There will be a new face at Northern Arizona University (NAU) football games this fall – only the face of this new “team member” is a robot on wheels. Mayo Clinic researchers are working with NAU to test the feasibility of using a telemedicine robot to assess athletes with suspectedconcussions during football games.
With sophisticated robotic technology, use of a specialized remote-controlled camera system allows patients to be “seen” by the neurology specialist, miles away, in real time. The robot is equipped with a specialized camera system and remotely operated by a neurologist from the Mayo Clinic in Phoenix campus who has the ability to assess a player for symptoms and signs of a concussion, and to consult with sideline medical personnel.
Researchers at UNC-Chapel Hill in the Dept. of Biochemistry and Biophysics have transformed cells from human skin into cells that produce insulin, the hormone used to treat diabetes.
The breakthrough may one day lead to new treatments or even a cure for the millions of people affected by the disease, researchers say.
The approach involves reprogramming skin cells into pluripotent stem cells, or cells that can give rise to any other fetal or adult cell type, and then inducing them to differentiate, or transform, into cells that perform a particular function – in this case, secreting insulin.
Several recent studies have shown that cells can be returned to pluripotent state using “defined factors” (specific proteins that control which genes are active in a cell), a technique pioneered by Dr. Shinya Yamanaka, a professor at Kyoto University in Japan.
However, the UNC study is the first to demonstrate that cells reprogrammed in this way can be coaxed to differentiate into insulin-secreting cells. Results of the study are published online in the Journal of Biological Chemistry.
“Not only have we shown that we can reprogram skin cells, but we have also demonstrated that these reprogrammed cells can be differentiated into insulin-producing cells which hold great therapeutic potential for diabetes,” said study lead author Yi Zhang, Ph.D., Howard Hughes Medical Institute investigator, professor of biochemistry and biophysics at UNC and member of the Lineberger Comprehensive Cancer Center.
“Of course, there are many years of additional studies that are required first, but this study provides hope for a cure for all patients with diabetes,” said John Buse, M.D., Ph.D., president of the American Diabetes Association and professor and chief of the endocrinology division in the UNC School of Medicine’s department of medicine.
About 24 million Americans suffer from diabetes, a disease that occurs when the body is unable to produce or use insulin properly. Virtually all patients with type I diabetes, the more severe of the two types, must rely on daily injections of insulin to maintain their blood sugar levels.
Recent research exploring a possible long-term treatment – the transplantation of insulin-producing beta cells into patients – has yielded promising results. But this approach faces its own challenges, given the extreme shortage of matched organ donors and the need to suppress patients’ immune systems.
The work by Zhang and other researchers could potentially address those problems, since insulin-producing cells could be made from diabetic patients’ own reprogrammed cells.
Zhang is collaborating with Buse to obtain skin samples from diabetes patients. He said he hoped his current experiments will take this approach one step closer to a new treatment or even a cure for diabetes.
With funding from the Wellcome Trust and F. Hoffmann La Roche, researchers at the University of Oxford, University of Notre Dame and F. Hoffmann La Roche have identified a mechanism that limits the ability of the body clock to adjust to changes in patterns of light and dark. And the team show that if you block the activity of this gene in mice, they recover faster from disturbances in their daily light/dark cycle that were designed to simulate jet-lag.
Nearly all life on Earth has an internal circadian body clock that keeps us ticking on a 24-hour cycle, synchronising a variety of bodily functions such as sleeping and eating with the cycle of light and dark in a solar day. When we travel to a different time zone our body clock eventually adjusts to the local time. However this can take up to one day for every hour the clock is shifted, resulting in several days of fatigue and discombobulation.
In mammals, the circadian clock is controlled by an area of the brain called the suprachiasmatic nuclei (SCN) which pulls every cell in the body into the same biological rhythm. It receives information from a specialised system in the eyes, separate from the mechanisms we use to ‘see’, which senses the time of day by detecting environmental light, synchronising the clock to local time. Until now, little was known about the molecular mechanisms of how light affects activity in the SCN to ‘tune’ the clock and why it takes so long to adjust when the light cycle changes.
To investigate this, the Oxford University team led by Dr Stuart Peirson and Professor Russell Foster, used mice to examine the patterns of gene expression in the SCN following a pulse of light during the hours of darkness. They identified around 100 genes that were switched on in response to light, revealing a sequence of events that act to retune the circadian clock. Amongst these, they identified one molecule, SIK1, that terminates this response, acting as a brake to limit the effects of light on the clock. When they blocked the activity of SIK1, the mice adjusted faster to changes in light cycle.
Dr Peirson explains: “We’ve identified a system that actively prevents the body clock from re-adjusting. If you think about, it makes sense to have a buffering mechanism in place to provide some stability to the clock. The clock needs to be sure that it is getting a reliable signal, and if the signal occurs at the same time over several days it probably has biological relevance. But it is this same buffering mechanism that slows down our ability to adjust to a new time zone and causes jet lag.”
Disruptions in the circadian system have been linked to chronic diseases including cancer, diabetes, and heart disease, as well as weakened immunity to infections and impaired cognition. More recently, researchers are uncovering that circadian disturbances are a common feature of several mental illnesses, including schizophrenia and bipolar disorder.
Russell Foster, Director of the recently established Oxford University Sleep and Circadian Neuroscience Institute supported by the Wellcome Trust, said: “We’re still several years away from a cure for jet-lag but understanding the mechanisms that generate and regulate our circadian clock gives us targets to develop drugs to help bring our bodies in tune with the solar cycle.Such drugs could potentially have broader therapeutic value for people with mental health issues.”
Eighty percent of people who quit smoking put on an average of 15 pounds, studies have shown, and those pounds are usually attributed to a person trading lighting up for pigging out. But according to the researchers at the Zurich University Hospital, the weight gain may not have to anything to do with an increase in calories. Rather, the weight might be a result of changes in the composition of a person’s intestinal flora after they quit. The study found that when a person stops smoking, the bacteria in their intestinal flora shifts to a type which burns energy more efficiently and breaks down more of what is ingested, thus creating more fat and less waste. The 20 study participants insisted their calorie intake stayed the same or fell after they quit smoking.
It’s been a banner year for PETA India. First, after lengthy discussions with PETA India’s scientists, the nation banned tests on animals for cosmetics and their ingredients. And now, thanks to the hard work of PETA India and scientists with our international affiliates, decision makers in India have officially proposed a ban on testing household products and their ingredients on animals, too!
PETA India Science Policy Adviser Dr. Chaitanya Koduri is a member of the Bureau of Indian Standards committee on household products. With his guidance, the committee recently proposed an amendment to testing regulations that would ban the last and replace it with a superior non-animal testing method. This means that the days of smearing chemicals on guinea pigs are nearly over. The test will be replaced with the more sophisticated—and humane—Human Repeat Insult Patch Test. The committee also proposed that household product manufacturers submit safety data based on for new ingredients.
The final approval for the ban is expected soon from the Drugs Controller General of India. PETA India, with the help of scientists from PETA and PETA U.K., used a similar strategy when it.
n the U.S., tests on animals for cosmetics and household products are still legal, although not required for cosmetics and most household products. However, more than 1,300 compassionate companies have pledged never to harm an animal anywhere in the world for their products, so until North America is cruelty-free, at least your household can be.
In a technical tour de force, Japanese researchers created eggs and sperm in the laboratory. Now, scientists have to determine how to use those cells safely — and ethically.
Since last October, molecular biologist Katsuhiko Hayashi has received around a dozen e-mails from couples, most of them middle-aged, who are desperate for one thing: a baby. One menopausal woman from England offered to come to his laboratory at Kyoto University in Japan in the hope that he could help her to conceive a child. “That is my only wish,” she wrote.
The requests started trickling in after Hayashi published the results of an experiment that he had assumed would be of interest mostly to developmental biologists1. Starting with the skin cells of mice in vitro, he created primordial germ cells (PGCs), which can develop into both sperm and eggs. To prove that these laboratory-grown versions were truly similar to naturally occurring PGCs, he used them to create eggs, then used those eggs to create live mice. He calls the live births a mere ‘side effect’ of the research, but that bench experiment became much more, because it raised the prospect of creating fertilizable eggs from the skin cells of infertile women. And it also suggested that men’s skin cells could be used to create eggs, and that sperm could be generated from women’s cells. (Indeed, after the research was published, the editor of a gay and lesbian magazine e-mailed Hayashi for more information.)
Despite the innovative nature of the research, the public attention surprised Hayashi and his senior professor, Mitinori Saitou. They have spent more than a decade piecing together the subtle details of mammalian gamete production and then recreating that process in vitro — all for the sake of science, not medicine. Their method now allows researchers to create unlimited PGCs, which were previously difficult to obtain, and this regular supply of treasured cells has helped to drive the study of mammalian reproduction. But as they push forward with the scientifically challenging transition from mice to monkeys and humans, they are setting the course for the future of infertility treatments — and perhaps even bolder experiments in reproduction. Scientists and the public are just starting to grapple with the associated ethical issues.
“It goes without saying that [they] really transformed the field in the mouse,” says Amander Clark, a fertility expert at the University of California, Los Angeles. “Now, to avoid derailing the technology before it’s had a chance to demonstrate its usefulness, we have to have conversations about the ethics of making gametes this way.”
Back to the beginning
In the mouse, germ cells emerge just after the first week of embryonic development, as a group of around 40 PGCs2. This little cluster goes on to form the tens of thousands of eggs that female mice have at birth, and the millions of sperm cells that males produce every day, and it will pass on the mouse’s entire genetic heritage. Saitou wanted to understand what signals direct these cells throughout their development.
Over the past decade, he has laboriously identified several genes — including Stella, Blimp1 andPrdm14 — that, when expressed in certain combinations and at certain times, play a crucial part in PGC development3, 4, 5. Using these genes as markers, he was able to select PGCs from among other cells and study what happens to them. In 2009, from experiments at the RIKEN Center for Developmental Biology in Kobe, Japan, he found that when culture conditions are right, adding a single ingredient — bone morphogenetic protein 4 (Bmp4) — with precise timing is enough to convert embryonic cells to PGCs2. To test this principle, he added high concentrations of Bmp4 to embryonic cells. Almost all of them turned into PGCs2. He and other scientists had expected the process to be more complicated.
Saitou’s approach — meticulously following the natural process — was in stark contrast to work that others were doing, says Jacob Hanna, a stem-cell expert at the Weizmann Institute of Science in Rehovot, Israel. Many scientists try to create specific cell types in vitro by bombarding stem cells with signalling molecules and then picking through the resulting mixture of mature cells for the ones they want. But it is never clear by what process these cells are formed or how similar they are to the natural versions. Saitou’s efforts to find out precisely what is needed to make germ cells, to get rid of superfluous signals and to note the exact timing of various molecules at work, impressed his colleagues. “There’s a really beautiful hidden message in this work — that differentiation of cells [in vitro] is really not easy,” says Hanna. Harry Moore, a stem-cell biologist at the University of Sheffield, UK, regards the careful recapitulation of germ-cell development as “a triumph”.
Until 2009, Saitou’s starting point had been cells taken from a live mouse epiblast — a cup-like collection of cells lining one end of the embryo that forms at the end of the first week of development, just before the PGCs emerge. But to truly master the process, Saitou wanted to start with readily available, cultured cells.
That was a project for Hayashi, who in 2009 had returned to Japan from the University of Cambridge, UK, where, like Saitou before him, he had completed a four-year stint in the laboratory of a pioneer in the field, Azim Surani. Surani speaks highly of the two scientists, saying that they “complement each other in temperament and in their style and approach to solving problems”. Saitou is “systematic” and “single-minded about setting and accomplishing his objectives”, whereas Hayashi “works more intuitively, and takes a broader view of the subject and has outwardly a more relaxed approach”, he says. “Together they form a very strong team indeed.”
Hayashi joined Saitou at Kyoto University, which he quickly found was different from Cambridge. There was much less time spent on theoretical discussions than Hayashi was used to; instead, one jumped into experiments. “In Japan we just do it. Sometimes that can be very inefficient, but sometimes it makes a huge success,” he says.
Hayashi tried to use epiblast cells — Saitou’s starting point — but instead of using extracted cells as Saitou did, he tried to culture them as a stable cell line that could produce PGCs. That did not work. Hayashi then drew on other research showing that one key regulatory molecule (activin A) and a growth factor (basic fibroblast growth factor) could convert cultured early embryonic stem cells into cells akin to epiblasts. That sparked the idea of using these two factors to induce embryonic stem cells to differentiate into epiblasts, and then to apply Saitou’s previous formula to push these cells to become PGCs. The approach was successful6.
To prove that these artificial PGCs were faithful copies, however, they had to be shown to develop into viable sperm and eggs. The process by which this happens is complicated and ill understood, so the team left the job to nature — Hayashi inserted the PGCs into the testes of mice that were incapable of producing their own sperm, and waited to see whether the cells would develop6. Saitou thought that it would work, but fretted. “It seemed like a 50/50 chance,” he says. “We were excited and worried at the same time.” But, on the third or fourth mouse, they found testes with thick, dark seminiferous tubules, stuffed with sperm. “It happened so properly. I knew they would generate pups,” says Hayashi. The team injected these sperm into eggs and inserted the embryos into female mice. The result was fertile males and females6 (see ‘Making babies’).
“They are setting the course for the future of infertility treatments.”
They repeated the experiment with induced pluripotent stem (iPS) cells — mature cells that have been reprogrammed to an embryo-like state. Again, the sperm were used to produce pups, proving that they were functional — a rare accomplishment in the field of stem-cell differentiation, where scientists often argue over whether the cells that they create are truly what they seem to be. “This is one of the few examples in the entire field of pluripotent-stem-cell research where a fully functional cell type has been unequivocally generated starting from a pluripotent stem cell in a dish,” says Clark.
They expected eggs to be more complex, but last year, Hayashi made PGCs in vitro with cells from a mouse with normal colouring and then transferred them into the ovaries of an albino mouse1. The resulting eggs were fertilized in vitro and implanted into a surrogate. “I knew it had worked,” he says, when he saw the pups’ dark eyes pressing through their translucent eyelids.
Other researchers have been able to replicate the process to generate laboratory-grown PGCs (although none contacted by Nature had used them to produce live animals). Artificial PGCs are of particular use to scientists who study epigenetics: the biochemical modifications to DNA that determine which genes are expressed. These modifications — most often the addition of methyl groups to individual DNA bases — in some instances carry a sort of historical record of what an organism has experienced (for example, exposure to foreign chemicals in the womb). In a similar way to how they work in other cells, epigenetic markers push PGCs to their fate during embryonic development, but PGCs are unique because when they develop into sperm and eggs, the epigenetic markers are erased. This allows the cells to create a new zygote that is capable of forming all cell types.
Faults in subtle epigenetic changes are expected to contribute to infertility and the emergence of disorders such as testicular cancer. Already, Surani’s and Hanna’s groups have used the artificial PGCs to investigate the role of individual enzymes in epigenetic regulation, which may one day show how the epigenetic networks are involved in disease.
Indeed, the in vitro-generated PGCs offer millions of cells for scientists to study, instead of the 40 or so that can be obtained by dissecting early embryos, says Hanna. “This is a big deal because here we have these rare cells — PGCs — that are undergoing dramatic genome-wide epigenetic changes that we barely understand,” he says. “The in vitro model has provided unprecedented accessibility to scientists,” agrees Clark.
But Hayashi and Saitou have little to offer to the infertile couples begging for their help. Before this protocol can be used in the clinic, there are large wrinkles to be ironed out.
Saitou and Hayashi have found that the offspring generated by their technique usually seem to be healthy and fertile, but the PGCs themselves are often not completely ‘normal’. For example, the second-generation PGCs often produce eggs that are fragile, misshapen and sometimes dislodged from the complex of cells that supports them1. When fertilized, the eggs often divide into cells with three sets of chromosomes rather than the normal two, and the rate at which the artificial PGCs successfully produce offspring is only one-third of the rate for normal in vitro fertilization (IVF). Yi Zhang, who studies epigenetics at Harvard Medical School in Boston, Massachusetts, and who has been using Saitou’s method, has also found that in vitro PGCs do not erase their previous epigenetic programming as well as naturally occurring PGCs. “We have to be aware that these are PGC-like cells and not PGCs,” he says.
In addition, two major technical challenges remain. The first is working out how to make the PGCs convert to mature sperm and eggs without transplanting them back into testes or ovaries; Hayashi is trying to decipher the signals that ovaries and testes give to the PGCs that tell them to become eggs or sperm, which he could then add to artificial PGCs in culture to lead them through these stages.
But the most formidable challenge will be repeating the mouse PGC work in humans. The group has already started tweaking human iPS cells using the same genes that Saitou pinpointed as being important in mouse germ-cell development, but both Saitou and Hayashi know that human signalling networks are different from those in mice. Moreover, whereas Saitou had ‘countless’ numbers of live mouse embryos to dissect, the team has no access to human embryos. Instead, the researchers receive 20 monkey embryos per week from a nearby primate facility, under a grant of ¥1.2 billion (US$12 million) over five years. If all goes well, Hayashi says, they could repeat the mouse work in monkeys within 5–10 years; with small tweaks, this method could then be used to produce human PGCs shortly after.
But making PGCs for infertility treatment will still be a huge jump, and many scientists — Saitou included — are urging caution. Both iPS and embryonic stem cells frequently pick up chromosomal abnormalities, genetic mutations and epigenetic irregularities during culture. “There could be potentially far-reaching, multi-generational consequences if something went wrong in a subtle way,” says Moore.
Proof that the technique is safe in monkeys would help to allay concerns. But how many healthy monkeys would need to be born before the method could be regarded as safe? And how many generations should be observed?
Eventually, human embryos will need to be made and tested, a process that will be slowed by restrictions on creating embryos for research. New, non-invasive imaging techniques will enable doctors to sort good from bad embryos with a high degree of accuracy7. Embryos that seem to be similar to normal IVF embryos could get the go-ahead for implantation into humans. This might happen with private funding or in countries with less-restrictive attitudes towards embryo research.
When the technology is ready, even more provocative reproductive feats might be possible. For instance, cells from a man’s skin could theoretically be used to create eggs that are fertilized with a partner’s sperm, then nurtured in the womb of a surrogate. Some doubt, however, that such a feat would ever be possible — the Hinxton Group, an international consortium of scientists that discusses stem-cell ethics and challenges, concluded that it would be difficult to get eggs from male XY cells and sperm from female XX cells. “The instructions that the female niche is supplying to the male cell do not coordinate with each other,” says Clark, a member of the consortium.
Saitou used iPS cells from male mice to create sperm and from female mice to create eggs, but he says that the reverse should be possible. If so, eggs and sperm from the same mouse could be generated and used for fertilization, producing something never seen before: a mouse created by self-fertilization. Neither Hayashi nor Saitou is ready to try this. “We would only do this [in mice] if there were a good scientific reason,” says Saitou. Right now he does not see one.
The two scientists already feel some pressure from patients and Japanese funding agencies to move forward. The technique could be a last hope for women who have had no luck with IVF, or for people who had cancer in childhood and have lost the ability to produce sperm or eggs. Hayashi warns those who write to him that a viable infertility treatment could be 10 or even 50 years in the future. “My impression is that it is very far away. I don’t want to give people unfeasible hope,” he says.
Patients see the end result — success in mice — and often ignore the years of painstaking work that led to such a technical tour de force. They do not realize that switching from mice to humans means starting again almost from scratch, says Hayashi. The human early embryo is so different from the mouse that it is almost “like starting over on a process that took more than ten years”.
Evolutionary path shows related virus can infect some mammals, raising concerns about spread.
The H7N9 influenza virus did not emerge alone. Researchers have traced the evolution of the deadly avian flu currently spreading in China, and have found evidence that it developed in parallel with a similar bird flu, H7N7, which can infect mammals.
Although there is no evidence that this H7N7 strain will infect humans, the authors of a study published today in Nature1 say that their finding reinforces the idea that H7 avian viruses are constantly mixing and exchanging genetic material — a process known as reassortment — in Asian poultry markets. This raises the threat that H7N7 will reassort and become able to spread to humans.
“H7 is out there in China and not just in the form of this H7N9,” says Richard Webby, a co-author of the study and an influenza specialist at St. Jude Children’s Research Hospital in Memphis, Tennessee.
Ducks, in particular, act as living mixing bowls for avian viruses. Domestic species encounter a large catalogue of wild-bird viruses, which swap genes to form versions that can spread to chickens and to humans.
Better surveillance of Chinese bird populations is needed to monitor the emergence of dangerous viruses such as H7N9, says lead author Yi Guan, an influenza specialist at the University of Hong Kong. In China, the virus has infected 135 people and resulted in 44 deaths since February. “This is a very different influenza ecosystem from other countries,” says Guan.
Guan’s team sampled wild birds and poultry markets around Shanghai in April, weeks after the H7N9 outbreak began there. The researchers collected throat and intestinal swabs from 1,341 birds, including chickens, ducks, geese, pigeons, partridges and quails, plus 1,006 water and faecal samples from bird markets. About 10% of samples tested positive for an influenza virus; of those, 15% were an H7 virus.
When the team sequenced the two viruses’ genomes and compared them to other bird-flu strains, they found H7N9 and H7N7 to be hybrids of wild Eurasian waterfowl strains, such as H7N3 and H11N9. The scientists think that those viruses swapped genes in domestic ducks before spreading to chickens, where they traded genes with a common chicken virus, H9N2. That improved the viruses’ ability to spread in chickens, which live in close contact with humans.
So far, the latest H7N7 strain has not infected a human. But Guan and his team found that ferrets could become infected with the virus, suggesting that a spread to humans is possible.
“It really shows that the emergence of these types of viruses can happen at any time,” says Camille Lebarbenchon, a viral ecologist at the University of Reunion Island in St Denis, France, who has also studied the evolution of H7N9 using archived viral sequences2.
David Morens, an influenza researcher and senior adviser at the US National Institutes of Health in Bethesda, Maryland, says that the evolutionary pathway that the viruses followed suggests that more surveillance and better sanitation practices at poultry markets are crucial to monitoring risks to human health.
But Ian Lipkin, an epidemiologist at Columbia University in New York City, says that surveillance is not a foolproof solution. “It’s inevitable that something is going to slip through the cracks.”
Ministers called on to intervene as regulators upgrade severity level of the leakage.
Pressure is mounting on the Japanese government to intervene in the clean-up of the Fukushima Daiichi nuclear power plant after experts voiced fears that the power company responsible for the facility is unable to cope.
The leakage earlier this month of hundreds of tonnes of radioactive water — the most serious incident at the beleaguered plant since it was devastated by a tsunami in March 2011 — highlights the failure by the Tokyo Electric Power Company (TEPCO) to properly manage the operation. If the government fails to act, prime minister Shinzo Abe’s pro-nuclear stance may be jeopardized, analysts told Nature.
“It’s clear that TEPCO is unable to solve the problems on its own,” says Tsutomu Toichi, managing director and chief economist at the Institute of Energy Economics in Tokyo. “The government has to step in to ensure these problems are solved quickly. It is going to have to provide funds, as well as a plan for moving forward, and explain this to the public in a way that is easy to understand.”
Wiktor Frid, a nuclear expert with the Swedish Radiation Safety Authority in Stockholm, adds, “That water leaked from a tank unnoticed for several days is alarming and extremely embarrassing for TEPCO”.
The leak has also led to renewed concerns over ocean contamination and food safety, with local fishing cooperatives suspending trial catches and one oceanographer saying that further leaks would have “severe” consequences for marine life.
The leak of some 300 tonnes of partially treated water that had been used to cool melted nuclear rods from the destroyed reactors was reported by TEPCO on 19 August. The radioactivity of the water stands at about 80 megabecquerels per litre, about 1% of what it was before treatment by an on-site purification system. Japan’s Nuclear Regulation Authority initially labelled the incident a level 1 event (known as an ‘anomaly’) on the International Nuclear Event Scale, but yesterday upgraded it to level 3(‘serious incident’), citing the large amount of contaminated water leaked and the fact that a safety buffer was not available for the water tank in question.
At present, TEPCO is storing more than 300,000 tonnes of radioactive water on the site of the destroyed Fukushima Daiichi plant. Radioactive caesium isotopes are being removed from the water by an advanced liquid-processing system built after the accident, but a facility for removing strontium isotopes is not yet ready. Tritium, another harmful radionuclide, cannot be safely removed by any known purification system because it is incorporated within water molecules.
The leaked water is thought to have seeped into the ground and will eventually reach the sea adjacent to the plant. The storage site near Fukushima’s reactor 4, where the leak was discovered, lies some 50 metres above sea level and is just a few hundred metres from the coast.
Measures proposed so far to prevent the polluted water from flowing into the sea — such as freezing or excavating the soil surrounding the storage site — seem to be either very expensive or technically unfeasible, says Joachim Knebel, a nuclear expert and chief science officer at the Karlsruhe Institute of Technology in Germany.
“We can’t really assess the situation from far away,” he says. “But it appears to me that none of the proposed measures would work. TEPCO would be well advised to seek international expertise in coping with the problems.”
Several countries, including Russia, have offered to assist with the company’s clean-up efforts, and TEPCO said last week that it will consider accepting outside help. On Monday, it also announced a series of measures, including the installation of a new central control system, to mitigate the risk of future leaks.
“Some tanks have automatic monitoring equipment and some don’t,” says Yo Koshimizu, a TEPCO spokesman. “We are currently determining whether to add such equipment to all of the tanks.”
Some 400 tonnes of cooling water are being collected in tanks each day. The growing fleet of storage tanks — which currently stands at about 1,000 — is a source of alarm for experts, who fear that huge amounts of contaminated water will eventually have to be dumped into the ocean. Worse still, some 300 tonnes of groundwater highly contaminated with caesium-137, which has a 30-year half-life, are thought to be flowing from beneath the destroyed reactors into the sea every day.
The potential for harm is huge, says Jota Kanda, an oceanographer at the Tokyo University of Marine Science and Technology who monitors radionuclide distribution in sediments and biota off Fukushima1.
“The effects of one relatively small leak may be insignificant,” he says. “But there are huge amounts of radionuclides in these tanks and the water may have to be stored for a long time to come. If more leaks were to occur the consequences might be severe.”
The Fukushima nuclear accident resulted in the largest ever accidental release of radioactivity to the oceans. Some 80% of all the radionuclides released from Fukushima ended up in the Pacific2. In some local fish, high residual levels of radioactivity were measured two years after the accident. Commercial fishing in the area is still banned.
But it is unclear how much residual radioactive contamination is still entering the sea from leaks around the Fukushima plant, says Scott Fowler, a marine ecologist at Stony Brook University in New York who has been involved in previous assessments of contamination levels in the ocean near Fukushima.
To track changes in coastal waters and predict when seafood species in the region may be safe to consume, it will be necessary to establish a ‘temporal data set’ — that is, to measure the levels and distributions of contaminant radionuclides at a given location over time, he says.
“Even if one assumes that leaks from the plant into the sea will eventually be stopped, residual contamination would continue to be present in the adjacent marine ecosystem for many years,” he says. “So the contamination of long-lived radionuclides in different organisms in the local marine food webs needs to be monitored continually.”
X-ray scattering study suggests insects’ wing muscles work by mechanism shared with vertebrate muscle.
To stay aloft, insects have to beat their wings very fast — up to 500 times a second in the case of mosquitoes. Exactly how they do this has long been debated. By capturing the molecular details of wing beats in live bumblebees, a study now argues that insect flight muscles do not work through a specialized mechanism but exploit properties shared with vertebrate muscles.
“It has long been known that many insects don’t move their flight muscles in the way vertebrates do,” says Hiroyuki Iwamoto, a biophysicist who conducted the work with his colleague Naoto Yagi at the Japan Synchrotron Radiation Research Institute (or SPring-8) in Hyogo. “The big question is whether the difference is unique to insect flight muscles or exploits a property common to all muscle proteins.”
Human muscles contract when they receive a signal from the motor nerves. This signal causes calcium ions to be released from membranes in the muscle. The calcium ions are captured by proteins called troponins on fibrous proteins called actin, causing the actin filaments to rotate and expose sites where the ‘head’ of myosin, a motor protein, can bind.
After the head binds to actin, the myosin molecule kinks, pulling on the actin filament to cause muscle to contract and burning energy in the process. But the mechanism is too costly in energy and requires too rapid a pumping of calcium to be repeated hundreds of times a second for insect flight.
Instead, “once insect flight muscles are activated by nerves, they oscillate spontaneously,” says Yale Goldman, a muscle physiologist at the University of Pennsylvania in Philadelphia.
These self-sustained oscillations are induced by “stretch activation”, in which the force generated by each of two out-of-phase, antagonistic flight muscles gets stronger as they are extended, pulling the wing back.
Stretch activation “appears to occur in most muscles that beat rhythmically, which includes human cardiac muscle”, says Kenneth Taylor, a molecular biophysicist at Florida State University in Tallahassee. But whereas heartbeats are governed by calcium signals, wing beats are not.
“Because repeated calcium release and uptake is not necessary, there is no upper limit to the wing-beat frequency,” says Iwamoto.
But, says Goldman, “what triggers it isn’t known. This has been a puzzle in the field.”
One possible answer, proposed in 1979, is that stretch activation arises because, as the muscle becomes more extended, more myosin heads are able to bind to actin2. But more recently it has been suggested that insect flight muscle might have a special adaptation that vertebrate muscle does not: a form of troponin that doesn’t need activation by calcium ions3.
In the new study, Iwamoto and Yagi measured changes in the arrangement of the molecular motor components of muscle while insects were in flight — or trying to fly, having been glued in place at the end of a narrow aluminium tube.
The researchers positioned the insects in the path of an X-ray beam. The pattern of bright spots formed when X-rays are scattered by the muscles contains information about the reorganization of their protein molecules. Iwamoto and Yagi followed these changes by collecting the X-ray data at high speed, synchronized to video footage of the bees at 5,000 frames per second.
The researchers concluded that in insect flight muscle, myosin heads rotate when muscle stretches, and this enables them to bind more strongly. In other words, stretch activation is a fundamental consequence of the interaction between actin and myosin in this kind of muscle, just as it is in some vertebrate muscle. The rotation of the myosin heads shows up in the X-ray data as an increase in the strength of one of the X-ray spots.
While X-ray scattering from live insects has been reported before4, the researchers have been able to monitor it much faster than previously — at 40 frames per wing beat. “The paper is very impressive from the technical standpoint,” Goldman says.
The findings “really help clarify the process of force generation in insect flight muscle,” says Taylor. “If you believe that myosin and actin function virtually the same way in all muscles, then it’s a big step in explaining muscle contraction in general,” he adds.
But Goldman warns, “this will be somewhat controversial, given the evidence that a special troponin might be the trigger.”