Modified Mycobacterium offers new TB vaccine platform

Summaries of newsworthy papers: Medicine: Modified Mycobacterium offers new TB vaccine platform; Nature: Teaching old diabetes treatments new tricks; Geoscience: An imperfect analogue; Nature: Bird digits point out evolutionary changes; Genetics: Sequencing of colorectal tumors and more

This press release contains:

Summaries of newsworthy papers:

Medicine: Modified Mycobacterium offers new TB vaccine platform
Nature: Teaching old diabetes treatments new tricks
Geoscience: An imperfect analogue
Nature: Bird digits point out evolutionary changes
Genetics: Sequencing of colorectal tumors
Geoscience: Mantle hydration beneath China by ancient subducted oceanic slabs
Chemical Biology: Surviving an acidic journey
And finally…Methods: Induced pluripotent stem cells from endangered species

Mention of papers to be published at the same time

Geographical listing of authors

PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of Press contacts for the Nature journals are listed at the end of this release.

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[1] Medicine: Modified Mycobacterium offers new TB vaccine platform

A modified Mycobacterium smegmatis bacterial strain expressing a secretion system encoded by genes from Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, has a potent ability to protect mice from infection with Mtb. The findings, published online this week in Nature Medicine, may yield useful new tools for development of a candidate vaccine against Mtb.

The locus for the esx-3 gene cluster is essential for Mtb survival, but not for M. smegmatis. William Jacobs, Jr. and colleagues show that the Mtb esx-3 genes can replace the similar genes in M. smegmatis, inducing propagation of protective CD4+ T immune cells in mice injected with the hybrid (or new strain of) M. smegmatis. The CD4+ T cell-dependent immunity against subsequent exposure to Mtb was as good as or better than that induced by BCG, the only vaccine against Mtb in current use. The authors note that further studies are needed to elucidate the mechanisms by which replacement of the esx-3 locus in M. smegmatis generates a vaccine strain capable of inducing robust clearance of Mtb in the mice.

Author contact:
William R. Jacobs, Jr (Albert Einstein College of Medicine, New York, NY, USA)
Tel: +1 718 678 1075; E-mail: [email protected]

[2] Nature: Teaching old diabetes treatments new tricks
DOI: 10.1038/nature10383

The feasibility of developing a new class of drugs that act on PPARg, a known target for diabetes treatment, is demonstrated in Nature this week. Such compounds could have anti-diabetic activity to match existing PPARg agonists but without the associated adverse effects.

PPARg, a receptor that controls fat-cell development, is the target for a class of highly-effective anti-diabetes drugs known as thiazolidinediones. Although thiazolidinediones are generally well tolerated, some patients experience negative side effects such as weight gain, heart failure and loss of bone mineral density. Bruce Spiegelman and colleagues synthesised novel small molecules that bind to PPARg, but elicit a different effect to that of classical agonists. One of these compounds, SR1664, demonstrates potent anti-diabetic effects in mice without causing weight gain. Moreover, in cell cultures, SR1664 does not interfere with bone formation.

The compounds developed in this study are unlikely to be administered to patients owing to unfavourable pharmacokinetic properties; however, these findings illustrate that the development of new classes of PPARg drugs is feasible.

Author contact:
Bruce Spiegelman (Harvard Medical School & Dana-Farber Cancer Institute, Boston, MA, USA)
Tel: +1 617 632 3567; E-mail: [email protected]

[3] Geoscience: An imperfect analogue
DOI: 10.1038/ngeo1245

The melting of the Greenland ice sheet during the last interglacial period — 130,000 to 114,000 years ago — was a result of both higher Arctic summer temperatures and the distribution of incoming solar radiation, reports a paper published online in Nature Geoscience. Consequently, the authors suggest that the last interglacial period is not an adequate analogue for future climate change.

Willem Jan van de Berg and colleagues used a series of numerical models and calculations to assess the factors that controlled the surface mass balance of the Greenland ice sheet during the last interglacial period. During this period, summer temperatures over Greenland were about two to four degrees Celsius higher than today, and the ice sheet was significantly smaller. The team estimates that only about 55% of that decline can be attributed to the higher summer temperatures. The rest they attribute to changes in the Earth’s orbit, which led to an increase in the amount of solar radiation reaching the high northern latitudes during the summer months.

In an accompanying News and Views, Andrey Ganopolski writes: “The last interglacial period cannot be considered as a straightforward analogue for future Greenland melt.”

Author contact:
Willem Jan van de Berg (Utrecht University, The Netherlands)
Tel: +31 30 253 3273; E-mail [email protected]

Andrey Ganopolski (Potsdam Institute for Climate Impact Research, Germany) N&V Author
Tel: +49 331 288 2594; E-mail: [email protected]

[4] Nature: Bird digits point out evolutionary changes

The developmental origins of bird digits are uncovered in this week’s Nature. Gene expression profiling in chickens shows that the anatomical location of the digits changed during evolution. These findings may help scientists to understand the differences between the identities of avian digits and those of their ancestors.

Birds are now almost universally seen as the descendants of theropod dinosaurs and have common features, such as the three-toed foot. However, discrepancies between palaeontological and embryological evidence of digit development have made it difficult to establish which avian wing digits correspond to which digits of the limbs of their dinosaur ancestors. Günter Wagner and colleagues use gene expression profiling in chicks to show that the first digits of wings and feet express the same RNA even though the first wing digit develops from embryological position 2. These findings suggest that during bird evolution, wing digit 1 underwent a shift that translocated it to position 2.

Whole-genome gene expression data can provide evidence about character identity, which is ultimately grounded in the gene regulatory network directing development. The results imply that the other wing digits also have unique identities, but these identities are much less clear.

Author contact:
Günter Wagner (Yale University, New Haven, CT, USA)
Tel: +1 203 737 3091; E-mail: [email protected]

[5] Genetics: Sequencing of colorectal tumors
DOI: 10.1038/ng.936

Genomic sequencing of colorectal cancer tumors is reported this week in Nature Genetics. Colorectal cancer is one of the leading causes of cancer related mortality.

Matthew Meyerson and colleagues report whole-genome sequencing of primary colorectal cancer tumors and matched non-cancerous tissue controls from nine patients. They identify a range of genomic rearrangements, with an average of 75 somatic rearrangements per tumor, and including networks of translocations between pairs of chromosomes. They identify a recurrent fusion of the genes VTI1A-TCF7L2 in 3 of 97 additional cases screened. Their findings in cell lines containing this fusion gene suggest a functional role for this fusion in cell growth and oncogenic progression.

Author contact:
Matthew Meyerson (Dana Farber Cancer Institute, Boston, MA, USA)
Tel: +1 617 632 4768; E-mail: [email protected]

[6] Geoscience: Mantle hydration beneath China by ancient subducted oceanic slabs
DOI: 10.1038/ngeo1250

The anomalously water-rich mantle beneath northeast China could be explained by the dehydration of subducted slabs of oceanic crust over the past billion years, according to a paper published online this week in Nature Geoscience.

Takeshi Kuritani and colleagues compiled geochemical measurements of ancient lavas erupted at the Earth’s surface in northeast China, but derived from the water-rich zone in the mantle below. The geochemistry shows that water was added to this source on two separate occasions in the past one billion years.

The researchers suggest that the first addition to the mantle occurred when water was squeezed out of an ancient oceanic slab as it was subducted beneath China. Later, yet more water was added during the dehydration of the subducting Pacific Ocean crust. The two mantle hydration events together can help explain the anomalously wet mantle beneath northeast China

Author contact:
Takeshi Kuritani (Osaka City University, Japan)
Tel: +81 6 6605 3179; E-mail: [email protected]

[7] Chemical Biology: Surviving an acidic journey
DOI: 10.1038/nchembio.644

A cooperative group of proteins that work together to protect cells from acid stress has been found in bacteria that transit through the human digestive tract, as reported online this week in Nature Chemical Biology.

When proteins encounter highly acidic environments, their normally stable structure can fall apart; if enough proteins lose their structure, the cell cannot operate normally and will die. Chaperones are a family of proteins that protect other proteins from losing their structure or help the proteins to regain their structure once lost.

Zengyi Chang, Peng Chen and colleagues look for ‘clients’ – or preferred protein substrates – of one of these chaperones by using a newly-designed non-natural amino acid to link the chaperone and its client together, allowing them to be identified as interacting. Among the clients, the authors discovered two more chaperones that subsequent tests demonstrated were working together with the initial chaperone to help other proteins more quickly regain their shape. This cooperative mechanism explains how bacteria might recover from their acidic travels.

Author contacts:
Peng Chen, (Peking University, Beijing, China)
Tel: +86 10 62755773; E-mail: [email protected]

Zengyi Chang, (Peking University, Beijing, China)
Tel: +86 10 62758822; E-mail: [email protected]

[8] And finally…Methods: Induced pluripotent stem cells from endangered species
DOI: 10.1038/nmeth.1706

Induced pluripotent stem (iPS) cells from two endangered species, the silver-maned drill monkey and the northern white rhinoceros, are reported in a paper published online this week in Nature Methods. Endangered species iPS cells will provide a source of material for the biological study of otherwise rare animals.

iPS cells have generated much excitement for human disease modeling and possibly for eventual therapy. But this technology may prove useful for other applications as well. For instance, iPS cells from endangered species could be useful for basic research, disease modeling and possibly for preservation efforts in these species.

Jeanne Loring and colleagues describe the generation of iPS cells from the silver-maned drill and the northern white rhinoceros. The latter species is close to extinction, with only eight living animals known today. The report is the first step towards application of iPS cell technology to species preservation, an effort that faces many challenges, such as efficient conversion of stem cells to functional gametes for assisted reproduction.

Author contact:
Jeanne Loring (The Scripps Research Institute, La Jolla, CA, USA)
Tel: +1 858 784 7767; E-mail: [email protected]

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

Nature (

[9] Phylogenomics reveals deep molluscan relationships
DOI: 10.1038/nature10382

[10] The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase
DOI: 10.1038/nature10404

[11] The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes
DOI: 10.1038/nature10443


[12] Adaptive braking by Ase1 prevents overlapping microtubules from sliding completely apart
DOI: 10.1038/ncb2323


[13] High frequency transposition for determining antibacterial mode of action
DOI: 10.1038/nchembio.643


[14] Self-reproduction of supramolecular giant vesicles combined with the amplification of encapsulated DNA
DOI: 10.1038/nchem.1127

[15] Efficient water oxidation catalysts based on readily available iron coordination complexes
DOI: 10.1038/nchem.1140

[16] Observation of Fe(V)=O using variable-temperature mass spectrometry and its enzyme-like C–H and C=C oxidation reactions
DOI: 10.1038/nchem.1132


[17] Germline deletion of the miR-17~92 cluster causes skeletal and growth defects in humans
DOI: 10.1038/ng.915

[18] Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia
DOI: 10.1038/ng.924

[19] Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome)
DOI: 10.1038/ng.923

[20] Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia
DOI: 10.1038/ng.913


[21] Significant increase in relief of the European Alps during mid-Pleistocene glaciations
DOI: 10.1038/ngeo1242


[22] The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells
DOI: 10.1038/ni.2091

[23] The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization
DOI: 10.1038/ni.2095

[24] Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria
DOI: 10.1038/ni.2096

[25] Human cytomegalovirus microRNA miR-US4-1 inhibits CD8+ T cell response by targeting ERAP1
DOI: 10.1038/ni.2097


[26] Large variation of vacancy formation energies in the surface of crystalline ice
DOI: 10.1038/nmat3096

[27] An artificial biomineral formed by incorporation of copolymer micelles in calcite crystals
DOI: 10.1038/nmat3103

[28] Gas detection by structural variations of fluorescent guest molecules in a flexible porous coordination polymer
DOI: 10.1038/nmat3104

[29] Digitally tunable physicochemical coding of material composition and topography in continuous microfibers
DOI: 10.1038/nmat3108


[30] p38 MAPK–mediated regulation of Xbp1s is crucial for glucose homeostasis
DOI: 10.1038/nm.2449

[31] Isolation and in vitro expansion of human colonic stem cells
DOI: 10.1038/nm.2470


[32] FaST linear mixed models for genome-wide association studies
DOI: 10.1038/nmeth.1681

[33] Toward the blood-borne miRNome of human diseases
DOI: 10.1038/nmeth.1682

[34] Firefly luciferase mutants as sensors of proteome stress
DOI: 10.1038/nmeth.1697


[35] Gold nanoparticles for high-throughput genotyping of long-range haplotypes
DOI: 10.1038/nnano.2011.141

[36] Experimental demonstration of a single-molecule electric motor
DOI: 10.1038/nnano.2011.142

[37] Graphene plasmonics for tunable terahertz metamaterials
DOI: 10.1038/nnano.2011.146

[38] Nanopore-based detection of circulating microRNAs in lung cancer patients
DOI: 10.1038/nnano.2011.147


[39] Constructing scenes from objects in human occipitotemporal cortex
DOI: 10.1038/nn.2903

[40] Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex I insults
DOI: 10.1038/nn.2916

[41] miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity
DOI: 10.1038/nn.2909

[42] Experience-dependent expression of miR132 regulates ocular dominance plasticity
DOI: 10.1038/nn.2920


[43] Cavity electromagnetically induced transparency and all-optical switching using ion Coulomb crystals
DOI: 10.1038/nphoton.2011.214

[44] Dynamic modulation of photonic crystal nanocavities using gigahertz acoustic phonons
DOI: 10.1038/nphoton.2011.208

Nature PHYSICS (

[45] A single nitrogen-vacancy defect coupled to a nanomechanical oscillator
DOI: 10.1038/nphys2070

[46] Direct imaging of the coexistence of ferromagnetism and superconductivity at the LaAlO3=SrTiO3 interface
DOI: 10.1038/nphys2079

[47] Coexistence of magnetic order and two-dimensional superconductivity at LaAlO3=SrTiO3 interfaces
DOI: 10.1038/nphys2080


[48] Apo and InsP3-bound crystal structures of the ligand-binding domain of an InsP3 receptor
DOI: 10.1038/nsmb.2112

[49] The Rad50 coiled-coil domain is indispensable for functions of the Mre11 complex
DOI: 10.1038/nsmb.2116

[50] Defects in RNA quality control factors reveal RNAi-independent nucleation of heterochromatin
DOI: 10.1038/nsmb.2122

[51] Spliceosome assembly is coupled to RNA polymerase II dynamics at the 3′ end of human genes
DOI: 10.1038/nsmb.2124

[52] Structural analysis of the interaction between Hsp90 and the tumor suppressor protein p53
DOI: 10.1038/nsmb.2114

*****The following paper is available to download from the press site and will appear on the Nature Neuroscience website shortly*****
[53] A Chemical Approach for Fluorescence Imaging and 3D Reconstruction of Transparent Mouse Brain
DOI: 10.1038/nn2928


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.

Adelaide: 20
Parkville: 20
Sydney: 19
Woodville: 20

Ghent: 23

Sao Paula: 18

Calgary: 20
Quebec: 13
Vancouver: 24

Beijing: 7, 26
Kashiwa: 46
Lanzhou: 37
Shanghai: 11, 35

Zagreb: 10

Aarhus: 43

Cachan: 45
Dijon: 17
Grenoble: 21, 45
Lille: 17
Montpellier: 17
Orleans: 10
Paris: 10, 17, 40
Rouen: 17
Villeurbanne: 45

Augsburg: 44, 47
Berlin: 33
Bonn: 33
Dresden: 12
Freiburg: 33
Garching: 52
Hamburg: 3, 18
Heidelberg: 33
Homburg: 33
Kiel: 33
Mainz: 9
Marburg: 40
Martinsried: 34
Munich: 34, 41, 44
Neuherberg: 33
Offenbach: 3
Saarbrucken: 33
Stuttgart: 47
Sulzbach: 33
Tuebingen: 32
Voelklingen: 33
Wurzburg: 33

Athens: 25

Dublin: 41

Haifa: 27
Rehovot: 5

Florence: 42
Pisa: 42

Hyogo: 28
Kanazawa: 28
Kyoto: 28
Kyushu: 23
Osaka: 6, 28
Saitama: 51, 53
Sendai: 6, 24
Tokyo: 14, 24, 31, 53
Yokohama: 24
Yokosuka: 6

Gangwon-do: 29
Seoul: 25, 29

De Bilt: 3
Enschede: 3
Leiden: 17, 44
Rotterdam: 18
Utrecht: 3, 31
Wageningen: 12

Bergen: 9

Lisbon: 18, 51

Singapore: 50

Barcelona: 5, 31
Girona: 15, 16
Madrid: 18, 31
Sevilla: 49

Jeddah: 52

Burgdorf: 20
Zurich: 26

Birmingham: 24
Bristol: 19
Cardiff: 19
Exeter: 27
Glasgow: 16, 19
Heslington: 27
Leeds: 27
Leicester: 24
Liverpool: 19
London: 19, 26
Manchester: 10, 27
Sheffield: 27

Auburn: 9
Berkeley: 21, 37
Duarte: 11
La Jolla: 24
Los Angeles: 32
Santa Barbara: 44
Stanford: 46, 52
Fort Collins: 1
New Haven: 2, 4, 49
Gainesville: 9
Jupiter: 2
Miami: 2
St. Augustine: 9
Chicago: 7
Bethesda: 50
College Park: 44
Frederick: 18
Boston: 2, 5, 11, 29, 30, 52
Cambridge: 5, 13, 29, 34, 41, 47
Chestnut Hill: 39
Medford: 36
Worcester: 30
Columbia: 38
New York
Bronx: 1
New York: 5, 17, 18, 24, 49
North Carolina
Chapel Hill: 5
Durham: 25
Philadelphia: 39, 48
Memphis: 23
College Station: 2
Houston: 22
Seattle: 20, 25


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

Rachel Twinn (Nature London)
Tel: +44 20 7843 4658; E-mail: [email protected]

Neda Afsarmanesh (Nature New York)
Tel: +1 212 726 9231; E-mail: [email protected]

Ruth Francis (Head of Press, Nature, London)
Tel: +44 20 7843 4562; E-mail: [email protected]

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

Nature Biotechnology (New York)
Michael Francisco
Tel: +1 212 726 9288; E-mail: [email protected]

Nature Cell Biology (London)
Sowmya Swaminathan
Tel: +44 20 7843 4656; E-mail: [email protected]

Nature Chemical Biology (Boston)
Elissa Bolt
Tel: +1 617 475 9241, E-mail: [email protected]

Nature Chemistry (London)
Stuart Cantrill
Tel: +44 20 7014 4018; E-mail: [email protected]

Nature Climate Change (London)
Olive Heffernan
Tel: +44 20 7014 4009; E-mail: [email protected]

Nature Genetics (New York)
Myles Axton
Tel: +1 212 726 9324; E-mail: [email protected]

Nature Geoscience (London)
Heike Langenberg
Tel: +44 20 7843 4042; E-mail: [email protected]

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

Nature Materials (London)
Vincent Dusastre
Tel: +44 20 7843 4531; E-mail: [email protected]

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

Nature Methods (New York)
Hugh Ash
Tel: +1 212 726 9627; E-mail: [email protected]

Nature Nanotechnology (London)
Peter Rodgers
Tel: +44 20 7014 4019; Email: [email protected]

Nature Neuroscience (New York)
Kalyani Narasimhan
Tel: +1 212 726 9319; E-mail: [email protected]

Nature Photonics (Tokyo)
Oliver Graydon
Tel: +81 3 3267 8776; E-mail: [email protected]

Nature Physics (London)
Alison Wright
Tel: +44 20 7843 4555; E-mail: [email protected]

Nature Structural & Molecular Biology (New York)
Sabbi Lall
Tel: +1 212 726 9326; E-mail: [email protected]

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Published: 04 Sep 2011

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