Monday, August 3, 2009


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Researchers have discovered that the sea lamprey, which emerged from jawless fish first appearing 500 million years ago, dramatically remodels its genome. Shortly after a fertilized lamprey egg divides into several cells, the growing embryo discards millions of units of its DNA.

The findings were published in the Proceedings of the National Academy of Sciences. The lead author is Jeramiah Smith, a postdoctoral fellow in genome sciences at the University of Washington (UW) working in the Benaroya Research Institute laboratory of Chris Amemiya, who is also a UW affiliate professor of biology.

Theirs is believed to be the first recorded observation of a vertebrate -- an animal with a spinal column -- extensively reorganizing its genome as a normal part of development. A few invertebrate species, like some roundworms, have been shown to undergo extensive genome remodeling. However, stability was thought to be vital in vertebrates' genomes to assure their highly precise, normal functioning. Only slight modifications to allow for immune response were believed to occur in the vertebrate genome, not broad-scale rearrangements.

Smith, Amemiya and their research team inadvertently discovered the dynamic transformations in the sea lamprey genome while studying the genetic origins of its immune system. The researchers were trying to deduce how the sea lamprey employs a copy-and-paste mechanism to generate diverse receptors for detecting a variety of pathogens.

The researchers were surprised to notice a difference between the genome structure in the germline -- the cells that become eggs and the sperm that fertilize them -- and the genome structure in the resulting embryonic cells. The DNA in the early embryonic cells had myriad breaks that resembled those in dying cells ...but the cells weren't dying. The embryonic cells had considerably fewer repeat DNA sequences than did the sperm cells and their precursors.

"The remodeling begins at the point when the embryo turns on its own genes and no longer relies on its mom's store of mRNA," said Smith.

The restructuring doesn't occur all at once, but continues for a long while during embryonic development. It took at lot of work for the scientists to see what was lost and when. They learned, among other findings, that the remodeled genome had fewer repeats and specific gene-encoding sequences. Deletions along the strands of DNA are also thought to move certain regulatory switches in the genome closer to previously distant segments.

The scientists don't know how this happens, or why. Smith said that his favorite hypothesis, yet unproven, is that the extra genetic material might play a role in the proliferation of precursor cells for sperm and eggs, and in early embryonic development. The genetic material might then be discarded either when it is no longer needed or to prevent abnormal growth.

The alteration of the sea lamprey genome and of invertebrates that restructure their genome appears to be tightly regulated, according to Smith, yet the resulting structural changes seem almost like the DNA errors that give rise to cancers or other genomic disorders in higher animals. Learning how sea lamprey DNA rearrangements are regulated during development might provide information on what stabilizes or changes the genome, he said, as well the role of restructuring in helping form different types of body cells, like fin, muscle, or liver cells.

If 20 percent of their genome disappears, how do sea lampreys pass along the full complement of their genes to their offspring?

"The germline -- those precursor cells for sperm and eggs -- is a continuous lineage through time," Smith explained. "The precursor cells for sperm and egg are set apart early in lamprey development. The genome in that cell population should never change." Genetic material is assumed to be lost only in the early embryonic cells destined to become body parts and not in cells that give rise to the next generation. The researchers have been looking for the primordial stem cells for sperm and eggs hidden away in the lamprey, but they are difficult to find.

Researchers do not yet know how the sea lamprey's genome guides the morphing it undergoes during its life. Sea lampreys have a long juvenile life as larvae in fresh water, where they eat on their own. Their short adult lives are normally spent in the sea as blood-sucking parasites. Their round, jawless mouths stick like suction cups to other fish. Several circular rows of teeth rasp through the skin of their unlucky hosts. Their appetite is voracious.

Later, as they return to streams and rivers along the northern Atlantic seaboard, sea lampreys atrophy until they are little more than vehicles for reproduction. After mating, they perish. Populations of sea lamprey were landlocked in the Great Lakes and other nearby large lakes after canals and dams were built in the early 1900's. They thrive by parasitizing (and killing) commercially important fish species and are considered a nuisance in the Great Lakes region.

Biologists are interested in the sea lamprey partly because of its alternating lifestyles, but largely because it represents a living fossil from around the time vertebrates originated. Close relatives of sea lampreys were on earth before the dinosaurs. It's possible that the sea lamprey's dynamic genome biology might someday be traced back in evolutionary history to a point near, and perhaps including, a common ancestor of all vertebrates living today, the authors of the study noted.

"Sea lampreys have a half billion years of evolutionary history," Smith said. "Evolutionary biologists and geneticists can compare their genomes to other vertebrates and humans to see what parts of the lamprey genome might have been present in our primitive ancestors. We might begin to understand how changes in the sea lamprey genome led to their distinct body structure and how fishes evolved from jawless to jawed."

Amemiya added, "We don't really know where this discovery about the sea lamprey's remodeling of its genome will take us. It's common in science for the implications of a finding not to be realized for several decades. It's less about connecting the dots to a specific application, and more about obtaining a broad understanding of how living things are put together."

(Photo: Great Lakes Fishery Commission)

University of Washington


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Using high-speed cinematography, scientists at Cambridge University have discovered that individual algal cells can regulate the beating of their flagella in and out of synchrony in a manner that controls their swimming trajectories. Their research was published on the 24th July in the journal Science.

The researchers studied the unicellular organism Chlamydomonas reinhardtii, which has two hair-like appendages known as flagella. The beating of flagella propels Chlamydomonas through the fluid and simultaneously makes it spin about an axis.

The researchers found that cells can beat their flagella in two fundamentally distinct modes: synchronised, with nearly identical frequencies and positions, and unsynchronised, with two rather different frequencies. Using a specialised apparatus to track the swimming trajectories of individual cells, the group showed that the periods of synchrony correspond to nearly straight-line motion, while sharp turns result from the asynchronous beating. Whereas previous studies had suggested that these modes were associated with different subpopulations of cells, the new work shows that the cells actually control the frequencies and thereby switch back and forth between the two modes. In essence, this suggests Chlamydomonas has two 'gears'.

Moreover, the researchers have developed a mathematical analysis that describes the two beating flagella as "coupled oscillators," in a way similar to models of synchronised flashing of fireflies and the "Mexican wave" of people in a stadium. Analyzing terabytes of data on the patterns of synchronisation, they showed that the strength of the coupling was consistent with it arising from the fluid flows set up by the beating flagella. These observations constitute the first direct demonstration that hydrodynamic interactions are responsible for synchronisation, which has long been predicted to lead to such coordination.

Professor Raymond E. Goldstein, the Schlumberger Professor of Complex Physical Systems in the Department of Applied Mathematics and Theoretical Physics (DAMTP) and lead author of the study, said: "These results indicate that flagellar synchronization is a much more complex problem than had been appreciated, and involves a delicate interplay of cellular regulation, hydrodynamics, and biochemical noise."

Funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the work is part of a larger effort to improve our knowledge of evolutionary transitions from single-cell organisms (like Chlamydomonas) to multicellular ones. In addition, the flagella of Chlamydomonas cells are nearly identical to the cilia in the human body. In many of life's processes, from reproduction to respiration, coordinated action of cilia plays a crucial role. For this reason, insight into synchronization and its control may have significant implications for human health and disease.

(Photo: Cambridge U.)

University of Cambridge


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Much as meteorologists predict the path and intensity of hurricanes, Indiana University's Alessandro Vespignani believes we will one day predict with unprecedented foresight, specificity and scale such things as the economic and social effects of billions of new Internet users in China and India, or the exact location and number of airline flights to cancel around the world in order to halt the spread of a pandemic.

In "Perspectives" section of the journal Science, Vespignani writes that advances in complex networks theory and modeling, along with access to new data, will enable humans to achieve true predictive power in areas never before imagined. This capability will be realized as the one wild card in the mix -- the social behavior of large aggregates of humans -- becomes more definable through progress in data gathering, new informatics tools and increases in computational power.

Vespignani is the James H. Rudy Professor of Informatics and adjunct professor of physics and statistics at IU, where he is also the director of the Center for Complex Networks and Systems Research (CNetS) at IU's Pervasive Technology Institute and the IU Bloomington School of Informatics and Computing.

Researchers have already shown they can track the movement of as many as 100,000 people at a time over six months using mobile phone data, and use worldwide currency traffic as a proxy for human mobility. There are sensors and tags generating data at micro, one-to-one interaction levels, much as Bluetooth, Global Positioning Systems and WiFi leave behind detailed traces of our lives.

Such are some of the new sources of basic information that researchers are using to gain knowledge about aggregated human behavior. This new "reality mining" should in turn enhance the ability of researchers and scientists to accurately forecast the effects of phenomena like catastrophic events, mass population movements or invasions of new organisms into ecosystems, Vespignani said.

"It is analogous to what happened in physics when we saw the shift from the study of atomic and molecular physics to the study of the physics of matter," he said. "Here we see a movement from the study of a small number of elements, or small social groups, to the study of the behavior of large-scale social systems consisting of millions of people that can be characterized in space, both social and geographic, and in time."

In his article "Predicting the Behavior of Techno-Social Systems," Vespignani also recognizes challenges in creating a predictive system that includes social adaptation. Large-scale data, for example, is still needed about how information spreads and society reacts in times of crisis, but he believes advancing communications databases may address that issue.

Quantifying effects of risk perception and awareness phenomena among individuals on the larger techno-social network's structure and dynamics needs to be designed into formal models, he added, and a need remains for the deployment of monitoring infrastructures capable of supplying real time information to computational models.

"While the needed integrated approach is still in its infancy, using network theory, mathematical biology, statistics, computer science and nonequilibrium statistical physics will play a key role in the creation of computational forecasting infrastructures," Vespignani said. "And that should help us design better energy distribution systems, plan for traffic-free cities and manage the deployment of the world's resources."

Vespignani's work on complex systems appears again in the same "Perspectives" section of Science as he is listed as co-author with five others on lead author Frank Schweitzer's "Economic Networks: The New Challenges."

Schweitzer, of the Swiss Federal Institute of Technology Zurich, led the research examining interdependencies of economic networks as complex systems. The paper, among other things, notes a need for advancing research on the complexities of the international financial network that in turn could lead to revision and extension of established paradigms in economic theory.

(Photo: Alessandro Vespignani)


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New research by neuroscientists at UCLA and Rutgers University provides evidence that fMRI can be used in certain circumstances to determine what a person is thinking. At the same time, the research suggests that highly accurate "mind reading" using fMRI is still far from reality. The research is scheduled to be published in the October 2009 issue of the journal Psychological Science.

In the study, 130 healthy young adults had their brains scanned in an MRI scanner at UCLA's Ahmanson–Lovelace Brain Mapping Center while they performed one of eight mental tasks, including reading words aloud, saying whether pairs of words rhyme, counting the number of tones they heard, pressing buttons at certain cues and making monetary decisions. The scientists calculated how accurately they could tell from the fMRI brain scans which mental task each participant was engaged in.

"We take 129 of the subjects and apply a statistical tool to learn the differences among people doing these eight tasks, then we take the 130th person and try to tell which of the tasks this person was doing; we do that for every person," said lead study author Russell Poldrack, a professor of psychology who holds UCLA's Wendell Jeffrey and Bernice Wenzel Term Chair in Behavioral Neuroscience.

"It turns out that we can predict quite well which of these eight tasks they are doing," he said. "If we were just guessing, we would get it right about 13 percent of the time. We get it right about 80 percent of the time with our statistical tool. It's not perfect, but it is quite good — but not nearly good enough to be admissible in court, for example.

"Our study suggests that the kinds of things that some people have talked about in terms of mind reading are probably still pretty far off," Poldrack said. "If we are only 80 percent accurate with eight very different thoughts and we want to figure out what you're thinking out of millions of possible thoughts, we're still very far away from achieving that."

Poldrack's study is one of the first to show that neuroscientists can make these kinds of predictions on new people, whose brain patterns the researchers have never seen before. In most previous studies, researchers made predictions about a person's mental state after having already studied that person's brain to understand its particular patterns.

"Our study indicates that different people's brains work very similarly," Poldrack said. "We often tend to focus on how different each person's brain is, but our study suggests that most healthy people's brains work in very similar ways; otherwise, this approach wouldn't work.

"We can tell a lot about what you're thinking using functional MRI, even though we have never seen your brain before," he said. "However, it is limited in that there are only eight things that we are letting you think about in this study."

The tools used in this research come from a scientific field known as machine learning, which is related to statistics and computer science, said Poldrack, who noted that this technology is heavily employed by companies like Amazon to predict what people will buy based on their previous purchases.

Nearly 10 years ago, neuroscientists showed that if they take brain images with fMRI while people look at different objects, such as faces, houses and chairs, they can use the tools of machine learning to predict with high accuracy what object the subjects are looking at — if the scientists first know from studying brain activity how each subject's brain responds to those objects.

(Photo: UCLA)



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The role of clouds in climate change has been a major question for decades. As the earth warms under increasing greenhouse gases, it is not known whether clouds will dissipate, letting in more of the sun's heat energy and making the earth warm even faster, or whether cloud cover will increase, blocking the Sun's rays and actually slowing down global warming.

In a study published in the July 24 issue of Science, researchers Amy Clement and Robert Burgman from the University of Miami's Rosenstiel School of Marine and Atmospheric Science and Joel Norris from Scripps Institution of Oceanography at UC San Diego begin to unravel this mystery. Using observational data collected over the last 50 years and complex climate models, the team has established that low-level stratiform clouds appear to dissipate as the ocean warms, indicating that changes in these clouds may enhance the warming of the planet.

Because of inconsistencies in historical observations, trends in cloudiness have been difficult to identify. The team broke through this cloud conundrum by removing errors from cloud records and using multiple data sources for the northeast Pacific Ocean, one of the most well-studied areas of low-level stratiform clouds in the world. The result of their analysis was a surprising degree of agreement between two multi-decade datasets that were not only independent of each other, but that employed fundamentally different measurement methods. One set consisted of collected visual observations from ships over the last 50 years, and the other was based on data collected from weather satellites.

"The agreement we found between the surface-based observations and the satellite data was almost shocking," said Clement, a professor of meteorology and physical oceanography at the University of Miami, and winner of the American Geophysical Union's 2007 Macelwane Award for her groundbreaking work on climate change. "These are subtle changes that take place over decades. It is extremely encouraging that a satellite passing miles above the earth would document the same thing as sailors looking up at a cloudy sky from the deck of a ship."

What was not so encouraging, however, was the fact that most of the state-of-the-art climate models from modeling centers around the world do not reproduce this cloud behavior. Only one, the Hadley Centre model from the U.K. Met Office, was able to reproduce the observations. "We have a long way to go in getting the models right, but the Hadley Centre model results can help point us in the right direction," said co-author Burgman, a research scientist at the University of Miami.

Together, the observations and the Hadley Centre model results provide evidence that low-level stratiform clouds, which currently shield the earth from the sun's radiation, may dissipate in warming climates, allowing the oceans to further heat up, which would then cause more cloud dissipation.

"This is somewhat of a vicious cycle potentially exacerbating global warming," said Clement. "But these findings provide a new way of looking at clouds changes. This can help to improve the simulation of clouds in climate models, which will lead to more accurate projections of future climate changes. "

One key finding in the study is that it is not the warming of the ocean alone that reduces cloudiness -- a weakening of the trade winds also appears to play a critical role. All models predict a warming ocean, but if they don't have the correct relationship between clouds and atmospheric circulation, they won't produce a realistic cloud response.

"I am optimistic that there will be major progress in understanding global cloud changes during the next several years," said Norris. "The representation of clouds in models is improving, and observational records are being reprocessed to remove spurious variability associated with satellite changes and other problems."

(Photo: NASA)

Rosenstiel School of Marine and Atmospheric Science


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A research team made up of four faculty members and 15 undergraduate students from the biology and mathematics departments at Missouri Western State University in Missouri and Davidson College in North Carolina, USA engineered the DNA of Escherichia coli bacteria, creating bacterial computers capable of solving a classic mathematical problem known as the Hamiltonian Path Problem.

The research extends previous work published last year in the same journal to produce bacterial computers that could solve the Burnt Pancake Problem.

The Hamiltonian Path Problem asks whether there is a route in a network from a beginning node to an ending node, visiting each node exactly once. The student and faculty researchers modified the genetic circuitry of the bacteria to enable them to find a Hamiltonian path in a three-node graph. Bacteria that successfully solved the problem reported their success by fluorescing both red and green, resulting in yellow colonies.

Synthetic biology is the use of molecular biology techniques, engineering principles, and mathematical modeling to design and construct genetic circuits that enable living cells to carry out novel functions. "Our research contributed more than 60 parts to the Registry of Standard Biological Parts, which are available for use by the larger synthetic biology community, including the newly split red fluorescent protein and green fluorescent protein genes," said Jordan Baumgardner, recent graduate of Missouri Western and first author of the research paper. "The research provides yet another example of how powerful and dynamic synthetic biology can be. We used synthetic biology to solve mathematical problems; others find applications in medicine, energy and the environment. Synthetic biology has great potential in the real world."

According to Dr. Eckdahl, the corresponding author of the article, synthetic biology affords a new opportunity for multidisciplinary undergraduate research training. "We have found synthetic biology to be an excellent way to engage students in research that connects biology and mathematics. Our students learn firsthand the value of crossing traditional disciplinary lines."

Journal of Biological Engineering




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