2013年7月6日星期六

How the brain creates the 'buzz' that helps ideas spread

How the brain creates the 'buzz' that helps ideas spread

UCLA psychologists have taken a significant step toward answering these questions, identifying for the first time the brain regions associated with the successful spread of ideas, often called "buzz."

The research has a broad range of implications, the study authors say, and could lead to more effective public health campaigns, more persuasive advertisements and better ways for teachers to communicate with students.

"Our study suggests that people are regularly attuned to how the things they're seeing will be useful and interesting, not just to themselves but to other people," said the study's senior author, Matthew Lieberman, a UCLA professor of psychology and of psychiatry and biobehavioral sciences and author of the forthcoming book "Social: Why Our Brains Are Wired to Connect." "We always seem to be on the lookout for who else will find this helpful, amusing or interesting, and our brain data are showing evidence of that. At the first encounter with information, people are already using the brain network involved in thinking about how this can be interesting to other people. We're wired to want to share information with other people. I think that is a profound statement about the social nature of our minds."

The study findings are published in the online edition of the journal Psychological Science, with print publication to follow later this summer.

"Before this study, we didn't know what brain regions were associated with ideas that become contagious, and we didn't know what regions were associated with being an effective communicator of ideas," said lead author Emily Falk, who conducted the research as a UCLA doctoral student in Lieberman's lab and is currently a faculty member at the University of Pennsylvania's Annenberg School for Communication. "Now we have mapped the brain regions associated with ideas that are likely to be contagious and are associated with being a good 'idea salesperson.' In the future, we would like to be able to use these brain maps to forecast what ideas are likely to be successful and who is likely to be effective at spreading them."

In the first part of the study, 19 UCLA students (average age 21), underwent functional magnetic resonance imaging (fMRI) brain scans at UCLA's Ahmanson-Lovelace Brain Mapping Center as they saw and heard information about 24 potential television pilot ideas. Among the fictitious pilots -- which were presented by a separate group of students -- were a show about former beauty-queen mothers who want their daughters to follow in their footsteps; a Spanish soap opera about a young woman and her relationships; a reality show in which contestants travel to countries with harsh environments; a program about teenage vampires and werewolves; and a show about best friends and rivals in a crime family.

The students exposed to these TV pilot ideas were asked to envision themselves as television studio interns who would decide whether or not they would recommend each idea to their "producers." These students made videotaped assessments of each pilot.

Another group of 79 UCLA undergraduates (average age 21) was asked to act as the "producers." These students watched the interns' videos assessments of the pilots and then made their own ratings about the pilot ideas based on those assessments.

Lieberman and Falk wanted to learn which brain regions were activated when the interns were first exposed to information they would later pass on to others.

"We're constantly being exposed to information on Facebook, Twitter and so on," said Lieberman. "Some of it we pass on, and a lot of it we don't. Is there something that happens in the moment we first see it -- maybe before we even realize we might pass it on -- that is different for those things that we will pass on successfully versus those that we won't?"

It turns out, there is. The psychologists found that the interns who were especially good at persuading the producers showed significantly more activation in a brain region known as the temporoparietal junction, or TPJ, at the time they were first exposed to the pilot ideas they would later recommend. They had more activation in this region than the interns who were less persuasive and more activation than they themselves had when exposed to pilot ideas they didn't like. The psychologists call this the "salesperson effect."

"It was the only region in the brain that showed this effect," Lieberman said. One might have thought brain regions associated with memory would show more activation, but that was not the case, he said.

"We wanted to explore what differentiates ideas that bomb from ideas that go viral," Falk said. "We found that increased activity in the TPJ was associated with an increased ability to convince others to get on board with their favorite ideas. Nobody had looked before at which brain regions are associated with the successful spread of ideas. You might expect people to be most enthusiastic and opinionated about ideas that they themselves are excited about, but our research suggests that's not the whole story. Thinking about what appeals to others may be even more important."

The TPJ, located on the outer surface of the brain, is part of what is known as the brain's "mentalizing network," which is involved in thinking about what other people think and feel. The network also includes the dorsomedial prefrontal cortex, located in the middle of the brain.

"When we read fiction or watch a movie, we're entering the minds of the characters -- that's mentalizing," Lieberman said. "As soon as you hear a good joke, you think, 'Who can I tell this to and who can't I tell?' Making this judgment will activate these two brain regions. If we're playing poker and I'm trying to figure out if you're bluffing, that's going to invoke this network. And when I see someone on Capitol Hill testifying and I'm thinking whether they are lying or telling the truth, that's going to invoke these two brain regions.

"Good ideas turn on the mentalizing system," he said. "They make us want to tell other people."

The interns who showed more activity in their mentalizing system when they saw the pilots they intended to recommend were then more successful in convincing the producers to also recommend those pilots, the psychologists found.

"As I'm looking at an idea, I might be thinking about what other people are likely to value, and that might make me a better idea salesperson later," Falk said.

By further studying the neural activity in these brain regions to see what information and ideas activate these regions more, psychologists potentially could predict which advertisements are most likely to spread and go viral and which will be most effective, Lieberman and Falk said.

Such knowledge could also benefit public health campaigns aimed at everything from reducing risky behaviors among teenagers to combating cancer, smoking and obesity.

"The explosion of new communication technologies, combined with novel analytic tools, promises to dramatically expand our understanding of how ideas spread," Falk said. "We're laying basic science foundations to addressimportant public health questions that are difficult to answer otherwise -- about what makes campaigns successful and how we can improve their impact."

As we may like particular radio DJs who play music we enjoy, the Internet has led us to act as "information DJs" who share things that we think will be of interest to people in our networks, Lieberman said.

"What is new about our study is the finding that the mentalizing network is involved when I read something and decide who else might be interested in it," he said. "This is similar to what an advertiser has to do. It's not enough to have a product that people should like."


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Seeing Sea stars: The missing link in eye evolution?

Seeing Sea stars: The missing link in eye evolution?

The researchers removed starfish with and without eyes from their food rich habitat, the coral reef, and placed them on the sand bottom one metre away, where they would starve. They monitored the starfishes' behaviour from the surface and found that while starfish with intact eyes head towards the direction of the reef, starfish without eyes walk randomly.

Dr Garm said: "The results show that the starfish nervous system must be able to process visual information, which points to a clear underestimation of the capacity found in the circular and somewhat dispersed central nervous system of echinoderms."

Analysing the morphology of the photoreceptors in the starfish eyes the researchers further confirmed that they constitute an intermediate state between the two large known groups of rhabdomeric and ciliary photoreceptors, in that they have both microvilli and a modified cilium.

Dr Garm added: "From an evolutionary point of view it is interesting because the morphology of the starfish eyes along with their optical quality (quality of the image) is close to the theoretical eye early in eye evolution when image formation first appeared. In this way it can help clarify what the first visual tasks were that drove this important step in eye evolution, namely navigation towards the preferred habitat using large stationary objects (here the reef)."

Most known starfish species possess a compound eye at the tip of each arm, which, except for the lack of true optics, resembles arthropod compound eye. Despite being known for about two centuries, no visually guided behaviour has ever been documented before.


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Mysterious radio flashes may be farewell greetings from massive stars collapsing into black holes

Mysterious radio flashes may be farewell greetings from massive stars collapsing into black holes

July 5, 2013 — Mysterious bright radio flashes that appear for only a brief moment on the sky and do not repeat could be the final farewell greetings of a massive star collapsing into a black hole, astronomers from Nijmegen and Potsdam argue.






Radio telescopes have picked up some bright radio flashes that appear for only a brief moment on the sky and do not repeat. Scientists have since wondered what causes these unusual radio signals. An article in this week's issue of Science suggests that the source of the flashes lies deep in the early cosmos, and that the short radio burst are extremely bright. However, the question of which cosmic event could produce such a bright radio emission in such a short time remained unanswered. The astrophysicists Heino Falcke from Radboud University Nijmegen and Luciano Rezzolla from the Max Planck Institute for Gravitational Physics in Potsdam provide a solution for the riddle. They propose that the radio bursts could be the final farewell greetings of a supramassive rotating neutron star collapsing into a black hole.

Spinning star withstands collapse

Neutron stars are the ultra-dense remains of a star that has undergone a supernova explosion. They are the size of a small city but have up to two times the mass of our Sun. However, there is an upper limit on how massive neutron stars can become. If they are formed above a critical mass of more than two solar masses, they are expected to collapse immediately into a black hole. Falcke & Rezzolla now suggest that some stars could postpone that final death through fast rotation for millions of years. Like a ballerina spinning around her own axis, centrifugal forces could stabilize these overweight neutron stars against collapse and leave them in a 'half-dead' state for up to a few million years. Nonetheless, the star is just buying time and even with this trick it cannot avoid the inevitable. Neutron stars have extremely strong magnetic fields threading their environment like huge propeller blades. Any left-over matter in the surrounding will be blown away by this magnetic fan and rotational energy is radiated away. Thus, while the half-dead star ages, it also slows down and becomes more and more compact, with gravity playing an ever stronger role. At some point the tired star can no longer withstand gravity's pull. It will cross the ultimate death-line and suddenly collapse to a black hole while transmitting a strong radio flash.

Emission disappears in black hole

Astrophysicists normally expect a gravitational collapse to be accompanied by bright fireworks of optical and gamma-ray radiation from the imploding matter. This characteristic emission, however, is not seen in the newly found fast radio bursts. Falcke & Rezzolla suggest that this is because the neutron star has already cleaned out its surroundings and the remaining stellar surface is quickly covered by the emerging event horizon.

'All the neutron star has left is its magnetic field, but black holes cannot sustain magnetic fields, so the collapsing star has to get rid of them,' explains Prof. Falcke. When the black hole forms, the magnetic fields will be cut off from the star and snap like rubber bands. As we show, this can indeed produce the observed giant radio flashes. All other signals you normally would expect -- gamma rays, x-rays -- simply disappear behind the event horizon of the black hole.'

Because of its single, ultra-rapid and unrepeatable signal, Falcke and Rezzolla named these objects 'blitzars', from the German blitz (flash). This is opposed to pulsars, which are rotating neutron stars that are flashing repeatedly like cosmic lighthouses and simply fade away.

Prof. Rezzolla adds: 'These fast radio bursts could be the first evidence of the birth of a black hole, whose formation is therefore accompanied by an intense, almost pure, radio-wave emission. Interestingly, a blitzar is at the same time the farewell signal of a dying neutron star and the first message of from a newly born black hole.'

The new theory proposed by Falcke & Rezzolla provides a first solid interpretation of the previously mysterious radio bursts. Their work has been submitted to the journal 'Astronomy & Astrophysics' and was posted on the arxiv.org preprint archive.

To further test their proposal, more observations of the so far elusive radio bursts are required. Falcke and his colleagues plan to use telescopes like the new LOFAR radio telescope to detect more of these dying stars in the future. This would allow them to locate the events quicker and more precisely, and to observe this new formation channel of black holes in the depths of the cosmos with keen 'radio eyes'.



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Solar prominences put on strange and beautiful show in the Sun's sky

Solar prominences put on strange and beautiful show in the Sun's sky

The features were discovered by Dr Xing Li and PhD student, Jeff Smith, of Aberystwyth University using the Atmospheric Imaging Assembly (AIA) telescope on board the Solar Dynamic Observatory (SDO) satellite. The findings have been presented at the RAS National Astronomy Meeting in St Andrews.

Prominences are -- relatively -- cold gaseous features, with temperatures around 5000 degrees Celsius compared to the surrounding the hot solar atmosphere of about 1-2 million degrees. They can be seen as towering features extending outwards from the Sun's surface, often in the shape of a loop. They are called filaments when viewed against the solar disc, appearing as dark stripes because the cold gases they contain absorb the light emitted from below. Solar prominences and filaments supply most of the material released in coronal mass ejections, eruptions from the Sun's atmosphere that can cause space weather and create geomagnetic storms on Earth.

Rotating discs in solar prominences were first observed decades ago, using ground-based telescopes, and have puzzled solar physicists since. The new SDO observations of a rotating disc reveal that the feature covered a temperature range from a few thousand to one million degrees Celsius. Li and Smith believe that the rotation was caused by turbulence produced at the interface of two gases of enormously different temperatures.

"We think the rotation is produced when hot gases enter a cold medium in an organised fashion. The magnetic field serves as a thermal barrier between the two media. The resulting rotation can last hours," said Li.

The persistent horizontal motion of feathery streamers from a solar prominence was observed by SDO over a period of more than 15 hours. Li and Smith believe that the likely cause was a large-scale, slow restructuring of the magnetic field through a process called magnetic reconnection.

In a further observation, lasting around three hours, a jet of superheated gases as hot as 1.5 -- 2 million degrees Celsius was sucked from the coronal cavity surrounding a prominence and spiralled up along a helical path to strike the top of prominence 50 000 km high.

"The feat of the jet hitting the top of the prominence, and the distances involved, is comparable to a ballistic missile hitting a satellite in geostationary orbit!" said Li.

Finally the SDO imagery showed counter-streaming flows at more than a million kilometres per hour along a filament channel consisting of many very thin threads.

"These fabulous motions suggest more complex magnetic structures of filaments/prominences than scientists previously thought," said Li.

Smith added: "These events are beautiful to observe and also set a fascinating challenge to get to the bottom of the physics involved."


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Variation between hot extrasolar planet atmospheres revealed

Variation between hot extrasolar planet atmospheres revealed

July 5, 2013 — First results from the analysis of eight 'hot Jupiter' exoplanets suggest that winds and clouds play an important role in the atmospheric make up of these exotic planets.






Catherine Huitson from Physics and Astronomy at the University of Exeter will present the results at the National Astronomy Meeting in St Andrews on Friday 5 July 2013.

Hot Jupiters are giant exoplanets, similar in size to Jupiter, that orbit so close to their stars that their atmospheres can reach temperatures of 1000-3000 degrees Celsius. Astronomers can detect which gases are present in their atmospheres by analysing the spectrum of starlight filtered through the planet's atmosphere when the planet passes in front of the star. Last year, a team led by the University of Exeter was awarded nearly 200 hours on the NASA/ESA Hubble Space Telescope to examine eight planets using this technique -- the largest survey of its type to date.

Catherine Huitson said: "These hot Jupiter planets are expected to have a vastly different composition from planets in our own Solar System like Jupiter, where temperatures at the cloud tops are around -150 degrees Celsius. The first planet we measured is one of the hottest to be observed, with a temperature of over 2000 degrees. The early results of the survey are now in, and they present a diverse range of puzzling properties."

The first, very hot planet observed showed an unexpected absence of titanium oxide. Current 3D models of hot Jupiter atmospheres suggest that grains of this heavy molecule should be circulated by fast winds, allowing gaseous titanium oxide to reach the observable upper atmosphere. The non-detection of the gas suggests that either the winds are not as strong as expected or the molecule is forming much larger grains that are too heavy be lifted.

Huitson explained, "Titanium oxide is a solid on Earth, but we expect it to be present in the atmosphere of the hottest hot Jupiters because of the extreme temperatures. This molecule is important because it could trap atmospheric heat high up forming a stratosphere -- the same role ozone plays on Earth. However, our results show that this molecule is not present in the upper atmosphere, meaning that we need to revise our understanding of how wind processes distribute materials."

The team also made a confirmed detection of water vapour in the atmosphere of two planets. Importantly, the water was found in the quantities predicted by theory, contrasting with previously observed planets.

"While our models tell us that water (as steam) should be present in hot Jupiter atmospheres, until now the molecule has only been seen in limited quantities and in fewer planets than expected," said Huitson.

"Seeing steam in two exoplanets is a great confirmation of current theory. Our new findings suggest that previous non-detections were caused by opaque, high-up clouds obscuring the parts of the atmosphere where steam is present."

The results presented at the National Astronomy Meeting represent initial findings and work by the team is still ongoing to analyse all the data from the eight-planet Hubble survey.

"A surprising diversity is emerging from the continuing observations among planets with similar temperatures, and the remaining results are sure to present even more surprises as we try to understand such extreme and unknown objects," said Huitson.



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Cosmic radio bursts point to cataclysmic origins

Cosmic radio bursts point to cataclysmic origins

The international research team, writing in the journal Science, rule out terrestrial sources for the four fast radio bursts and say their brightness and distance suggest they come from cosmological distances when the Universe was just half its current age.

The burst energetics indicate that they originate from an extreme astrophysical event involving relativistic objects such as neutron stars or black holes.

Study lead Dan Thornton, a PhD student at England's University of Manchester and Australia's Commonwealth Scientific and Industrial Research Organisation, said the findings pointed to some extreme events involving large amounts of mass or energy as the source of the radio bursts.

He said: "A single burst of radio emission of unknown origin was detected outside our Galaxy about six years ago but no one was certain what it was or even if it was real, so we have spent the last four years searching for more of these explosive, short-duration radio bursts. This paper describes four more bursts, removing any doubt that they are real. The radio bursts last for just a few milliseconds and the furthest one that we detected was 11 billion light years away."

Astonishingly, the findings -- taken from a tiny fraction of the sky -- also suggest that there should be one of these signals going off every 10 seconds. Max-Planck Institute Director and Manchester professor, Michael Kramer, explained: "The bursts last only a tenth of the blink of an eye. With current telescopes we need to be lucky to look at the right spot at the right time. But if we could view the sky with 'radio eyes' there would be flashes going off all over the sky every day."

The team, which included researchers from the UK, Germany, Italy, Australia and the US, used the CSIRO Parkes 64metre radio telescope in Australia to obtain their results.

Co-author Professor Matthew Bailes, from the Swinburne University of Technology in Melbourne, thinks the origin of these explosive bursts may be from magnetic neutron stars, known as 'magnetars'. He said: "Magnetars can give off more energy in a millisecond than our Sun does in 300,000 years and are a leading candidate for the burst."

The researchers say their results will also provide a way of finding out the properties of space between Earth and where the bursts occurred. Author Dr Ben Stappers, from Manchester's School of Physics and Astronomy, said: "We are still not sure about what makes up the space between galaxies, so we will be able to use these radio bursts like probes in order to understand more about some of the missing matter in the Universe. We are now starting to use Parkes and other telescopes, like the Lovell Telescope of the University of Manchester, to look for these bursts in real time."


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2013年7月5日星期五

Spider webs more effective at ensnaring charged insects

Spider webs more effective at ensnaring charged insects

July 4, 2013 — Flapping insects build up an electrical charge that may make them more easily snared by spider webs, according to a new study by University of California, Berkeley, biologists.






The positive charge on an insect such as a bee or fly attracts the web, which is normally negatively or neutrally charged, increasing the chances that an insect flying by will contact and stick to the web, said UC Berkeley post-doctoral fellow Victor Manuel Ortega-Jimenez.

He also suspects that light flexible spider silk, the kind used for make the spirals on top of the stiffer silk that forms the spokes of a web, may have developed because it more easily deforms in the wind and electrostatic charges to aid prey capture.

"Electrostatic charges are everywhere, and we propose that this may have driven the evolution of specialized webs," he said.

Ortega-Jimenez, who normally studies hummingbird flight, became interested in spider webs while playing with his four-year-old daughter.

"I was playing with my daughter's magic wand, a toy that produces an electrostatic charge, and I noticed that the positive charge attracted spider webs," he said. "I then realized that if an insect is positively charged too it could perhaps attract an oppositely charged spider web to affect the capture success of the spider web."

In fact, insects easily develop several hundred volts of positive charge from the friction of wings against air molecules or by contacting a charged surface. This is small compared to the several thousand volts we develop when walking across a rug and which gives us a shock when we touch a doorknob, but is sufficient to allow a bee to electrostatically draw pollen off a flower before landing.

To test his spider web hypothesis, Ortega-Jimenez sought out cross-spider (Araneus diadematus) webs along streams in Berkeley and brought them into the lab. He then used an electrostatic generator to charge up dead insects -- aphids, fruit flies, green-bottle flies, and honey bees -- and drop them into a neutral, grounded web.

"Using a high speed camera, you can clearly see the spider web is deforming and touching the insect before it reaches the web," he said. Insects without a charge did not do this. "You would expect that if the web is charged negatively, the attraction would increase."

Ortega-Jimenez plans to conduct further tests at UC Berkeley to determine whether this effect occurs in the wild, and find out whether static charges on webs attract more dirt and pollen and thus are a major reason orb web weavers rebuild them daily.



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2013年7月3日星期三

Greenhouse gas likely altering ocean foodchain: Atmospheric CO<sub>2</sub> has big consequences for tiny bacteria

Greenhouse gas likely altering ocean foodchain: Atmospheric CO2 has big consequences for tiny bacteria

In climate change, as in everything, there are winners and losers. As atmospheric carbon dioxide levels and temperature rise globally, scientists increasingly want to know which organisms will thrive and which will perish in the environment of tomorrow.

The answer to this question for nitrogen-fixing cyanobacteria (bacteria that obtain energy through photosynthesis, or "blue-green algae") turns out to have implications for every living thing in the ocean. Nitrogen-fixing is when certain special organisms like cyanobacteria convert inert -- and therefore unusable -- nitrogen gas from the air into a reactive form that the majority of other living beings need to survive. Without nitrogen fixers, life in the ocean could not survive for long.

"Our findings show that CO2 has the potential to control the biodiversity of these keystone organisms in ocean biology, and our fossil fuel emissions are probably responsible for changing the types of nitrogen fixers that are growing in the ocean," said David Hutchins, professor of marine environmental biology at the USC Dornsife College of Letters, Arts and Sciences and lead author of an article about this research that appeared in Nature Geoscience on June 30.

"This may have all kinds of ramifications for changes in ocean food chains and productivity, even potentially for resources we harvest from the ocean such as fisheries production," Hutchins said.

Hutchins and his team studied two major groups of nitrogen-fixing cyanobacteria: Trichodesmium, which forms large floating colonies big enough to see with the naked eye and makes vast "blooms" in the open ocean, and Crocosphaera, which is also very abundant but is a single-celled, microscopic organism.

Previous research showed that these two types of cyanobacteria should be some of the biggest "winners" of climate change, thriving in high CO2 levels and warmer oceans. However, those previous studies only examined one or two strains of the organisms.

That's where USC's unique resource comes into play -- the university is home to a massive culture library of strains and species of the organisms assembled by USC Associate Professor Eric Webb.

Using the culture library, the team was able to show that some strains grow better at CO2 levels not seen since the start of the Industrial Revolution, while others will thrive in the future "greenhouse" Earth.

"It's not that climate change will wipe out all nitrogen fixers; we've shown that there's redundancy in nature's system. Rather, increasing atmospheric carbon dioxide changes specifically which nitrogen fixers are likely to thrive," Hutchins said. "And we're not entirely certain how that will change the ocean of tomorrow."


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Listening to blood cells: Simple test could use sound waves for diagnosing blood-related diseases

Listening to blood cells: Simple test could use sound waves for diagnosing blood-related diseases

July 2, 2013 — New research reveals that when red blood cells are hit with laser light, they produce high frequency sound waves that contain a great deal of information. Similar to the way one can hear the voices of different people and identify who they are, investigators reporting in the July 2 issue of Biophysical Journal, published by Cell Press, could analyze the sound waves produced by red blood cells and recognize their shape and size. The information may aid in the development of simple tests for blood-related diseases.






"We plan to make specialized devices that will allow the detection of individual red blood cells and analyze the photoacoustic signals they produce to rapidly diagnose red blood cell pathologies," says senior author Dr. Michael Kolios, of Ryerson University, Toronto.

Deviations from the regular biconcave shape of a red blood cell are a significant indicator of blood-related diseases, whether they result from genetic abnormalities, from infectious agents, or simply from a chemical imbalance. For example, malaria patients' red blood cells are irregularly swollen, while those of patients with sickle cell anemia take on a rigid, sickle shape.

Using a special photoacoustic microscope that detects sound, the investigators were able to differentiate healthy red blood cells from irregularly shaped red blood cells with high confidence, using a sample size of just 21 cells. Because each measurement takes only fractions of a second, the method could eventually be incorporated into an automated device for rapid characterization of red blood cells from a single drop of blood obtained in the clinic.

"We are currently developing a microfluidic device, which integrates the laser and probes and flows single cells through the target area. This would enable measuring thousands of cells in a very short period of time with minimal user involvement," says first author Eric Strohm, who is a graduate student in Dr. Kolios' laboratory. The investigators are applying the method to other types of cells as well, including white blood cells, and they are also using it to detect changes in photoacoustic signals that occur when blood cells clump together to form dangerous blood clots.



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2013年7月2日星期二

Vitamin C helps control gene activity in stem cells

Vitamin C helps control gene activity in stem cells

July 1, 2013 — Vitamin C affects whether genes are switched on or off inside mouse stem cells, and may thereby play a previously unknown and fundamental role in helping to guide normal development in mice, humans and other animals, a scientific team led by UC San Francisco researchers has discovered.






The researchers found that vitamin C assists enzymes that play a crucial role in releasing the brakes that keep certain genes from becoming activated in the embryo soon after fertilization, when egg and sperm fuse.

The discovery might eventually lead to the use of vitamin C to improve results of in vitro fertilization, in which early embryos now are typically grown without the vitamin, and also to treat cancer, in which tumor cells abnormally engage or release these brakes on gene activation, the researchers concluded in a study published June 30, 2013 in the journal Nature.

In the near term, stem-cell scientists may begin incorporating vitamin C more systematically into their procedures for growing the most healthy and useful stem cells, according to UCSF stem-cell scientist Miguel Ramalho-Santos, PhD, who led the study. In fact, the unanticipated discovery emerged from an effort to compare different formulations of the growth medium, a kind of nutrient broth used to grow mouse embryonic stem cells in the lab.

Rather than building on any previous body of scientific work, the identification of the link between vitamin C and the activation of genes that should be turned on in early development was serendipitous, Ramalho-Santos said. "We bumped into this result," he said.

Working in Ramalho-Santos' lab, graduate student Kathryn Blaschke and postdoctoral fellow Kevin Ebata, PhD, were comparing different commercial growth media for mouse stem cells. The researchers began exploring how certain ingredients altered gene activity within the stem cells. Eventually they discovered that adding vitamin C led to increased activity of key enzymes that release the brakes that can prevent activation of an array of genes.

The brakes on gene activation that vitamin C helps release are molecules called methyl groups. These methyl groups are added to DNA at specific points along the genome to prevent specific genes from getting turned on.

During the development of multicellular organisms, humans among them, different patterns of methylation arise in different cells as methyl groups are biochemically attached to DNA at specific points along the genome during successive cell divisions. Normally this gradual methylation, a key part of the developmental program, is not reversible.

But after fertilization and during early development, a class of enzymes called "Tet" acts on a wide array of the methyl groups on the DNA to remove these brakes, so that genes can be activated as needed.

The UCSF researchers demonstrated that Tet enzymes require vitamin C for optimal activity as they act to remove the methyl groups from the DNA and to stimulate gene activity that more faithfully mimics in cultured stem cells what occurs at early stages of development in the mouse embryo.

"Potential roles for vitamin C in the clinic -- including in embryo culture media used during in vitro fertilization, which currently do not contain vitamin C, and in cancers driven by aberrant DNA methylation -- deserve exploration," Ramalho-Santos, said.

In addition, scientists previously have found that many adult tissues also have stem cells, which can generate a variety of cell types found within a specific tissue. This raises the possibility that vitamin C might help maintain healthy stem cell populations in the adult, according to Ramalho-Santos.

"Although we did not in this paper address the function of Vitamin C in adult tissues, given the roles that Tet enzymes are now known to play in adult tissues, we anticipate that Vitamin C might also regulate Tet function in the adult," Ramalho-Santos said. "This remains to be determined."

Vitamin C already has become a popular supplement in recent decades, and potential health benefits of vitamin C supplementation continue to be investigated in clinical trials. It has been more than 80 years since vitamin C was first recognized as vital to prevent scurvy, a now rare connective-tissue disease caused by the failure of another enzyme that also relies on vitamin C.

The function of vitamin C as an antioxidant to prevent chemical damage is the likely reason why some commercial suppliers of growth media have included it in their products, Ramalho-Santos said, but other antioxidant molecules cannot replace Vitamin C in the enhancement of the activity of Tet enzymes.

Despite its importance, humans, unlike most animals and plants, cannot synthesize their own Vitamin C and must obtain it through their diet. The mouse makes vitamin C, but that fact does not diminish the expectation that the new findings will also apply to human development, according to Ramalho-Santos. Only adult liver cells in the mouse make vitamin C, he said.

Ramalho-Santos now aims to explore the newly discovered phenomenon in the living mouse. "The next step is to study vitamin C and gene expression in vivo," he said.



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