This press release contains:
· Summaries of newsworthy papers:
Medicine: Gene therapy restores sense of smell
Genetics: Sequencing of small-cell lung cancer exomes
Immunology: Defining early steps in human hematopoiesis
And finally…Climate Change: Robust joint projections for health metrics
· Geographical listing of authors
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[1] Medicine: Gene therapy restores sense of smell
DOI: 10.1038/nm.2860
A gene therapy approach for restoring cilia development and olfactory responses is reported online this week in Nature Medicine. These findings provide a proof-of-principle that gene therapy may be used in certain genetic disorders to rescue cilia development and restore sensory function.
Ciliopathies are a group of genetic disorders caused by defects in the formation or function of cilia, which are organelles that protrude from the surface of cells. Sensory defects, including blindness, and loss of hearing or smell may accompany these disorders.
Jeffrey R. Martens and colleagues find a mutation in Intraflagellar Transport Protein 88 (IFT88) that is associated with human ciliopathies. Mice deficient in this protein have shortened and malformed cilia on neurons within the nose and are unable to perceive odors. The team shows that delivery of adenoviral vectors expressing IFT88 into the nose of these mutant mice rescues cilia defects and neuronal responses to odorant molecules. They also discover that gene therapy restores suckling and feeding behaviors that are mediated by olfactory function in these mice.
Author contact:
Jeffrey R. Martens (University of Michigan, Ann Arbor, MI, USA)
Tel: +1 734 615 9026; Email: [email protected]
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[2] & [3] Genetics: Sequencing of small-cell lung cancer exomes
DOI: 10.1038/ng.2396
DOI: 10.1038/ng.2405
The exomes of 82 small-cell lung cancer samples from patients have been sequenced and analyzed, according to two independent reports published online this week in Nature Genetics. The studies identify several potential targets for therapeutic intervention.
Small-cell lung cancer (SCLC) is an aggressive type of tumor with poor prognosis. This type of cancer is rarely treated by surgery, making systematic genomic analyses of large numbers of tumors difficult. For the first time, two groups have sequenced the exomes from a total of 82 small-cell lung cancer samples and identified new genes recurrently mutated in this type of cancer.
Roman Thomas and colleagues sequenced 29 SCLC exomes and identified mutations in a number of genes involved in histone modification. Somasekar Seshagiri, Charles Rudin and colleagues sequenced the exomes of 36 primary SCLC tumors and 17 SCLC cell lines, individually derived from SCLC tumors. They identified 22 significantly mutated genes, including genes that encode kinases, G-protein coupled receptors and chromatin modifying proteins. They also identified amplification of the SOX2 gene in 27% of samples, suggesting SOX2 has an important role as a cancer-causing gene in small cell lung cancer.
Authors contact:
Roman Thomas (University of Cologne, Germany) Author paper [2]
Tel: +49 221 478 98771; E-mail: [email protected]
Somasekar Seshagiri (Genentech, South San Francisco, CA) Author paper [3]
Tel: +1 650 225 3351; E-mail: [email protected]
Charles Rudin (Johns Hopkins University, Baltimore, MD) Author paper [3]
Tel: +1 410 502 0678; E-mail: [email protected]
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[4] Immunology: Defining early steps in human hematopoiesis
DOI:10.1038/ni.2405
A unique cell population found in human bone marrow is described this week in Nature Immunology. This subset, that expresses the homing molecule L-selectin, is the earliest stage yet reported that gives rise to certain types of white blood cells. The identification of this population will aid our understanding of normal blood cell development and importantly might lend cues during irregular development that leads to various forms of leukemia.
Gay Crooks and colleagues scrutinized human bone marrow cells for their developmental potential in culture dishes and in immunodeficient mice that develop blood cells upon transplantation with human stem and progenitor cells. They identified the L-selectin-positive subset that is a developmental intermediate between quiescent hematopoietic stem cells – the source of all blood cells – and a previously identified subset that are developmentally skewed to form antibody-producing B cells. They show this subset lacks the ability to form red blood cells or platelets, but can make multiple types of white blood cells, including T cells and natural killer cells.
Importantly, the newly identified bone marrow cells differ from the early progenitors found in newborn umbilical cord blood. Although cord blood cells are more readily accessible and highly proliferative, they exhibit a more restricted developmental potential, suggesting that cord blood cells are more specialized than the newly identified bone marrow cells.
Author contact:
Gay Crooks (David Geffen School of Medicine University of California, Los Angeles, CA, USA)
Tel: +1 310 206 0205; E-mail: [email protected]
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[5] And finally…Climate Change: Robust joint projections for health metrics
DOI: 10.1038/nclimate1682
Uncertainties in computer-based projections of the impacts of climate change on human heath are reduced if uncertainties in temperature and humidity are combined rather than being regarded as independent, reports a paper published online in Nature Climate Change this week. This work suggests that uncertainties of all variables need to be considered together when completing impact assessments.
Impacts of climate change on human health often depend on many different factors. Erich Fischer and Reto Knutti investigated the uncertainties in impact assessments when using climate projections, and their results reveal the potential for joint assessment of projection uncertainties in the range of variables used in climate impact studies.
Author contact:
Erich Fischer (ETH, Zurich, Switzerland)
Tel: +41 44 632 82 41; 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
[6] Distinct contribution of stem and progenitor cells to epidermal maintenance
DOI: 10.1038/nature11393
[7] Interaction landscape of membrane-protein complexes in Saccharomyces cerevisiae
DOI: 10.1038/nature11354
[8] Structural basis for RNA-duplex recognition and unwinding by the DEAD-box helicase Mss116p
DOI: 10.1038/nature11402
[9] Nonlinear dendritic processing determines angular tuning of barrel cortex neurons in vivo
DOI: 10.1038/nature11451
[10] Alternating-access mechanism in conformationally asymmetric trimers of the betaine transporter BetP
DOI: 10.1038/nature11403
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NATURE CELL BIOLOGY
[11] IKKβ/NF-κB disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes
DOI: 10.1038/ncb2562
[12] Endocytosis of the seven-transmembrane RGS1 protein activates G-protein-coupled signalling in Arabidopsis
DOI: 10.1038/ncb2568
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NATURE CHEMISTRY
[13] Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe
DOI: 10.1038/nchem.1435
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NATURE CHEMICAL BIOLOGY
[14] Cytochrome P450-catalysed L-tryptophan nitration in thaxtomin phytotoxin biosynthesis
DOI: 10.1038/nchembio.1048
[15] A Novel Type V TA System Where mRNA for Toxin GhoT is Cleaved by Antitoxin GhoS
DOI: 10.1038/nchembio.1062
[16] The physical state of lipid substrates provides transacylation specificity for tafazzin
DOI: 10.1038/nchembio.1064
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NATURE CLIMATE CHANGE
[17] Major flood disturbance alters river ecosystem evolution
DOI: 10.1038/nclimate1665
[18] Climate-change impact assessment for inlet-interrupted coastlines
DOI: 10.1038/nclimate1664
[19] Blanket peat biome endangered by climate change
DOI: 10.1038/nclimate1672
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NATURE GENETICS
[20] Common variants at 6p21.1 are associated with large artery atherosclerotic stroke
DOI: 10.1038/ng.2397
[21] Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma
DOI: 10.1038/ng.2387
[22] Mapping cis- and trans-regulatory effects across multiple tissues in twins
DOI: 10.1038/ng.2394
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NATURE GEOSCIENCE
[23] Modelled suppression of boundary-layer clouds by plants in a CO2-rich atmosphere
DOI: 10.1038/ngeo1554
[24] Episodic tremor and slow slip potentially linked to permeability contrasts at the Moho
DOI: 10.1038/ngeo1559
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NATURE MATERIALS
[25] Spin excitations in a single La2CuO4 layer
DOI: 10.1038/nmat3409
[26] Hidden polymorphs drive vitrification in B2O3
DOI: 10.1038/nmat3416
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Nature MEDICINE
[27] Antiretroviral dynamics determines HIV evolution and predicts therapy outcome
DOI: 10.1038/nm.2892
[28] Multigenerational Epigenetic Adaptation of the Hepatic Wound-Healing Response
DOI: 10.1038/nm.2893
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NATURE METHODS
[29] Ultrafast force-clamp spectroscopy of single molecules reveals load dependence of myosin working stroke
DOI: 10.1038/nmeth.2152
[30] Iterative correction of Hi-C data reveals new features of chromosome organization
DOI: 10.1038/nmeth.2148
[31] Coupling endonucleases with DNA end-processing enzymes for gene disruption.
DOI: 10.1038/nmeth.2177
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NATURE NANOTECHNOLOGY
[32] All-optical active switching in individual semiconductor nanowires
DOI:10.1038/nnano.2012.144
[33] Probing the conductance superposition law in single-molecule circuits with parallel paths
DOI:10.1038/nnano.2012.147
[34] Sensing single remote nuclear spins
DOI:10.1038/nnano.2012.152
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Nature NEUROSCIENCE-
[35] Biasing the content of hippocampal replay during sleep
DOI: 10.1038/nn.3203
[36] Chronic alcohol remodels prefrontal neurons and disrupts NMDA receptor-mediated fear extinction encoding
DOI: 10.1038/nn.3204
[37] Rho-kinase Regulates Energy Balance by Targeting Leptin Receptor Signaling
DOI: 10.1038/nn.3207
[38] Optogenetics in primates: monkey see monkey look
DOI: 10.1038/nn.3210
[39] Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson's disease
DOI: 10.1038/nn.3209
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Nature PHYSICS
[40] Coherent multi-flavour spin dynamics in a fermionic quantum gas
DOI: 10.1038/nphys2409
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Nature STRUCTURAL & MOLECULAR BIOLOGY
[41] Spatial elucidation of motion in proteins by ensemble-based structure calculation using exact NOEs
DOI: 10.1038/nsmb.2355
[42] Controlling synaptotagmin activity by electrostatic screening
DOI: 10.1038/nsmb.2375
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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
Adelaide: 20
Gosford: 20
Melbourne: 2
Newcastle: 20, 28
New South Wales: 19
Perth: 20
Townsville: 20
BELGIUM
Brussels: 6
Ghent: 2
CANADA:
Hamilton: 16
Regina: 7
Toronto: 7
Vancouver: 7
CHINA
Guangzhou: 15
CYPRUS
Nicosia: 23
FRANCE
Grenoble: 2
Illkirch: 2
Lyon: 15
Paris: 1, 2, 26
Villejuif: 2
GERMANY
Bad Berka: 2
Berlin: 2
Bonn: 2
Cologne: 2
Dortmund: 2
Dresden: 25
Frankfurt: 10, 41
Freiburg: 2
Goettingen: 42
Hamburg: 23, 40
Heidelberg: 2
Jena: 2
Mainz: 23
Munich: 20
Regensburg: 10
Stuttgart: 34
Ulm: 34
HONG KONG
Hong Kong: 34
ICELAND
Reykjavik: 20, 22
ISRAEL
Haifa: 9
ITALY
Florence: 39
Milan: 20
Naples: 21
Pavia: 39
Rende: 21
Rome: 21
San Giovanni Rotondo: 2
Sesto Fiorentino: 29
JAPAN
Higashi: 24
Nankoku: 24
Tokyo: 41
Tsukuba: 34
KOREA
Incheon: 37
Seoul: 37
NETHERLANDS
Amsterdam: 2
Delft: 18
Groningen: 2
Rotterdam: 20
Wageningen: 23
NORWAY
Oslo: 2
SWEDEN
Lund: 19
SWITZERLAND
Geneva: 22
Lausanne: 25
Villigen: 25
Zurich: 2, 5, 41
UNITED KINGDOM
Ascot: 19
Berkshire: 34
Birmingham: 17
Bristol: 19, 22, 25
Cambridge: 6, 22
Coventry: 14
Didcot: 25
Edinburgh: 20
Exeter: 19
Leeds: 1, 17
Liverpool: 2
London: 1, 14, 17, 20, 22, 25
Oxford: 20, 22
UNITED STATES OF AMERICA
Alabama
Birmingham: 1
Alaska
Fairbanks: 17
California
La Jolla: 25
Los Angeles: 4
San Carlos: 14
San Francisco: 3
Stanford: 2, 13, 22
Colorado
Aurora: 2
Connecticut
New Haven: 33
Delaware
Newark: 14
Florida
Gainesville: 14
Jacksonville: 20
Lake Alfred: 14
Illinois
Chicago: 39
Maryland
Baltimore: 1, 3, 20, 27
Bethesda: 1, 9, 20, 36
Massachusetts
Boston: 2, 37
Cambridge: 2, 20, 27, 30, 35
Charlestown: 37
Worcester: 30
Michigan
Ann Arbor: 1
Minnesota
Rochester: 20
Mississippi
Jackson: 20
New York
Bronx: 11
Ithaca: 14
New York: 2, 16, 22, 33
Upton: 25, 33
North Carolina
Chapel Hill: 12, 36
Durham: 1
Pennsylvania
Philadelphia: 21, 32
University Park: 15
Rhode Island
Providence: 15
Tennessee
Memphis: 2
Nashville: 2
Texas
Austin: 8
Bryan: 13
College Station: 13, 15
Dallas: 2
Houston: 1, 20
Temple: 13
Woodlands: 8
Washington
Seattle: 2, 20, 38
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PRESS CONTACTS…
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]
Eiji Matsuda (Nature Tokyo)
Tel: +81 3 3267 8751; 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)
Kim Tolleson
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)
Rory Howlett
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)
Ray Parker
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)
Michelle Montoya
Tel: +1 212 726 9331; E-mail: [email protected]
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