Hot off the presses! Jul 02 Nature

The Jul 02 issue of the Nature is now up on Pubget (About Nature): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• We are all Iranians
  - Nature 460(7251):11-12 (2009)
  Iran's endogenous civil-rights movement needs international solidarity, not political meddling. Academics, universities and non-governmental organizations can help.
• Time for early action
  - Nature 460(7251):12 (2009)
  Carbon dioxide is not the only warming agent worth tackling now in the bid to cool the planet.
• Geosciences: Losing Louisiana
  - Nature 460(7251):14 (2009)
  
• Cancer biology: Double agent
  - Nature 460(7251):14 (2009)
  
• Neuroscience: Early bird learns the tune
  - Nature 460(7251):14 (2009)
  
• Physiology: Ground control
  - Nature 460(7251):14 (2009)
  
• Ecology: Putting height on the map
  - Nature 460(7251):14 (2009)
  
• Evolutionary development: The birth of a thymus
  - Nature 460(7251):14-15 (2009)
  
• Biology: Shell shocker
  - Nature 460(7251):15 (2009)
  
• Chemistry: Fire boxed
  - Nature 460(7251):15 (2009)
  
• Astronomy: Little neighbours
  - Nature 460(7251):15 (2009)
  
• Genomics: Murky associations
  - Nature 460(7251):15 (2009)
  
• Journal club
  - Nature 460(7251):15 (2009)
  
• African science drops down G8 agenda
  - Nature 460(7251):16 (2009)
  Researchers lament poor progress on commitments to developing nations. The G8 summit will boost the fortunes of L'Aquila — but the news might not be so good for African science.PERI-PERCOSSI/EPA/CORBIS In the run-up to the G8 summit meeting in Italy from 8–10 July, African science leaders are counting the cost of unfulfilled commitments to their continent made at previous G8 meetings. At the 2005 Gleneagles Summit in the United Kingdom, the rich G8 nations endorsed many of the proposals put forward by the Commission for Africa, launched by former British prime minister Tony Blair in 2004. These included creating centres of excellence in science and technology across the continent, and setting up African institutes of technology. "To my knowledge, no new centres of excellence have been set up," says Mohamed Hassan, executive director of the Academy of Sciences for the Developing World (TWAS) in Trieste, Italy, and president of the African Academy of Sciences. "It's very disappointing." The agenda of this year's G8 summit, which is being held in the earthquake-ravaged town of L'Aquila, renews the focus on Africa, with goals such as tackling the effects of climate change and safeguarding biodiversity on the continent. Yet support for African science is unlikely to be a priority for discussion, says Hassan. At a G8 satellite meeting on science and international development, organized by TWAS and the Italian foreign ministry and held on 26 June in Trieste, the focus was firmly on Afghanistan. The delegates agreed that international science academies should work with Afghanistan's science ministry to establish a development plan for the coming decade. But African science was not discussed, says Hassan: "I don't think it will be on the G8 agenda." Myles Wickstead, head of the Commission for Africa secretariat until late 2005, also has low expectations for the forthcoming G8 meeting, not least because the Italian government cancelled a meeting of the G8 science and technology ministers that was due to take place on 25 June (see Nature 459, 1041; 2009). "There is very little we can expect for science and technology at the Italian summit," Wickstead says. "What has happened to the concept of African institutes of science and technology?" The United Kingdom's former chief science adviser, David King, who was involved in drawing up the Commission for Africa proposals and is now director of the Smith School of Enterprise and the Environment in Oxford, UK, says that continued pressure needs to be placed on the G8 nations to deliver on their promises. "Questions need to be asked about the priorities set out in Gleneagles," he told Nature. "What has happened to the concept of African institutes of science and technology?" A key stumbling block has been the G8's failure to commit to donating US$3 billion over 10 years to set up the centres and $500 million a year over 10 years to strengthen universities, as recommended by the Commission for Africa in 2005. But Hassan says that some of the blame must rest with the African nations. With the exception of South Africa and possibly Rwanda, African nations will not reach the target agreed in 2003 by the African Union, a confederation of 53 African states, of investing 1% of their gross domestic product in science by 2010, he says. "African governments have to put their house in order first. If they show progress in investing in science and technology, this will encourage donors." Red tape Tensions over who should be responsible for African science-and-technology aid have certainly hampered progress, says Wickstead. Despite high-level discussions in December last year between the two key players — the African Union and its implementing partner, the New Partnership for Africa's Development (NEPAD) — a single fund for African science still does not exist, he says (see Nature 457, 14; 2009). "Africa has not yet developed a comprehensive plan for science that the donor community can get behind and support," he says. Despite this, bioscientists in Africa have benefited from four networks set up by the NEPAD and the African Union since 2003, aided by a Can$30-million (US$26-million) grant from the Canadian government. Diran Makinde, director of the West African Biosciences Network, says that Spain has contributed €3 million (US$4.2 million) and Finland €400,000 to bioscience initiatives in Africa. But he adds that the contribution from G8 nations has been small in comparison to what was promised, and that the networks could face tough times if they are not able to secure longer-term funding. ADVERTISEMENT Calestous Juma, a Kenyan professor of international development at the John F. Kennedy School of Government in Cambridge, Massachusetts, says that a better forum is now needed for discussions about harnessing science for African development. If the momentum generated by Tony Blair before Gleneagles bore little fruit, he says, it is unlikely that a less-engaged Italian leadership will be able to achieve much. Although progress on the G8 commitments to science has been slow, other forums are moving forwards. The European Union, for example, launched a science partnership with the African Union in October 2008. Several initiatives are being funded through the partnership, including grants for Africa researchers that total €36 million over 3 years — with the first call for proposals to be launched at the end of 2009. Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Chief scientist quits California stem-cell agency
  - Nature 460(7251):17 (2009)
  Departure raises questions over leadership at flagship centre. The California Institute for Regenerative Medicine (CIRM) in San Francisco is again under the microscope, following the resignation of its chief scientific officer and a call for its restructuring. Marie Csete: "I felt I would have more impact by advising the leadership of the board on my way out."N. Priestley Marie Csete, a doctor and stem-cell biologist, has resigned from CIRM's top science job, effective from 1 August. The move leaves CIRM without medical leadership as it prepares to issue US$210 million in grants for stem-cell research that aim towards clinical trials. "When it became clear to me that my considered clinical advice was not respected, I concluded that it made no sense for me to stay at CIRM," she says. When Csete left Emory University in Atlanta, Georgia, to join CIRM in March 2008, she gave up her lab and divorced her husband John Doyle. He is a professor at the California Institute of Technology in Pasadena, an institution she would be inviting to apply for research funding and so needed to avoid contravening state conflict-of-interest laws. "We were willing to sacrifice a lot for me to be in a position to make a positive impact at CIRM," she says. "I wanted to see it to the end." Her accomplishments at the agency include restructuring CIRM's grant programmes, cultivating relationships with grantees and laying the groundwork for international collaborations. "Her medical and scientific experience made her a superb proponent of CIRM's main mission, which is to make stem cells medically useful," says Jeanne Loring, a stem-cell researcher at the Burnham Institute in La Jolla, California. "It won't be easy to replace her." In a message to staff, CIRM president Alan Trounson praised Csete's "highly valuable contributions to our science operations". Csete says she hopes her leaving will mark "a new start" for the agency. "I had tried everything I could to change what I think needed to change from the inside, and that was not going to happen," she says. "I felt I would have more impact by stepping away and advising the leadership of the board on my way out about ways to revise the structure and management of the agency to make it more optimal." Csete would not provide details on what changes she feels are needed. But her frustration echoes previous tensions over leadership structure that led in part to the early departure of CIRM's first president, Zach Hall, in 2007. The agency's structure is spearheaded by Robert Klein, CIRM's architect, and includes Trounson and a 29-member governing board. Last year, two state senators asked California's bipartisan, independent oversight agency, the Little Hoover Commission, to study CIRM's governance. On 25 June, the commission reported that CIRM's governance structure "locks in inefficiencies" and "inhibits CIRM's ability to adjust to changing scientific and political landscapes". The commission recommended that CIRM downsize its board to 15 members, add members without ties to CIRM grantees, boost the efficiency and transparency of grant reviews, clarify the overlapping roles of chair and president, and "create succession plans for board leadership", a reference to Klein's statement that he will leave the agency next year. Hall says the recommendations are "useful, thoughtful and should be seriously considered", but says "the leadership of the agency has taken a position that any change at all threatens the entirety of stem-cell research, and that's unfortunate". ADVERTISEMENT Indeed, CIRM said in a statement that it was disappointed with the Little Hoover Commission's recommendations, which would "slow the agency's progress toward cures". But CIRM board member Jeff Sheehy wrote on a blog that CIRM's "knee jerk" reaction, delivered in a statement dated 24 June — before the Hoover group released its final report — "suggests a renegade agency outside the control of its board or the state of California". The report is unlikely to spur immediate change, as the state legislature, which would need to enact many of the recommendations, is preoccupied with California's budget crisis. Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Snapshot: Vanishing meadows
  - Nature 460(7251):17 (2009)
  The dire state of seagrass. J. FREUND Seagrass meadows around the world are in dire shape, according to the first comprehensive global assessment of these economically and biologically essential areas. More than a quarter of all seagrass meadows have disappeared in the past 130 years, says a new synthesis of quantitative data from 215 sites (M. Waycott et al. Proc. Natl Acad. Sci. USA doi:10.1073/pnas.0905620106; 2009). The rate of decline has grown from less than 1% per year before 1940, to 7% per year since 1990. As well as supporting wildlife such as dugong (Dugong dugon, pictured) and green turtles (Chelonia mydas), seagrass meadows also serve as a vital nursery for fish, supporting populations for coral reefs and commercial fisheries. Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• How to fix a broken heart?
  - Nature 460(7251):18-19 (2009)
  Heart disease kills more people than any other condition, yet cell therapies for it remain frustratingly elusive. On page 113.
• Italians sue over stem cells
  - Nature 460(7251):19 (2009)
  Three scientists are appealing against the Italian government's decision to exclude human embryonic stem cells from a recent call for proposals to fund stem-cell biology. The scientists' lawyer, Vittorio Angiolini, who specializes in bioethics and human rights, filed the appeal with Rome's administrative court on 24 June.
• Budget request tackles habitat changes
  - Nature 460(7251):20 (2009)
  The US Fish and Wildlife Service (FWS) is looking to get back on its research feet, in the wake of revelations in recent years that a top official manipulated scientific results involving endangered species. A budget request now wending its way through Congress could provide an 11–14% budget increase, including beefed-up funding to investigate how species will be affected by climate change.
• Lawsuit puts flu-vaccine contract in doubt
  - Nature 460(7251):21 (2009)
  Biotech company sued by creditors. A US office tasked with readying the country for influenza pandemics received an unpleasant surprise last week, when creditors filed a lawsuit intended to force one of its new grantees into bankruptcy. The lawsuit was filed the day before the Biomedical Advanced Research and Development Authority (BARDA) in Washington DC announced it had awarded a US$35-million contract to Protein Sciences, a biotechnology company in Meriden, Connecticut. The contract is to support the development of vaccines against pandemic flu viruses, such as the H1N1 strain circling the globe. The award could be extended to $147 million over five years, and require 50 million doses of vaccine to be produced. But the company's success or failure may depend on the outcome of a lawsuit filed on 22 June by vaccine maker Emergent BioSolutions of Rockville, Maryland, and two other creditors that say Protein Sciences has failed to pay back more than $11 million in loans. Protein Sciences has developed a way to produce flu vaccines in insect cells — a method that some hope will break the industry's reliance on the tried-and-tested but slow process of making them in chicken eggs. Its seasonal-flu vaccine is being considered by the Food and Drug Administration; a decision about its approval could come this year, says chief operating officer Manon Cox. In March 2008, the company received word that it would probably win a contract from BARDA; but then Emergent offered to buy it, and the two firms entered into negotiations. Concerned that the merger might threaten the company's ability to produce an influenza vaccine, BARDA held back its final decision. "Emergent BioSolutions at that time did not have the necessary know-how, resources and people to use the technology that Protein Sciences had developed," says BARDA director Robin Robinson. Negotiations between the two companies collapsed when Protein Sciences' shareholders voted against the agreement, but by then the company had already accepted a $10-million loan from Emergent. BARDA conducted two financial audits of Protein Sciences last year, Robinson says, and assured itself that the company would be able to pay back its creditors. But Cox says that the financial climate, and lawsuits filed by Emergent after negotiations broke down, made it difficult to raise funds. ADVERTISEMENT Although the loan was due to be repaid at the end of May, Robinson says he had not expected a lawsuit, and he declined to speculate about the fate of BARDA's contract until the case is heard in court later this month. "Basically, we just see this as feuding between two companies," he says. BARDA, meanwhile, will receive an influx of funds from the $7.7-billion spending on pandemic flu that was signed into law last week. Spending on vaccines is not specified, but the money will be used mainly for the public-health programmes and supplies needed to cope with the H1N1 pandemic, says Robinson, without sacrificing its investments in vaccine technology. Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• UK Met Office hit by cuts to climate project
  - Nature 460(7251):21 (2009)
  The UK government has slashed its financial support for the Met Office's climate programme. The move came in the same week that prime minister Gordon Brown laid out ambitious talk of a US$100-billion fund to help developing countries to cope with climate change (see "_Nature _ doi:10.
• Indian university system overhauled
  - Nature 460(7251):22 (2009)
  National commission set to regulate higher education. Indian universities are likely to find themselves under a new oversight body, human resource development minister Kapil Sibal announced last week. Physicist Yash Pal led the committee that recommended setting up a six-member National Commission for Higher Education and Research (NCHER) to reform higher education. The commission would replace nearly a dozen regulatory bodies and bring all streams of higher education, including engineering, medicine, agriculture and law, under its purview. Many Indian scientists welcomed the move, although some are sceptical. Chemist C. N. R. Rao, former science adviser to Prime Minister Manmohan Singh, says that the current infrastructure has led to graduates without the quality to compete on the world stage. India ranks behind such smaller powerhouses as Taiwan, Singapore and South Korea in the number of high-impact scientific papers published. Adding another regulatory body is unlikely to address such problems, Rao says. "It is fine if it remains just an advisory body," he says. "But if it starts controlling the entire educational sectors from medicine to law, it will be simply weighed down by bureaucracy." According to the committee's report, the NCHER will create new norms for accrediting universities. Approvals for "deemed" universities, which are aspiring independent institutions wanting university status, will be stopped, and the existing ones must be re-accredited. India's deemed universities have mushroomed in recent years, to 123 in total. The report also proposes bolstering funding of state universities and encourages recruitment of foreign faculty. Pushpa Bhargava, a biologist and founder of the Centre for Cellular and Molecular Biology in Hyderabad, says the recommendations "should be implemented seriously". As an example of shoddy accreditation, he says he has been approached by a private college that asked to borrow academic staff on a short-term basis so that it could have professors on hand for a three-day visit from regulatory body the All India Council for Technical Education. That council, along with others, would be subsumed under the new commission. ADVERTISEMENT Sibal said the recommendations would be implemented within 100 days. The NCHER's chairman will be appointed by President Pratibha Patil, and its members selected by a search committee that will include the prime minister and the leader of the opposition. "It is a very good thing that has happened for educational reform," Mamannamana Vijayan, president of the Indian National Science Academy, told Nature. "We now need to turn to the question of how to reform the structure of Indian science." Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Impasse at talks leaves whales high and dry
  - Nature 460(7251):23 (2009)
  
• Key polar research centres sign up to cooperative deal
  - Nature 460(7251):23 (2009)
  
• Recession deals a glancing blow to nanomaterials
  - Nature 460(7251):23 (2009)
  
• African institutions gain support networks
  - Nature 460(7251):23 (2009)
  African research, by many measures the least competitive in the world, got a financial pick-me-up this week. On 2 July, the UK Wellcome Trust launched a £30-million (US$50-million) plan to support more than 50 institutions across the continent, organized in themed networks that will study water and sanitation, infectious diseases and population health. "There are other collaborations and networks but the lack of research capacity in Africa is a huge problem and it's going to take more than one initiative to achieve this," says Jimmy Whitworth, the Wellcome Trust's head of international activities. The funding will be used to revamp laboratories, to train laboratory personnel and to support competitive grants aimed at encouraging African scientists to remain working in their home countries. Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Soundbites: Talking climate targets
  - Nature 460(7251):23 (2009)
  Scotland's climate-change minister, Stewart Stevenson, as his country passed legislation on 24 June to reduce greenhouse-gas emissions by 42% by 2020, and by 80% by 2050. US President Barack Obama hails the passage of the Waxman-Markey energy and climate-change bill through the House of Representatives on 26 June — by the narrow margin of 219 to 212 votes (see Nature 459, 493; 2009). UK prime minister Gordon Brown suggests on 26 June that an international fund of US$100 billion a year will be needed by 2020 to help developing countries to mitigate and adapt to climate change (see Nature doi:10.1038/news.2009.604; 2009). Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Heritage alert for Central American reef
  - Nature 460(7251):23 (2009)
  N. WU/SCIENCE FACTION/CORBIS Belize's barrier-reef system (pictured) — the largest of its kind in the Northern Hemisphere — has been put on a danger list by the World Heritage Committee to encourage international support for its preservation. The committee, part of the United Nations Educational, Scientific and Cultural Organization (UNESCO), included the reef because it is threatened by development and the cutting back of mangroves. It has been on the World Heritage List of naturally important sites since 1996. Also placed on the danger list is the Los Katios National Park in Colombia, which is at risk from logging. UNESCO added a further two natural sites to its World Heritage List: the Wadden Sea wetlands belonging to Germany and the Netherlands, and the Dolomites mountain range in Italy. Add your own comment You can be as critical or controversial as you like, but please don't get personal or offensive, and do keep it brief. Remember this is for feedback and discussion - not for publishing papers, press releases or advertisements, for example. If you ramble on in an annoying way too often, we may remove your posting privileges. You need to be registered with Nature to leave a comment. Please log in or register as a new user. You will be re-directed back to this page. * Log in / register
• Don't cry politicization
  - Nature 460(7251):24 (2009)
  Last month, three of the leading proponents of biomedical research in the US Congress levelled an unlikely charge at President Barack Obama's proposal to focus health research on cancer and autism: they said the plan amounted to the 'politicization' of science. The first response to such a claim might be to marvel that any member of Congress could even pretend to take umbrage that a politician was involved in allocating money to the National Institutes of Health (NIH).
• Nuclear energy: The hybrid returns
  - Nature 460(7251):25-28 (2009)
  It seems like such a natural fit. Nuclear fission has proved that it can produce greenhouse-gas-free energy: the roughly 440 nuclear plants operating in 31 countries around the world collectively have the capacity to generate some 370 gigawatts of electrical power, or about 15% of the global total.
• Atmospheric science: Climate's smoky spectre
  - Nature 460(7251):29-32 (2009)
  Steve Warren spent his spring break island-hopping with a couple of friends, but they didn't go to bask in the sun. Instead, his team from the University of Washington in Seattle toured the Canadian Arctic, digging pits in the snow and collecting hundreds of samples to take back to the lab.
• Invitation to help compile an index of biodiversity in cities
  - Nature 460(7251):33 (2009)
  In 2002 the World Summit on Sustainable Development assigned to the Convention on Biological Diversity (CBD) a target for 2010 of significantly reducing the rate of biodiversity loss. If we hope to chart positive trends in biodiversity conservation, then cities must now make a pivotal contribution.
• We must reverse the Bush legacy of stem-cell problems
  - Nature 460(7251):33 (2009)
  Your Editorial 'Stem-cell clarity' (Nature 459, 615–616; 2009) calls for reason in deliberations by the US National Institutes of Health (NIH) on public comments about proposed NIH guidelines for stem-cell research.
• The pleasure and importance of printed journals
  - Nature 460(7251):33 (2009)
  I am shocked to read in Nature News online that the American Chemical Society intends to stop all personal subscriptions to its printed journals by 2010, and to start introducing major changes this year ('Chemistry publisher moving towards online-only journals' http://tinyurl.com/llae53).
• When DNA goes on trial
  - Nature 460(7251):34-35 (2009)
  The science of DNA profiling is firm, but the way that the adversarial justice system interprets probability can cause controversy, argues Peter Gill.
• Evolutionary embryos
  - Nature 460(7251):35-36 (2009)
  A central question in biology is how multicellular organisms develop from a single cell and how development is controlled. The standard view is that the process is deterministic, following directives governed by information located in the genome.
• Stuffed spectacular
  - Nature 460(7251):36-37 (2009)
  Roll up, roll up! See the giant Indricotherium, a plant-eating mammal from Mongolia that weighed as much as four adult African elephants!
• Evolution's influence on art nouveau
  - Nature 460(7251):37 (2009)
  Characterized by sinuous shapes and subtle colours, the glass vases, bowls and other objects made by the nineteenth-century French artist-designer Emile Gallé and his factory are still highly regarded. But his interest in botany and evolution is less well known.
• Developmental biology: A cellular view of regeneration
  - Nature 460(7251):39-40 (2009)
  How the salamander regrows an entire limb after injury has flummoxed the wisest of scientists. A closer look at the cells involved in limb regeneration shows that remembering past origins may be crucial for this feat.
• Biogeochemistry: Climatic plant power
  - Nature 460(7251):40-41 (2009)
  Levels of atmospheric carbon dioxide constrain vegetation types and thus also non-biological uptake during rock weathering. That's the reasoning used to explain why CO2 levels did not fall below a certain point in the Miocene.
• Immunology: A metabolic switch to memory
  - Nature 460(7251):41-42 (2009)
  Two therapeutic drugs have been found to enhance memory in immune cells called T cells, apparently by altering cellular metabolism. Are changes in T-cell metabolism the key to generating long-lived immune memory?
• Nanooptics: Photons pushed together
  - Nature 460(7251):42-44 (2009)
  Photons don't interact well with each other, which is a real headache for researchers developing all-optical transistors for computing applications. But a single molecule can mediate photon–photon affairs.
• Cell biology: The not-so-odd couple
  - Nature 460(7251):44-45 (2009)
  Actively dividing cells do so at a risk — with each division, chromosome ends tend to shorten. Pairing proteins that promote cell division with a chromosome-end repair factor is a smart way to solve this problem.
• Applied physics: A leak of information
  - Nature 460(7251):45-46 (2009)
  As capacitors, the ubiquitous components of electronic circuitry, get smaller, keeping them insulating is a challenge. But that's not necessarily bad news — some conductivity might be just the thing for data storage.
• Obituary: Robert Furchgott (1916–2009)
  - Nature 460(7251):47 (2009)
  Nobel laureate who pioneered research into nitric oxide.
• Elite and stochastic models for induced pluripotent stem cell generation
  - Nature 460(7251):49-52 (2009)
  Induced pluripotent stem cells offer unprecedented potential for disease research, drug screening, toxicology and regenerative medicine. However, the process of reprogramming is inefficient and often incomplete. Here I consider reasons for bottlenecks in induced pluripotent stem cell generation, and propose a model in which most or all cells have the potential to become pluripotent.
• Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells
  Raya A Rodríguez-Pizà I Guenechea G Vassena R Navarro S Barrero MJ Consiglio A Castellà M Río P Sleep E González F Tiscornia G Garreta E Aasen T Veiga A Verma IM Surrallés J Bueren J Belmonte JC - Nature 460(7251):53-59 (2009)
  The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and provided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great therapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value fo! r cell therapy applications.
• Cells keep a memory of their tissue origin during axolotl limb regeneration
  - Nature 460(7251):60-65 (2009)
  During limb regeneration adult tissue is converted into a zone of undifferentiated progenitors called the blastema that reforms the diverse tissues of the limb. Previous experiments have led to wide acceptance that limb tissues dedifferentiate to form pluripotent cells. Here we have reexamined this question using an integrated GFP transgene to track the major limb tissues during limb regeneration in the salamander Ambystoma mexicanum (the axolotl). Surprisingly, we find that each tissue produces progenitor cells with restricted potential. Therefore, the blastema is a heterogeneous collection of restricted progenitor cells. On the basis of these findings, we further demonstrate that positional identity is a cell-type-specific property of blastema cells, in which cartilage-derived blastema cells harbour positional identity but Schwann-derived cells do not. Our results show that the complex phenomenon of limb regeneration can be achieved without complete dedifferentiation! to a pluripotent state, a conclusion with important implications for regenerative medicine.
• Telomerase modulates Wnt signalling by association with target gene chromatin
  - Nature 460(7251):66-72 (2009)
  Stem cells are controlled, in part, by genetic pathways frequently dysregulated during human tumorigenesis. Either stimulation of Wnt/-catenin signalling or overexpression of telomerase is sufficient to activate quiescent epidermal stem cells in vivo, although the mechanisms by which telomerase exerts these effects are not understood. Here we show that telomerase directly modulates Wnt/-catenin signalling by serving as a cofactor in a -catenin transcriptional complex. The telomerase protein component TERT (telomerase reverse transcriptase) interacts with BRG1 (also called SMARCA4), a SWI/SNF-related chromatin remodelling protein, and activates Wnt-dependent reporters in cultured cells and in vivo. TERT serves an essential role in formation of the anterior–posterior axis in Xenopus laevis embryos, and this defect in Wnt signalling manifests as homeotic transformations in the vertebrae of Tert -/- mice. Chromatin immunoprecipitation of the endogenous TERT protein from ! mouse gastrointestinal tract shows that TERT physically occupies gene promoters of Wnt-dependent genes. These data reveal an unanticipated role for telomerase as a transcriptional modulator of the Wnt/-catenin signalling pathway.
• An intermediate-mass black hole of over 500 solar masses in the galaxy ESO 243-49
  - Nature 460(7251):73-75 (2009)
  Ultraluminous X-ray sources are extragalactic objects located outside the nucleus of the host galaxy with bolometric luminosities1 exceeding 1039 erg s-1. These extreme luminosities—if the emission is isotropic and below the theoretical (Eddington) limit, where the radiation pressure is balanced by the gravitational pressure—imply the presence of an accreting black hole with a mass of 102–105 solar masses (). The existence of such intermediate-mass black holes is in dispute, and though many candidates have been proposed, none are widely accepted as definitive. Here we report the detection of a variable X-ray source with a maximum 0.2–10 keV luminosity of up to 1.1 1042 erg s-1 in the edge-on spiral galaxy ESO 243-49, with an implied conservative lower limit for the mass of the black hole of 500.
• A single-molecule optical transistor
  - Nature 460(7251):76-80 (2009)
  The transistor is one of the most influential inventions of modern times and is ubiquitous in present-day technologies. In the continuing development of increasingly powerful computers as well as alternative technologies based on the prospects of quantum information processing, switching and amplification functionalities are being sought in ultrasmall objects, such as nanotubes, molecules or atoms1, 2, 3, 4, 5, 6, 7, 8, 9. Among the possible choices of signal carriers, photons are particularly attractive because of their robustness against decoherence, but their control at the nanometre scale poses a significant challenge as conventional nonlinear materials become ineffective. To remedy this shortcoming, resonances in optical emitters can be exploited, and atomic ensembles have been successfully used to mediate weak light beams7. However, single-emitter manipulation of photonic signals has remained elusive and has only been studied in high-finesse microcavities10, 11, ! 12, 13 or waveguides8, 14. Here we demonstrate that a single dye molecule can operate as an optical transistor and coherently attenuate or amplify a tightly focused laser beam, depending on the power of a second 'gating' beam that controls the degree of population inversion. Such a quantum optical transistor has also the potential for manipulating non-classical light fields down to the single-photon level. We discuss some of the hurdles along the road towards practical implementations, and their possible solutions.
• Giant tunnel electroresistance for non-destructive readout of ferroelectric states
  - Nature 460(7251):81-84 (2009)
  Ferroelectrics possess a polarization that is spontaneous, stable and electrically switchable1, and submicrometre-thick ferroelectric films are currently used as non-volatile memory elements with destructive capacitive readout2. Memories based on tunnel junctions with ultrathin ferroelectric barriers would enable non-destructive resistive readout3. However, the achievement of room-temperature polarization stability and switching at very low thickness is challenging4, 5. Here we use piezoresponse force microscopy at room temperature to show robust ferroelectricity down to 1 nm in highly strained BaTiO3 films; we also use room-temperature conductive-tip atomic force microscopy to demonstrate resistive readout of the polarization state through its influence on the tunnel current6, 7. The resulting electroresistance effect scales exponentially with ferroelectric film thickness, reaching 75,000% at 3 nm. Our approach exploits the otherwise undesirable leakage current—domi! nated by tunnelling at these very low thicknesses—to read the polarization state without destroying it. We demonstrate scalability down to 70 nm, corresponding to potential densities of >16 Gbit inch-2. These results pave the way towards ferroelectric memories with simplified architectures, higher densities and faster operation, and should inspire further exploration of the interplay between quantum tunnelling and ferroelectricity at the nanoscale.
• The role of terrestrial plants in limiting atmospheric CO2 decline over the past 24 million years
  - Nature 460(7251):85-88 (2009)
  Environmental conditions during the past 24 million years are thought to have been favourable for enhanced rates of atmospheric carbon dioxide drawdown by silicate chemical weathering1, 2, 3, 4, 5, 6, 7. Proxy records indicate, however, that the Earth's atmospheric carbon dioxide concentrations did not fall below about 200–250 parts per million during this period8. The stabilization of atmospheric carbon dioxide concentrations near this minimum value suggests that strong negative feedback mechanisms inhibited further drawdown of atmospheric carbon dioxide by high rates of global silicate rock weathering. Here we investigate one possible negative feedback mechanism, occurring under relatively low carbon dioxide concentrations and in warm climates, that is related to terrestrial plant productivity and its role in the decomposition of silicate minerals9, 10, 11. We use simulations of terrestrial and geochemical carbon cycles and available experimental evidence to show t! hat vegetation activity in upland regions of active orogens was severely limited by near-starvation of carbon dioxide in combination with global warmth over this period. These conditions diminished biotic-driven silicate rock weathering and thereby attenuated an important long-term carbon dioxide sink. Although our modelling results are semi-quantitative and do not capture the full range of biogeochemical feedbacks that could influence the climate, our analysis indicates that the dynamic equilibrium between plants, climate and the geosphere probably buffered the minimum atmospheric carbon dioxide concentrations over the past 24 million years.
• Seismic reflection images of a near-axis melt sill within the lower crust at the Juan de Fuca ridge
  - Nature 460(7251):89-93 (2009)
  The oceanic crust extends over two-thirds of the Earth's solid surface, and is generated along mid-ocean ridges from melts derived from the upwelling mantle1. The upper and middle crust are constructed by dyking and sea-floor eruptions originating from magma accumulated in mid-crustal lenses at the spreading axis2, 3, 4, 5, 6, but the style of accretion of the lower oceanic crust is actively debated7. Models based on geological and petrological data from ophiolites propose that the lower oceanic crust is accreted from melt sills intruded at multiple levels between the Moho transition zone (MTZ) and the mid-crustal lens8, 9, 10, 11, consistent with geophysical studies that suggest the presence of melt within the lower crust12, 13, 14, 15, 16. However, seismic images of molten sills within the lower crust have been elusive. Until now, only seismic reflections from mid-crustal melt lenses2, 17, 18 and sills within the MTZ have been described19, suggesting that melt is eff! iciently transported through the lower crust. Here we report deep crustal seismic reflections off the southern Juan de Fuca ridge that we interpret as originating from a molten sill at present accreting the lower oceanic crust. The sill sits 5–6 km beneath the sea floor and 850–900 m above the MTZ, and is located 1.4–3.2 km off the spreading axis. Our results provide evidence for the existence of low-permeability barriers to melt migration within the lower section of modern oceanic crust forming at intermediate-to-fast spreading rates, as inferred from ophiolite studies9, 10.
• Neural mechanisms of rapid natural scene categorization in human visual cortex
  - Nature 460(7251):94-97 (2009)
  The visual system has an extraordinary capability to extract categorical information from complex natural scenes. For example, subjects are able to rapidly detect the presence of object categories such as animals or vehicles in new scenes that are presented very briefly1, 2. This is even true when subjects do not pay attention to the scenes and simultaneously perform an unrelated attentionally demanding task3, a stark contrast to the capacity limitations predicted by most theories of visual attention4, 5. Here we show a neural basis for rapid natural scene categorization in the visual cortex, using functional magnetic resonance imaging and an object categorization task in which subjects detected the presence of people or cars in briefly presented natural scenes. The multi-voxel pattern of neural activity in the object-selective cortex evoked by the natural scenes contained information about the presence of the target category, even when the scenes were task-irrelevant ! and presented outside the focus of spatial attention. These findings indicate that the rapid detection of categorical information in natural scenes is mediated by a category-specific biasing mechanism in object-selective cortex that operates in parallel across the visual field, and biases information processing in favour of objects belonging to the target object category.
• Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase
  - Nature 460(7251):98-102 (2009)
  With 8.9 million new cases and 1.7 million deaths per year, tuberculosis is a leading global killer that has not been effectively controlled1, 2. The causative agent, Mycobacterium tuberculosis, proliferates within host macrophages where it modifies both its intracellular and local tissue environment, resulting in caseous granulomas with incomplete bacterial sterilization3, 4. Although infection by various mycobacterial species produces a cyclic AMP burst within macrophages that influences cell signalling, the underlying mechanism for the cAMP burst remains unclear5, 6, 7. Here we show that among the 17 adenylate cyclase genes present in M. tuberculosis, at least one (Rv0386) is required for virulence. Furthermore, we demonstrate that the Rv0386 adenylate cyclase facilitates delivery of bacterial-derived cAMP into the macrophage cytoplasm. Loss of Rv0386 and the intramacrophage cAMP it delivers results in reductions in TNF- production via the protein kinase A and cAMP ! response-element-binding protein pathway, decreased immunopathology in animal tissues, and diminished bacterial survival. Direct intoxication of host cells by bacterial-derived cAMP may enable M. tuberculosis to modify both its intracellular and tissue environments to facilitate its long-term survival.
• Enhancing CD8 T-cell memory by modulating fatty acid metabolism
  - Nature 460(7251):103-107 (2009)
  CD8 T cells, which have a crucial role in immunity to infection and cancer, are maintained in constant numbers, but on antigen stimulation undergo a developmental program characterized by distinct phases encompassing the expansion and then contraction of antigen-specific effector (TE) populations, followed by the persistence of long-lived memory (TM) cells1, 2. Although this predictable pattern of CD8 T-cell responses is well established, the underlying cellular mechanisms regulating the transition to TM cells remain undefined1, 2. Here we show that tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6), an adaptor protein in the TNF-receptor and interleukin-1R/Toll-like receptor superfamily, regulates CD8 TM-cell development after infection by modulating fatty acid metabolism. We show that mice with a T-cell-specific deletion of TRAF6 mount robust CD8 TE-cell responses, but have a profound defect in their ability to generate TM cells that is characterized b! y the disappearance of antigen-specific cells in the weeks after primary immunization. Microarray analyses revealed that TRAF6-deficient CD8 T cells exhibit altered expression of genes that regulate fatty acid metabolism. Consistent with this, activated CD8 T cells lacking TRAF6 display defective AMP-activated kinase activation and mitochondrial fatty acid oxidation (FAO) in response to growth factor withdrawal. Administration of the anti-diabetic drug metformin restored FAO and CD8 TM-cell generation in the absence of TRAF6. This treatment also increased CD8 TM cells in wild-type mice, and consequently was able to considerably improve the efficacy of an experimental anti-cancer vaccine.
• mTOR regulates memory CD8 T-cell differentiation
  - Nature 460(7251):108-112 (2009)
  Memory CD8 T cells are a critical component of protective immunity, and inducing effective memory T-cell responses is a major goal of vaccines against chronic infections and tumours1, 2, 3. Considerable effort has gone into designing vaccine regimens that will increase the magnitude of the memory response, but there has been minimal emphasis on developing strategies to improve the functional qualities of memory T cells4. Here we show that mTOR (mammalian target of rapamycin5, also known as FRAP1) is a major regulator of memory CD8 T-cell differentiation, and in contrast to what we expected, the immunosuppressive drug rapamycin has immunostimulatory effects on the generation of memory CD8 T cells. Treatment of mice with rapamycin following acute lymphocytic choriomeningitis virus infection enhanced not only the quantity but also the quality of virus-specific CD8 T cells. Similar effects were seen after immunization of mice with a vaccine based on non-replicating virus-l! ike particles. In addition, rapamycin treatment also enhanced memory T-cell responses in non-human primates following vaccination with modified vaccinia virus Ankara. Rapamycin was effective during both the expansion and contraction phases of the T-cell response; during the expansion phase it increased the number of memory precursors, and during the contraction phase (effector to memory transition) it accelerated the memory T-cell differentiation program. Experiments using RNA interference to inhibit expression of mTOR, raptor (also known as 4932417H02Rik) or FKBP12 (also known as FKBP1A) in antigen-specific CD8 T cells showed that mTOR acts intrinsically through the mTORC1 (mTOR complex 1) pathway to regulate memory T-cell differentiation. Thus these studies identify a molecular pathway regulating memory formation and provide an effective strategy for improving the functional qualities of vaccine- or infection-induced memory T cells.
• Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages
  - Nature 460(7251):113-117 (2009)
  The generation and expansion of diverse cardiovascular cell lineages is a critical step during human cardiogenesis, with major implications for congenital heart disease. Unravelling the mechanisms for the diversification of human heart cell lineages has been hampered by the lack of genetic tools to purify early cardiac progenitors and define their developmental potential1, 2, 3, 4. Recent studies in the mouse embryo have identified a multipotent cardiac progenitor that contributes to all of the major cell types in the murine heart5, 6, 7, 8. In contrast to murine development, human cardiogenesis has a much longer onset of heart cell lineage diversification and expansion, suggesting divergent pathways. Here we identify a diverse set of human fetal ISL1+ cardiovascular progenitors that give rise to the cardiomyocyte, smooth muscle and endothelial cell lineages. Using two independent transgenic and gene-targeting approaches in human embryonic stem cell lines, we show that! purified ISL1+ primordial progenitors are capable of self-renewal and expansion before differentiation into the three major cell types in the heart. These results lay the foundation for the generation of human model systems for cardiovascular disease and novel approaches for human regenerative cardiovascular medicine.
• A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells
  - Nature 460(7251):118-122 (2009)
  The cytokine leukaemia inhibitory factor (LIF) integrates signals into mouse embryonic stem (ES) cells to maintain pluripotency. Although the Jak–Stat3 pathway is essential and sufficient to mediate LIF signals1, 2, it is still unclear how these signals are linked to the core circuitry of pluripotency-associated transcription factors, consisting of Oct3/4 (also called Pou5f1), Sox2 and Nanog 3, 4. Here we show that two LIF signalling pathways are each connected to the core circuitry via different transcription factors. In mouse ES cells, Klf4 is mainly activated by the Jak–Stat3 pathway and preferentially activates Sox2, whereas Tbx3 is preferentially regulated by the phosphatidylinositol-3-OH kinase–Akt and mitogen-activated protein kinase pathways and predominantly stimulates Nanog. In the absence of LIF, artificial expression of Klf4 or Tbx3 is sufficient to maintain pluripotency while maintaining the expression of Oct3/4. Notably, overexpression of Nanog supp! orts LIF-independent self-renewal of mouse ES cells in the absence of Klf4 and Tbx3 activity. Therefore, Klf4 and Tbx3 are involved in mediating LIF signalling to the core circuitry but are not directly associated with the maintenance of pluripotency, because ES cells keep pluripotency without their expression in the particular context.
• Genome-wide silencing in Drosophila captures conserved apoptotic effectors
  Chew SK Chen P Link N Galindo KA Pogue K Abrams JM - Nature 460(7251):123-127 (2009)
  Apoptosis is a conserved form of programmed cell death firmly established in the aetiology, pathogenesis and treatment of many human diseases. Central to the core machinery of apoptosis are the caspases and their proximal regulators. Current models for caspase control involve a balance of opposing elements, with variable contributions from positive and negative regulators among different cell types and species1. To advance a comprehensive view of components that support caspase-dependent cell death, we conducted a genome-wide silencing screen in the Drosophila model. Our strategy used a library of double-stranded RNAs together with a chemical antagonist of Inhibitor of apoptosis proteins (IAPs) that simulates the action of native regulators in the Reaper and Smac (also known as Diablo) families2. Here we present a highly validated set of targets that is necessary for death provoked by several stimuli. Among these, Tango7 is identified as a new effector. Cells depleted ! for this gene resisted apoptosis at a step before the induction of effector caspase activity, and the directed silencing of Tango7 in Drosophila prevented caspase-dependent programmed cell death. Unlike known apoptosis regulators in this model system3, Tango7 activity did not influence stimulus-dependent loss of Drosophila DIAP1 (also known as th and IAP1), but instead regulated levels of the apical caspase Dronc (Nc). Similarly, the human Tango7 counterpart, PCID1 (also known as EIF3M), impinged on caspase 9, revealing a new regulatory axis affecting the apoptosome.
• The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting
  - Nature 460(7251):128-132 (2009)
  Pluripotency of embryonic stem (ES) cells is controlled by defined transcription factors1, 2. During differentiation, mouse ES cells undergo global epigenetic reprogramming, as exemplified by X-chromosome inactivation (XCI) in which one female X chromosome is silenced to achieve gene dosage parity between the sexes3, 4, 5. Somatic XCI is regulated by homologous X-chromosome pairing6, 7 and counting8, 9, 10, and by the random choice of future active and inactive X chromosomes. XCI and cell differentiation are tightly coupled11, as blocking one process compromises the other8, 12 and dedifferentiation of somatic cells to induced pluripotent stem cells is accompanied by X chromosome reactivation2. Recent evidence suggests coupling of Xist expression to pluripotency factors occurs13, but how the two are interconnected remains unknown. Here we show that Oct4 (also known as Pou5f1)14 lies at the top of the XCI hierarchy, and regulates XCI by triggering X-chromosome pairing an! d counting. Oct4 directly binds Tsix and Xite, two regulatory noncoding RNA genes of the X-inactivation centre15, 16, and also complexes with XCI trans-factors, Ctcf and Yy1 (ref. 17), through protein–protein interactions. Depletion of Oct4 blocks homologous X-chromosome pairing and results in the inactivation of both X chromosomes in female cells. Thus, we have identified the first trans-factor that regulates counting, and ascribed new functions to Oct4 during X-chromosome reprogramming.
• A Breederax for Dalia
  - Nature 460(7251):140 (2009)
  All play and no work is a recipe for disaster.