This press release contains:
Summaries of newsworthy papers:
Chemical Biology: Natural products reveal new targets for cancer therapy
Methods & Biotechnology: ‘Off-targets’ of zinc-finger nucleases
Genetics: Exome sequencing of hepatocellular carcinoma
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 http://press.nature.com. Press contacts for the Nature journals are listed at the end of this release.
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[1] Chemical Biology: Natural products reveal new targets for cancer therapy
DOI: 10.1038/nchembio.625
Targets for anti-cancer therapy discovered by studying a collection of natural products that similarly inhibit the growth of human cancer cells are reported online this week in Nature Chemical Biology.
Some naturally occurring small molecules can inhibit growth of human cancer cells, but the mechanism underlying these growth inhibitory properties is often unknown.
Matthew Shair and colleagues indentified the targets oxysterol-binding protein (OSBP) and OSBP-related proteins for natural products in cancer cells. OSBP and OSBP-related proteins have been implicated in signal transduction, lipid transport and lipid metabolism but were not known to impact cancer cell growth or survival.
The identification of a series of molecules that inhibit cancer cell growth by targeting these proteins provides the tools needed to further investigate the relationship between OSBP and OSBP-related proteins and cancer and provides new targets that should stimulate research into new therapies.
Author contact:
Matthew Shair (Harvard University, Cambridge, MA, USA)
Tel +1 617 495 5008; E-mail: [email protected]
[2] & [3] Methods & Biotechnology: ‘Off-targets’ of zinc-finger nucleases
DOI 10.1038/nmeth.1670
DOI 10.1038/nbt.1948
The off-target effects of a genome-editing technology called zinc-finger nucleases (ZFNs) are reported online this week in Nature Biotechnology and Nature Methods. Both studies provide insights into the precision of this tool.
ZFNs are enzymes that can make modifications at selected sites in the genome and are therefore promising tools for both basic research and gene therapy. But precision, in such a tool, is everything. Off-target effects, where the ZFN modifies a genomic position other than the one it is designed to target, can cause problems for many applications but have not been studied experimentally across the entire genome.
Two independent studies describe methods to carry out such experimental tests and report their findings. In Nature Methods, David Liu and colleagues use an in vitro, deep sequencing–based assay to study the cleavage specificities of two ZFN pairs. They observe cleavage of off-target sequences that are present in the human genome and see evidence that these sites are cleaved when the ZFN pairs are expressed in cells.
In Nature Biotechnology, Luigi Naldini, Christof von Kalle and colleagues identify the cleavage sites of four ZFN pairs by using a virus that integrates into the genome where breaks have occurred. Although most cuts are at the expected locations, the team notes that off-target events are found at other locations that were not predicted by computational methods.
Whereas both studies focus on a ZFN that is in clinical trials, neither is done in the clinically relevant cell type. The results of such analyses are likely to vary with cell type and with different expression levels of the ZFN. These reports strongly indicate that additional study of ZFN off-target effects in clinically relevant cells is warranted.
Author contacts:
David Liu (Harvard University, Cambridge, MA, USA) Author paper [2]
Tel: +1 617 496 1067; E-mail: [email protected]
Luigi Naldini (San Raffaele Institute, Milan, Italy) Author paper [3]
Tel: +39 022 643 4681; E-mail: [email protected]
Christof von Kalle (National Center for Tumor Diseases, Heidelberg, Germany) Author paper [3]
Tel: +49 6221 56 6991; E-mail: [email protected]
[4] Genetics: Exome sequencing of hepatocellular carcinoma
DOI: 10.1038/ng.903
Sequencing of the exomes—the coding region of the genome—of individuals with hepatocelullar carcinoma (HCC) is reported this week in Nature Genetics.
HCC is the third leading cause of cancer related deaths worldwide, and carries a high mortality rate. Infection with either hepatitis B or hepatitis C virus, as well as environmental factors including alcohol consumption, are known risk factors for HCC.
Kenneth Kinzler and colleagues sequenced the exomes of ten individuals with hepatitis C virus (HCV) associated HCC. They identified inactivating mutations in the ARID2 gene and establish this as an HCC tumor suppressor gene. They examine additional cases, and found that ARID2 is mutated in 18.2% of individuals in their sample with HCV associated HCC.
Author contact:
Kenneth Kinzler (Johns Hopkins University, Baltimore, MD, USA)
Tel: +1 410 955 2928; E-mail: [email protected]
Items from other Nature journals to be published online at the same time:
Nature (http://www.nature.com/nature)
[5] Structure of the membrane domain of respiratory complex I
DOI: 10.1038/nature10330
[6] Modulation of Rab GTPase function by a protein phosphocholine transferase
DOI: 10.1038/nature10335
[7] Protection of repetitive DNA borders from self-induced meiotic instability
DOI: 10.1038/nature10331
[8] Polar acto-myosin contractility destabilizes the position of the cytokinetic furrow
DOI: 10.1038/nature10286
NATURE BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)
[9] Quantitative fluorescence imaging of protein diffusion and interaction in living cells
DOI: 10.1038/nbt.1928
[10] A resource of vectors and ES cells for targeted deletion of microRNAs in mice
DOI: 10.1038/nbt.1929
NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology)
[11] MAP4 and CLASP1 operate as a safety mechanism to maintain a stable spindle position in mitosis
DOI: 10.1038/ncb2297
[12] Endolysosomal sorting of ubiquitylated caveolin-1 is regulated by VCP and UBXD1 and impaired by VCP disease mutations
DOI: 10.1038/ncb2301
[13] The T-box transcription factor Eomesodermin acts upstream of Mesp1 to specify cardiac mesoderm during mouse gastrulation
DOI: 10.1038/ncb2304
[14] RalA and RalBP1 regulate mitochondrial fission at mitosis
DOI: 10.1038/ncb2310
NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)
[15] Mechanistic evidence for a front side, SNi-type reaction in a retaining glycosyltransferase
DOI: 10.1038/nchembio.628
NATURE CHEMISTRY (http://www.nature.com/nchem)
[16] A route to enantiopure RNA precursors from nearly racemic starting materials
DOI: 10.1038/nchem.1108
[17] Peptide–nucleotide microdroplets as a step towards a membrane-free protocell model
DOI: 10.1038/nchem.1110
NATURE CLIMATE CHANGE (http://www.nature.com/nclimate)
Driving technology transfer
DOI: 10.1038/nclimate1193
NATURE GENETICS (http://www.nature.com/naturegenetics)
[18] Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder
DOI: 10.1038/ng.907
[19] Germline mutations in RAD51D confer susceptibility to ovarian cancer
DOI: 10.1038/ng.893
[20] The genome of the extremophile crucifer Thellungiella parvula
DOI: 10.1038/ng.889
[21] Exome sequencing supports a de novo mutational paradigm for schizophrenia
DOI: 10.1038/ng.902
NATURE GEOSCIENCE (http://www.nature.com/ngeo)
[22] Diapirs as the source of the sediment signature in arc lavas
DOI: 10.1038/ngeo1214
[23] A continuum of stress, strength and slip in the Cascadia subduction zone
DOI: 10.1038/ngeo1215
[24] Ice speed of a calving glacier modulated by small fluctuations in basal water pressure
DOI: 10.1038/ngeo1218
NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)
[25] The inducible kinase IKKi is required for IL-17-dependent signaling associated with neutrophilia and pulmonary inflammation
DOI: 10.1038/ni.2080
[26] Treatment with IL-17 prolongs the half-life of chemokine CXCL1 mRNA via the ubiquitin ligase TRAF5 and the splicing-regulatory factor SF2 (ASF)
DOI: 10.1038/ni.2081
NATURE MATERIALS (http://www.nature.com/naturematerials)
[27] Highly monodisperse core–shell particles created by solid-state reactions
DOI: 10.1038/nmat3077
[28] Self-assembly of a sulphur-terminated graphene nanoribbon within a single-walled carbon nanotube
DOI: 10.1038/nmat3082
[29] Magnetic manipulation of self-assembled colloidal asters
DOI: 10.1038/nmat3083
[30] Co3O4 nanocrystals on graphene as a synergistic catalyst for oxygen reduction reaction
DOI: 10.1038/nmat3087
[31] Programming magnetic anisotropy in polymeric microactuators
DOI: 10.1038/nmat3090
Nature MEDICINE (http://www.nature.com/naturemedicine)
[32] Oncogenic PIK3CA-driven mammary tumors frequently recur via PI3K pathway-dependent and PI3K pathway-independent mechanisms
DOI: 10.1038/nm.2402
[33] Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization
DOI: 10.1038/nm.2401
[34] Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2
DOI: 10.1038/nm.2416
NATURE METHODS (http://www.nature.com/nmeth)
[35] Cell-type specific optogenetic mice for dissecting neural circuitry function
DOI: 10.1038/nmeth.1668
NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)
[36] Tunable metallic-like conductivity in biofilms comprised of microbial nanowires
DOI: 10.1038/nnano.2011.119
Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)
[37] Harmonin inhibits presynaptic Cav1.3 Ca2+ channels in mouse inner hair cells
DOI: 10.1038/nn.2895
[38] Hippocampal CA1 pyramidal cells form functionally distinct sublayers
DOI: 10.1038/nn.2894
[39] Anisotropic encoding of three-dimensional space by place cells and grid cells
DOI: 10.1038/nn.2892
NATURE PHOTONICS (http://www.nature.com/nphoton)
[40] Sensitive mid-infrared detection in wide-bandgap semiconductors using extreme non-degenerate two-photon absorption
DOI: 10.1038/nphoton.2011.168
[41] Stable and efficient quantum-dot light-emitting diodes based on solution-processed multilayer structures
DOI: 10.1038/nphoton.2011.171
Nature PHYSICS (http://www.nature.com/naturephysics)
[42] Nonlinear phononics as an ultrafast route to lattice control
DOI: 10.1038/nphys2055
[43] Atomically controlled quantum chains hosting a Tomonaga–Luttinger liquid
DOI: 10.1038/nphys2051
Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
[44] An autoinhibitory helix in the C-terminal region of phospholipase C-b mediates Gaq activation
DOI: 10.1038/nsmb.2095
[45] Trimeric structure and flexibility of the L1ORF1 protein in human L1 retrotransposition
DOI: 10.1038/nsmb.2097
[46] Structure-function studies of nucleocytoplasmic transport of retroviral genomic RNA by mRNA export factor TAP
DOI: 10.1038/nsmb.2094
[47] Biogenic mechanisms and utilization of small RNAs derived from human protein-coding genes
DOI: 10.1038/nsmb.2091
[48] Simultaneous visualization of the extracellular and cytoplasmic domains of the epidermal growth factor receptor
DOI: 10.1038/nsmb.2092
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.
ARGENTINA
Buenos Aires: 24
Río Negro: 27
CANADA
Saskatoon: 30
CHINA
Beijing: 4, 35
Changsha: 19
Guangzhou: 19
Hefei: 19
Shenzhen: 19
DENMARK
Copenhagen: 19, 44
FRANCE
Paris: 8
GERMANY
Dresden: 8
Essen: 12
Freiburg: 13
Goettingen: 39
Hamburg: 42
Heidelberg: 3, 9
Kassel: 43
Martinsried: 44
Regensburg: 44
Stuttgart: 22
Tübingen: 46, 48
Ulm: 28
Würzburg: 43
ITALY
Meldola: 33
Milan: 3, 42
JAPAN
Hiroshima: 24
Ibaraki: 42
Miyazaki: 36
Sapporo: 24
Tachikawa: 24
Tokyo: 1
Tokyo : 42, 45
Tsukuba: 24
Yokohama: 17
KOREA
Jinju: 20
NETHERLANDS
Utrecht: 4
NEW ZEALAND
Wellington: 23
NORWAY
Bergen: 32
POLAND
Warsaw: 8
SAUDI ARABIA
Thuwal: 20
SERBIA
Belgrade: 27
SINGAPORE
Singapore: 35
SOUTH AFRICA
Pretoria: 21
SOUTH KOREA
Daejeon: 36
Seoul: 31
Ulsan: 15
SPAIN
Barcelona: 33
Bilbao: 28
San Sebastian: 28
SWITZERLAND
Villigen: 43
Zürich: 12, 27
UNITED KINGDOM
Aberdeen: 18
Belfast: 18
Birmingham: 18
Bristol: 17, 18
Cambridge: 7, 10, 18
Cardiff: 18
Coventry: 11
Dundee: 18
Edinburgh: 18
Exeter: 18
Glasgow: 18
Herts: 37
Leeds: 18
Leicester: 18
Liverpool: 18
London: 18, 37
Manchester: 18
Newcastle upon Tyne: 18
Nottingham: 28
Oxford: 13, 18, 33
Sheffield: 18
Southampton: 18
Sutton: 18
York: 15
UNITED STATES OF AMERICA
Alabama
Huntsville: 21
California
Berkeley: 27
La Jolla: 16
Richmond: 3
Santa Barbara: 22
Stanford: 30
Colorado
Aurora: 19, 34
Denver: 34
Connecticut
New Haven: 5
Florida
Gainesville: 41
Orlando: 40
Georgia
Atlanta: 39, 40
Iowa
Iowa City: 39
Illinois
Argonne: 29
River Forest: 39
Urbana: 20
Indiana
West Lafayette: 20
Massachusetts
Amherst: 11, 36
Boston: 2, 4, 32, 34, 45
Cambridge: 1, 2, 6, 32, 35
Charlestown: 2
Somerville: 6
Woods Hole: 22
Worcester: 36
Maryland
Baltimore: 4
Bethesda: 14
Frederick: 19
Rockville: 47
Michigan
Ann Arbor: 27, 36, 47
Missouri
Saint Louis: 12
Michigan
Ann Arbor: 42
North Carolina
Chapel Hill: 14
Durham: 14, 35
New Hampshire
Lebanon: 36
New Jersey
Newark: 38
New Brunswick: 33
Princeton: 33
New Mexico
Los Alamos: 40
New York
Brooklyn: 37
New York: 6, 21, 37, 46
Palisades: 22
Ohio
Cleveland: 25, 26
Rhode Island
Providence: 22
Texas
Houston: 32
Washington
Seattle: 23
Wisconsin
Madison: 34
PRESS CONTACTS…
For media inquiries relating to embargo policy for all the Nature Research Journals:
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Tel: +44 20 7843 4658; E-mail: [email protected]
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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
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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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