BACKTRACKING ON DNA

Accuracy is essential for life, so in converting the information stored in DNA into a form in which it can be used, a high level of precision is required. Dr Tanniemola Liverpool from the Department of Mathematics, working with colleagues from the University of Leeds, has developed a mathematical model for how the required accuracy is achieved.

A gene is the basic physical and functional unit of heredity. Genes are made up of DNA, which is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA, and the information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about three billion bases, and more than 99 percent of those bases are the same in all people. The order, or sequence, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences.

DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder.

An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a blueprint for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell. The journey from gene to protein is complex and consists of two major steps: transcription and translation, which together are known as gene expression.

During the process of transcription, the information stored in a gene’s DNA is transferred to a similar molecule called RNA in the cell nucleus. During transcription errors occasionally occur, and these can lead to defects in the protein being manufactured. In fact, an error of only 1 in 100,000 nucleotides is enough to give rise to proteins that do not function, which would lead ultimately to cell death.

The process of transcription is carried out by specialized enzymes known as RNA polymerases (RNAP) that move along the DNA, base by base. However, due to thermal fluctuations within the cell, the chemical reactions involved in transcription don't always follow the most likely (minimum energy) path and consequently there is a probability of around 1 in a 1,000 that a base-pair is incorrectly transcribed. Therefore, in order for cells to maintain the high level of accuracy required for life, they must have a mechanism for dealing with errors. Liverpool and colleagues have developed a theoretical model for how the required accuracy is achieved.

In the early 70s it was pointed out that in order to keep track of the information required to proof read (ie, check for and correct errors), the cell had to have processes that dissipate (waste) energy, otherwise they would contradict the second law of thermodynamics which states that unless energy is supplied, disorder (ie, lack of information) tends to increase. Experiments have suggested a number of possible mechanisms by which this might occur, but it is difficult to figure out which, if any, is the primary one, so exactly how these processes occur remains a mystery.

Liverpool’s paper, published today in Physical Review Letters, develops a mathematical model for proofreading in the transcription process, based on the fact that the RNAP does not move only in one direction along the DNA, but often makes random backward excursions as it transcribes the gene. The model shows how these ‘backtracks’ can improve the accuracy of transcription, and predicts the dependence of the probability of finding errors on the backtracking dynamics.

The results of the model suggest future experiments which can be used to discriminate between the different possible mechanisms. They should also shed light on error correction in other biological processes such as the translation of RNA to protein.

(Photo: Bristol U.)

University of Bristol

FIRST ACOUSTIC METAMATERIAL 'SUPERLENS' CREATED BY U. OF I. RESEARCHERS

A team of researchers at the University of Illinois has created the world’s first acoustic “superlens,” an innovation that could have practical implications for high-resolution ultrasound imaging, non-destructive structural testing of buildings and bridges, and novel underwater stealth technology.

The team, led by Nicholas X. Fang, a professor of mechanical science and engineering at Illinois, successfully focused ultrasound waves through a flat metamaterial lens on a spot roughly half the width of a wavelength at 60.5 kHz using a network of fluid-filled Helmholtz resonators.

According to the results, published in the May 15 issue of the journal Physical Review Letters, the acoustic system is analogous to an inductor-capacitor circuit. The transmission channels act as a series of inductors, and the Helmholtz resonators, which Fang describes as cavities that house resonating waves and oscillate at certain sonic frequencies almost as a musical instrument would, act as capacitors.

Fang said acoustic imaging is somewhat analogous to optical imaging in that bending sound is similar to bending light. But compared with optical and X-ray imaging, creating an image from sound is “a lot safer, which is why we use sonography on pregnant women,” said Shu Zhang, a U. of I. graduate student who along with Leilei Yin, a microscopist at the Beckman Institute, are co-authors of the paper.

Although safer, the resultant image resolution of acoustic imaging is still not as sharp or accurate as conventional optical imaging.

“With acoustic imaging, you can’t see anything that’s smaller than a few millimeters,” said Fang, who also is a researcher at the institute. “The image resolution is getting better and better, but it’s still not as convenient or accurate as optical imaging.”

The best tool for tumor detection is still the optical imaging, but exposure to certain types of electromagnetic radiation such as X-rays also has its health risks, Fang noted.

“If we wish to detect or screen early stage tumors in the human body using acoustic imaging, then better resolution and higher contrast are equally important,” he said. “In the body, tumors are often surrounded by hard tissues with high contrast, so you can’t see them clearly, and acoustic imaging may provide more details than optical imaging methods.”

Fang said that the application of acoustic imaging technology goes beyond medicine. Eventually, the technology could lead to “a completely new suite of data that previously wasn’t available to us using just natural materials,” he said.

In the field of non-destructive testing, the structural soundness of a building or a bridge could be checked for hairline cracks with acoustic imaging, as could other deeply embedded flaws invisible to the eye or unable to be detected by optical imaging.
“Acoustic imaging is a different means of detecting and probing things, beyond optical imaging,” Fang said.

Fang said acoustic imaging could also lead to better underwater stealth technology, possibly even an “acoustic cloak” that would act as camouflage for submarines. “Right now, the goal is to bring this ‘lab science’ out of the lab and create a practical device or system that will allow us to use acoustic imaging in a variety of situations,” Fang said.

(Photo: L. Brian Stauffer)

University of Illinois

BEYOND CO2: STUDY REVEALS GROWING IMPORTANCE OF HFCS IN CLIMATE WARMING

Some of the substances that are helping to avert the destruction of the ozone layer could increasingly contribute to climate warming, according to scientists from NOAA’s Earth System Research Laboratory and their colleagues in a new study published in the journal Proceedings of the National Academy of Sciences.

The authors took a fresh look at how the global use of hydrofluorocarbons (HFCs) is expected to grow in coming decades. Using updated usage estimates and looking farther ahead than past projections (to the year 2050), they found that HFCs — especially from developing countries — will become an increasingly larger factor in future climate warming.

“HFCs are good for protecting the ozone layer, but they are not climate friendly,” said David W. Fahey, a scientist at NOAA and second author of the new study. “Our research shows that their effect on climate could become significantly larger than we expected, if we continue along a business-as-usual path.”

HFCs currently have a climate change contribution that is small (less than 1 percent) in comparison to the contribution of carbon dioxide (CO2) emissions. The authors have shown that by 2050 the HFCs contribution could rise to 7 to 12 percent of what CO2 contributes. And if international efforts succeed in stabilizing CO2 emissions, the relative climate contribution from HFCs would increase further.

HFCs, which do not contain ozone-destroying chlorine or bromine atoms, are used as substitutes for ozone-depleting compounds such as chlorofluorocarbons (CFCs) in such uses as refrigeration, air conditioning, and the production of insulating foams. The Montreal Protocol, a 1987 international agreement, has gradually phased out the use of CFCs and other ozone-depleting substances, leading to the development of long-term replacements such as HFCs.

Though the HFCs do not deplete the ozone layer, they are potent greenhouse gases. Molecule for molecule, all HFCs are more potent warming agents than CO2 and some are thousands of times more effective. HFCs are in the “basket of gases” regulated under the 1997 Kyoto Protocol, an international treaty to reduce emissions of greenhouse gases.

The new study factored in the expected growth in demand for air conditioning, refrigerants, and other technology in developed and developing countries. The Montreal Protocol’s gradual phasing out of the consumption of ozone-depleting substances in developing countries after 2012, along with the complete phase-out in developed countries in 2020, are other factors that will lead to increased usage of HFCs and other alternatives.

Decision-makers in Europe and the United States have begun to consider possible steps to limit the potential climate consequences of HFCs. The PNAS study examined several hypothetical scenarios to mitigate HFC consumption. For example, a global consumption limit followed by a four percent annual reduction would cause HFC-induced climate forcing to peak in the year 2040 and then begin to decrease before the year 2050.

“While unrestrained growth of HFC use could lead to significant climate implications by 2050, we have shown some examples of global limits that can effectively reduce the HFCs’ impact,” said John S. Daniel, a NOAA coauthor of the study.

(Photo: NOAA)

National Oceanic and Atmospheric Administration

NATURAL DEEP EARTH PUMP FUELS EARTHQUAKES AND ORE

For the first time scientists have discovered the presence of a natural deep earth pump that is a crucial element in the formation of ore deposits and earthquakes.

The process, called creep cavitation, involves fluid being pumped through pores in deformed rock in mid-crustal shear zones, which are approximately 15 km below the Earth’s surface.

The fluid transfer through the middle crust also plays a key role in tectonic plate movement and mantle degassing.

The discovery was made by examining one millimetre sized cubes of exposed rock in Alice Springs, which was deformed around 320 million years ago during a period of natural mountain formation.

“We are seeing the direct evidence for one of the processes that got ore forming fluids moving up from the mantle to the shallow crust to form the ore deposits we mine today, it is also one of the mechanisms that can lead to earthquakes in the middle crust,” Dr Hough said.The evidence is described in a paper published in the latest edition of Nature entitled Creep cavitation can establish a dynamic granular fluid pump in ductile shear zones.

One of the paper’s author’s CSIRO Exploration and Mining scientist Dr Rob Hough said that this was the first direct observation of fluids moving through the mid-crustal shear zone.

“We are seeing the direct evidence for one of the processes that got ore forming fluids moving up from the mantle to the shallow crust to form the ore deposits we mine today, it is also one of the mechanisms that can lead to earthquakes in the middle crust,” Dr Hough said.

Research leader Dr Florian Fusseis, from the University of Western Australia, said that the discovery could provide valuable information in understanding how earthquakes are formed.

“While we understand reasonably well why earthquakes happen in general, due to stress build-up caused by motions of tectonic plates, the triggering of earthquakes is much more complex,” Dr Fusseis said.

“To understand the ‘where’ and ‘when’ of earthquakes, the ‘how’ needs to be understood first. We know that earthquakes nucleate by failure on a small part of a shear zone.”

Dr Fusseis said that while their sample did not record an earthquake it gave them an insight into the structures that could be very small and localized precursors of seismic failure planes.

The discovery was made possible through the use of high-resolution Synchrotron X-ray tomographic, scanning electron microscope observations at the nanoscale and advanced visualisation using iVEC in Western Australia.

The authors of the paper propose that the fluid movement, described as the granular fluid pump, is a self sustaining process where pores open and close allowing fluid and gas to be pumped out.

(Photo: University of Western Australia Dr Florian Fusseis)

Commonwealth Scientific and Industrial Research Organisation (CSIRO)

A MYSTERY SOLVED: SPACE SHUTTLE SHOWS 1908 TUNGUSKA EXPLOSION WAS CAUSED BY COMET

The mysterious 1908 Tunguska explosion that leveled 830 square miles of Siberian forest was almost certainly caused by a comet entering Earth's atmosphere, says new Cornell research. The conclusion is supported by an unlikely source: the exhaust plume from the NASA space shuttle launched a century later.

The research, accepted for publication (June 24) by the journal Geophysical Research Letters, published by the American Geophysical Union, connects the two events by what followed each about a day later: brilliant, night-visible clouds, or noctilucent clouds, that are made up of ice particles and only form at very high altitudes and in extremely cold temperatures.

"It's almost like putting together a 100-year-old murder mystery," said Michael Kelley, the James A. Friend Family Distinguished Professor of Engineering at Cornell, who led the research team. "The evidence is pretty strong that the Earth was hit by a comet in 1908." Previous speculation had ranged from comets to meteors to black holes.

The researchers contend that the massive amount of water vapor spewed into the atmosphere by the comet's icy nucleus was caught up in swirling eddies with tremendous energy by a process called two-dimensional turbulence, which explains why the noctilucent clouds formed a day later many thousands of miles away.

Noctilucent clouds are the Earth's highest clouds, forming naturally in the mesosphere at about 55 miles over the polar regions during the summer months when the mesosphere is around minus 180 degrees Fahrenheit (minus 117 degrees Celsius).

The space shuttle exhaust plume, the researchers say, resembled the water vapor from the comet. A single space shuttle flight injects 300 metric tons of water vapor into the Earth's thermosphere, and the water particles have been found to travel to the Arctic and Antarctic regions, where they form the clouds after settling into the mesosphere. The thermosphere is the layer of the atmosphere above the mesosphere.

Kelley and collaborators saw the noctilucent cloud phenomenon days after the space shuttle Endeavour (STS-118) launched on Aug. 8, 2007. Similar cloud formations had been observed following launches in 1997 and 2003.

Following the 1908 explosion, known as the Tunguska Event, the night skies shone brightly for several days across Europe, particularly Great Britain -- more than 3,000 miles away. Kelley said he became intrigued by the historical eyewitness accounts of the aftermath, and concluded that the bright skies must have been the result of noctilucent clouds. The comet would have started to break up at about the same altitude as the release of the exhaust plume from the space shuttle following launch. In both cases, water vapor was injected into the atmosphere.

The scientists have attempted to answer how this water vapor traveled so far without scattering and diffusing, as conventional physics would predict.

"There is a mean transport of this material for tens of thousands of kilometers in a very short time, and there is no model that predicts that," Kelley said. "It's totally new and unexpected physics."

This "new" physics, the researchers contend, is tied up in counter-rotating eddies with extreme energy. Once the water vapor got caught up in these eddies, the water traveled very quickly -- close to 300 feet per second.

Scientists have long tried to study the wind structure in these upper regions of the atmosphere, which is difficult to do by such traditional means as sounding rockets, balloon launches and satellites, explained Charles Seyler, Cornell professor of electrical engineering and paper co-author.

"Our observations show that current understanding of the mesosphere-lower thermosphere region is quite poor," Seyler said.

(Photo: M.J. Taylor and C.D. Burton/Utah State University)

Cornell University

BIO-ACOUSTIC RECORDERS COULD ANSWER QUESTION: DO WIND FARMS POSE RISKS TO MIGRATORY BIRDS?

Are wind turbines dangerous to migrating birds? Nobody really knows for sure because two-thirds of migrating bird species fly at night, making direct study of their habits and potential hazards a challenge, said Cornell researchers at the Cornell Workshop on Large-Scale Wind-Generated Power, June 13.

The workshop for U.S. and international experts took place in Hollister Hall, June 12-13 and scientists addressed issues associated with the growing use of wind power to generate electricity in the United States.

Radar, combined with state-of-the-art bio-acoustic listening devices, could be an effective way to record birds' flight calls at night and then quantify and identify species migrating past potential and existing wind-power sites, asserted Chris Clark, director of the Bioacoustics Research Program at Cornell's Lab of Ornithology, and Andrew Farnsworth, a postdoctoral associate at the lab and an expert on migrating birds, in a presentation. The bioacoustics program has developed such listening devices as well as the software to analyze them, Clark said.

Farnsworth showed a brief video of radar data from the network of weather surveillance radars in the continental United States, superimposed over a map of the country, revealing migrations in the night sky between sunset and sunrise on Oct. 1, 2008. The color-coded radar map illustrated areas of precipitation over the coasts as well as vast movements of tens of millions of birds, bats and insects across the entire country. In the densest areas, the color-scales indicated movement of 2,000 birds per cubic kilometer.

"You're talking about a massive movement of birds overnight," Farnsworth said.

Migrating birds evolved with past and present weather patterns, which means migration pathways tend to overlap with high-wind areas that have the greatest potential for wind-energy development, Farnsworth said. Though research shows that windows in tall buildings and housecats may be the greatest threat to migrating birds, the risks that wind turbines pose for these birds are not clear, he added.

Although radar data can show the magnitude, location, timing, speed and direction of migration patterns and provide information on key stopover sites, they do not identify types of birds or accurate flight altitudes, Farnsworth said. But combining radar data with data from flight call recordings and tracking tags on birds could allow researchers to identify many species in key areas.

Clark added that recorders are cost effective, can be automated for many months at remote sites, provide data on many species simultaneously, increase the probability of tracking secretive and endangered species, and could allow regulatory agencies to develop computer models to assess risks to birds from wind turbines.

He acknowledged, however, that using such acoustic technology could produce a massive "data crunch"; a single microphone over a three-to-four-month period can record 120 to 140 gigabytes of data, so data from several hundred microphones would be too much to process without advanced software. Also, researchers would need to better recognize the wide variety of flight calls and learn to integrate data from radar with those from acoustics and tracking tags, he added.

More research is needed, Clark stressed, to determine at what altitudes species tend to fly and whether birds sense turbine blades and avoid them.

Cornell has "opportunities and responsibilities" to make use of its multidisciplinary talents and resources, be proactive and engage the public to "do things today to save tomorrow," Clark asserted.

(Photo: Andrew Farnsworth/Lab of Ornithology)

Cornell University