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Article Released Sun-31st-May-2009 17:31 GMT
Contact: Ruth Institution: Nature Publishing Group
 Stem cell genetic reprogramming

Summaries of newsworthy papers include Genome scan uncovers genetic risks of testis cancer, Genetic variation influences adverse reaction to common antibiotic, Replay of neural patterns during sleep, Let the right pollen in, Dynamic ferroelectric memory, Suppressing suppressors, Why does high-throughput screening work?, Smells right

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 31 May 2009

This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

Nature: Stem cell genetic reprogramming

Genetics: Genome scan uncovers genetic risks of testis cancer

Genetics: Genetic variation influences adverse reaction to common antibiotic

Neuroscience: Replay of neural patterns during sleep

Nature: Let the right pollen in

Nature: Dynamic ferroelectric memory

Immunology: Suppressing suppressors

Chemical Biology: Why does high-throughput screening work?

And finally…Neuroscience: Smells right

· 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] Nature: Stem cell genetic reprogramming
DOI: 10.1038/nature08129

Researchers have generated stem cells from patients with a rare genetic disease, corrected the cells’ defect and reprogrammed to pluripotency, a paper published online in Nature this week reports. .The team have effectively put the cells through gene therapy and, although they did not use them to treat patients, the results have potential value for cell therapy applications.

Fanconi anaemia (FA) is a genetic disorder, manifesting in skeletal anomalies, increased incidence of solid tumours and leukaemias, and bone marrow failure. Juan Carlos Izpisúa Belmonte and colleagues use somatic cells from patients with the disease and corrected the genetic defect by gene therapy. They go on to reprogram them to pluripotency and generate patient-specific induced pluripotent stem (iPS) cells.

The group generated 19 iPS cell lines that appear indistinguishable from human embryonic and iPS cells from healthy individuals. The corrected FA-specific iPS cells can give rise to disease-free haematopoietic progenitors.

Author contact:
Juan Carlos Izpisúa Belmonte (The Salk Institute for Biological Studies, La Jolla, CA, USA)
Tel: +1 858 453 4100, ext. 1130; E-mail: belmonte@salk.edu


[2] & [3] Genetics: Genome scan uncovers genetic risks of testis cancer
DOI: 10.1038/ng.394
DOI: 10.1038/ng.393

Gene variants accounting for some of the differences between men in their risk of developing testis cancer have been identified according to two studies published online this week in Nature Genetics.

Testicular germ cell tumor is the most common malignancy in men between the ages of 15 and 45 years and is five times more common in men of European ancestry than in those of African ancestry. To find gene variants associated with risk of this disease, Michael Stratton, Katherine Nathanson and colleagues examined thousands of men of European ancestry in the UK and US.

One of the risk-associated genes they found – KITLG – also confers differences in skin and hair color. Since KITLG risk variants are more common in populations with recent European origins than in those with recent African origins, these genetic differences may explain some of the population differences in the incidence of the disease.

Author contacts:
Michael Stratton (The Wellcome Trust & Sanger Institute, Oxford, UK) Author paper [2]
Tel: +44 12 2349 4757; E-mail: mrs@sanger.ac.uk

Katherine Nathanson (University of Pennsylvania, Philadelphia, PA, USA) Author paper [3]
Tel: +1 215 573 9840; E-mail: knathans@mail.med.upenn.edu


[4] Genetics: Genetic variation influences adverse reaction to common antibiotic
DOI: 10.1038/ng.379

A common genetic difference between people influences their chance of developing a rare but serious liver injury as a side effect of taking the antibiotic flucloxacillin, as reported in a paper published online in this week’s issue of Nature Genetics.

Flucloxacillin is widely used in Europe and Australia to treat staphylococcus bacterial infections. In their study, Daly and colleagues found that individuals carrying the risk-associated gene variant were 80-100 times more likely than non-carriers to suffer liver injury in response to this antibiotic.

The risk-associated gene variant is relatively common in Northern Europe, but less prevalent in Africa and Asia. Despite being at substantially higher risk than non-carriers, only a small proportion of carriers actually develop liver problems in response to flucloxacillin. Thus, further tests will be needed to determine whether a genetic test would be clinically useful in guiding treatment options.

Author contact:
Ann Daly (Newcastle University, UK)
Tel: + 44 191 222 7031; E-mail: a.k.daly@ncl.ac.uk


[5] Neuroscience: Replay of neural patterns during sleep
DOI: 10.1038/nn.2337

Learning-related patterns of neural activity replay in the brain during sleep, and it has been suggested that this replay may be important for the consolidation of memory. A paper in this week’s Nature Neuroscience reports the first observation of replay activity in the medial prefrontal cortex (mPFC), finding that it coincides with similar patterns in the hippocampus, an area known to contribute to memory formation and retrieval.

Sidney Wiener and colleagues recorded activity from groups of mPFC neurons in rats while they learned which way to turn in a maze and while the animals slept post-learning. As the animals learned their way around the maze, the activity of the mPFC neurons changed. Similar patterns of activity were replayed afterwards while they rats slept. These replay events usually occurred at the same time as stereotyped activity in the hippocampus.

The medial prefrontal cortex is thought to play a critical role in decision-making, and has previously been implicated in memory. These results however are the first to look at its activity during sleep, supporting the idea that neural activity during sleep may play a role in memory consolidation.

Author contacts:
Sidney Wiener (College de France, Paris, France)
Tel: +33 1 44 27 16 21; E-mail: sidney.wiener@college-de-france.fr

Francesco Battaglia (University of Amsterdam, Netherlands)
Tel: +31 205 257 968; E-mail: F.P.Battaglia@uva.nl


[6] Nature: Let the right pollen in
DOI: 10.1038/nature08027

Many of us are familiar with the human response to plant pollen, particularly in the spring. This week in Nature researchers describe the mechanism by which the poppy recognizes pollens and determines whether they are compatible for reproduction or not. The researchers suggest that their work will be useful to plant breeders, making the production of certain hybrids more efficient and economical.

Self-incompatibility is an important mechanism used in many species to prevent inbreeding by ensuring rejection of ‘self’ pollen. Vernonica Franklin-Tong and colleagues clone three alleles of a pollen-expressed gene, PrpS, from Papaver rhoeas, the poppy. They show that it functions as the receptor that recognizes either incompatible or compatible pollens, adding to our knowledge of the evolution of cell–cell recognition systems.

Author contact:
Vernonica Franklin-Tong (University of Birmingham, UK)
Tel: +44 121 414 3702; E-mail: v.e.franklin-tong@bham.ac.uk


[7] Nature: Dynamic ferroelectric memory
DOI: 10.1038/nature08128

In this week’s Nature, researchers resolve some of the problems involved with developing dynamic ferroelectric memory — one of the proposed alternatives to flash memory.

As alternative technologies for non-volatile memories are looked at, ferroelectric random access memory, which uses a ferroelectric layer to read from and write on, is seen as a promising candidate. But current methods are plagued with issues such as storage density and a destructive readout process. Manuel Bibes and colleagues use a thin layer of barium titanate under intense strain and can still detect giant electroresistance. This allows a tunnelling current to run through the layer, making it possible to read out the polarization state of the material.

The physical size of the bits can be scaled down to dimensions that would make possible high densities of 16 gigabits per square inch for these devices. The researchers argue that their new paradigm for polarization readout has the potential to greatly simplify memory architecture.

Author contact :
Manuel Bibes (Unité Mixte de Physique CNRS/Thales, Palaiseau, France)
Tel: +33 1 6941 5849; E-mail: manuel.bibes@thalesgroup.com


[8] Immunology: Suppressing suppressors
DOI: 10.1038/ni.1743

The discovery of an inhibitory signaling circuit that blocks the generation and function of regulatory T cells is reported online in Nature Immunology.

Regulatory T cells prevent the development of autoimmune diseases, such as diabetes, by suppressing unwanted immune responses.

Hongbo Chi and colleagues identify the receptor S1P1 as the crucial inhibitor to these regulatory T cells. Mice lacking S1P1 display an increased number of regulatory T cells and these cells are more suppressive. Conversely, mice overexpressing S1P1 develop autoimmunity as a result of severely diminished number of regulatory T cells.

These results may have clinical importance as presently there are trials underway to manipulate S1P1 function for another reason. The new work broadens the list of activities attributed to S1P1, and identifies the unique sensitivity of regulatory T cells to signaling via this receptor.

Author contact:
Hongbo Chi (St. Jude Children's Research Hospital, Memphis, TN, USA)
Tel: +1 901 595 6282; E-mail: hongbo.chi@stjude.org


[9] Chemical Biology: Why does high-throughput screening work?
DOI: 10.1038/nchembio.180

A new analysis of drug screening libraries reveals a bias towards chemicals likely to be recognized by biological targets. The study, published online this week in Nature Chemical Biology, explains, in part, why these screening techniques have been successful in the past and why they are likely to have important implications for how to increase future success rates of drug discovery.

The dominant approach for finding new drugs, high-throughput screening – HTS – allows researchers to quickly conduct biochemical tests on millions of candidate drugs. The total number of possible chemicals that could be used in a screen is at least 1060. In contrast, a large HTS chemical library used in a pharmaceutical company might contain less than one billionth as many chemicals. With such a small sampling of the total ‘chemical space’ it would seem unlikely that HTS would work. But it does. Brian Shoichet and colleagues have developed a method to quantify the extent to which chemicals in screening libraries look like the chemicals found in nature and they find evidence that screening libraries are substantially biased towards these ‘biological’ chemicals.

The results suggest an important explanation for the current success rate of high-throughput screening and also provide clues as to why it fails for some targets. For these failures, the results suggest new chemicals, currently missing from screening libraries, could be added to increase the likelihood of finding drug leads.

Author contact:
Brian Shoichet (University of California San Francisco, CA, USA)
Tel: +1 415 514 4126; E-mail: shoichet@cgl.ucsf.edu


[10] And finally…Neuroscience: Smells right
DOI: 10.1038/nn.2324

Smells that are similar to each other evoke similar activity pattern in the brain, reports a functional imaging study published online this week in Nature Neuroscience.

Jay Gottfried and colleagues used fMRI to track changes in brain activity in the posterior piriform cortex as people sniffed various odors. They found that when patterns of activity in the posterior piriform cortex were similar, people were more likely to indicate that the odors they were sniffing smelt similar. This was not simply due to the chemical structure of the molecules making up the odors, as odors with very different chemical structures were rated as smelling similar.

This overlap between brain activation and perception was not found in other areas of the brain previously linked to processing smells. This study suggests that the posterior piriform cortex is likely to be critical for categorizing scents.

Author contacts:
Jay Gottfried (Northwestern University Feinberg School of Medicine, Evanston, IL, USA)
Tel: +1 312 503 1834; E-mail: j-gottfried@northwestern.edu

***************************************************************************************************************
Items from other Nature journals to be published online at the same time and with the same embargo:

Nature (http://www.nature.com/nature)

[11] A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome
DOI: 10.1038/nature08086

[12] Genome-wide silencing in Drosophila captures conserved apoptotic effectors
DOI: 10.1038/nature08087

NATURE BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)

[13] MicroRNA-mediated species-specific attenuation of influenza A virus
DOI: 10.1038/nbt.1542

[14] Proteomic analysis of S-nitrosylation and denitrosylation by resin-assisted capture
DOI: 10.1038/nbt.1545

NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)

[15] Phage-encoded combinatorial chemical libraries based on bicyclic peptides
DOI: 10.1038/nchembio.184

[16] Glucosinolate engineering identifies a g-glutamyl peptidase
DOI: 10.1038/nchembio.185

NATURE CHEMISTRY (http://www.nature.com/nchem)

[17] Specific fluorogenic probes for ozone in biological and atmospheric samples
DOI: 10.1038/nchem.240

NATURE GENETICS (http://www.nature.com/naturegenetics)

[18] Acquired mutations in TET2 are common in myelodysplastic syndromes
DOI: 10.1038/ng.391

[19] Lin28 promotes transformation and is associated with advanced human malignancies
DOI: 10.1038/ng.392

NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)

[20] Interleukin 17 acts in synergy with B cell–activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus
DOI: 10.1038/ni.1741

[21] The E3 ubiquitin ligase Nrdp1 ‘preferentially’ promotes TLR-mediated production of type I interferon
DOI: 10.1038/ni.1742

Nature MEDICINE (http://www.nature.com/naturemedicine)

[22] Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis
DOI: 10.1038/nm.1975

[23] Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon–dependent exhaustion
DOI: 10.1038/nm.1973

[24] Biomechanical regulation of blood vessel growth during tissue vascularization
DOI: 10.1038/nm.1985

NATURE METHODS (http://www.nature.com/nmeth)

[25] Reaching the protein folding speed limit with large, sub-microsecond pressure jumps
DOI: 10.1038/nmeth.1336

[26] Protein interaction platforms: visualization of interacting proteins in yeast
DOI: 10.1038/nmeth.1337

Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)

[27] Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking
DOI: 10.1038/nn.2322

[28] Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity
DOI: 10.1038/nn.2338

Nature PHYSICS (http://www.nature.com/naturephysics)

[29] Detaching the antiferromagnetic quantum critical point from the Fermi-surface reconstruction in YbRh2Si2
DOI: 10.1038/nphys1299

[30] Experimental onset threshold and magnetic pressure pile-up for 3D reconnection
DOI: 10.1038/nphys1300

[31] Coherent ultrafast magnetism induced by femtosecond laser pulses
DOI: 10.1038/nphys1285

[32] Lévy flights of photons in hot atomic vapours
DOI: 10.1038/nphys1286

***************************************************************************************************************

***The following paper will be published electronically on Nature Structural and Molecular Biology's website on 28 May at 2000 London time / 1500 US Eastern time. This paper is under embargo until this time, though the rest of the above articles on this release remain under embargo until 31 May at 1800 London time / 1300 US Eastern time ***

[33] Structure of a functional H/ACA ribonucleoprotein pseudouridine synthase bound to a substrate RNA
DOI: 10.1038/nsmb.1624

***************************************************************************************************************

***The following paper was published electronically on Nature Biotechnology's website on 24 May at 1800 London time / 1300 US Eastern time. This paper is no longer under embargo, though the rest of the articles on this release remain under embargo until 31 May at 1800 London time / 1300 US Eastern time ***

[34] Genome sequence of the recombinant protein production host Pichia pastoris
DOI: 10.1038/nbt.1544

***************************************************************************************************************
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: 19

AUSTRIA
Vienna: 22

BELGIUM
Ghent: 34
Ghent-Zwijnaarde: 34
Leuven: 18, 30

BRAZIL
Joao Pessoa: 32

CANADA:
Vancouver: 19

CHINA
Shanghai: 21

DENMARK
Frederiksberg: 16

FRANCE
Bordeaux: 28
Bron: 20
Evry: 7
Lyon: 10, 20
Montpellier: 20
Orsay: 7
Oullins: 20
Palaiseau: 7
Paris: 5
Strasbourg: 31
Toulouse: 22
Valbonne: 32

GERMANY
Berlin: 10
Dresden: 29
Ebersberg: 34
Goettingen: 29
Leipzig: 10
Magdeburg: 10, 28
Mainz: 22
Martinsried: 22
Munich: 22

IRELAND
Dublin: 19

ISRAEL
Rehovot: 22

ITALY
Brescia: 1
Milan: 19

JAPAN
Akita: 23
Osaka: 11
Tokyo: 23

NETHERLANDS
Amsterdam: 5
Nijmegen: 18

PORTUGAL
Coimbra: 22

SPAIN
Barcelona: 1, 19
Bellaterra: 1
Madrid: 1

SWEDEN
Stockholm: 24
Uppsala: 24

SWITZERLAND
Lausanne: 15, 24, 30

UNITED KINGDOM
Birmingham: 6
Cambridge: 2, 7, 12, 15
Cardiff: 6
Dundee: 4
Hinxton: 2
Leeds: 2
Liverpool: 4
London: 4
Manchester:
Newcastle: 4
Nottingham: 4
Sutton: 2
Warwick: 6

UNITED STATES OF AMERICA

California
La Jolla: 1
San Francisco: 9

Colorado
Fort Collins: 27

Connecticut
New Haven: 8
New London: 4

Florida
Tallahassee: 33

Georgia
Athens: 33
Atlanta: 27

Illinois
Chicago: 10
Evanston: 10
Urbana: 25

Maryland
Bethesda: 8

Massachusetts
Boston: 4, 19, 26
Cambridge: 19, 26

New Jersey
Piscataway: 27

New Mexico
Los Alamos: 30

New York
New York: 4, 13, 19

North Carolina
Durham: 4, 14
Research Triangle: 4

Pennsylvania
Philadelphia: 3
Pittsburgh: 17

Tennessee
Memphis: 8, 19

Texas
Dallas: 12
Houston: 11

Washington
Seattle: 3, 19

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: r.twinn@nature.com

Neda Afsarmanesh (Nature New York)
Tel: +1 212 726 9231; E-mail: n.afsarmanesh@natureny.com

Ruth Francis (Head of Press, Nature, London)
Tel: +44 20 7843 4562; E-mail: r.francis@nature.com

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

Nature Biotechnology (New York)
Craig Mak
Tel: +1 212 726 9384; E-mail: c.mak@natureny.com

Nature Cell Biology (London)
Bernd Pulverer
Tel: +44 20 7843 4892; E-mail: cellbio@nature.com

Nature Chemical Biology (Boston)
Andrea Garvey
Tel: +1 617 475 9241, E-mail: chembio@boston.nature.com

Nature Chemistry (London)
Stuart Cantrill
Tel: +44 20 7014 4018; E-mail: s.cantrill@nature.com

Nature Genetics (New York)
Lily Khidr
Tel: +1 212 726 9324; E-mail: natgen@natureny.com

Nature Geoscience (London)
Heike Langenberg
Tel: +44 20 7843 4042; E-mail: h.langenberg@nature.com

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: immunology@natureny.com

Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: medicine@natureny.com

Nature Methods (New York)
Hugh Ash
Tel: +1 212 726 9627; E-mail: methods@natureny.com

Nature Nanotechnology (London)
Peter Rodgers
Tel: +44 20 7014 4019; Email: p.rodgers@nature.com

Nature Neuroscience (New York)
Kalyani Narasimhan
Tel: +1 212 726 9319; E-mail: neurosci@natureny.com

Nature Photonics (Tokyo)
Oliver Graydon
Tel: +81 3 3267 8776; E-mail: o.graydon@natureasia.com

Nature Physics (London)
Alison Wright
Tel: +44 20 7843 4555; E-mail: a.wright@nature.com

Nature Structural & Molecular Biology (New York)
Michelle Montoya
Tel: +1 212 726 9326; E-mail: nsmb@natureny.com

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