Monday 26 November 2012

High-Speed Video Helps Scientists Understand Hummingbird Pollination


High-Speed Video Helps Scientists Understand Hummingbird Pollination

November 25, 2012
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Photo by Scott Streit
Hummingbirds are part of the family Trochilidae and are among the smallest birds on the planet, with most species measuring between 7.5 to 13 cm. Now, a new high-speed video has helped scientists understand why hummingbirds always pollinate flowers that hang upside down.
The scientists published their findings in the journal Functional Ecology. Hummingbirds are native to the Americas, and are one of the only types of birds that can hover while flying. This expends a lot of energy, and as such, they have one of the fastest metabolisms of any animal. While they eat small insects, hummingbirds typically drink the sugar-rich nectar from flowers to gain calories. Many hummingbird species have co-evolved with certain plant species, but it has remained a mystery why they visit flowers that hang upside-down.

In this experiment, biologists fed Anna’s hummingbirds (Calypte anna) from artificial flowers that pointed horizontally, upside-down, or tilted at a 45-degree angle. The flowers were filled with nectar and fitted with a mask to measure how much oxygen the birds were using while hovering. The upside-down flowers required the hummingbirds to tilt their heads back awkwardly, and required 10% more energy to feed than horizontal flowers.
Because it’s more costly energy-wise to drink from such flowers, researchers speculate that the orientation must be beneficial in some other way. They believe that flowers that don’t hang upside-down are possibly more exposed to rain, which would dilute the nectar, and since hummingbirds can taste the sweetness of the nectar, they may avoid flowers that contain less sugar.
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Body posture of an Anna’s Hummingbird when feeding from horizontal (a), tilted (b), and vertical (c) feeders. Credit: Copyright Nir Sapir

Slowing Cargo Ships Results in Major Reductions in Pollution


Slowing Cargo Ships Results in Major Reductions in Pollution

November 23, 2012
cargo-ship-ocean
Cargo ship on the ocean. Photo via Environ. Sci. Technol., 2012, 46 (22), pp 12600–12607
A new study indicates that slowing down vessels near coastlines by 10 to 15 miles per hour can dramatically reduce air pollution from the ships. However, only a few US ports have initiated efforts to apply this.
The scientists published their findings in the journal Environmental Science and Technology. A speed limit of 14 mph, down from the current speeds of 25 to 29 mph would cut nitrogen oxides by 55% and soot by 70%. It would also reduce carbon dioxide by 60%.
cargo-ship-hyundai
Cargo ship in Vancouver’s harbor. Photo by Flickr/ecstaticist
There are 100,000 ships carrying 90% of the world’s cargo, and the resulting air pollution is problematic for people living near ports. The ports of Los Angeles/Long Beach and New York/New Jersey are already part of a voluntary monitoring program and this has already cut down emissions significantly in those areas. They’ve been in place for a number of years. Setting a speed limit is an elusive goal for port cities because shipping traffic is regulated by international treaties.
All vessels, when they are within 10 nautical miles of a US port, must slow down to 14 mph. Ports that are part of the volunteer programs slow ships out further out, up to 40 miles offshore.
A ship’s fuel consumption and emissions increase drastically when they go faster. In order to increase air quality, speed reductions would need to be maintained long-term. The shipping industry is responsible for 3% of the world’s carbon dioxide emissions and shipping emissions are expected to grow 2 to 3 percent every year over the next three decades [PDF] as shipping traffic grows, according to the International Maritime Organization.
Some states, like California, have banned ships from burning dirty kinds of fuel and are rolling out other clean port initiatives. As a result, smog-causing nitrogen oxides from the Los Angeles port have declined 30% between 2005 and 2011, while particulate matter has decreased about 70%.

Experiment Using Photons Could Detect Quantum-Scale Black Holes


Experiment Using Photons Could Detect Quantum-Scale Black Holes

November 23, 2012
quantum-gravity-granularity-space
Jacob Bekenstein’s proposed experiment fires a photon through a transparent block to check whether space-time is pixelated. Image by J. Bekenstein
A new tabletop experiment using a single photon was proposed to show whether space-time is made up of indivisible units. Space isn’t smooth, and physicists think that on the quantum scale, it is composed of indivisible subunits, like the dots of a pointillist drawing. This pixelated landscape is thought to be populated by black holes, smaller than one trillionth of one trillionth of the diameter of a hydrogen atom, which continuously pop in and out of existence.
The pre-print of this study is available through arXiv. This hypothesis was proposed decades ago in order to unify quantum theory with Einstein’s theory of gravity, which is the only one of nature’s four fundamental forces not to have been incorporated into the Standard Model of Particle Physics.
Physicists have tried to use the Large Hadron Collider, gravitational wave detectors and observations of distant cosmic explosions in order to determine whether space is grainy, but so far the results have proven to be inconclusive.
This new tabletop experiment was proposed by Jacob Bekenstein, a theoretical physicist at the Hebrew University of Jerusalem, and it uses readily available equipment.
The experiment was designed to examine on the scale of 1.6 × 10−35 (1.6E-35) meters. This Planck length is the theoretical limit at which the macroscopic concept of distance ceases to have any meaning and quantum fluctuations begin to make space-time resemble a foamy sea.
Instead of using instruments, Bekentstein proposes to fire a single photon through a transparent block, and indirectly measure the minuscule distance that the block moves as a result of the photon’s imparted momentum.
The photon’s wavelength and the mass as well as the size of the block are carefully chosen so that the momentum is just large enough to move the block’s center of mass by one Planck length. If space-time is grainy on this scale, then the photon is less likely to make it through the block. If quantum fluctuations in length are important on Planck scale, a sea of black holes, each with a Planck-scale radius, will readily form. Anything that falls inside of these black holes will be unable to escape until the hole dissipates. If the center of mass of the moving block falls into one of these holes, the block’s movement will be impeded. Photons are much larger than the Planck length, and as such aren’t bothered by these quantum black holes.
The conservation of momentum in this experiment requires that the photon can’t make it through the block if it fails to move by a Planck length. So if fewer photons than expected are seen by the detector, this would mean that the block’s movement has been impeded by black holes, and that space-time exhibits quantum features at the Planck scale.
Distinguishing between possible quantum gravitational effects from others will be challenging, states Igor Pikovski, a quantum physicist at the Vienna Center for Quantum Science and Technology. It is unknown at what exact scale quantum gravity plays a significant role. There is plenty of room for granularity at much larger lengths, but there is no theory that could provide this answer, he continues.

British and American Teams Hunt for Life Under Antarctic Ice


British and American Teams Hunt for Life Under Antarctic Ice

November 22, 2012
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A British field camp in Antarctica will soon host efforts to drill through the ice to reach Lake Ellsworth. Photo by BAS
Next week, UK glaciologists are heading to Lake Ellsworth to prepare for a new drilling stage that will start December 5. They hope to reach the lake and start examining sediments to find signs of life.
The team will try to understand the history of the West Antarctic Ice Sheet, which has the potential to reveal how the glacier has waxed and waned over time.
Roughly 380 subglacial lakes have been discovered and mapped in Antarctica, and they have been explored remotely with ice-penetrating radar, gravity measurements, and seismic sensors. The lakes were created by geothermal heat that melts the Antarctic ice from below. Gravity and pressure force the melt water to flow, and it collects under the ice.
drilling-map-antarctica
Trapped under ice, infographic via Nature
If everything goes according to plan, Lake Ellsworth will be the second lake to be breached after Lake Vostok was reached in February. A US team is heading to Lake Whillans, a small, shallow body of water close to the edge of the Ross Ice Shelf. The discovery of exotic microbial life, which could have evolved untouched for millennia, is one of the aspects of this research. Scientists have already discovered bacteria that mine their energy from rocks and minerals, and they assume that there are many specialized microbes living underneath Antarctica.
The Russian team at Lake Vostok found evidence of heat-loving bacteria living in the bedrock surrounding the lake. The clues came from DNA in the sediment that was trapped in accretion ice. The upper layers of the lake itself appeared to be lifeless. No native microbes were turned up from a preliminary analysis of lake water.
Lake Ellsworth might have more microbes because it offers fewer hiding places. It’s 12 km in length, 3 km in width, with an average depth of about 150 meters. Vostok is 250 km long by 40 km in width, which makes it one of Earth’s largest freshwater bodies. It’s also nestled in a subglacial valley near the continental divide, where overlying ice moves at its slowest. The site, at about −30 °C, is twice as warm as the ice on the Vostok plateau in East Antarctica.
The goal is to reach Ellsworth in three days using a drill that will melt the ice with a high-pressure jet of water, heated up to 90 °C. Once the borehole is completed, the team has about 24 hours to deploy a sediment corer before the hole freezes over.
The equipment was prepared so that it doesn’t contaminate the lake with microbes from the surface. The main challenge involves completing all of the sampling operations within this very short window of time.

European Union’s Initiative to Clean Up Waterways Faces Opposition


European Union’s Initiative to Clean Up Waterways Faces Opposition

November 21, 2012
dead-fish-europe-waterways
European proposals to regulate pharmaceuticals in aquatic organisms could already be dead in the water. Photo by ALESSANDRO ABBONIZIO/AFP/GETTY
The EU is about to stop a precedent-setting initiative that was designed to tackle a common side effect of drugs, their impact on aquatic life. The landmark regulations intended on cleaning up Europe’s waterways of pharmaceuticals is likely to be quashed when it reaches a key vote in the EU Parliament next week.
The proposal would limit the concentrations in water of widely-used contraceptives and anti-inflammatory drugs, and it has sparked intense lobbying by the water and pharmaceutical industries which state that the science is uncertain and costs are too high.
EU member states, alarmed by the cost of estimates of tens of billions of euros, seem to have agreed. While researchers and environmentalists question these estimates, and argue that it should be judged on the strong scientific science behind it, rather than financial concerns.
Many of the EU’s rivers are home to male fish that are intersex, which means that they display female sexual characteristics, including female reproductive anatomy. Some males also produce vitellogenin, a protein found in eggs that can be induced in males by high hormone exposure. The UK found that in 2004, 86% of the fish sampled at 51 sites around the country were intersex.
Toxicologists think that this is due to the endocrine-disrupting chemicals, which are the active ingredient in contraceptive pills. Ethynyl oestradiol (EE2) is excreted by people using the contraceptive pill, and manages to get into the waterways.
In January, the EU proposed that its member states limit the drug’s annual average concentrations in surface waters to no more than 0.035 nanograms per liter. The European Commission also asked lawmakers to take action on diclofenac, an anti-inflammatory drug that disrupts cell function in the liver, kidneys and gills of fish.
This EE2 standard would have represented a severe cut in pollution levels. If the European Parliament’s environment committee rejects the bill, then it would be doomed in the full parliamentary vote scheduled for next year. This outcome is now highly likely, based on previous committee discussions. The vote and discussion is set to take place on November 28.
Upgrading the wastewater treatment technology could eliminate most of the pollution. The water and pharmaceutical industries acknowledge that EE2 is present in rivers and that it is responsible for intersex fish. However, they state that there is little evidence of harm, noting that none of Europe’s freshwater fish populations are plummeting.
Some of the member states argue for more evidence of harmful effects, while some think that any standard for pharmaceuticals in water should be delayed until 2027.
A study on fathead minnows (Pimephales promelas) in a lake in Canada has shown that exposure to high levels of EE2 triggered a population crash.
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European Commission’s proposed water standards. Infographic via Nature.

Laboratory-Based Astrophysics Leads to Dedicated Discipline


Laboratory-Based Astrophysics Leads to Dedicated Discipline

November 21, 2012
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A type of turbulence simulated in a lab experiment could help to explain why the Sun’s corona is so hot. Photo by SDO/NASA
The gigantic orange magnets at MIT were originally built decades ago to confine hydrogen nuclei in the search for nuclear fusion. However, since 1998 plasma physicist Jan Egedal has been using them to simulate magnetic fields in the thin wind of charged particles emanating from Sol. Egedal hopes to figure out how the solar wind can transfer energy.
These kinds of laboratory astrophysical experiments, in which efforts were made to mimic the behavior of space-borne plasmas and other phenomena, have had to rely on the apparatus of energy research or fundamental physics. Now, astrophysicists are trying to make the field a discipline in its own right, with its dedicated funding and equipment.
In June, the American Astronomical Society (AAS) in Washington DC created its first new discipline in 30 years, dedicated to laboratory-based astrophysics. At the American Physical Society’s plasma-physics meeting last month in Providence, Rhode Island, there were an unprecedented number of lab-astrophysics sessions. Even some NASA scientists are saying that the agency should devote some funding from every space mission to lab astrophysics.
Egedal is exploring questions posed by two solar wind missions, the ESA’s Cluster and NASA’s Wind. The work is attractive in times of tight budgets because the cost of most experiments tends to be hundreds of thousands of dollars instead of the hundreds of millions needed for space missions.
Last month, the first lab measurement of astrophysical turbulence in which two magnetic waves collide to generate a third one, a phenomenon that has been used to explain why Sol’s corona is thousands of times hotter than its surface and how massive amounts of energy move between galaxies, was described. Using the Large Plasma Device, a 21-meter-long plasma generator at the University of California, Los Angeles, two Alfvén waves were generated and collided. The daughter wave was mapped and this confirmed the celestial mechanism. This experiment cost less than $100,000 to perform.
Dedicated funding for lab astrophysics would be good news for Egedal, who is beginning to outgrow his current apparatus and wanting to build a new one.

New Study Questions the Benefits of Mammograms


New Study Questions the Benefits of Mammograms

November 22, 2012
mammography-scan
Photo by Doctor’s Hospital
Mammography is routinely used to screen healthy women for breast cancer, and its use has led to the widespread detection and treatment of tumors that would have never caused any symptoms, according to a new study published in the New England Journal of Medicine.
The study examined the effects of mammography screens on breast-cancer incidence between 1976 and 2008 in women in the USA over 40 years of age. The researchers concluded that over one million women that were diagnosed with breast cancer would have never developed any symptoms. In 2008, it’s estimated that over 70,000 women had such breast cancer tumors diagnosed, which accounts for 31% of all breast cancers diagnosed in women 40 and older.
The study raises questions about the value of mammography screening. Overdiagnosis is a larger problem than previously recognized. The diagnosed women underwent treatments that involved surgery, radiation, hormones and chemotherapy for abnormalities that wouldn’t have caused any illness.
This study doesn’t address the situation of women who have an inherited genetic predisposition towards breast cancer. These women need to be screened actively with mammography.
With the advent of a widespread screening program, diagnoses of early-stage breast cancer have more than doubled in the last three decades, with an increase of 122 cases for every 100,000 women. The authors of the study argue that if the screening was working as intended and stopping those cancers from progressing to a more harmful disease, then one would expect to see a roughly equivalent decrease in late diagnoses.
The number of late-diagnosed cancers decreased only by 8 cases per 100,000 women. This implies that many of the early cases being detected through screening would not have caused symptomatic disease.
The study does have its critics and the even the researchers aren’t against screening, stating that “It does save lives. But a need to be more concerned about the harms [of screening] becomes more apparent from the results of our study.”

Sunday 25 November 2012

Magnets Used to Eradicate Cancer Cells


Magnets Used to Eradicate Cancer Cells

October 9, 2012
magnet-cancer
A group of South Korean researchers has developed a new method to cause cell death in both living fish and lab bowel cancer cells using a magnetic field. This application of electro-magnetism triggers a death signal that leads to programmed cell death.
The researchers published their findings in the journal Nature Materials. Treating cancer effectively is difficult, since most therapies don’t discriminate between cancer cells and healthy ones. There are many different approaches, all with varying degrees of success. In this study, the team was experimenting with the introduction of iron oxide nanoparticles, which attach to antibodies, into a biological system.
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A schematic representation of the magnetic switch for apoptosis signalling in in vitro cells and in a zebrafish. Credit: (c) Nature Materials (2012) doi:10.1038/nmat3430
The antibodies bind to tumor cell receptors. Once a magnetic field is introduced, the nanoparticles bunch up or cluster, which triggers a natural response that’s called the death signal. Apoptosis is what occurs, causing the destruction of the cancer cells and the tumor. This process continually occurs in living organisms and is marked by events that lead to changes in cells causing their deaths.
Researchers took advantage of this process by causing such chemicals to be sent to tumor cells. Zinc-doped iron oxide nanoparticles were applied to colon cancer cells, which naturally bind to antibodies that bind strongly to the death receptor on the colon cancer cells. Once the magnetic field is applied, the death receptor sends out a signal telling the system to attack the cell.
In their experiment, the team discovered that more than half of the tumor cells exposed to such a treatment were eradicated, while none of the untreated cells died. Other experiments using zebra fish resulted in the growth of abnormal tails.

Medicine Nobel Prize Awarded to Researchers for Reprogramming Mature Cells to a Pluripotent State


Medicine Nobel Prize Awarded to Researchers for Reprogramming Mature Cells to a Pluripotent State

October 9, 2012
nobel-winners
John Gurdon (left) and Shinya Yamanaka showed how to reprogram cells into their embryonic states.
The discovery that mature, adult cells can be reprogrammed back to an embryonic-like state has won this year’s Nobel Prize in Physiology or Medicine. It was awarded to two pioneers of stem-cell research, John Gurdon and Shinya Yamanaka.
Reprogrammed cells are able to regain pluripotency, the potential to differentiate into many mature cell types. Researchers hope that these cells will eventually be used in regenerative medicine, providing replacement tissue for damaged or diseased organs.
pluripotent-cells
Human induced pluripotent stem cells that have been turned into human nerve cells (red). The technique, which won this year’s Nobel Prize in Medicine, allows scientists to make stem cells from skin cells. (Bruce Conklin/Gladstone Institutes)
Gurdon is based at the Gurdon Institute in Cambridge, UK, and was the first person to demonstrate that cells could be reprogrammed 50 years ago. At that time, researchers thought that cellular specialization was a one-way process and that it couldn’t be reversed. Gurdon was able to prove the opposite, by removing the nucleus from a frog egg cell and replacing it with the nucleus from a tadpole’s intestinal cell. This process was also able to turn back the clock of the substitute nucleus. Even though it had already committed itself to specialization, inside the egg cell, it was able to act like an egg’s nucleus and direct the development of a normal tadpole.
Mammalian cells didn’t prove as amenable to this process as frog cells. This technique is known as cloning by nuclear transfer and it took nearly 35 years before the first cloned animal, Dolly the sheep, was born in 1996.
Shinya Yamanaka of Kyoto University, Japan, used cultured mouse cells to identify the genes that kept embryonic cells immature. Then, he tested whether any of these genes could reprogram mature cells to make them pluripotent.
In the mid-2000s, Yamanaka was close to this feat. A few months after the 2006 meeting of the International Society for Stem Cell Research in Toronto, Canada, Yamanaka announced his surprisingly simple recipe to complete his task. The activation of only four genes was enough to turn adult fibroblast cells back into pluripotent stem cells. Such induced pluripotency would allow the cells to be coaxed into different types of mature cells, including nerve and heart cells.
Both scientists state that translating these discoveries into regenerative therapies will take time, which is why it’s important for people to support it.

Stanford Scientists Examine How UV Radiation Affects the Protective Functions of Human Skin


Stanford Scientists Examine How UV Radiation Affects the Protective Functions of Human Skin

October 10, 2012
UV exposure makes human tissue more likely to tear under pressure
The researchers found that UV exposure makes human tissue more likely to tear under pressure. This means that sun-damaged skin is more prone to cracking and chapping, leaving deeper layers vulnerable to infection. Credit: David Freud
Scientists at Stanford University examined how varying doses of UVB radiation changes the protective functions of human skin, finding that beyond DNA damage and cancer risk, UV rays also change the way the outermost skin cells hold together and respond to strain.
Reinhold Dauskardt, professor of materials science and engineering at Stanford, has been studying skin for years. But when he sent his students to look for data on the mechanical properties of skin, they came back empty-handed. A lot was known about skin structure and disease, but few papers actually talked about its mechanical function – its ability to stretch and resist tension without tearing. “That motivated us to get more interested in the skin itself,” said Dauskardt.
He and his team, including doctoral student Krysta Biniek and postdoctoral researcher Kemal Levi, focused on the outmost layer of skin, the stratum corneum. It protects deeper layers from drying out or getting infected, and it’s also our first line of defense against UV radiation. Their study was published Oct. 1 in the Proceedings of the National Academy of Sciences.
They found that beyond the well-documented DNA damage and cancer risk, UV rays also change the way the outermost skin cells hold together and respond to strain.
Innovative methods
Ironically, the methodology behind these discoveries about skin damage originated in the field of photovoltaics, where sunshine is seen as a good thing. A grant from the U.S. Department of Energy supported Dauskardt’s research into the effects of prolonged UV exposure on materials – in particular, the materials that make up solar panels.
“Here we were looking at solar cells then suddenly thinking, ‘Hey, we should be looking at applying these techniques to skin,’” Dauskardt said.
The researchers subjected samples of human tissue to varying doses of UVB radiation. (UVB is the range of ultraviolet wavelengths that are largely absorbed by the epidermis and do not penetrate to deeper layers.) Then they tested the mechanical limits of the samples by putting them under different kinds of stress until they tore.
We’ve all experienced the sensations of dryness, stiffness or chapping after washing our hands with harsh soap, sitting by a space heater or under the air conditioning vent, or spending too long in the sun. Now we can begin to understand the mechanical properties behind those sensations. This is the first time that such methods have been applied to the study of skin.
The human fortress
Our body’s outermost defensive layer, the stratum corneum has a “brick-and-mortar” structure. The “bricks” in this model are dead cells called corneocytes, which are filled with a matrix of keratin filaments. Our skin’s rigidity – its ability to resist deformation under pressure – is due largely to the bonds between these strands of protein. The researchers were surprised to find that while the keratin was structurally changed by UVB exposure, the stiffness of the tissue wasn’t affected. When the skin samples were pulled apart, samples with greater UVB exposure were just as resistant.
The “mortar” of skin defense, on the other hand, took a beating from the UV rays. Between the corneocytes is a layer of lipids – fatty, waxy substances that hold the skin cells together and keep water from getting though. In a process called bulge testing, thin strips of skin were mounted over the opening of a cavity filled with pressurized water so they ballooned outward.
The team found that UV exposure increased the tissue’s tendency to absorb water and loosened the bonds between the lipids, making the tissue more likely to tear under pressure. This means that sun-damaged skin is more prone to cracking and chapping, leaving deeper layers vulnerable to infection.
In another technique borrowed from materials science, the researchers used a double cantilever beam model to test the cohesive properties of skin. Imagine restaurant chopsticks being pried open, but with a tissue sample glued into the region that gets torn apart. UV damage made the individual corneocytes separate more easily, especially in deeper layers of the stratum corneum.
This result suggests that another component of the “mortar,” proteins called corneodesmosomes, were also being damaged. These proteins are crucial to desquamation – the process of shedding dead skin cells, which allows us to replace the entire stratum corneum every two to four weeks. While the long-term impact of UV exposure on the desquamation mechanism has not been studied yet, damage to corneodesmosomes could mean deeper, lasting damage to the skin’s protective abilities.
Double the damage
All this rigorous stress testing revealed a grim fact: The sun takes a dramatic toll on our mechanical barrier function.
“UV exposure doesn’t just make the stratum corneum weaker,” said Dauskardt. “It also increases the actual stresses that cause the stratum corneum to fail. So it’s sort of a double-whammy, which we didn’t expect.” In other words, UV radiation introduces more force that drives skin cells apart while making the cells more helpless to resist.
This double threat is especially relevant to public health, as global climate change will gradually change the way people interact with the sun. The spectrum of sunlight that penetrates to Earth’s surface is increasing, while warmer temperatures cause people to wear less clothing and make them more vulnerable.
Mechanical testing is also confirming the vital importance of wearing sunscreen to protect the skin’s integrity.
“It’s totally cool,” said Dauskardt. “You put a sunscreen on the sample and it causes a huge change in the way the skin is affected.” This line of research offers a straightforward strategy for finding the best protection. These methods can quickly and accurately model how different sun protection products affect the skin’s mechanics. Dauskardt has already started comparative testing of sunscreens and thinks the work could be relevant in settling a currently raging debate about which types are most effective.
Dauskardt said the project is an example of breakthrough results arising from unlikely cooperation. “What’s so cool about bioengineering research today is that we’re taking medical challenges and looking at them with current engineering and scientific methods. This whole interdisciplinary approach is incredibly powerful, and you never know what it’s going to reveal.”
Source: Kelly Servick, Stanford University News
Image: David Freud

A Program to Encode Self-Assembling Collagen Proteins


A Program to Encode Self-Assembling Collagen Proteins

October 10, 2012
lab encodes collagen
A program developed at Rice University details stable forms of collagen proteins for synthesis in the lab. The ability to synthesize custom collagen could lead to better drug design and treatment of disease. The colored portion of the molecule in this illustration shows positively charged lysine and negatively charged aspartate interacting in the required axial geometry that stabilizes the triple helix. Credit: Hartgerink Lab/Rice University
A newly published study describes the making and testing of collagen based on a new computer program that predicts the most stable structures of nanometer-sized collagen.
Houston – The human body is proficient at making collagen. And human laboratories are getting better at it all the time.
In a development that could lead to better drug design and new treatments for disease, Rice University researchers have made a major step toward synthesizing custom collagen. Rice scientists who have learned how to make collagen – the fibrous protein that binds cells together into organs and tissues – are now digging into its molecular structure to see how it forms and interacts with biological systems.
Jeffrey Hartgerink, an associate professor of chemistry and of bioengineering, and his former graduate student Jorge Fallas, now a postdoctoral researcher at the University of Washington, wrote a new computer program that predicts the most stable structures of nanometer-sized collagen. In nature, these small structures link into chains that serve as connective tissue in the body. Hartgerink and Fallas followed up the computer research by making and testing the collagen detailed in their calculations.
Their success, reported in the online journal Nature Communications, will be of interest to physicians and scientists who work in reconstructive surgery, cosmetics and tissue engineering as well as to researchers investigating collagen protein interactions that could lead to new treatments for cancer and other diseases.
“Collagen is an odd protein. On one hand, it’s the most abundant protein in the human body,” said Hartgerink, who in a previous work unveiled a new way to synthesize self-assembling collagen. “It basically is the connective fiber that holds cells together; without it you’d turn into a big puddle.
“By mass, collagen is the most common protein there is. But it’s different from almost any other you might look at,” he said.
Hartgerink likened collagen to DNA with a structural twist, as it has not two but three intertwining peptide strands. “Watson and Crick, when they were first trying to understand DNA, figured out the underlying code for how all the base pairs fit together,” he said. “Collagen is similar, except there are three strands. In this paper, we’ve started to crack the code of which amino acids go with what others to stabilize the structure.”
While scientists have made a great deal of progress defining the structures of other proteins, “only a small group of us have been interested in collagen. And because of that, our understanding of it has lagged behind,” he said.
In their new work, Hartgerink and Fallas analyzed charged interactions between amino acids that attract one strand to another (and in this case, yet another) to form the triple helix. “We look at positively charged and negatively charged amino acids and where they need to be aligned to result in stabilization,” Hartgerink said.
In the same way three-color images must be properly aligned for a viewer to see a complete picture, the three strands of a collagen protein must be in register for the protein to carry out its function.
“Collagen does more than hold cells together,” he said. “It also binds other proteins that have interesting functions. Those proteins will attach to collagen, and then cells come along and bind to those proteins. Based on that interaction, a cell will then ‘decide’ how to behave or differentiate into a different type of cell.”
Hartgerink said that property makes collagen especially valuable for biological scaffolds, materials that are under intense study as a way to grow new body parts – even entire organs – to replace damaged ones.
Hartgerink said strand alignment also determines a collagen helix’s stability. The computer program designed by Fallas and Hartgerink calculates the stability of each possible alignment of a given set of peptide strands – 27 in all – to find the best matches of positively and negatively charged amino acids. It then assigns each set a score, based on the net positive or negative charge of the entire helix.
“If we have a positive charge in a peptide sequence, it will destabilize the triple helix, and we score that as a minus 1,” he said. “If we have a negative charge, that also destabilizes the helix and we also score that as a minus 1. But if those charges line up in what we call the axial geometry, it negates the destabilization. This triple helix would have a score of 0, which is good.
“We create huge, theoretical populations of collagen sequences and score all of them,” he said. “We find out which are closest to this magical score of 0 and throw out all the other ones.” That tells the researchers which sequences are likely to self-assemble into the most stable helixes. “The math looks complicated, but a personal computer can generate one of these sequences in one or two minutes of processing time. It’s not super sophisticated.” He said the code will be available on his group’s home page for other researchers to try.
Hartgerink’s lab, based at Rice’s BioScience Research Collaborative, has the unusual capacity to carry out both theoretical and experimental sides of the work. While the program generates test sequences in minutes on a desktop computer, synthesis and analysis of actual collagen takes much more effort.
“Once you have a sequence, you want to test it to see if it actually works,” he said. “The math is useless if it’s not predicting reality. Our proof-of-principle showed the computer code can be used to design a triple helix that folds properly. Now that we know how to do this, we can think about making collagen biomaterials for things like scaffolding, or to test protein/collagen receptor interactions, which people have been trying to demonstrate for a long time.”
>He said the new work could help researchers decipher collagen’s role in the metastasis of cancer. “Cancer cells need to be able to degrade collagen in order to move from organ to organ. We need to understand the structure of collagen to learn how they do that,” Hargerink said. “Blood clots happen because specific proteins recognize a collagen sequence. If we don’t understand the structure, we can’t assist clotting to heal a wound or help people who have overclotting problems.
“All these targets are critical but they’re very difficult to approach when we don’t fundamentally understand collagen structure,” he said. “We’re not solving all those problems here, but this is a good first step.”
The work was supported by the National Science Foundation, the Robert A. Welch Foundation and the Norman Hackerman Advanced Research Program of Texas.
Source: Mike Williams, Rice University
Image: Hartgerink Lab/Rice University

Humans Are Less in Control of Their Brains Than Previously Thought


Humans Are Less in Control of Their Brains Than Previously Thought

October 11, 2012
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Most of the actions that people take for granted are the result of a set of complex decisions that the brain deals with. The decisions about how to aim the body, how hard to hold handles, and how to raise cups are something that no one often consciously thinks of, yet the brain does all of these without missing a beat. A new Northwestern University study shows that not only does the brain handle such complex decisions, it also hides this information from the conscious mind.
The scientists published their findings in the journal Perception. When you pick up an object, your brain automatically decides how to control your muscles based on what your eyes see, states Yangqing Xu, lead author of the study and doctoral candidate in psychology at Northwestern. When you pick up a mug with your right hand, you need to add a clockwise twist to your grip in order to compensate for the extra weight you see on the left side of the mug, she continues.
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We explore objects to familiarize ourselves with their visual aspects.
The researchers showed that the use of this visual information is so powerful and automatic, that humans cannot turn it off. When people see an objected weighted in one direction, they can’t help but feel the weight in that direction, even when the researchers tricked them.
In the scientists’ first experiment, people were asked to grasp a vertical stick with a weight hanging from its left or right side. People easily reported which side they felt the weight was on, even when they closed their eyes. Then, the researchers used a set of mirrors to occasionally flip the view of the object, so that it looked like the weight was on the other side. Although people were able to report on which side they felt the weight, the visual image strongly influenced the direction they felt that the weight was coming from, especially with lighter objects.
While researchers experimented with trying to convince their subjects the nature of the trick, people could still not ignore the visual information. It even worked on the researchers themselves, who designed the experiment.
The brain is constantly making decisions that people don’t know about or don’t understand. The decisions are logical and based on vast experience.

Chinese Soft Shelled Turtle Evacuates Majority of Urea through its Mouth


Chinese Soft Shelled Turtle Evacuates Majority of Urea through its Mouth

October 12, 2012
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Image via Akwarium Gdynia
When Chinese soft-shelled turtles (Pelodiscus sinensis) need to urinate, they open their mouths, according to a new study. As odd as it might seem, this actually makes sense for this amphibious organism.
The researchers published their findings in The Journal of Experimental Biology. These reptiles don’t have any gills, but they have structures inside their mouths that work like gills. This means that P. sinensis has the option of breathing underwater, though most of the time they just reach up and breathe air. But what researchers found perplexing was that when the turtles were on dry land, they would stick their heads in puddles and swish water around in their mouths. This was one of the clues that led researchers to consider that there was something more happening than respiration.
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Credit: Frank Greenaway/GettyImages
The scientists bought P. sinensis specimens at a market in Singapore and found ways to collect their urine. They attached a flexible latex tube to each underside. They discovered that the animals were getting rid of a vast majority of their urea, which is a major component of urine, through their mouths instead of their undersides.
The team speculates that this might be because the animals have to drink a lot of water to make urine, which can be unhealthy in salt water environments where these turtles spend most of their time. If they are just rinsing out the water around their mouths, they avoid having to get rid of the salt.

Chemical Model Shows How First Life Forms Might Have Packaged RNA


Chemical Model Shows How First Life Forms Might Have Packaged RNA

October 15, 2012
chemical model that mimics a possible step in the formation of cellular life on Earth
Shown are RNA strands (blue) and RNA enzymes (red) coming together within droplets of dextran. Scientists at Penn State have shown that this compartmentalization helps to catalyze chemical reactions. Credit: C. A. Strulson
Using polymers, scientists at Penn State created primitive cell-like structures that they infused with RNA, demonstrating how the molecules would react chemically under conditions that may have been present on Earth four-billion years ago.
Researchers at Penn State University have developed a chemical model that mimics a possible step in the formation of cellular life on Earth four-billion years ago. Using large “macromolecules” called polymers, the scientists created primitive cell-like structures that they infused with RNA — the genetic coding material that is thought to precede the appearance of DNA on Earth — and demonstrated how the molecules would react chemically under conditions that might have been present on the early Earth. The journal Nature Chemistry will post the research as an Advance Online Publication on 14 October 2012.
In modern biology, all life, with the exception of some viruses, uses DNA as its genetic storage mechanism. According to the “RNA-world” hypothesis, RNA appeared on Earth first, serving as both the genetic-storage material and the functional molecules for catalyzing chemical reactions, then DNA and proteins evolved much later. Unlike DNA, RNA can adopt many different molecular conformations and so it is functionally interactive on the molecular level. In the soon-to-be-published research paper, two professors of chemistry, Christine Keating and Philip Bevilacqua, and two graduate students, Christopher Strulson and Rosalynn Molden, probe one of the nagging mysteries of the RNA-world hypothesis.
“A missing piece of the RNA-world puzzle is compartmentalization,” Bevilacqua said. “It’s not enough to have the necessary molecules that make up RNA floating around; they need to be compartmentalized and they need to stay together without diffusing away. This packaging needs to happen in a small-enough space — something analogous to a modern cell — because a simple fact of chemistry is that molecules need to find each other for a chemical reaction to occur.”
To test how early cell-like structures could have formed and acted to compartmentalize RNA molecules even in the absence of lipid-like molecules that make up modern cellular membranes, Strulson and Molden generated simple, non-living model “cells” in the laboratory. “Our team prepared compartments using solutions of two polymers called polyethylene glycol (PEG) and dextran,” Keating explained. “These solutions form distinct polymer-rich aqueous compartments, into which molecules like RNA can become locally concentrated.”
The team members found that, once the RNA was packed into the dextran-rich compartments, the molecules were able to associate physically, resulting in chemical reactions. “Interestingly, the more densely the RNA was packed, the more quickly the reactions occurred,” Bevilacqua explained. “We noted an increase in the rate of chemical reactions of up to about 70-fold. Most importantly, we showed that for RNA to ‘do something’ — to react chemically — it has to be compartmentalized tightly into something like a cell. Our experiments with aqueous two-phase systems (ATPS) have shown that some compartmentalization mechanism may have provided catalysis in an early-Earth environment.”
Keating added that, although the team members do not suggest that PEG and dextran were the specific polymers present on the early Earth, they provide a clue to a plausible route to compartmentalization — phase separation. “Phase separation occurs when different types of polymers are present in solution at relatively high concentrations. Instead of mixing, the sample separates to form two distinct liquids, similar to how oil and water separate.” Keating explained. “The aqueous-phase compartments we manufactured using dextran and PEG can drive biochemical reactions by increasing local reactant concentrations. So, it’s possible that some other sorts of polymers might have been the molecules that drove compartmentalization on the early Earth.” Strulson added that, “In addition to the RNA-world hypothesis, these results may be relevant to RNA localization and function in non-membrane compartments in modern biology.”
The team members also found that the longer the string of RNA, the more densely it would be packed into the dextran compartment of the ATPS, while the shorter strings tended to be left out. “We hypothesize that this research result might indicate some kind of primitive sorting method,” Bevilacqua said. “As RNA gets shorter, it tends to have less enzyme activity. So, in an early-Earth system similar to our dextran-PEG model system, the full-length, functional RNA would have been sorted and concentrated into one phase, while the shorter RNA that is not only less functional, but also threatens to inhibit important chemical reactions, would not have been included.”
The scientists hope to continue their investigations by testing their model-cell method with other polymers. Keating added, “We are interested in looking at compartmentalization in polymer systems that are more closely related to those that may have been present on the early Earth, and also those that may be present in contemporary biological cells, where RNA compartmentalization remains important for a wide range of cellular processes.”
This research was funded by the National Science Foundation (grant CHE-0750196).
Source: Pennsylvania State University
Image: C. A. Strulson