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ScienceDaily (May 27, 2012) It took some 10 million years for Earth to recover from the greatest mass extinction of all time, latest research has revealed.
Life was nearly wiped out 250 million years ago, with only 10 per cent of plants and animals surviving. It is currently much debated how life recovered from this cataclysm, whether quickly or slowly. Recent evidence for a rapid bounce-back is evaluated in a new review article by Dr ZhongQiang Chen, from the China University of Geosciences in Wuhan, and Professor Michael Benton from the University of Bristol. They find that recovery from the crisis lasted some 10 million years, as explained May 27 in Nature Geoscience. There were apparently two reasons for the delay, the sheer intensity of the crisis, and continuing grim conditions on Earth after the first wave of extinction. The end-Permian crisis, by far the most dramatic biological crisis to affect life on Earth, was triggered by a number of physical environmental shocks -- global warming, acid rain, ocean acidification and ocean anoxia. These were enough to kill off 90 per cent of living things on land and in the sea. Dr Chen said: "It is hard to imagine how so much of life could have been killed, but there is no doubt from some of the fantastic rock sections in China and elsewhere round the world that this was the biggest crisis ever faced by life." Current research shows that the grim conditions continued in bursts for some five to six million years after the initial crisis, with repeated carbon and oxygen crises, warming and other ill effects. Some groups of animals on the sea and land did recover quickly and began to rebuild their ecosystems, but they suffered further setbacks. Life had not really recovered in these early phases because permanent ecosystems were not established. Professor Benton, Professor of Vertebrate Palaeontology at the University of Bristol, said: "Life seemed to be getting back to normal when another crisis hit and set it back again. The carbon crises were repeated many times, and then finally conditions became normal again after five million years or so." Finally, after the environmental crises ceased to be so severe, more complex ecosystems emerged. In the sea, new groups, such as ancestral crabs and lobsters, as well as the first marine reptiles, came on the scene, and they formed the basis of future modern-style ecosystems. Professor Benton added: "We often see mass extinctions as entirely negative but in this most devastating case, life did recover, after many millions of years, and new groups emerged. The event had re-set evolution. However, the causes of the killing -- global warming, acid rain, ocean acidification -- sound eerily familiar to us today. Perhaps we can learn something from these ancient events."
It's in the Genes: Research Pinpoints How Plants Know When to Flower
ScienceDaily (May 26, 2012) Scientists believe they've pinpointed the last crucial piece of the 80-year-old puzzle of how plants "know" when to flower.
Determining the proper time to flower, important if a plant is to reproduce successfully, involves a sequence of molecular events, a plant's circadian clock and sunlight. Understanding how flowering works in the simple plant used in this study -- Arabidopsis -should lead to a better understanding of how the same genes work in more complex plants grown as crops such as rice, wheat and barley, according to Takato Imaizumi, a University of Washington assistant professor of biology and corresponding author of a paper in the May 25 issue of the journal Science. "If we can regulate the timing of flowering, we might be able to increase crop yield by accelerating or delaying this. Knowing the mechanism gives us the tools to manipulate this," Imaizumi said. Along with food crops, the work might also lead to higher yields of plants grown for biofuels. At specific times of year, flowering plants produce a protein known as FLOWERING LOCUS T in their leaves that induces flowering. Once this protein is made, it travels from the leaves to the shoot apex, a part of the plant where cells are undifferentiated, meaning they can either become leaves or flowers. At the shoot apex, this protein starts the molecular changes that send cells on the path to becoming flowers. Changes in day length tell many organisms that the seasons are changing. It has long been known that plants use an internal time-keeping mechanism known as the circadian clock to measure changes in day length. Circadian clocks synchronize biological processes during 24hour periods in people, animals, insects, plants and other organisms. Imaizumi and the paper's co-authors investigated what's called the FKF1 protein, which they suspected was a key player in the mechanism by which plants recognize seasonal change and know when to flower. FKF1 protein is a photoreceptor, meaning it is activated by sunlight. "The FKF1 photoreceptor protein we've been working on is expressed in the late afternoon every day, and is very tightly regulated by the plant's circadian clock," Imaizumi said. "When this protein is expressed during days that are short, this protein cannot be activated, as there is no daylight in the late afternoon. When this protein is expressed during a longer day, this photoreceptor makes use of the light and activates the flowering mechanisms involving FLOWERING LOCUS T. The circadian clock regulates the timing of the specific photoreceptor for flowering. That is how plants sense differences in day length." This system keeps plants from flowering when it's a poor time to reproduce, such as the dead of winter when days are short and nights are long. The new findings come from work with the plant Arabidopsis, a small plant in the mustard family that's often used in genetic research. They validate predictions from a mathematical
model of the mechanism that causes Arabidopsis to flower that was developed by Andrew Millar, a University of Edinburgh professor of biology and co-author of the paper. "Our mathematical model helped us to understand the operating principles of the plants' daylength sensor," Millar said. "Those principles will hold true in other plants, like rice, where the crop's day-length response is one of the factors that limits where farmers can obtain good harvests. It's that same day-length response that needs controlled lighting for laying chickens and fish farms, so it's just as important to understand this response in animals. "The proteins involved in animals are not yet so well understood as they are in plants but we expect the same principles that we've learned from these studies to apply." First author on the paper is Young Hun Song, a postdoctoral researcher in Imaizumi's UW lab. The other co-authors are Benjamin To, who was a UW undergraduate student when this work was being conducted, and Robert Smith, a University of Edinburgh graduate student. The work was funded by the National Institutes of Health, and the United Kingdom's Biotechnology and Biological Sciences Research Council.
New Type of Male Contraceptive? Key Gene Essential for Sperm Development Discovered
ScienceDaily (May 24, 2012) A new type of male contraceptive could be created thanks to the discovery of a key gene essential for sperm development.
The finding could lead to alternatives to the conventional male contraceptives that rely on disrupting the production of hormones, such as testosterone. These treatments can cause side-effects such as irritability, mood swings and acne. Research, led by the University of Edinburgh, has shown how a gene -- Katnal1 -- is critical to enable sperm to mature in the testes. If scientists can regulate the Katnal1 gene in the testes, they could prevent sperm from maturing completely, making them ineffective without changing hormone levels. The research, which is published in the journal PLoS Genetics, could also help in finding treatments for cases of male infertility when malfunction of the Katnal1 gene hampers sperm development. Dr Lee Smith, Reader in Genetic Endocrinology at the University of Edinburgh's Centre for Reproductive Health, said: "If we can find a way to target this gene in the testes, we could potentially develop a non-hormonal contraceptive. "The important thing is that the effects of such a drug would be reversible because Katnal1 only affects sperm cells in the later stages of development, so it would not hinder the early stages of sperm production and the overall ability to produce sperm. "Although other research is being carried out into non-hormonal male contraceptives, identification of a gene that controls sperm production in the way Katnal1 does is a unique and significant step forward in our understanding of testis biology." Scientists found that male mice that were modified so they did not have the Katnal1 gene were infertile. Further investigation showed that this was because the gene was needed to allow the sperm to develop and mature. The researchers showed that Katnal1 was needed to regulate the scaffolding structures known as microtubules, which form part of the cells that support and provide nutrients to developing sperm. Breaking down and rebuilding these microtubules enables the sperm cells to move within the testes as they mature. Katnal1 acts as the essential controller of this process.
mission's principal investigator and professor of planetary science at the University of Arizona. Lauretta added that "this information is critical for assessing the likelihood of an impact from our target asteroid and provides important constraints on its mass and density, allowing us to substantially improve our mission design." The OSIRIS-REx spacecraft is to launch in 2016, reach asteroid (101955) 1999 RQ36 in 2019, examine it up close during a 505-day rendezvous, then return at least 60 grams (~1.9 ounces) of it to Earth in 2023. "In addition to the exciting Yarkovsky results, the low density shows that 1999 RQ36 is probably a loose aggregate of rocks--a so called rubble pile," said Jason Dworkin, the mission's project scientist and Chief of Astrochemistry at NASA's Goddard Space Flight Center in Greenbelt, Md. "This makes it an ideal target for OSIRIS-REx to collect loose surface material."
The researchers believe that this type of array could also be used to test the performance of individual invisibility cloaks, especially in instances where they may be positioned close together. In this study, for example, the cloaks worked very well when light was shone along the rows; however, when it was shown at different angles, imperfections were clearly visible.
The speed of the coil and the velocity imparted to the drug can be controlled by the amount of current applied; the MIT team generated pressure profiles that modulate the current. The resulting waveforms generally consist of two distinct phases: an initial high-pressure phase in which the device ejects drug at a high-enough velocity to "breach" the skin and reach the desired depth, then a lower-pressure phase where drug is delivered in a slower stream that can easily be absorbed by the surrounding tissue. Through testing, the group found that various skin types may require different waveforms to deliver adequate volumes of drugs to the desired depth. "If I'm breaching a baby's skin to deliver vaccine, I won't need as much pressure as I would need to breach my skin," Hogan says. "We can tailor the pressure profile to be able to do that, and that's the beauty of this device." Samir Mitragotri, a professor of chemical engineering at the University of California at Santa Barbara, is developing new ways to deliver drugs, including via jet injection. Mitragotri, who was not involved with the research, sees the group's technology as a promising step beyond jet injection designs currently on the market. "Commercially available jet injectors provide limited control, which limits their applications to certain drugs or patient populations," Mitragotri says. "[This] design provides excellent control over jet parameters, including speed and doses this will enhance the applicability of needleless drug devices." The team is also developing a version of the device for transdermal delivery of drugs ordinarily found in powdered form by programming the device to vibrate, turning powder into a "fluidized" form that can be delivered through the skin much like a liquid. Hunter says that such a powder-delivery vehicle may help solve what's known as the "cold-chain" problem: Vaccines delivered to developing countries need to be refrigerated if they are in liquid form. Often, coolers break down, spoiling whole batches of vaccines. Instead, Hunter says a vaccine that can be administered in powder form requires no cooling, avoiding the cold-chain problem.
Like Curry? New Biological Role Identified for Compound Used in Ancient Medicine
ScienceDaily (May 25, 2012) Oregon State University scientists just identified a new reason why some curry dishes, made with spices humans have used for thousands of years, might be good for you.
New research has discovered that curcumin, a compound found in the cooking spice turmeric, can cause a modest but measurable increase in levels of a protein that's known to be important in the "innate" immune system, helping to prevent infection in humans and other animals. This cathelicidin antimicrobial peptide, or CAMP, is part of what helps our immune system fight off various bacteria, viruses or fungi even though they hadn't been encountered before. Prior to this, it was known that CAMP levels were increased by vitamin D. Discovery of an alternative mechanism to influence or raise CAMP levels is of scientific interest and could open new research avenues in nutrition and pharmacology, scientists said. Turmeric is a flavorful, orange-yellow spice and an important ingredient in many curries, commonly found in Indian, South Asian and Middle Eastern cuisine. It has also been used for 2,500 years as a medicinal compound in the Ayurvedic system of medicine in India -- not to mention being part of some religious and wedding ceremonies. In India, turmeric is treated with reverence. The newest findings were made by researchers in the Linus Pauling Institute at OSU and published in the Journal of Nutritional Biochemistry, in collaboration with scientists from the University of Copenhagen in Denmark. The work was supported by the National Institutes of Health. "This research points to a new avenue for regulating CAMP gene expression," said Adrian Gombart, an associate professor of biochemistry and biophysics in the Linus Pauling Institute. "It's interesting and somewhat surprising that curcumin can do that, and could provide another tool to develop medical therapies." The impact of curcumin in this role is not nearly as potent as that of vitamin D, Gombart said, but could nonetheless have physiologic value. Curcumin has also been studied for its antiinflammatory and antioxidant properties. "Curcumin, as part of turmeric, is generally consumed in the diet at fairly low levels," Gombart said. "However, it's possible that sustained consumption over time may be healthy and help protect against infection, especially in the stomach and intestinal tract." In this study, Chunxiao Guo, a graduate student, and Gombart looked at the potential of both curcumin and omega-3 fatty acids to increase expression of the CAMP gene. They found no particular value with the omega-3 fatty acids for this purpose, but curcumin did have a clear effect. It caused levels of CAMP to almost triple. There has been intense scientific interest in the vitamin D receptor in recent years because of potential therapeutic benefits in treating infection, cancer, psoriasis and other diseases, the
researchers noted in their report. An alternative way to elicit a related biological response could be significant and merits additional research, they said. The CAMP peptide is the only known antimicrobial peptide of its type in humans, researchers said. It appears to have the ability to kill a broad range of bacteria, including those that cause tuberculosis and protect against the development of sepsis.
revealed several important details -- for example, the interaction between two parts of the Argonaute protein, called the PAZ and Mid domains, with the two ends of guide RNAs -Joshua-Tor's goal was to solve the structure of the entire human Argonaute protein in complex with a single human guide RNA. Overcoming a complicated series of technical challenges, her team has achieved this goal by analyzing the structure of a full-length human Argonaute-2 protein bound to a small RNA called miR-20a, which is known to play a role in cancer development. Although Argonautes from higher organisms diverged from their archebacterial cousins more than three billion years ago, the team's analysis shows remarkable similarity between the two structures, especially in the regions that are important for target recognition and slicing activity. "Our structure shows that the guide RNA, which is anchored at both ends by the PAZ and Mid domains, kinks and twists its way through the structure of the entire protein, making several points of contact within each domain and with the linker loops that join them," explains Joshua-Tor. "The guide RNA thus acts like a backbone that rigidly locks together the otherwise flexible Argonaute protein and gives it stability." The researchers speculate that the path threaded through the Argonaute by the guide RNAs could have evolved to maximize mutual stability, in turn making the protein-RNA complexes long-lived. This long life is critical for many biological processes that are mediated by Argonautes. "This is also the kind of information that might help us to design better synthetic guide RNAs for therapeutic use," explains Joshua-Tor. "It will also be useful to researchers who are trying to find more precise ways of blocking Argonaute activity."
With that penultimate act, the Space Exploration Technologies Corporation of Hawthorne, Calif., or SpaceX, made history as the first private company to send a craft, the Dragon, to the station. The grab which NASA refers to as a grapple occurred at 9:56 a.m. Eastern time on Friday. It looks like weve got us a Dragon by the tail, said Donald R. Pettit, the NASA astronaut on the station who was operating the robotic arm. Andre Kuipers, an European Space Agency astronaut, then took over the robotic arm to pull the Dragon to a docking port on the station, locking it there just after noon. After the hatches are opened on Saturday, the astronauts aboard the station will spend six days unloading the cargo brought up by the Dragon and replacing it with items to take back to Earth. The Dragon is to undock on Thursday and parachute into the Pacific Ocean off California. SpaceX launched the Dragon capsule on top of its Falcon 9 rocket on Tuesday. The company and NASA spent several days conducting tests to check the Dragons operations. On Thursday, it flew 1.5 miles beneath the station to test its communication and navigation systems. It passed those tests, then looped around the space station to begin its final approach. By design, the approach was slow, with built-in pauses. As part of the testing process, the crew sent commands to the capsule to stop or temporarily move away, ensuring that Dragon could be safely sent off if something went badly awry.
SpaceX did run into some difficulties with Dragons navigation sensors, one that took thermal images and one that bounced laser pulses, and that delayed the capture by a couple of hours. This is, I think, going to be recognized as a significantly historical step forward in space travel, SpaceXs chief executive, Elon Musk, said during a news conference. Hopefully the first of many to come. Mr. Musks dreams are far grander than delivering cargo to the space station. Although he would like to carry astronauts to the station in a few years, that would still be merely retracing accomplishments that the American and Russian space programs achieved decades ago. Its evolutionary, not revolutionary, Mr. Musk agreed in an interview last month. To accomplish Mr. Musks very long-term goal sending people to Mars, which he regards as essential for ensuring the survival of humanity SpaceX must create new technologies that fundamentally change the current equation of space travel, in which most of the vehicle is thrown away each time. Mr. Musk talks of reusable rockets, but his first attempt to accomplish that recovering the first stage of the Falcon 9 via parachute failed. Twice, in 2010, SpaceX tried this method, but each time the rocket stage disintegrated as it fell. On this flight, SpaceX gave up trying. A new idea is for the engines to fire again after they drop off, and the rocket stages would fly back to land to be refueled. SpaceX plans to begin tests of this vertical takeoff and landing concept, dubbed Grasshopper, this year. Mr. Musk also talks of building a giant rocket powered by next-generation engines using new fuels, bigger than the Falcon Heavy rocket he is hoping to launch within the next two years. Its going to be very big, he said. Very huge. Bigger than the Saturn V that launched NASA astronauts to the moon? Could be, he said with a smile. He said he would provide more details later this year or in 2013. SpaceX has also consistently underestimated the time it would take to accomplish its tasks. In 2006, when NASA selected it to develop the cargo ship, SpaceX said the first trip to the station would take three years; it took six. SpaceX also has a large backlog of commercial satellites it is under contract to launch. This track record may be relevant to Mr. Musks stated goal: he said he thought SpaceX could send people to Mars in 15 years 20 years at most. In that prediction, he said he hoped he was not off by a factor of two. Ill be 80, he said.
The secretary of the interior, Ken Salazar, said the plan would allow the rivers managers to release excess water more than twice as much as average flows through and over the hydroelectric dam at will to help propel silt and sediment downstream into the canyon. By mimicking the rivers original dynamics, Interior Department officials said, the flows could help restore the backwater ecosystems in which native fish are most at home. The goal is partly to enhance sandbars that create backwaters for an endangered fish, the humpback chub. The excess sand also nourishes beaches used by wildlife, hikers and rafters. Environmental groups like the Grand Canyon Truststrongly support the high-flow releases, which have been carried out experimentally three times before, most recently in 2008. In a telephone news conference, Mr. Salazar said the releases would be timed for when storms or snowmelt have carried large amounts of silt just downriver from the dam. The first high-flow release under the new protocol will probably come this fall, he added. The triggering conditions are related to the amount of sediment in the system, he said. When heavy rains occur in the Paria River watershed, which drains rocky territory in southwestern Utah, they frequently flush tons of silt into the Colorado, which the Paria meets below the dam.
The flexible flow plan will remain in effect through 2020. While normal flows through the turbines of the Glen Canyon Dam range from 8,000 to 22,500 cubic feet per second, the highflow events could reach 45,000 cubic feet per second and last anywhere from one hour to four days. At the highest flow, there is too much water to go through the hydroelectric turbines, and the excess is funneled over the dam. Anne Castle, assistant interior secretary for water and science, said in the news conference that the delivery of power to the six million customers served by the dam would not be significantly affected. The department also announced plans to change its management of nonnative trout in the river. The agency has been killing nonnative trout, which crowd out the humpback chub, at sites along the Colorado. The practice brought protests from American Indian groups, including the Zuni tribe, for whom these areas are sacred, Interior Department officials said. The new plan, described as experimental, instead envisions live removal of the trout for restocking in other waters, Ms. Castle said. Were trying to understand better the impact of those changes on the nonnative fish that are being removed and on the endangered fish, she said.
Fossil fuel-burning power plants, in particular coal-burning units, are a major source of the carbon dioxide that is rapidly warming the planet and altering the climate in ways that could impact crops and water supplies, raise sea level and lead to weather extremes. Even with the move toward alternative, sustainable and low-carbon sources of energy, ranging from solar and wind to hydrothermal, coal- and natural gas-burning power plants are being built at an increasing rate around the world. At some point, Smit said, carbon capture will be the only way to reduce carbon emissions sufficiently to stave off the worst consequences of climate change. Although no commercial power plants currently capture carbon dioxide on a large scale, a few small-scale and pilot plants do, using today's best technology: funneling emissions through a bath of nitrogen-based amines, which grab carbon dioxide from the flue gases. The amines are then boiled to release the CO2. Additional energy is required to compress the carbon dioxide so that it can be pumped underground. The energy needed for this process decreases the amount that can go into making electricity. Calculations show that for a coal-fired power plant, that could amount to approximately 30 percent of total energy generated. Solid materials should be inherently more energy-efficient than amine scrubbing, because the CO2 can be driven off at lower temperatures. But materials differ significantly in how tightly they grab CO2 and how easily they release it. The best process will be a balance between the two, Smit said. Smit and his UC Berkeley group worked with Bhown and EPRI scientists to establish the best criteria for a good carbon capture material, focusing on the energy costs of capture, release and compression, and then developed a computer model to calculate this energy consumption for any material. Smit then obtained a database of 4 million zeolite structures compiled by Rice University scientists and ran the structures through his model. Zeolites are porous materials made of silicon dioxide, the same composition as quartz. The team also computed the energy efficiency of 10,000 MOF structures, which are composites of metals like iron with organic compounds that, together, form a porous structure. That structure has been touted as a way to store hydrogen for fuel or to separate gases during petroleum refining. "The surprise was that we found many materials, some already known but others hypothetical, that could be synthesized" and work more energy efficiently than amines, Smit said. The best materials used 30 percent less energy than the amine process, though future materials may work even better. The computer model will work for structures other than zeolites and MOFs, Smit said. Bhown said that the theoretically best material will probably have a parasitic energy cost of about 10 percent, so processes that use 20 percent or less are more attractive. GPUs dramatically speed calculations Key to the team's success was using graphics processing units (GPUs) instead of standard computer central processing units (CPUs), GPUs reduced each structure's calculation, which involves complex quantum chemistry, from 10 days to 2 seconds. Bhown noted that most people believe that some economic incentives or regulatory frameworks are needed to implement carbon capture, and the EPRI's goal is to help the industry identify the best technologies for doing so. A survey that EPRI conducted recently suggested that developing any new technology would take 10-15 years even with adequate funding. "The collaboration between different parts of the Department of Energy illustrates what can be achieved if researchers working on the most fundamental aspects of carbon capture collaborate with their industry counterparts" says Karma Sawyer, DOE program director.
"This study shows how engineering and fundamental science can speed-up the process of discovery and implementation of promising materials ready to test in the field." "The hope is that there is a system set up such that, when someone comes up with a promising material, we can rapidly test it and get it to a readiness level pretty quickly," he said. "We are all excited by this work and look forward to pursuing it further." Other coauthors of the study are graduate students Li-Chiang Lin and Joseph A. Swisher of UC Berkeley; Adam H. Berger of the EPRI; Richard L. Martin, Chris H. Rycroft and Maciej Haranczyk of LBNL's Computational Research Division; post-doctoral fellows Jihan Kim and Kuldeep Jariwala of LBNL's Materials Science Division; and Michael W. Deem of the Departments of Bioengineering and Physics and Astronomy at Rice University. This work has been supported by the Department of Energy through National Energy Technology Laboratory, Advanced Research Projects Agency -- Energy (ARPA-E) and Office of Science, and through EPRI's Office of Technology Innovation. Smit is also director of the Department of Energy-funded Energy Frontier Research Center at UC Berkeley.
stubbornly persistent illusion. Immortality doesnt mean a perpetual existence in time without end, but rather resides outside of time altogether. This was clear with the death of my sister Christine. After viewing her body at the hospital, I went out to speak with family members. Christines husband Ed started to sob uncontrollably. For a few moments I felt like I was transcending the provincialism of time. I thought about the 20-watts of energy, and about experiments that show a single particle can pass through two holes at the same time. I could not dismiss the conclusion: Christine was both alive and dead, outside of time. Christine had had a hard life. She had finally found a man that she loved very much. My younger sister couldnt make it to her wedding because she had a card game that had been scheduled for several weeks. My mother also couldnt make the wedding due to an important engagement she had at the Elks Club. The wedding was one of the most important days in Christines life. Since no one else from our side of the family showed, Christine asked me to walk her down the aisle to give her away. Soon after the wedding, Christine and Ed were driving to the dream house they had just bought when their car hit a patch of black ice. She was thrown from the car and landed in a banking of snow. Ed, she said I cant feel my leg. She never knew that her liver had been ripped in half and blood was rushing into her peritoneum. After the death of his son, Emerson wrote Our life is not so much threatened as our perception. I grieve that grief can teach me nothing, nor carry me one step into real nature. Whether its flipping the switch for the Science experiment, or turning the driving wheel ever so slightly this way or that way on black-ice, its the 20-watts of energy that will experience the result. In some cases the car will swerve off the road, but in other cases the car will continue on its way to my sisters dream house. Christine had recently lost 100 pounds, and Ed had bought her a surprise pair of diamond earrings. Its going to be hard to wait, but I know Christine is going to look fabulous in them the next time I see her.
Disease That Stunts Infants' Growth Traced to Same Gene That Makes Kids Grow Too Fast
ScienceDaily (May 27, 2012) UCLA geneticists have identified the mutation responsible for IMAGe syndrome, a rare disorder that stunts infants' growth. The twist? The mutation occurs on the same gene that causes Beckwith-Wiedemann syndrome, which makes cells grow too fast, leading to very large children.
Published in the May 27 edition ofNature Genetics, the UCLA findings could lead to new ways of blocking the rapid cell division that allows tumors to grow unchecked. The discovery also offers a new tool for diagnosing children with IMAGe syndrome, which until now has been difficult to accurately identify. The discovery holds special significance for principal investigator Dr. Eric Vilain, a professor of human genetics, pediatrics and urology at the David Geffen School of Medicine at UCLA. Nearly 20 years ago, as a medical resident in his native France, Vilain cared for two boys, ages 3 and 6, who were dramatically short for their ages. Though unrelated, both children shared a mysterious malady marked by minimal fetal development, stunted bone growth, sluggish adrenal glands, and undersized organs and genitals. "I never found a reason to explain these patients' unusual set of symptoms," explained Vilain, who is also director of the UCLA Institute for Society and Genetics. "I've been searching for the cause of their disease since 1993." When Vilain joined UCLA as a genetics fellow, the two cases continued to intrigue him. His mentor, then UCLA geneticist Dr. Edward McCabe, recalled a similar case from his previous post at Baylor College of Medicine. The two of them obtained blood samples from the three cases and analyzed the patients' DNA for mutations in suspect genes, but uncovered nothing. Vilain and McCabe approached the Journal of Clinical Endocrinology and Metabolism, and in 1999 published the first description of the syndrome, which they dubbed IMAGe, an acronym of sorts for the condition's symptoms: intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia and genital anomalies. Over the next decade, about 20 cases were reported around the world. But the cause of IMAGe syndrome remained a mystery. Help arrived unexpectedly last year when Vilain received an email from Argentinian physician Dr. Ignacio Bergada, who had unearthed the 1999 journal article. He told Vilain about a large family he was treating in which eight members suffered the same symptoms described in the study. All of the family members agreed to send their DNA samples to UCLA for study. Vilain realized that he had stumbled across the scientific equivalent of winning the lottery. He assembled a team of UCLA researchers to partner with Bergada and London endocrinologist Dr. John Achermann. "At last we had enough samples to help us zero in on the gene responsible for the syndrome," Vilain said. "Sequencing technology had also advanced in sophistication over the past two decades, allowing us to quickly analyze the entire family's DNA samples." Vilain's team performed a linkage study, which identifies disease-related genetic markers passed down from one generation to another. The results steered Vilain to a huge swath of Chromosome 11. The UCLA Center for Clinical Genomics performed next-generation sequencing, a powerful new technique that enabled the scientists to scour the enormous area in just two weeks and
tease out a slender stretch that held the culprit mutation. The team also uncovered the same mutation in the original three cases described by Vilain in 1999. A word of explanation: Located on 23 pairs of chromosomes, human genes hold the codes for making cellular proteins, the building blocks for our bodies. Most of the human diseases resulting from mutations in a single gene can be blamed on changes in a protein-coding sequence. By scanning the entire exome, or protein-coding factory of the genome, clinical geneticists can interpret every gene variant to track down the mutations that produce a patient's disease and rapidly reach a clear-cut diagnosis. "We discovered a mutation in a tiny sliver of the chromosome that appeared in every family member affected by IMAGe syndrome," said Vilain. "This was a big step forward. Now we can use gene sequencing as a tool to screen for the disease and diagnose children early enough for them to benefit from medical intervention. "We were a little surprised, because the mutation was located on a famous gene recognized for causing Beckwith-Wiedemann syndrome," he added. "The two diseases are polar opposites of each other." Children born with Beckwith-Wiedemann syndrome -- named for the two doctors who discovered it -- grow very large with big adrenal glands, elongated bones and oversized internal organs. Because their cells grow so fast, children with the disorder typically die of cancer at a young age. The disease affects one in 15,000 births. "Finding opposite functions in the same gene is a rare biological phenomenon" emphasized Vilain. "When the mutation appeared in the slim section we identified, the infant developed IMAGe syndrome. If the mutation fell anywhere else in the gene, the child was born with Beckwith-Wiedemann. That's really quite remarkable." IMAGe syndrome patients also tend to die young due to poor adrenal activity, which physicians treat with hormone-replacement therapy. The findings proved that Vilain and his colleagues had identified the correct mutation, bringing his 20-year odyssey to a successful end. "Our findings leave no doubt that this set of symptoms is a true syndrome and not just a figment of my imagination," said Vilain. "What makes this special for me is finally being able to unravel what caused the lifethreatening disease in the two patients I saw nearly 20 years ago," he added. "As a clinical scientist, the reward for successful research is uncovering new clues that allow us to help patients feel better by improving their medical care." The IMAGe mutation's ability to miniaturize organisms and halt growth could offer intriguing clinical benefits, he noted. "Our next effort will focus on manipulating the mutation's strong influence on growth to shrink tumors in the adrenal glands and other internal organs," explained Vilain. Vilain's coauthors included first author Valerie Arboleda, Hane Lee, Alice Fleming, Abhik Banerjee, Emmanuele Delot, Imilce Rodriguez-Fernandez, Esteban Dell'Angelica, Stanley Nelson and Julian Martinez-Agosto, all of UCLA; Bruno Ferraz-de-Souza of University of San Paulo in Brazil; Bergada of Hospital de Ninos Ricardo Gutierrez, Argentina; and Achermann of University College London Institute of Child Health. The study was funded by the Doris Duke Charitable Foundation, Wellcome Trust and National Institute of Child Health and Human Development (grants RO1HD068 and 1F31HD068136).
Garlic Constituent Blocks Biofilm Formation, Could Benefit Cystic Fibrosis Patients and Others
ScienceDaily (May 27, 2012) E Pluribus Unum, the de facto motto of the United States, could just as well apply to biofilm-forming bacteria. Bacterial biofilms are far more resistant than individual bacteria to the armories of antibiotics we have devised to combat them. Now Tim Holm Jakobsen and Michael Givskov of the University of Copenhagen, and their many collaborators have pinpointed a constituent of garlic that attacks a key step in the development of biofilms, in an effort they hope may offer help in particular for patients with cystic fibrosis.
The research is published in the May 2012 issue of Antimicrobial Agents and Chemotherapy. In earlier work, Givskov and his colleagues showed that "crude extracts of garlic inhibit the expression of a large number of genes that are controlled by bacterial quorum sensing [communication among bacterial cells involved in biofilm development], and that extracts promote a rapid clearing of pulmonary Pseudomonas aeruginosainfection in mice," he says. "These findings encouraged us to identify and assess the efficacy of the pure active compound." That compound turned out to be ajoene, the major constituent of a multitude of sulfurcontaining compounds produced when garlic is crushed, says Jakobsen. The team then showed in P. aeruginosa that ajoene inhibits expression of 11 genes that are controlled by quorum sensing. "These key genes are regarded as crucial for the ability of P. aeruginosa to cause disease," he says. "We also found ajoene to reduce the production of rhamnolipid, a compound that shields the biofilm bacteria from the white blood cells that otherwise would destroy bacteria, and that by combining ajoene with the antibiotic tobramycin, it was possible to kill over 90 percent of bacteria living in a biofilm," says Jakobsen. "Our study is part of a series of comprehensive investigations of natural compounds targeting bacterial quorum sensing systems, and it further strengthens previous proof of concept research we conducted on the potential of compounds which block communication among pathogen cells in contrast to simply killing bacteria, as conventional antibiotics do," says Jakobsen. Such alternative approaches "may postpone or minimize development of antibiotic resistance," he adds. Jakobsen says the garlic project grew out of a major donation from the German Cystic Fibrosis Association. "In CF patients,P. aeruginosa infection leads to bronchieciasis, pulmonary fibrosis, respiratory failure, and death," he says. "Despite intensive antibiotic traatment, CF patients have a life expectancy of about 40 years, and the main cause of death in CF patients remains complications associated with [this infection]." Jakobsen's team and the German CF Association have patented the action of ajoene against biofilms, and are seeking a pharmacutical partner to develop antimicrobial drugs based on ajoene. Jakobsen notes that garlic has been used medicinally "for thousands of years." Garlic not only has antibacterial properties; it has anti-viral, anti-fungal, and anti-protozoal properties as well, and it has beneficial effects on the cardiovascular and immune systems, as well, he says.
New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests
ScienceDaily (May 26, 2012) Recent recommendations from the U.S. Preventive Services Task Force (USPSTF) advising elimination of routine prostate-specific antigen (PSA) screening for prostate cancer in healthy men are likely to encounter serious pushback from primary care physicians, according to results of a survey by Johns Hopkins investigators.
In a survey of 125 primary care doctors, the researchers found that while doctors agreed with older recommendations to curtail routine screening in men over age 75 and among those not expected to live 10 or more years, a large number said they faced significant barriers to stopping PSA testing in men who had been receiving it regularly. The most frequently cited reason by 74.4 percent of physicians was, "My patients expect me to continue getting yearly PSA tests," followed by 66 percent of them who said, "It takes more time to explain why I'm not screening than to just continue screening." More than half of those surveyed in the new study believed that, "By not ordering a PSA, it puts me at risk for malpractice." The survey was conducted in November 2011, right after draft recommendations were made to end routine screening of all men, but before last week, when the draft recommendations were officially approved. "It can be very difficult for doctors to break down the belief that all cancer screening tests are invariably good for all people all the time," says Craig E. Pollack, M.D., M.H.S., an assistant professor in the Division of General Internal Medicine at the Johns Hopkins University School of Medicine, and leader of the study published online in the journal Cancer. "Everyone agrees that PSA screening isn't as good as we want it to be. If we had a test that was a slam dunk, it would be different. But now we know that for many men, the benefits may be small and the harms significant." Each year, more than 33,000 American men die of prostate cancer, and 20 million get the PSA test to detect the disease early. According to the USPSTF, evidence suggests the potential harms caused by PSA screening of healthy men as a means of identifying prostate cancer outweigh its potential to save lives and that routine annual screening should be eliminated in the healthy. Elevated PSA readings are not necessarily evidence of prostate cancer, and can lead to unnecessary prostate biopsy. In addition, even when biopsies reveal signs of prostate cancer cells, evidence shows that a large proportion will never cause harm, even if left untreated. The disease in older men often progresses slowly so that those who have it frequently die of other causes. Treatments for prostate cancer can include the removal of the prostate, radiation or other therapies, each of which has the potential to cause serious problems like erectile dysfunction, complete impotence, urinary incontinence or bowel damage. And men who choose to "watch and wait" after elevated PSA readings must live with the anxiety of knowing they have an untreated cancer that could start to progress. In the new study, Pollack and his colleagues found that while most physicians said they took age and life expectancy into account when deciding to order PSA screening, many also said they had a hard time estimating life expectancy in their patients and could use a better tool. H. Ballentine Carter, M.D., a professor of urology at Johns Hopkins and the senior investigator on the study, is planning to investigate the potential of individualized prostate cancer screening recommendations. Specifically, he and colleagues plan to create a decision-
making tool that incorporates age, life expectancy, family history and prior PSA results in order to help doctors and their patients make better choices for prostate cancer screening. In another report derived from results of Pollack's and Carter's survey, published in April in the Archives of Internal Medicine, the researchers say nearly half of the providers agreed with the new USPSTF recommendations to eliminate routine screening for healthy men. Still, less than two percent said they would no longer order routine PSA screening in response to the draft recommendations; 21.9 percent said they would be much less likely to do so; 38.6 percent said they would be somewhat less likely to do so; and 37.7 percent said they would not change their screening practices. "Men often expect PSA screening to be part of their annual physical," Pollack says. "To change their minds, we need to address their perceptions about screening, allow time for screening discussions and reduce concerns regarding malpractice litigation." The studies were supported in part by a Maryland Cigarette Restitution Fund Research Grant to Johns Hopkins. Other Johns Hopkins researchers involved with the studies included Elizabeth A. Platz, Sc.D., M.P.H.; Nrupen A. Bhavsar, Ph.D., M.P.H.; Gary Noronha, M.D.; Gene E. Green, M.D.; and Sean Chen, B.A.
There is nothing better than a ripe, red, homegrown tomato, and now researchers reporting online on May 24 in Current Biology, a Cell Press publication, have figured out just what it is that makes some of them so awfully good (and your average supermarket tomato so bland). "We now know exactly what we need to do to fix the broken tomato," said Harry Klee of the University of Florida. Tomato flavor depends on sugars, acids, and a host of less well-defined aroma volatiles (so named for the ease with which they vaporize, sending scent molecules into the air). Klee's team set out to define the chemicals that are most important to our fondness for one particular tomato or another. First, they assembled chemical profiles of 278 tomato samples representing152 heirloom varieties, most of which were bred before the ubiquitous commercial tomatoes of today even existed. That effort turned up an unexpectedly large chemical diversity within the heirloom tomatoes -- with variation in some volatile contents of as much as 3,000-fold across cultivars. That diversity presented the researchers with an opportunity to really explore what makes consumers favor one tomato over another. They did a series of taste tests with a consumer panel using a subset of those heirlooms that represented the most chemical diversity. Panelists rated their overall liking of each variety as well as the overall tomato flavor intensity, sweetness, and sourness. Panelists also rated supermarket tomatoes in the same way. A sophisticated statistical analysis of the chemistry and taste test results showed that flavor intensity traces to 12 different compounds and sweetness to another 12, including 8 that were also important for overall flavor. The researchers also found that some flavor volatiles influence the perception of sweetness through our sense of smell. "In other words," Klee says, "there are volatile chemicals unrelated to sugars that make things taste sweeter." That raises the tantalizing possibility that this feature might be played up in tomatoes and other foods to make us experience no-calorie sweetness through our noses instead of our tongues. The analysis also showed that some of the volatiles most abundantly present in tomatoes offer little in terms of our enjoyment of them in comparison to other and much more rare ingredients. "This is the first step to restoring good flavor in commercial tomatoes," Klee says, and that could go a long way. "Consumers care deeply about tomatoes," he says. "Their lack of flavor is a major focus of consumer dissatisfaction with modern agriculture. One could do worse than to be known as the person who helped fix flavor."
We Pump Water from Underground. It Flows to the Ocean. The Oceans Are Getting Deeper.
Its easy to see how overwatering our crops would deplete the groundwater supply and cause land nearby to sink, but could it cause sea level to rise on a global scale? Yes, according to a model published in Nature Geosciences, that attributes 42% of the sea-level rise over the past half century to groundwater use. Ninety percent of readily available freshwater is underground, and water used for drinking or crop irrigation must, of course, be brought above ground. That water then evaporates or flows into rivers, entering the water cycle and eventually the oceans, making them deeper. Sea levels rose by 1.8 millimeters per year in the last half of the century, but calculations of the contribution from melting ice and rising sea temperatures (which causes water to expand) accounted for only 1.1 millimeters of that. This new model found that the remaining sea-level rise could be explained by groundwater depletion. Some more data is needed to prove the link conclusively, but it suggests that the global consequences of groundwater deserve a more serious look.
helped it to respond to climate change very rapidly. However, changes to interactions may hinder other species, potentially putting them at risk of extinction." Co-author Professor Jane Hill, of the Department of Biology at the University of York, said: "There will be winners and losers from climate change. It is important that we begin to understand how the complex interactions between species affect their ability to adapt to climate change so we can identify those that might be at risk and where to focus conservation efforts."
ScienceDaily (May 24, 2012) A forensic approach that links changes deep below a volcano to signals at the surface is described by scientists from the University of Bristol in a paper published May 24 in Science. The research could ultimately help to predict future volcanic eruptions with greater accuracy.
Using forensic-style chemical analysis, Dr Kate Saunders and colleagues directly linked seismic observations of the deadly 1980 Mount St. Helens eruption to crystal growth within the magma chamber, the large underground pool of liquid rock beneath the volcano. Over 500 million people live close to volcanoes which may erupt with little or no clear warning, causing widespread devastation, disruption to aviation and even global effects on climate. Many of the world's volcanoes are monitored for changes such as increases in seismicity or ground deformation. However, an on-going problem for volcanologists is directly linking observations at the surface to processes occurring underground. Dr Saunders and colleagues studied zoned crystals, which grow concentrically like tree rings within the magma body. Individual zones have subtly different chemical compositions, reflecting the changes in physical conditions within the magma chamber and thus giving an indication of volcanic processes and the timescales over which they occur. Chemical analysis of the crystals revealed evidence of pulses of magma into a growing chamber within the volcano. Peaks in crystal growth were found to correlate with increased seismicity and gas emissions in the months prior to the eruption. Dr Saunders said: "Such a correlation between crystal growth and volcanic seismicity has been long anticipated, but to see such clear evidence of this relationship is remarkable." This forensic approach can be applied to other active volcanoes to shed new light upon the nature and timescale of pre-eruptive activity. This will help scientists to evaluate monitoring signals at restless volcanoes and improve forecasting of future eruptions. The research was funded by the Natural Environment Research Council (NERC).
Synchronized Brains: Feeling Strong Emotions Makes People's Brains 'Tick Together'
ScienceDaily (May 24, 2012) Experiencing strong emotions synchronizes brain activity across individuals, a research team at Aalto University and Turku PET Centre in Finland has revealed.
Human emotions are highly contagious. Seeing others' emotional expressions such as smiles triggers often the corresponding emotional response in the observer. Such synchronization of emotional states across individuals may support social interaction: When all group members share a common emotional state, their brains and bodies process the environment in a similar fashion. Researchers at Aalto University and Turku PET Centre have now found that feeling strong emotions makes different individuals' brain activity literally synchronous. The results revealed that especially feeling strong unpleasant emotions synchronized brain's emotion processing networks in the frontal and midline regions. On the contrary, experiencing highly arousing events synchronized activity in the networks supporting vision, attention and sense of touch. "Sharing others' emotional states provides the observers a somatosensory and neural framework that facilitates understanding others' intentions and actions and allows to 'tune in' or 'sync' with them. Such automatic tuning facilitates social interaction and group processes," says Adjunct Professor Lauri Nummenmaa from the Aalto University, Finland. "The results have major implications for current neural models of human emotions and group behavior. It also deepens our understanding of mental disorders involving abnormal socioemotional processing," Nummenmaa says. Participants' brain activity was measured with functional magnetic resonance imaging while they were viewing short pleasant, neutral and unpleasant movies.
Locating Ground Zero: How the Brain's Emergency Workers Find the Disaster Area
ScienceDaily (May 24, 2012) Like emergency workers rushing to a disaster scene, cells called microglia speed to places where the brain has been injured, to contain the damage by 'eating up' any cellular debris and dead or dying neurons. Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have now discovered exactly how microglia detect the site of injury, thanks to a relay of molecular signals. Their work, recently published in Developmental Cell, paves the way for new medical approaches to conditions where microglia's ability to locate hazardous cells and material within the brain is compromised.
"Considering that they help keep our brain healthy, we know surprisingly little about microglia," says Francesca Peri, who led the work. "Now, for the first time, we've identified the mechanism that allows microglia to detect brain injury, and how that emergency call is transmitted from neuron to neuron." When an emergency occurs, cries can alert bystanders, who will dial the emergency number. A call will go out over the radio, and ambulances, police or fire engines in the area will respond as needed. In the brain, Peri and colleagues found, injured neurons send out their own distress cry: they release a molecule called glutamate. Neighbouring neurons sense that glutamate and respond by taking up calcium. As glutamate spreads out from the injury site, this creates a wave of calcium swallowing. Along that wave, as neurons take up calcium they release a third molecule, called ATP. When the wave comes within reach, a microglial cell detects that ATP and takes it as a call to action, moving in that direction -- essentially tracing the wave backwards until it reaches the injury. Scientists knew already that microglia can detect ATP, but this molecule doesn't last long outside of cells, so there were doubts about how ATP alone could be a signal that carried far enough to reach microglia located far from the site of injury. The trick, as Peri and colleagues discovered, is the long-lasting glutamate-driven calcium wave that can travel the length of the
brain. Thanks to this wave, the ATP signal is not just emitted by the injured cells, but is repeatedly sent out by the neurons along the way, until it reaches microglia. Dirk Sieger and Christian Moritz in Peri's lab took advantage of the fact that zebrafish have transparent heads, which allow scientists to peer down a microscope straight into the fish's brain. They used a laser to injure a few of the fish's brain cells, and watched fluorescentlylabelled microglia move in on the injury. When they genetically engineered zebrafish to make neurons' calcium levels traceable under the microscope, too, the scientists were able to confirm that when the calcium wave reached microglia, these cells immediately started moving toward the injury. Knowing all the steps in this process, and how they feed into each other, could help to design treatments to improve microglia's detection ability, which go awry in conditions such as Alzheimer's and Parkinson's diseases.