrenia-like behaviors in the mice. Treating the mice with a drug that prevented these histone modifications reversed this effect.

Previous clinical studies have found that combining antipsychotic drugs with valproate, a drug that is known to prevent the histone modifications studied here, can increase the therapeutic benefits of antipsychotic drugs. This study suggests a mechanism by which valproate (and other drugs that target histone modifications) could increase the therapeutic benefit of antipsychotic treatment.

Author contact:

Javier Gonzalez-Maeso (Mount Sinai School of Medicine, New York, NY, USA)

Tel: +1 212 659 8873; E-mail: [email protected]

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[3] & [4] Genetics: Sequencing of malaria parasite genomes

DOI: 10.1038/ng.2373

DOI: 10.1038/ng.2375

The sequencing of new genomes of Plasmodium parasites, responsible for malaria in humans and monkeys, is reported in two related studies published online this week in Nature Genetics.

Plamodium vivax infects about 100 million people each year, and is responsible for over half of the malaria cases outside of Africa. P. vivax has been called the neglected Plasmodium, due to its more limited study as compared to the P. falciparum parasite. Another Plasmodium, P. cynomolgi, is a closely related species to P. vivax and a cause of malaria in Asian Old World monkeys, providing an important model system for characterizing P. vivax and human malaria.

Jane Carlton and colleagues report the sequencing, assembly and annotation of four P. vivax strains from diverse geographic locations. Though the species has been sequenced in the past, the authors triple the number of sequences, bringing the total to six, and provide a global sampling, which has been challenging due to the difficulties in culturing this species. They also provide the first genome-wide estimates of genetic variation in this species – They find twice as much genetic variation as in a comparable collection of P. falciparum, providing insight into the pathogens evolution. Their findings also have implications for design of therapies, and warn that eradication strategies could face challenges.

In a second study, Kazuyuki Tanabe, Jane Carlton and colleagues report the first reference genome sequence for P. cynomolgi, sequencing the whole genomes of three diverse strains. The authors provide a map of genetic variation in this species, providing a resource for mapping traits and functional studies. Their comparative genomic analysis with P. vivax and P. knowlesi provides insights into the monkey malaria clade, and suggesting genes involved in host specificity.

Author contacts:

Jane Carlton (New York University, NY, USA) Author paper [3] & [4]

Tel: +1 212 992 6981; E-mail: [email protected]

Kazuyuki Tanabe (Osaka University, Japan) Author paper [4]

Tel: +81 6 6879 8279; E-mail: [email protected]

Ananias Escalante (Arizona State University, Tempe, AZ, USA) Author paper [3] & [4]

Tel: +1 480 965 3739; E-mail [email protected]

John Barnwell (Centers for Disease Control, Atlanta, GA, USA) Author paper [3] & [4]

Tel: +1 404 718 4420; E-mail: [email protected]

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[5] Medicine: Cancer chemotherapy backfires

DOI: 10.1038/nm.2890

Chemotherapy damages normal tissue, causing it to secrete novel factors that sustain the growth of residual tumor cells, leading to treatment resistance, reports a study published online this week in Nature Medicine.

Peter Nelson and colleagues studied the effects of a subtype of cancer chemotherapy regimes that cause DNA damage and trigger an inflammatory response on normal fibroblast cells found in the environment of prostate tumors. This reaction to chemotherapy in the normal tissue stimulates the secretion of the protein, Wnt16B, by fibroblasts, which is then taken up by neighboring tumor cells. Wnt16B acts to trigger oncogenic signaling pathways fostering survival of cancer cells and dampening the response to chemotherapy.

The study also reports that Wnt16B is elevated in the normal tissue surrounding tumors of human breast, ovarian and prostate cancer patients after chemotherapy treatment, supporting the importance of this tumor microenvironment signaling pathway in therapy responses.

Author contact:

Peter Nelson (Fred Hutchinson Cancer Research Center, Seattle, WA, USA)

Tel: +1 206 667 3377; E-mail: [email protected]

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[6] Geoscience: Volcanic sulphur on early Earth

DOI: 10.1038/ngeo1534

Intense bursts of volcanic activity between 3.5 and 3.2 billion years ago delivered massive quantities of sulphur dioxide to the atmosphere, suggests a paper published online this week in Nature Geoscience. The breakdown of these sulphur dioxide aerosols by UV radiation can explain the unusual sulphur isotope trends reported from rocks of this age.

Pascal Philippot and colleagues measured the sulphur isotope values of sulphides in 3.5-billion-year-old volcanic ash deposits from South Africa. A comparison with the isotopic composition of co-occurring sulphates in this region is most consistent with a volcanic sulphur source that was altered by UV radiation. They suggest that the pulses of volcanic activity they detect were related to a major episode of continental crust growth.

Author contact:

Pascal Philippot (Institut de Physique du Globe de Paris, France)

Tel: +33 1 83 95 73 87; E-mail: [email protected]

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[7] Genetics: Genome sequencing provides insights into dysentery epidemics

DOI: 10.1038/ng.2369

Genome sequencing of a global collection of Shigella sonnei, the most common cause of shigellosis, or baciliary dysentery, in developing countries is reported in a study published online this week in Nature Genetics. Their study provides insights into the course of recent shigellosis epidemics.

S. sonnei are human-adapted E. coli responsible for approximately 150 million cases of dysentery each year. S. sonnei historically were a primary cause of baciliary dysentery in developed countries, but have recently emerged also in transitional developing countries, often connected to economic developments and improvements in sanitation and water quality.

Nicholas Thomson and colleagues sequenced the whole genomes of 132 geographically and temporally distributed S. sonnei isolated over the course of 65 years. Their phylogenetic analysis provides a detailed evolutionary history, showing when epidemic strains emerged, and tracing the routes of spread. They show that current infections are caused by a small number of clones from several defined lineages, which have recently dispersed out of Europe. They also suggest that antimicrobial resistance has played a role in the dissemination. Finally, the authors suggest that the increased incidence in transitional countries with improved water quality can be attributed to reduced exposure to P. shigelloides, which provides cross-immunity and is found in some contaminated water.

Author contact:

Nicholas Thomson (Sanger Institute, Cambridge, UK)

Tel: +44 1223 494 783; E-mail: [email protected]

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[8] Methods: How genes team up to induce cancer

DOI: 10.1038/nmeth.2130

A mouse model which can be used to identify oncogenic combinations that are associated with tumor development is presented online this week in Nature Methods.

Tumors arise from cells that accumulate a certain number of gene mutations. The particular combination of mutations will determine whether a tumor arises and how aggressive it is. To identify mutations that cooperatively induce cells to become cancerous, Robert Eferl and colleagues developed mice in which they could control the expression of random combinations of three mutated oncogenes in specific tissues. They called this model ‘Multi-Hit’.

By studying the tumors that arise in these animals, researchers can identify the oncogenic co-operativity that is associated with tumor development or a more aggressive tumor phenotype. The authors used the Multi-Hit model to study the role of three known mutations in lung cancer formation and invasiveness.

Author contact:

Robert Eferl (Medical University of Vienna, Austria)

Tel: +43 140 1605 7571; E-mail: [email protected]

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[9] Geoscience: Early and pulsed growth of eastern Tibet

DOI: 10.1038/ngeo1538

High topography may have existed at the eastern margin of the Tibetan Plateau during the early stages of collision between the Indian and Asian continents about 30 million years ago, suggests a study published online this week in Nature Geoscience. Previously, the high elevations across much of eastern Tibet were thought to have developed just 10 to 15 million years ago.

Erchie Wang, Eric Kirby and colleagues dated episodes of topographic growth in eastern Tibet by analysing the timing of rock cooling caused as erosion in the mountains exhumed rocks toward the cool Earth surface. After an initial, early period of steady topographic growth, the plateau’s margin later grew during two rapid pulses of mountain building. The authors suggest that this prolonged and episodic nature of the mountain growth may indicate that two different physical mechanisms helped to build the high topography in eastern Tibet.

Author contacts:

Erchie Wang (Chinese Academy of Sciences, Beijing, China)

E-mail: [email protected]

Eric Kirby (Pennsylvania State University, University Park, PA, USA)

Tel: +1 814 865 0732; E-mail: [email protected]

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[10] And finally…Neuroscience: Learning from others’ mistakes

DOI: 10.1038/nn.3180

Neurons in the monkey medial frontal cortex signal when another monkey makes a decision error, according to a study published online this week in Nature Neuroscience. Monkeys and humans are known to be able to learn from others’ errors, and these results shed light on one brain area where the necessary information may be encoded.

Masaki Isoda and colleagues had pairs of monkeys take turns choosing between two options, one of which would result in the delivery of a reward to both animals, while the other option would result in no reward for either animal. Monkeys were able to use the outcomes of their partner’s actions to help them make better choices. In the medial frontal cortex, there was a group of neurons that increased their firing rates when the other monkey made an error. Activity for about half the neurons was correlated with the omission of reward in general, but the other half specifically responded to the erroneous action of the partner.

Previous work in humans has suggested that the medial frontal cortex is important for error monitoring when learning from others, but this is the first demonstration that there are neurons which exclusively represent others’ errors.

Author contact:

Masaki Isoda (Okinawa Institute of Science and Technology, Japan)

Tel: +81 48 467 9611; 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

[11] NRT/PTR transporters are essential for translocation of glucosinolate defence compounds to seeds

DOI: 10.1038/nature11285

[12] Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts

DOI: 10.1038/nature11317

[13] The prokaryote messenger c-di-GMP triggers stalk cell differentiation in Dictyostelium

DOI: 10.1038/nature11313

NATURE CELL BIOLOGY

[14] Synthetic lethality between Rb, p53 and Dicer or miR-17–92 in retinal progenitors suppresses retinoblastoma formation

DOI: 10.1038/ncb2556

NATURE CHEMICAL BIOLOGY

[15] Expanding the genetic code of Drosophila melanogaster

DOI: 10.1038/nchembio.1043

NATURE CHEMISTRY

[16] Anion-induced reconstitution of a self-assembling system to express a chloride-binding Co10L15 pentagonal prism
DOI: 10.1038/nchem.1407

[17] A simple and accessible synthetic lectin for glucose recognition and sensing

DOI: 10.1038/nchem.1409

NATURE CLIMATE CHANGE

[18] Increasing drought under global warming in observations and models

DOI: 10.1038/nclimate1633

[19] Global diversity of drought tolerance and grassland climate-change resilience

DOI: 10.1038/nclimate1634

NATURE GENETICS

[20] Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci

DOI: 10.1038/ng.2360

[21] Genome-wide association study identifies a susceptibility locus for thyrotoxic periodic paralysis at 17q24.3

DOI: 10.1038/ng.2367

NATURE GEOSCIENCE

[22] Groundwater arsenic concentrations in Vietnam controlled by sediment age

DOI: 10.1038/ngeo1540

NATURE IMMUNOLOGY

[23] The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-kB

DOI:10.1038/ni.2378

NATURE MATERIALS

[24] A Janus cobalt-based catalytic material for electro-splitting of water

DOI: 10.1038/nmat3385

Nature MEDICINE

[25] Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion

DOI: 10.1038/nm.2871

[26] Neutrophils mediate insulin resistance in high fat diet fed mice via secreted elastase

DOI: 10.1038/nm.2885

NATURE METHODS

[27] A high-throughput approach for measuring temporal changes in the interactome

DOI: 10.1038/nmeth.2131

[28] Direct observation of mammalian cell growth and size regulation

DOI: 10.1038/nmeth.2133

Nature NEUROSCIENCE

[29] Behavior-dependent specialization of identified hippocampal interneurons

DOI: 10.1038/nn.3176

[30] Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly

DOI: 10.1038/nn.3183

Nature PHYSICS

[31] Observing the operational significance of discord consumption

DOI: 10.1038/nphys2376

[32] Quantum discord as resource for remote state preparation

DOI: 10.1038/nphys2377

[33] Local thermometry of neutral modes on the quantum Hall edge

DOI: 10.1038/nphys2384

Nature STRUCTURAL & MOLECULAR BIOLOGY

[34] Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer

DOI: 10.1038/nsmb.2351

[35] PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53

DOI: 10.1038/nsmb.2353

[36] DDR complex facilitates global association of RNA polymerase V to promoters and evolutionarily young transposons

DOI: 10.1038/nsmb.2354

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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.

AUSTRALIA

Brisbane: 16

Canberra: 31

Melbourne: 7

St Lucia: 31

AUSTRIA

Graz: 8

Tulln: 8

Vienna: 8, 29, 32

BELGIUM

Antwerp: 20

Ghent: 14

Leuven: 14, 30

BRAZIL

Campinas: 7

CANADA:

Montreal: 1

Toronto: 25

Vancouver: 27

CHINA
Beijing: 9, 35
Hong Kong: 21

DENMARK

Copenhagen: 22

Frederiksberg: 11

Lyngby: 22

Roskilde: 22

Vedbaek: 14

FRANCE

Gif-sur-Yvette: 24

Grenoble: 24

Paris: 6, 7, 24

Vandoeuvre-les-Nancy: 6

GERMANY

Berlin: 20, 24, 30

Bonn: 20

Cologne: 20

Düsseldorf: 30

Essen: 14

Goettingen: 20, 30

Hamburg: 20

Julich: 20

Leipzig: 20

Magdeburg: 20

Münster: 30

Potsdam: 9

Wurzburg: 11

INDIA

New Delhi: 3

ISRAEL

Ramat-Gan: 28

ITALY

Ferrara: 20

JAPAN

Kyoto: 4

Nagano: 12

Nagasaki: 4

Okinawa: 10

Osaka: 10

Saitama: 10

Shimotsuga: 4

Suita: 4

Tokyo: 4, 10

Tsukuba: 4

NETHERLANDS

Leiden: 14

Nijmegen: 20

Rotterdam: 20

NEW ZEALAND

Hamilton: 9

SINGAPORE

Singapore: 31, 32

SOUTH KOREA

Kyeonggi-do: 7

Seoul: 7

SPAIN

Leioa: 2

Madrid: 8, 11

UNITED KINGDOM

Bristol: 17

Cambridge: 7, 15, 16, 20

Dundee: 13, 20

Glasgow: 7

Oxford: 29, 31, 32

UNITED STATES OF AMERICA

Arizona

Phoenix: 2, 9

Tempe: 3, 4

California

Berkeley: 5

La Jolla: 26

Los Angeles: 36

Menlo Park: 12

Novato: 5

Colorado

Boulder: 18

District of Columbia

Washington: 12

Florida

Tampa: 35

Georgia

Atlanta: 3, 4

Iowa

Iowa City: 20

Kansas

Manhattan: 19

Maryland

Baltimore: 20

Bethesda: 7

Chevy Chase: 14

Massachusetts

Boston: 20, 25, 28, 34, 35

Cambridge: 2, 3, 26, 28, 33

Charlestown: 25

Framingham: 25

Michigan

Ann Arbor: 1

Minnesota

Minneapolis: 19

Rochester: 35

Nebraska

Lincoln: 34

New Jersey

Princeton: 33

New York

Albany: 18

Ithaca: 12

New York: 2, 3, 4, 23

North Carolina

Chapel Hill: 23

Research Triangle: 23

Oregon

Eugene: 19

Portland: 5, 23

Pennsylvania

Lancaster: 23

Pittsburgh: 20

University Park: 7, 9

Tennessee

Memphis: 14, 25

Texas

Smithville: 35

Virginia

Ashland: 16

Washington

Seattle: 5, 12

VIETNAM

Hanoi: 22

Ho Chi Minh City: 7

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Published: 05 Aug 2012

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