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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 Nature: Stem cell genetic reprogramming
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.
Juan Carlos Izpisúa Belmonte (The Salk Institute for Biological Studies, La Jolla, CA, USA)
Tel: +1 858 453 4100, ext. 1130; E-mail: [email protected]
 &  Genetics: Genome scan uncovers genetic risks of testis cancer
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.
Michael Stratton (The Wellcome Trust & Sanger Institute, Oxford, UK) Author paper 
Tel: +44 12 2349 4757; E-mail: [email protected]
Katherine Nathanson (University of Pennsylvania, Philadelphia, PA, USA) Author paper 
Tel: +1 215 573 9840; E-mail: [email protected]
 Genetics: Genetic variation influences adverse reaction to common antibiotic
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.
Ann Daly (Newcastle University, UK)
Tel: + 44 191 222 7031; E-mail: [email protected]
 Neuroscience: Replay of neural patterns during sleep
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.
Sidney Wiener (College de France, Paris, France)
Tel: +33 1 44 27 16 21; E-mail: [email protected]
Francesco Battaglia (University of Amsterdam, Netherlands)
Tel: +31 205 257 968; E-mail: [email protected]
 Nature: Let the right pollen in
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.
Vernonica Franklin-Tong (University of Birmingham, UK)
Tel: +44 121 414 3702; E-mail: [email protected]
 Nature: Dynamic ferroelectric memory
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: [email protected]
 Immunology: Suppressing suppressors
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.
Hongbo Chi (St. Jude Children's Research Hospital, Memphis, TN, USA)
Tel: +1 901 595 6282; E-mail: [email protected]
 Chemical Biology: Why does high-throughput screening work?
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.
Brian Shoichet (University of California San Francisco, CA, USA)
Tel: +1 415 514 4126; E-mail: [email protected]
 And finally…Neuroscience: Smells right
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.
Jay Gottfried (Northwestern University Feinberg School of Medicine, Evanston, IL, USA)
Tel: +1 312 503 1834; E-mail: [email protected]
Items from other Nature journals to be published online at the same time and with the same embargo:
 A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome
 Genome-wide silencing in Drosophila captures conserved apoptotic effectors
NATURE BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)
 MicroRNA-mediated species-specific attenuation of influenza A virus
 Proteomic analysis of S-nitrosylation and denitrosylation by resin-assisted capture
NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)
 Phage-encoded combinatorial chemical libraries based on bicyclic peptides
 Glucosinolate engineering identifies a g-glutamyl peptidase
NATURE CHEMISTRY (http://www.nature.com/nchem)
 Specific fluorogenic probes for ozone in biological and atmospheric samples
NATURE GENETICS (http://www.nature.com/naturegenetics)
 Acquired mutations in TET2 are common in myelodysplastic syndromes
 Lin28 promotes transformation and is associated with advanced human malignancies
NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)
 Interleukin 17 acts in synergy with B cell–activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus
 The E3 ubiquitin ligase Nrdp1 ‘preferentially’ promotes TLR-mediated production of type I interferon
Nature MEDICINE (http://www.nature.com/naturemedicine)
 Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis
 Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon–dependent exhaustion
 Biomechanical regulation of blood vessel growth during tissue vascularization
NATURE METHODS (http://www.nature.com/nmeth)
 Reaching the protein folding speed limit with large, sub-microsecond pressure jumps
 Protein interaction platforms: visualization of interacting proteins in yeast
Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)
 Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking
 Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity
Nature PHYSICS (http://www.nature.com/naturephysics)
 Detaching the antiferromagnetic quantum critical point from the Fermi-surface reconstruction in YbRh2Si2
 Experimental onset threshold and magnetic pressure pile-up for 3D reconnection
 Coherent ultrafast magnetism induced by femtosecond laser pulses
 Lévy flights of photons in hot atomic vapours
***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 ***
 Structure of a functional H/ACA ribonucleoprotein pseudouridine synthase bound to a substrate RNA
***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 ***
 Genome sequence of the recombinant protein production host Pichia pastoris
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.
Leuven: 18, 30
Joao Pessoa: 32
Lyon: 10, 20
Magdeburg: 10, 28
Barcelona: 1, 19
Lausanne: 15, 24, 30
Cambridge: 2, 7, 12, 15
UNITED STATES OF AMERICA
La Jolla: 1
San Francisco: 9
Fort Collins: 27
New Haven: 8
New London: 4
Boston: 4, 19, 26
Cambridge: 19, 26
Los Alamos: 30
New York: 4, 13, 19
Durham: 4, 14
Research Triangle: 4
Memphis: 8, 19
Seattle: 3, 19
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)
Tel: +1 212 726 9384; E-mail: [email protected]
Nature Cell Biology (London)
Tel: +44 20 7843 4892; E-mail: [email protected]
Nature Chemical Biology (Boston)
Tel: +1 617 475 9241, E-mail: [email protected]
Nature Chemistry (London)
Tel: +44 20 7014 4018; E-mail: [email protected]
Nature Genetics (New York)
Tel: +1 212 726 9324; E-mail: [email protected]
Nature Geoscience (London)
Tel: +44 20 7843 4042; E-mail: [email protected]
Nature Immunology (New York)
Tel: +1 212 726 9372; E-mail: [email protected]
Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]
Nature Methods (New York)
Tel: +1 212 726 9627; E-mail: [email protected]
Nature Nanotechnology (London)
Tel: +44 20 7014 4019; Email: [email protected]
Nature Neuroscience (New York)
Tel: +1 212 726 9319; E-mail: [email protected]
Nature Photonics (Tokyo)
Tel: +81 3 3267 8776; E-mail: [email protected]
Nature Physics (London)
Tel: +44 20 7843 4555; E-mail: [email protected]
Nature Structural & Molecular Biology (New York)
Tel: +1 212 726 9326; E-mail: [email protected]
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