This press release contains:
· Summaries of newsworthy papers:
Medicine: Skin patch delivers influenza vaccination
Neuroscience: Pinpointing the molecular culprit in Down syndrome
Genetics: Lumiracoxib-related liver injury
Nature: Pathway linked to leukaemia progression
Geoscience: Uneven climate modification
Nature: Tracking oncology diversity
Methods:
· Mention of papers to be published at the same time with the same embargo
· 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] Medicine: Skin patch delivers influenza vaccination
DOI: 10.1038/nm.2182
Influenza vaccination can we achieved using microneedle covered patches applied to the skin, as reported online this week in Nature Medicine. The study, conducted in mice, found that the microneedle patches were more efficient at clearing the lungs of virus and improved the immune system’s antibody memory.
Traditional methods of immunization—needle injection into muscle tissue—face obstacles in the delivery system of antibodies. New methods strive to achieve high levels of mass immunization through enhancing patient compliance and reducing biohazard waste.
Mark Prausnitz and colleagues propose a simple and safe method for vaccine delivery by dissolving micron-scale needles onto a patch that painlessly pierces the skin and administers the vaccine. Since the skin is an active immune organ, it contains copious antigen-presenting cells. The authors found that in the mice tested with the patch, there was increased efficacy of vaccination towards influenza.
Author contact:
Mark Prausnitz (Georgia Institute of Technology, Atlanta, GA, USA)
Tel: +1 404 894 5135
E-mail: [email protected]
[2] Neuroscience: Pinpointing the molecular culprit in Down syndrome
DOI: 10.1038/nn.2600
A study published in Nature Neuroscience this week reports that normalizing the gene expression of two of the hundreds of affected genes in a mouse model of Down syndrome (DS) can be beneficial in combating some of the effects of the disease.
Animals generally have two copies of each gene—one set inherited from each parent— with the exception of sex chromosomes. In DS patients, however, there is an extra copy of chromosome 21 which results in severe learning disabilities and cognitive impairments. Despite the availability of several mouse models of DS that recapture some of the behavioral and neurodevelopment deficits of DS, finding the gene or set of genes directly responsible for DS has been elusive.
Tarik Haydar and colleagues show that reducing the expression of two of the affected genes—Olig1 and Olig2—in a mouse model of DS can help correct the imbalance of brain activity in DS mice. Olig1 and Olig2 are essential during embryonic development, as these genes regulate the numbers of interneurons—a type of neuron that controls the levels of inhibition in the brain. An imbalance between excitation and inhibition has been reported in DS patients. Although these results show promise, it remains unclear whether altering the gene dosage of Olig1 and Olig2 would be beneficial to correct the behavioral impairments seen in DS mouse models. It also remains to be seen whether the behavioral deficits associated with DS are normalized by lowering the level of Olig1 and Olig2.
Although it is difficult to directly link these results to the cognitive impairments or extrapolate to the disease condition in humans with DS, these findings could help identify some potential therapeutic targets for combating the initial development of DS.
Author contact:
Tarik Fuad Haydar (Boston University, MA, USA)
Tel: +1 617 638 4249
E-mail: [email protected]
[3] Genetics: Lumiracoxib-related liver injury
DOI: 10.1038/ng.632
Genetic variants associated with susceptibility to liver injury that is caused by Lumiracoxib—a non-steroidal anti-inflammatory drug developed to treat osteoarthritis and acute pain—are reported this week in Nature Genetics. This suggests that individuals at risk of liver injury could be identified by genotyping and then excluded from lumiracoxib treatment.
Concerns over liver toxicity have led to the withdrawal or non-approval of lumiracoxib in drug markets worldwide. Charles Paulding and colleagues report a genome-wide association study for susceptibility to lumiracoxib-related liver injury in lumiracoxib-treated patients with liver injury and matched lumiracoxib-treated patients without liver injury. They replicated these results identifying genetic variants at the major histocompatibility class II region—important in the development of the immune system and autoimmunity—associated with lumiracoxib-related liver injury.
Author contact:
Charles Paulding (Novartis Institutes for BioMedical Research, Cambridge, MA, USA)
Tel: +1 617 871 7483
E-mail: [email protected]
[4] Nature: Pathway linked to leukaemia progression
DOI: 10.1038/nature09171
The discovery of a signalling pathway that influences the progression of chronic myelogenous leukaemia (CML) may aid the development of new therapies against this white blood cell cancer, a Nature study suggests.
CML, which is linked with a specific chromosomal abnormality, can progress from a chronic phase with milder symptoms to an acute blast crisis phase where cancerous cells proliferate uncontrollably. Tannishtha Reya and colleagues use mouse models to show that progression of the bone marrow cancer is controlled by the cell fate regulator Musashi2 (Msi2).
The team show that Msi2 expression increases as human CML progresses, and these rising levels are thought to influence the expression of other proteins linked to cell differentiation. Levels of the protein Numb, for example, decrease as the disease progresses; restoring Numb expression impairs disease development and progression in mouse models. Overall, the study indicates that Msi2 may be a useful early indicator of poor prognosis, and that strategies targeting the Musashi–Numb pathway could eventually prove useful therapeutically.
Author contact:
Tannishtha Reya (Duke University Medical Center, Durham, NC, USA)
Tel: +1 919 613 8756
E-mail: [email protected]
[5] Geoscience: Uneven climate modification
DOI: 10.1038/ngeo915
The amount of intervention required for optimum managing of climate change differs by region, and diverges for India and China, according to a study published online this week in Nature Geoscience. Use of solar-radiation management leads to a reduction in extremes of temperature and precipitation for most regions, but if this option is pursued, it could prove difficult to achieve global consensus on the desired level of climate modification.
Katharine Ricke and colleagues simulated the climate outcomes if different amounts of reflecting aerosols were to be added to the upper atmosphere as a means of mitigating climate change. They performed a number of climate simulations for 54 scenarios with distinct modifications of the reflectivity of the upper atmosphere. The authors conclude that precipitation and temperature cannot be stabilized by the same degree of climate modification, and that it may not be possible to stabilize climate simultaneously in China and India.
Author contact:
Katharine Ricke (Carnegie Mellon University, Pittsburgh, PA, USA)
Tel: +1 612 382 8145
E-mail: [email protected]
[6] Nature: Tracking oncology diversity
DOI : 10.1038/nature09173
A key challenge for oncologists is to understand the biology underlying tumours that look similar in terms of their cellular anatomy but that are molecularly distinct and therefore responsive to different treatments.
In a study in this week’s Nature, Richard Gilbertson and his colleagues home in on the genetic mutations specific to different subgroups of ‘ependymomas’ — tumours of the brain and spinal cord.
Through the mapping of the expression profiles of messenger and micro RNA molecules, Gilbertson and his group identified distinct subgroups of ependymomas that likely arise in different kinds of neuronal stem cells. By assessing alterations in the copy number of certain DNA sequences, they identified subgroup-specific amplifications and deletions of genes not previously thought to be involved in the cancer.
The authors have also produced the first mouse model of ependymoma by introducing an ependymoma-specific mutation found in one class of these tumours into the corresponding type of mouse neural stem cells thought to be responsible for this cancer type.
Author contact:
Richard Gilbertson (St Jude Children's Research Hospital, Memphis, TN, USA)
Tel: +1 901 595 3913
E-mail: [email protected]
[7] Methods: Following the expression of a single human gene
DOI 10.1038/nmeth.1482
By tagging the products from a single gene locus with green fluorescent protein (GFP), the kinetics of transcription can be followed in single cells, demonstrates work published online this week in Nature Methods.
The extent and timing of transcription — where RNA copies of DNA sequences are made — is tightly regulated and varies widely between genes. Current methods that target transcripts provide information on the average level of mRNA expression but cannot be used to investigate the speed or fluctuation of transcription.
By inserting a single copy of a gene, driven by a viral or its internal promoter and containing a docking site for GFP at the far side of the gene, Yaron Shav-Tal and colleagues monitor expression of this gene over time, count how many mRNA molecules are produced at the locus, and measure the speed of transcription. Comparing the kinetics of transcription from the viral and the internal promoter, the team observed considerable differences¾for example, that the former showed ongoing transcription whereas the latter was turned off during certain stages of cell division. Performing this kinetic analysis in real time on single loci in single cells will allow the detailed study of the regulation of gene transcription and its interplay with cell division.
Author contact:
Yaron Shav-Tal (Bar-Ilan University, Israel)
Tel: +972 3 5331 8589
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
[8] Microbial metalloproteomes are largely uncharacterized
DOI: 10.1038/nature09265
[9] Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification
DOI: 10.1038/nature09303
NATURE BIOTECHNOLOGY
[10] Rapid profiling of a microbial genome using mixtures of barcoded oligonucleotides
DOI: 10.1038/nbt.1653
[11] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling
DOI: 10.1038/nbt.1654
NATURE CELL BIOLOGY
[12] Plasma membrane contributes to the formation of pre-autophagosomal structures
DOI: 10.1038/ncb2078
[13] Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation
DOI: 10.1038/ncb2082
[14] The metabolic enzyme CTP synthase forms cytoskeletal filaments
DOI: 10.1038/ncb2087
NATURE CHEMISTRY
[15] Cooperative catalysis by carbenes and Lewis acids in a highly stereoselective route to y-lactams
DOI: 10.1038/nchem.727
[16] A polyhedron made of tRNAs
DOI: 10.1038/nchem.733
[17] Triply interlocked covalent organic cages
DOI: 10.1038/nchem.739
NATURE GENETICS
[18] Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
DOI: 10.1038/ng.626
[19] Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis
DOI: 10.1038/ng.631
[20] Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis
DOI: 10.1038/ng.627
NATURE GEOSCIENCE
[21] Microbial sequestration of phosphorus in anoxic upwelling sediments
DOI: 10.1038/ngeo913
[22] A seasonal cycle in the export of bottom water from the Weddell Sea
DOI: 10.1038/ngeo916
NATURE IMMUNOLOGY
[23] Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression
DOI: 10.1038/ni.1902
[24] Integrin CD11b negatively regulates TLR-triggered inflammatory responses by activating Syk and promoting degradation of MyD88 and TRIF via Cbl-b
DOI: 10.1038/ni.1908
NATURE MATERIALS
[25] From (pi, 0) magnetic order to superconductivity with (pi, pi) magnetic resonance in Fe1.02Te1-xSex
DOI: 10.1038/nmat2800
[26] High magnetic field scales and critical currents in SmFeAs(O,F) crystals: promising for applications
DOI: 10.1038/nmat2795
[27] Spin injection/detection via an organic-based magnetic semiconductor
DOI: 10.1038/nmat2797
[28] A multiferroic material to search for the permanent electric dipole moment of the electron
DOI: 10.1038/nmat2799
[29] Ballistic nanofriction
DOI: 10.1038/nmat2798
Nature MEDICINE
[30] CIB1 is a regulator of pathological cardiac hypertrophy
DOI: 10.1038/nm.2181
[31] A molecularly engineered split reporter for imaging protein-protein interactions with positron emission tomography
DOI: 10.1038/nm.2185
NATURE METHODS
[32] Amplification-free digital gene expression profiling from minute cell quantities
DOI: 10.1038/nmeth.1480
[33] High-throughput in vivo vertebrate screening
DOI: 10.1038/nmeth.1481
NATURE NANOTECHNOLOGY
[34] Delivery of molecules into cells using carbon nanoparticles activated by femtosecond laser pulses
DOI: 10.1038/nnano.2010.126
Nature NEUROSCIENCE
[35] The reorganization and reactivation of hippocampal maps predict spatial memory performance
DOI: 10.1038/nn.2599
[36] Network mechanisms of theta related neuronal activity in hippocampal CA1 pyramidal neurons
DOI: 10.1038/nn.2597
Nature PHYSICS
[37] Disordered insulator in an optical lattice
DOI: 10.1038/nphys1726
Nature STRUCTURAL & MOLECULAR BIOLOGY
[38] The C-terminus of p53 binds the N-terminal domain of MDM2
DOI: 10.1038/nsmb.1872
[39] Structural basis for the transcriptional regulation of membrane lipid homeostasis
DOI: 10.1038/nsmb.1847
[40] Antagonistic role of hnRNP A1 and KSRP in the regulation of let-7a biogenesis
DOI: 10.1038/nsmb.1874
[41] Replication stress checkpoint signalling controls tRNA gene transcription
DOI: 10.1038/nsmb.1857
[42] A direct role for Hsp90 in pre-RISC formation in Drosophila
DOI: 10.1038/nsmb.1875
[43] Global analysis reveals SRp20- and SRp75-specific mRNPs in cycling and neural cells
DOI: 10.1038/nsmb.1862
***********************************************************************
***The following paper was published electronically on Nature Medicine’s website on 8 July and is therefore no longer under embargo. The rest of the above articles on this release remain under embargo until 18 July at 1800 London time / 1300 US Eastern time ***
[44] Musashi-2 regulates normal hematopoiesis and accelerates leukemogenesis
DOI: 10.1038/nm.2187
***********************************************************************
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: 18
CANADA:
Calgary: 19, 20
Edmonton: 19, 20, 41
Halifax: 20
London: 20
Montreal: 19
Toronto: 6, 19, 20
Vancouver: 18
CHINA
Beijing: 13, 25
Hangzhou: 24
Shanghai: 13, 24
CZECH REPUBLIC
Brno: 18
Prague: 28
DENMARK
Copenhagen: 18
FRANCE
Dijon: 18
Grenoble: 25
Lyon: 18
GERMANY
Berlin: 25
Bremen: 21
Dresden: 43
Freiburg: 18
Hannover: 30
Heidelberg: 18
Julich: 28
Kiel: 22
Munich: 23
Ulm: 44
IRELAND
Dublin: 18
ISRAEL
Jerusalem: 38
Ramat Gan: 7
Tel-Aviv: 18
ITALY
Ancona: 20
Bari: 20
Bologna: 20
Bosisio Parini:
Cagliari: 18
Como: 20
Cuneo: 20
Desio: 20
Florence: 20
Genoa: 20
Lecco: 20
Magenta: 20
Milan: 20
Modena: 29
Monza: 20
Naples: 20
Padova: 20
Palermo: 20
Parma: 20
Pisa: 20
Rome: 20
Rozzano: 20
San Giovanni Rotondo: 20
Treviglio: 20
Trieste: 20, 29
Turin: 20
Udine: 20
Verona: 20
JAPAN
Saitama: 42
Tokyo: 42
LITHUANIA
Vilnius: 19
POLAND
Lodz: 16
Szczecin: 19
Warsaw: 26
Wroclaw: 26
SINGAPORE
Singapore: 4, 18
SOUTH KOREA
Seoul: 4
SPAIN
Barcelona: 18
SWEDEN
Stockholm: 18, 21
Uppsala: 18
SWITZERLAND
Zurich: 26
UNITED KINGDOM
Cambridge: 12, 31
Edinburgh: 40
Liverpool: 17
London: 4
Newcastle: 6
Nottingham: 6
Oxford: 5, 35
UNITED STATES OF AMERICA
Alabama
Birmingham: 6
Arizona
Phoenix: 18
California
Berkeley: 8, 18
Davis: 20
Duarte: 18
Fremont: 18
Irvine: 20
La Jolla: 8, 16, 18
Loma Linda: 9
Los Angeles: 18
Pasadena: 14
San Francisco: 18
Santa Barbara: 16, 28
Stanford: 18, 31
Colorado
Boulder: 10
Denver: 10
Connecticut
New Haven: 18, 20, 28
Florida
Gainesville: 19
Georgia
Athens: 8
Atlanta: 1, 34
Suwanee: 8
Illinois
Evanston: 15, 23
Urbana: 37
Louisiana
New Orleans: 25
Maryland
Baltimore: 25
Bethesda: 2, 18
College Park: 25
Gaithersburg: 25
Massachusetts
Boston: 2, 18, 32, 44
Cambridge: 3, 32, 33, 44
Charlestown: 32
Michigan
Detroit: 18
Minnesota
Minneapolis: 18
Rochester: 18, 19
New Jersey
Princeton: 14
New Mexico
Los Alamos: 26
New York
Manhasset: 19, 20
New York: 6, 11, 18, 19, 36, 38
Palisades: 22
Rochester: 4
Troy: 16
North Carolina
Chapel Hill: 9, 30
Durham: 4, 18
Ohio
Cincinnati: 30
Columbus: 27
Pennsylvania
North Wales: 44
Pittsburgh: 5, 38
South Carolina
Charleston: 39
Tennessee
Memphis: 6, 39
Oak Ridge: 25
Texas
Houston: 18, 19, 20
Utah
Salt Lake City: 18
Virginia
Ashburn: 36
Richmond: 19
Washington
Seattle: 4, 6, 18
Wisconsin
Madison: 27
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]
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 Chemistry (London)
Stuart Cantrill
Tel: +44 20 7014 4018
E-mail: [email protected]
Nature Genetics (New York)
Myles Axton
Tel: +1 212 726 9324
E-mail: [email protected]
Nature Geoscience (London)
Heike Langenber
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 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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