Category Archives: Life Science

Gamers Use Foldit to Solve Enzyme Configuration in 3 Weeks That Stumped Scientists for Over a Decade

Gamers have solved the structure of a retrovirus enzyme whose configuration had stumped scientists for more than a decade. The gamers achieved their discovery by playing Foldit, a very cool online game that allows players to collaborate and compete in predicting the structure of protein molecules that I wrote about before: Foldit – the Protein Folding Game. You can download it, play, and help move our understanding forward.

After scientists repeatedly failed to piece together the structure of a protein-cutting enzyme from an AIDS-like virus, they called in the Foldit players. The scientists challenged the gamers to produce an accurate model of the enzyme. They did it in only three weeks.

This class of enzymes, called retroviral proteases, has a critical role in how the AIDS virus matures and proliferates. Intensive research is under way to try to find anti-AIDS drugs that can block these enzymes, but efforts were hampered by not knowing exactly what the retroviral protease molecule looks like.

“We wanted to see if human intuition could succeed where automated methods had failed,” said Dr. Firas Khatib of the University of Washington Department of Biochemistry. Khatib is a researcher in the protein structure lab of Dr. David Baker, professor of biochemistry.

Remarkably, the gamers generated models good enough for the researchers to refine and, within a few days, determine the enzyme’s structure. Equally amazing, surfaces on the molecule stood out as likely targets for drugs to de-active the enzyme.

“These features provide exciting opportunities for the design of retroviral drugs, including AIDS drugs,” wrote the authors of a paper appearing Sept. 18 in Nature Structural & Molecular Biology. The scientists and gamers are listed as co-authors.

This is the first instance that the researchers are aware of in which gamers solved a longstanding scientific problem.

“The focus of the UW Center for Game Sciences,” said director Dr. Zoran Popovic, associate professor of computer science and engineering, “is to solve hard problems in science and education that currently cannot be solved by either people or computers alone.”

The solution of the virus enzyme structure, the researchers said, “indicates the power of online computer games to channel human intuition and three-dimensional pattern matching skills to solve challenging scientific problems.”

With names like Foldit Contenders Group and Foldit Void Crushers Group, the gamer teams were fired up for the task of real-world molecule modeling problems. The online protein folding game captivates thousands of avid players worldwide and engages the general public in scientific discovery.

Direct manipulation tools, as well as assistance from a computer program called Rosetta, encourage participants to configure graphics into a workable protein model. Teams send in their answers, and UW researchers constantly improve the design of the game and its puzzles by analyzing the players’ problem-solving strategies.

Figuring out the shape and misshape of proteins contributes to research on causes of and cures for cancer, Alzheimer’s, immune deficiencies and a host of other disorders, as well as to environmental work on biofuels.

Dr. Seth Cooper, of the UW Department of Computing Science and Engineering, is a co-creator of Foldit and its lead designer and developer. He studies human-computer exploration methods and the co-evolution of games and players.

“People have spatial reasoning skills, something computers are not yet good at,” Cooper said. “Games provide a framework for bringing together the strengths of computers and humans. The results in this week’s paper show that gaming, science and computation can be combined to make advances that were not possible before.”

Games like Foldit are evolving. To piece together the retrovirus enzyme structure, Cooper said, gamers used a new Alignment Tool for the first time to copy parts of know molecules and test their fit in an incomplete model.

According to Popovic, “Foldit shows that a game can turn novices into domain experts capable of producing first-class scientific discoveries. We are currently applying the same approach to change the way math and science are taught in school.”

Amber Pieces Containing Remains from Dinosaurs and Birds Show Feather Evolution

Dinosaur feather evolution trapped in Canadian amber

a study of amber found near Grassy Lake in Alberta – dated from what is known as the Late Cretaceous period – has unearthed a full range of feather structures that demonstrate the progression. “We’re finding two ends of the evolutionary development that had been proposed for feathers trapped in the same amber deposit,” said Ryan McKellar of the University of Alberta, lead author of the report.

The team’s find confirms that the filaments progressed to tufts of filaments from a single origin, called barbs. In later development, some of these barbs can coalesce into a central branch called a rachis. As the structure develops further, further branches of filments form from the rachis.

“We’ve got feathers that look to be little filamentous hair-like feathers, we’ve got the same filaments bound together in clumps, and then we’ve got a series that are for all intents and purposes identical to modern feathers,” Mr McKellar told BBC News.

“We’re catching some that look to be dinosaur feathers and another set that are pretty much dead ringers for modern birds.”
…
a picture is emerging that many dinosaurs were not the dull-coloured, reptilian-skinned creatures that they were once thought to be. “If you were to transport yourself back 80 million years to western North America and walk around the forest… so many of the animals would have been feathered,” said Dr Norell.

“We’re getting more and more evidence… that these animals were also brightly coloured, just like birds are today.”

Very cool. Science really is great.

Large Crabs Invading Antarctic as Waters Warm

Giant red king crabs

Large crabs are invading the Antarctic environment and due to their numbers and practices could cause havoc. They look yummy though. And eating them would be doing nature a favor unlike the overfishing of the oceans. Abstract of the open access article, A large population of king crabs in Palmer Deep on the west Antarctic Peninsula shelf and potential invasive impacts:

Lithodid crabs (and other skeleton-crushing predators) may have been excluded from cold Antarctic continental shelf waters for more than 14 Myr [million years]. The west Antarctic Peninsula shelf is warming rapidly and has been hypothesized to be soon invaded by lithodids. A remotely operated vehicle survey in Palmer Deep, a basin 120 km onto the Antarctic shelf, revealed a large, reproductive population of lithodids, providing the first evidence that king crabs have crossed the Antarctic shelf. DNA sequencing and morphology indicate the lithodid is Neolithodes yaldwyni Ahyong & Dawson, previously reported only from Ross Sea waters. We estimate a N. yaldwyni population density of 10 600 kmâˆ’2 and a population size of 1.55 Ã— 106 in Palmer Deep, a density similar to lithodid populations of commercial interest around Alaska and South Georgia. The lithodid occurred at depths of more than 850 m and temperatures of more than 1.4Â°C in Palmer Deep, and was not found in extensive surveys of the colder shelf at depths of 430–725 m. Where N. yaldwyni occurred, crab traces were abundant, megafaunal diversity reduced and echinoderms absent, suggesting that the crabs have major ecological impacts. Antarctic Peninsula shelf waters are warming at approximately 0.01Â°C yrâˆ’1; if N. yaldwyni is currently limited by cold temperatures, it could spread up onto the shelf (400–600 m depths) within 1–2 decades. The Palmer Deep N. yaldwyni population provides an important model for the potential invasive impacts of crushing predators on vulnerable Antarctic shelf ecosystems.

Fun Webcast from WWF: Astonish Me

Made in celebration of the World Wildlife Fund‘s 50th anniversary.

Insightful Problem Solving in an Asian Elephant

Another example of very cool animal behavior. This Asian Elephant, seemed to consider the problem, devise a solution and then go get a stool to reach food that could not be reached without a tool.

Insightful Problem Solving in an Asian Elephant

The “aha” moment or the sudden arrival of the solution to a problem is a common human experience. Spontaneous problem solving without evident trial and error behavior in humans and other animals has been referred to as insight. Surprisingly, elephants, thought to be highly intelligent, have failed to exhibit insightful problem solving in previous cognitive studies. We tested whether three Asian elephants (Elephas maximus) would use sticks or other objects to obtain food items placed out-of-reach and overhead. Without prior trial and error behavior, a 7-year-old male Asian elephant showed spontaneous problem solving by moving a large plastic cube, on which he then stood, to acquire the food. In further testing he showed behavioral flexibility, using this technique to reach other items and retrieving the cube from various locations to use as a tool to acquire food. In the cube’s absence, he generalized this tool utilization technique to other objects and, when given smaller objects, stacked them in an attempt to reach the food. The elephant’s overall behavior was consistent with the definition of insightful problem solving. Previous failures to demonstrate this ability in elephants may have resulted not from a lack of cognitive ability but from the presentation of tasks requiring trunk-held sticks as potential tools, thereby interfering with the trunk’s use as a sensory organ to locate the targeted food.
…
Further inspired by KÃ¶hler’s chimpanzee studies, in experiment 4 we conducted 8 additional sessions to investigate whether Kandula would stack items to reach food. For these sessions, the baited branches were hung at a height that could be reached by stacking three butcher block cutting boards or by the use of other objects. In addition, the elephant was given sticks and other enrichment items. Kandula first touched several items and then moved two items, a plastic disk and a block under the suspended branches, placing one front foot on each in an unsuccessful attempt to reach for the branch. He solved the problem in an unexpected novel manner, moving and standing on the object closest in size to the absent cube, a large ball. Standing on unstable platforms such as this had not been previously observed. He repeated this behavior 9 times during this session. During the session’s last minutes, Kandula picked up a block ~2 m from the food and placed it directly on top of a block that he placed under the food in a previous attempt. He stood on the stacked blocks and attempted to reach the food but was unsuccessful. He stacked two blocks again in the second and sixth sessions but each time his trunk was several inches from the food.

This is very cool research. I do wonder why they didn’t provide more videos (and in a more user-friendly format than .mov files). I made them available via YouTube.

It seems like a very interesting area to have more experiments with more elephants (and continuing to work with Kandula: he seems to be very curious elephant, good for him).

What Happens If the Overuse of Antibiotics Leads to Them No Longer Working?

Antibiotics have been a miraculous tool to keep up healthy. Like vaccines this full value of this tool is wasted if it is used improperly. Vaccines value is wasted when they are not used enough. Antibiotics lose potency when they are overused. The overuse of anti-biotics on humans is bad (especially the huge amount of just lazy, not scientific use). But the massive overuse in livestock is much worse, it seems to me.

The health system in the USA is broken in a huge way in which it is broken is the failure to address creating systemic behavior that promotes human health and instead just treating illness. It is much better to avoid a situation where we breed super bugs and then try to treat those super bugs that have evolved to be immune to the antibiotics we have to use.

When antibiotics no longer work

While the source of the current salmonella outbreak remains murky, we can reasonably speculate about the genesis of the bug’s drug-resistance: the reportedly endemic overuse of antibiotics by the agricultural industry.

Drugs are given to livestock for multiple reasons. An obvious one is for the treatment of diseases. When livestock are sick, veterinarians administer a significant dosage in hopes of eliminating the animal’s affliction. Another reason is preventative. Animals in close quarters are more susceptible to infection, so farmers will often administer medicine to healthy animals in order to nip anything nasty in the bud. Most controversially, though, members of the agricultural industry use antibiotics for the express purpose of promoting livestock growth.

It’s a well-known, if not entirely intuitive, fact that healthy animals who are fed small, or “sub-therapeutic,” doses of antibiotics will wind up larger than their unmedicated counterparts. In many such cases, these drugs are given to livestock through their feed or water, and without the prescription or oversight of a veterinarian, according to Dr. Gail Hansen, a senior officer at the Pew Campaign on Human Health and Industrial Farming.

An estimated 80 percent of all antibiotics in the U.S. are given to food-producing livestock, according to the FDA. And approximately 83 percent of that medicine is “administered flock- or herd-wide at low levels for non-therapeutic purposes, such as growth promotion and routine disease prevention,” according to a lawsuit filed against the FDA in May. These figures could have very real consequences for public health, because the Catch-22 of this antibiotic abandon is the widespread development of drug-resistant bacteria, colloquially referred to as “super-bugs.”
…
In 2006, the European Union banned all use of antibiotics on livestock for growth promotion. And the U.S. Senate will consider similar legislation this year. Sen. Dianne Feinstein, D-Calif., reintroduced the “Preservation of Antibiotics for Medical Treatment Act” last month, which would significantly rein in agricultural drug use, and strictly prohibit the application of sub-therapeutic doses of drugs that have benefits for humans.

Still, the agricultural industry disputes data about its use of antibiotics and the rise of super-bugs, and it has aggressively fought efforts to legislate the matter. As a result, it’s hard to tell how far the legislation might proceed.

The end of the era of antibiotics

How did this happen? The driving forces are Darwin and human carelessness. Bacteria are constantly evolving, adapting to the changing conditions they face. Antibiotics usually kill bacteria. But sometimes a bacteria will develop a biological defense – particularly if too small a dose is used.
…
Antibiotics require a prescription in America, but our nation is still very much a part of the problem. Patients routinely demand these drugs, and doctors acquiesce, for respiratory infections and other ailments that will not respond to antibiotics because they are caused by a virus. We use soap with antimicrobial agents when regular soap does equally well. And we allow farmers to feed antibiotics to livestock in horrifying amounts, not to treat illnesses but to make farming more efficient.

The Potential Role of Concentrated Animal Feeding Operations in Infectious Disease Epidemics and Antibiotic Resistance

This working group, which was part of the Conference on Environmental Health Impacts of Concentrated Animal Feeding Operations: Anticipating Hazards—Searching for Solutions, considered the state of the science around these issues and concurred with the World Health Organization call for a phasing-out of the use of antimicrobial growth promotants for livestock and fish production. We also agree that all therapeutic antimicrobial agents should be available only by prescription for human and veterinary use.

Antibiotic Resistance in Livestock: More at Risk Than Steak
Continue reading →

Evolution in New York City Wildlife

Evolution Right Under Our Noses by Carl Zimmer

White-footed mice, stranded on isolated urban islands, are evolving to adapt to urban stress. Fish in the Hudson have evolved to cope with poisons in the water. Native ants find refuge in the median strips on Broadway. And more familiar urban organisms, like bedbugs, rats and bacteria, also mutate and change in response to the pressures of the metropolis. In short, the process of evolution is responding to New York and other cities the way it has responded to countless environmental changes over the past few billion years. Life adapts.
…
Dr. Wirgin and his colleagues were intrigued to discover that the Hudson’s population of tomcod, a bottom-dwelling fish, turned out to be resistant to PCBs. “There was no effect on them at all,” Dr. Wirgin said, “and we wanted to know why.”

In March, he and his colleagues reported that almost all the tomcod in the Hudson share the same mutation in a gene called AHR2. PCBs must first bind to the protein encoded by AHR2 to cause damage. The Hudson River mutation makes it difficult for PCBs to grab onto the receptor, shielding the fish from the chemical’s harm.

The AHR2 mutation is entirely missing from tomcod that live in northern New England and Canada. A small percentage of tomcod in Long Island and Connecticut carry the mutation. Dr. Wirgin and his colleagues concluded that once PCBs entered the Hudson, the mutant gene spread quickly.

Carl Zimmer again does a good job of explaining science in an engaging way. It is interesting to learn about science and evolution in urban environments. Lots of life manages to survive the challenges of urban life and it is interesting to learn what scientists are finding about that life.

Cambrian Explosion Song

via Smithsonian’s Surprising Science:

What does a music teacher do when he ends up teaching science? He teaches about evolution and the geologic timeline with music, of course, and that’s what Canadian elementary school teacher John Palmer did. He originally played “Cambrian Explosion” as a rock/hip hop creation in class but has since recorded an acoustic version. (The trio is called Brighter Lights, Thicker Glasses and consists of Palmer on the guitar/vocals, Michael Dunn on the dobro and Brian Samuels [from UBC civil engineering department] on the cello.)

The video was filmed in the Beaty Biodiversity Museum (Canada) atrium with the blue whale exhibit in the background.

Biologists Identified a New Way in Which Bacteria Hijack Healthy Cells

Associate professor of biological sciences Zhao-Qing Luo, foreground, and graduate student Yunhao Tan identified a new way in which bacteria modify healthy cells during infection. Shown on the computer screen are cells infected with a mutant strain of the bacteria Legionella pneumophila used in their research.

Purdue University biologists identified a new way in which bacteria hijack healthy cells during infection, which could provide a target for new antibiotics. Zhao-Qing Luo, the associate professor of biological sciences who led the study, said the team discovered a new enzyme used by the bacterium Legionella pneumophila – which causes Legionnaires’ disease – to control its host cell in order to take up residence.

“Legionnaires’ disease is a severe form of pneumonia, and this finding could lead to the design of a new therapy that saves lives,” Luo said. “At the same time it also provides great insight into a general mechanism of both bacterial infection and cell signaling events in higher organisms including humans.”

Successful infection by Legionella pneumophila requires the delivery of hundreds of proteins into the host cells that alter various functions to turn the naturally hostile environment into one tailor-made for bacterial replication. These proteins tap into existing communication processes within the cells in which an external signal, such as a hormone, triggers a cascade of slight modifications to proteins that eventually turns on a gene that changes the cell’s behavior, he said.

“Pathogens are successful because they know how information in our cells is relayed and they amplify some signals and block others in order to evade the immune system and keep the cell from defending itself,” Luo said. “Despite our understanding of this, we do not know much about how the proteins delivered by the bacteria accomplish this – how they work. This time we were able to pinpoint an enzyme and see how it disrupted and manipulated a specific signaling pathway in order to create a better environment for itself.”

The signaling pathway involved was only recently identified, and the discovery by Luo and graduate student Yunhao Tan also provides a key insight into its process. The signaling pathway involves a new form of protein modification called AMPylation in order to relay instructions to change cell behavior and has been found to be used by almost all organisms, Luo said.

The bacterium affects the host cell’s functions differently during different phases of the infection process, tapping into signaling pathways to turn on and off certain natural cellular activities. SidD stops the AMPylation process four hours after the start of infection in order to reverse an earlier modification that would be detrimental to the cell if left in place, he said.

Read the full press release.

Hydromedusae, Siphonophora, Cnidarians, Ctenophores

Jellyfish is a common name for gelatinous water dwelling animals. The diversity of these invertebrates is amazing. And what actually counts as a jellyfish is not easy to determine. Watch this great video to learn about Cnidarians, Urochordata, Polychaetes and Ctenophores.