Tag Archives: Life Science

Glaciers Contribute Significant Iron to North Atlantic Ocean

Research area: During the course of two expeditions to the Greenland ice sheet in May and July 2008, Bhatia and her colleagues collected samples from sites at three land-terminating glaciers. The meltwater from these glaciers travels through a flood plain and eventually drains into Qasigiatsigit Lake, before finally emptying into the fjord. (courtesy Maya Bhatia, Woods Hole Oceanographic Institution)

Research area: During the course of two expeditions to the Greenland ice sheet in May and July 2008, Bhatia and her colleagues collected samples from sites at three land-terminating glaciers. The meltwater from these glaciers travels through a flood plain and eventually drains into Qasigiatsigit Lake, before finally emptying into the fjord. (courtesy Maya Bhatia, Woods Hole Oceanographic Institution)

All living organisms rely on iron as an essential nutrient. In the ocean, iron’s abundance or scarcity means all the difference as it fuels the growth of plankton, the base of the ocean’s food web.

A new study by biogeochemists and glaciologists at Woods Hole Oceanographic Institution (WHOI) identifies a unexpectedly large source of iron to the North Atlantic – meltwater from glaciers and ice sheets, which may stimulate plankton growth during spring and summer. This source is likely to increase as melting of the Greenland ice sheet escalates under a warming climate.

 

The study was published online in Nature Geoscience on March 10, 2013.

“There’s only been one other study looking at the amount of iron that’s being released in meltwater runoff itself,” says Maya Bhatia, a graduate of the MIT/WHOI Joint Program in Oceanography and Applied Ocean Sciences and Engineering, and the study’s lead author, “and that had reported high nanomolar concentrations. So to find iron in concentrations several orders of magnitude higher – in the micromolar range – was very surprising.”

Iron from wind-blown dust and river runoff fuels annual plankton blooms in the world’s ocean. Ice sheets and glaciers are now also thought to contribute iron from sediments on the bottom of calved icebergs and glacially-derived dust. Until now, meltwater runoff from glaciers and ice sheets was considered too dilute to carry much iron, although previous research has shown a strong correlation between the plankton blooms and the runoff from Greenland ice sheet.

“Glacial runoff has only recently been considered a potentially important source of nutrients that are useable, or bioavailable, to downstream ecosystems,” says Bhatia. “We believe our study now adds iron to that list of nutrients, and underscores the potential for a unique but as-yet-undetermined chemical impact from increasing ice sheet meltwater runoff.”

During the course of two expeditions to the Greenland ice sheet in May and July 2008, Bhatia and her colleagues collected samples from sites at several land-terminating glaciers on the western side of the Greenland ice sheet. The glaciers’ meltwater empties into a large lake, which eventually drains into an estuary system before reaching the open ocean. Their study reports levels of dissolved iron orders of magnitude higher than previously found for Greenland glacial runoff rivers.  When the WHOI team extrapolated their findings to calculate the contribution of iron from the entire ice sheet, they estimated its value to be within the range of that from dust deposition in the North Atlantic, which is believed to be the primary source of bioavailable iron to this ocean. This value is only an order of magnitude lower than the estimated annual contribution of iron from rivers worldwide.

When an ice sheet or glacier melts, most of the water doesn’t simply run off the surface of the ice sheet. Instead it first drains to the bedrock below the ice sheet through cracks and conduits called moulins and then exits in large runoff rivers.

“A lot of people think of a glacier and an ice sheet as a big block of ice,” says Bhatia, “but it’s actually quite a porous, complicated system underneath a glacier, with lots of moulins and crevasses leading to the bottom. Once you get into the bottom, there are large tunnels that these waters are passing through.” The more time the water spends in contact with the bedrock and sediments beneath the glacier, the more nutrients it picks up, including iron.

The WHOI team says further research is needed to determine how much of this iron actually reaches the open ocean, as their study followed the meltwater from the edge of the glaciers to the large lake they empty into. For this study, the team assumed that the amount of iron filtered out as the water moves through estuaries before reaching the marine environment would be roughly the same for glacial systems as it is for river systems.

The researchers hope to do more work to confirm the study’s numbers by sampling over a larger geographical area. Additional research could also confirm whether this influx of iron is in a form that can be easily utilized by phytoplankton and therefore stimulates primary production in the ocean.

“We don’t have enough historical measurements to say that this iron contribution is an increase over past conditions, but if it is working the way we think it is, the contribution would be greater as meltwater discharge increases,” Bhatia says. “It is interesting to think that, as ice sheets melt, there are biogeochemical considerations beyond changing sea level.”

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Computer Model May Help Athletes and Soldiers Avoid Brain Damage and Concussions

Concussions can occur in sports and in combat, but health experts do not know precisely which jolts, collisions and awkward head movements during these activities pose the greatest risks to the brain. To find out, Johns Hopkins engineers have developed a powerful new computer-based process that helps identify the dangerous conditions that lead to concussion-related brain injuries. This approach could lead to new medical treatment options and some sports rule changes to reduce brain trauma among players.

 

The research comes at a time when greater attention is being paid to assessing and preventing the head injuries sustained by both soldiers and athletes. Some kinds of head injuries are difficult to see with standard diagnostic imaging but can have serious long-term consequences. Concussions, once dismissed as a short-term nuisance, have more recently been linked to serious brain disorders.

“Concussion-related injuries can develop even when nothing has physically touched the head, and no damage is apparent on the skin,” said K. T. Ramesh, the Alonzo G. Decker Jr. Professor of Science and Engineering who led the research at Johns Hopkins. “Think about a soldier who is knocked down by the blast wave of an explosion, or a football player reeling after a major collision. The person may show some loss of cognitive function, but you may not immediately see anything in a CT-scan or MRI that tells you exactly where and how much damage has been done to the brain. You don’t know what happened to the brain, so how do you figure out how to treat the patient?”

To help doctors answer this question, Ramesh led a team that used a powerful technique called diffusion tensor imaging, together with a computer model of the head, to identify injured axons, which are tiny but important fibers that carry information from one brain cell to another. These axons are concentrated in a kind of brain tissue known as “white matter,” and they appear to be injured during the so-called mild traumatic brain injury associated with concussions. Ramesh’s team has shown that the axons are injured most easily by strong rotations of the head, and the researchers’ process can calculate which parts of the brain are most likely to be injured during a specific event.

The team described its new technique in the Jan. 8 edition of theJournal of Neurotrauma. The lead author, Rika M. Wright, played a major role in the research while completing her doctoral studies in Johns Hopkins’ Whiting School of Engineering, supervised by Ramesh. Wright is now a postdoctoral research fellow at Carnegie Mellon University. Ramesh is continuing to conduct research using the technique at Johns Hopkins with support from the National Institutes of Health.

Beyond its use in evaluating combat and sports-related injuries, the work could have wider applications, such as detecting axonal damage among patients who have received head injuries in vehicle accidents or serious falls. “This is the kind of injury that may take weeks to manifest,” Ramesh said. “By the time you assess the symptoms, it may be too late for some kinds of treatment to be helpful. But if you can tell right away what happened to the brain and where the injury is likely to have occurred, you may be able to get a crucial head-start on the treatment.”

Armed with this knowledge, Ramesh and his colleagues want to use their new technology to examine athletes, particularly football and hockey players, who are tackled or struck during games in ways that inflict that violent side-to-side motion on the head. In the recent journal article, the authors point out that many professional sports games are recorded in high-definition video from multiple angles. This, they write, could allow researchers to reconstruct the motions involved in sport collisions that lead to the most serious head injuries.

The authors also noted that some sports teams equip their players’ helmets or mouth guards with instruments that can measure the acceleration of the head during an impact. Such data, entered into the researchers’ computer model, could help determine the likely location of brain damage. These results, combined with neuropsychological tests, could be used to guide the athlete’s treatment and rehabilitation, the authors said, and to help a sports team decide when an athlete should be allowed to resume playing. This strategy also may help reduce the risk to athletes arising from a degenerative disease linked to repeated concussions.

More research, testing and validation must be conducted before the computer model can become useful in a clinical setting. This will include animal experiments and the correlation of data from event reconstruction to make sure the model accurately identifies brain injuries.

Ideally, Ramesh would like to collect digital brain images from soldiers and athletes before they enter combat or join highly physical sports activities. “We would then be able to track a high-risk population and keep records detailing what types of head injuries they experience,” he said. “Then, we could look at how their brains may have changed since the original images were collected. This will also help guide the physicians and health professionals who provide treatment after critical events.”

Scientists make mouse model of human cancer, demonstrate cure

Scientists report the first successful blocking of tumor development in a genetic mouse model of an incurable human cancer.

“To my knowledge, this is the first time that a mouse model of a genetically defined malignant human cancer has been generated in which the formation of the tumor from beginning to end can be monitored and in which blocking the pathway cures the mouse of the tumor,” said Dr. Luis Parada, chair of the department of developmental biology at UT Southwestern and senior author of the study published in Cell and online. The study’s first author is Dr. Wei Mo, a postdoctoral researcher in the department.

 

“We showed that blocking the activity of a receptor molecule named CXCR4 in these tumors – through genetic manipulation or by chemical blockade – inhibited tumor development. Together, these data reveal a potential target for therapy of these uncommon but currently untreatable malignant peripheral nerve sheath tumors (MPNSTs),” Dr. Parada added.

The study is a collaboration between Dr. Parada’s laboratory and that of Dr. Lu Q. Le, co-senior author of the study and assistant professor of dermatology. Dr. Le also is co-director of the adult Comprehensive Neurofibromatosis Clinic at UT Southwestern, the first such clinic in North Texas, which is part of the Simmons Comprehensive Cancer Center. The researchers noted that co-authors at The University of Texas MD Anderson Cancer Center and Baylor College of Medicine, Houston, greatly accelerated the research effort.

MPNSTs are rare but highly aggressive tumors that are resistant to therapy and are typically fatal. The malignancies can occur sporadically or in a subset of patients with a condition called neurofibromatosis 1 (NF1) – one of the most commonly inherited disorders of the nervous system, which affects an estimated 1 in 3,500 people.

The severity of NF1 can vary widely, even among family members, from mild dermatological symptoms to benign tumors that wrap around nerves and can be disfiguring, debilitating, and even life-threatening, depending on where they form, Dr. Le said. In addition, individuals with an improperly-functioning NF1 gene have an increased risk of developing cancerous tumors such as MPNSTs, he said.

The researchers generated a mouse model that spontaneously develops MPNSTs and compared gene expression activity in cancerous tumors and in the precursor cells that give rise to the tumors, which are the kind of cells in which MPNSTs develop.

They found that a protein (CXCR4), which is essential for tumor growth, is more abundant in cancerous cells than in precursor cells. In addition, they found that a molecule produced by the cancer cells themselves (CXCL12) works with CXCR4 to further the growth of cancer by stimulating the expression of the cyclin D1 protein, which promotes cell division via a signaling pathway outlined in the study.

When they examined human MPNSTs, the scientists found increased expression of CXCR4 accompanied by activity in the same pathway as the one identified in the mice, the researchers said.

Next, they blocked the activity of CXCR4 in the MPNST mice using either genetic manipulation or an FDA-approved antagonist drug for CXCR4 called AMD3100. Both strategies inhibited cancer development in mice whose tumors expressed increased levels of CXCR4, and were less effective in tumors without increased CXCR4 expression. They identified the same situation in the human cancer cells, the researchers report.

“We are very encouraged by these findings because they provide us with new directions and therapeutic windows to combat this deadly cancer, where none exist today,” said Dr. Le, who added that the researchers are currently planning human trials.

Researchers Solve Mystery of Mutations in Antibodies

Scientists have discovered a new role for many of the changes that occur to antibodies as they mature to fight disease. The discovery could change the thinking about how the human immune system protects against foreign substances and might eventually lead to the development of better antibody-based drugs.

The researchers found that the immune system not only makes changes to antibodies that enhance their ability to bind to foreign substances like viruses, but also optimizes them to be more stable.

 

Humans naturally produce a collection of antibodies, called the germ-line repertoire, that is activated when foreign substances are detected. That detection causes immune cells to modify antibodies to a mature form that is more effective in fighting a particular invader.

Scientists have known for some time that many of the mutations that occur in this maturation process do not actually help the antibodies bind more effectively to the foreign substances.

Research groups at Ohio State University and The Scripps Research Institute (TSRI) in La Jolla, Calif., showed in this new work that many mutations occur so that the antibody remains stable. They also showed that many of the mutations that improve the binding actually destabilize the molecule, suggesting that additional peripheral mutations might be required to ensure that antibodies function properly.

“We mainly have thought of antibodies as being very stable molecules that are tolerant of the mutations needed to make them into better binders,” said Thomas Magliery, assistant professor in the Department of Chemistry and Biochemistry at Ohio State and a lead author of the study. “But what we know now is that many of the binding mutations lead to instability, and that many of the peripheral mutations that looked unimportant really compensate for the destabilizing ones.”

The research is reported in the online early edition of Proceedings of the National Academy of Sciences.

With the use of a technique called X-ray crystallography, the team was able to show that an antibody with only the destabilizing mutations in the binding site disturbed networks of nearby atoms that are likely to be important for stability. But exactly how the more distant peripheral mutations stabilize the mature antibodies is not yet clear.

The discovery may suggest that the immune system actively works to keep antibodies stable, but offered only a hint about how it might do that.

Besides shedding new light on how the immune system functions, the discovery could also lead to more effective drugs.

“So-called biologics, which are mostly antibody-based drugs at this point, often suffer from problems with aggregation or storage because of instability,” said Magliery. “Studying these peripheral mutations might help solve that problem.”

Order in the chaos of a cell membrane

Model of a cell membrane with embedded glycolipids, or more precisely glycosylphosphatidylinositols, GPIs (left), and the formation of a molecular lattice in a monolayer at the water-air boundary (right). © MPI of Colloids and Interfaces

Model of a cell membrane with embedded glycolipids, or more precisely glycosylphosphatidylinositols, GPIs (left), and the formation of a molecular lattice in a monolayer at the water-air boundary (right). © MPI of Colloids and Interfaces

An explanation has been proposed for the way in which ordered structures arise in cell membranes. Scientists from the Max Planck Institute of Colloids and Interfaces in Potsdam have discovered how complex compounds of sugar and lipids – known as glycolipids – order themselves in cell membranes into rafts, namely small, highly organised domains. The arrangement of glycolipids on the surface of plant and animal cell membranes regulates numerous cellular processes. If errors occur in this process, diseases like PNH and BSE can arise.

 

Lipids, i.e. fats and fat-like substances, arise all over the human body. They are the body’s most important energy storage system and are crucial structural components of cell membranes. Compounds formed from complex sugar components and fats are known as glycolipids. Those are vital communicators found in the membranes of every human cell, and constantly exchange information about the type and state of the cell. Numerous metabolic processes depend on glycolipids and their recognition. Even the immune system identifies and combats many pathogens using certain sugar structures located on the surface of the pathogen cells.

Glycosylphosphatidylinositols (GPIs) belong to the group of natural glycolipids. They are found on the surface of plant and animal cell membranes, where they appear either as free molecules or as membrane anchors for various proteins. The arrangement in clusters and their preference for denser and, in part, highly-organised micro-domains in the membrane are seen as essential for the effective functioning of a cell. These minuscule clusters are extremely important for the regulation of many cellular processes, and their malfunction can have very serious consequences. For example, it has been proven that the accumulation, missing or alteration of GPI-anchored molecules can trigger the development of serious diseases like BSE and paroxysmal nocturnal hemoglobinuria (PNH). Scientists at the Max Planck Institute of Colloids and Interfaces in Golm near Potsdam have gained new insight into how GPIs structure themselves in membranes.

Crystalline lipid areas never previously observed in membranes

It was assumed up to now that the arrangement of the GPIs in clusters and rafts was determined by the water-repelling section of the glycolipids embedded in the cell membrane. The chemical structure of the hydrophobic ends is actually responsible for strong interactions with similarly rigid neighbouring molecules. If the number of the molecules that interact with each other is big enough, rigid and partly organised domains may arise like icebergs on the surface of the ocean.

Cristina Stefaniu and her colleagues have now discovered that, in addition to the hydrophobic ends, the large GPI head groups, which contain sugar, mainly contribute to the formation of the rafts. This means that the hydrophylic part of the molecule is able to build strong interactions with the neighbouring GPI molecules. This part of the molecule is located precisely on the boundary between the membrane surface and the liquid medium. “The interactions between neighbouring GPI molecules result in the formation of crystalline orders that have not previously been observed for other membrane lipids”, says Cristina Stefaniu.

Hydrogen bonds connect the hydrophylic head groups

The scientists reached this new conclusion about the order in membranes by studying a model molecule. This is a GPI fragment that was synthesised by the groups headed by Peter Seeberger and Daniel Varón Silva and that imitates the behaviour of entire GPIs. It forms a very thin film, just one molecule thick, on the surface of the water. This so-called monolayer is the simplified model of a half cell membrane which the researchers analysed using synchrotron x-ray scattering. “Surprisingly, the highly ordered structure in the GPI monolayer is predominantly determined by the bulky hydrophilic head groups that connect through hydrogen bonds”, says Stefaniu. A hydrogen bond is a relatively weak chemical bond and usually links two molecules through the bonding of a hydrogen atom from one molecule with an oxygen or nitrogen atom from the other molecule. Thus the monolayers of the GPI fragment are characterised by both the order of the hydrophilic lipid chains and the crystalline arrangement of the GPI head groups.

“The molecular lattices observed here have not yet been described for lipid monolayers,” says Cristina Stefaniu. “A similar order forms in lipid bilayers if they are stored at temperatures close to zero degrees Celsius.” The strong interactions between the head groups can only be disrupted and the molecular lattice destroyed through the addition of a highly concentrated urea solution, which breaks the hydrogen bonds, eliminates the strong interactions of the head groups and destroys the molecular lattice. In addition, the scientists proved that ordered clusters can arise in mixtures of the GPI fragment with typical membrane lipids, which only form unordered films. Thus, the GPIs are able to generate order in the chaos of a membrane. This special skill could be very important for the GPI interactions in real cell membranes.

 

Impact craters may have been cradles of life

Even comparatively small meteorite impact craters may have played a key role in the origin and evolution of early life on Earth, according to a researcher at The University of Western Australia. Geologist Martin Schmieder, a research associate in UWA’s School of Earth and Environment, said study results suggested that heat generated by an asteroid impact took at least several hundred thousand years to dissipate.

Dr Schmieder, the lead author of an article published this month in the prestigious journal Geochimica et Cosmochimica Acta, said as impact craters cooled, they provided an ideal environment for microbial life to thrive.

 

He and fellow researcher Dr Fred Jourdan, Director of the Western Australian Argon Isotope Facility at Curtin University, are experts in the study of rocks and minerals from craters produced by the hypervelocity impact of incoming asteroids and comets (termed meteorites once they have hit the Earth’s surface).  Impact craters are common features in the solar system.

“As a case study, we analysed impact-molten rock samples from the 23km-diameter and 76-million-year-old Lappajärvi crater in Finland, and were quite surprised by the results,” Dr Schmieder said.

Temperatures during an impact event can reach several thousand degrees Celsius, capable of melting portions of the target rock.  Smaller to medium-size impact craters less than 30km across represent the largest crater population on Earth and other planetary bodies, compared with giant impact basins such as those on the Moon that are visible to the naked eye on a clear night.

Earlier estimates for the duration of cooling in smaller impact craters were based on theoretical simulations and suggested a relatively short cool-down period of about 10,000 years after the impact.  Drs Schmieder and Jourdan used the so-called argon-argon dating technique based on the natural radioactive decay of potassium to argon to measure the age of different minerals formed on impact.

“Our new argon-argon data tell us that the Lappajärvi crater did not cool down as rapidly as expected but within at least several 100,000 years, and perhaps more than a million years,” Dr Jourdan said.

“Cooling impact craters are hot natural laboratories in which hot hydrothermal fluids circulate.  We think they provided ideal starting conditions for the origin and evolution of microbial life on early Earth more than two billion years ago.”

Dr Schmieder said of the 185 meteorite impact structures recognised on Earth, 29 were in Australia, and new impact sites were discovered worldwide nearly every year.

“Although usually associated with massive havoc and destruction, asteroid impacts also acted as extraterrestrial boosters of life in the past,” he said.

“A prime example is the giant Chicxulub impact that helped wipe out the dinosaurs 66 million years ago and eventually paved the way for mammals and mankind.”

The researchers believe the large Acraman impact in South Australia more than 500 million years earlier probably had a major influence on the evolutionary radiation of the first multicellular life forms during the Ediacaran, a geologic time period named after the fossil-bearing Ediacara Hills in Australia’s Flinders Ranges, when complex life started to blossom.

Drs Schmieder and Jourdan are currently carrying out a government-funded global research project on a number of terrestrial impact craters, some of them located in Australia.

“Large meteorite impacts are outstanding and fascinating geologic events, and we will soon investigate other ancient impact craters on all continents to more deeply explore their geologic age and potential role in the history of life on Earth and possibly Mars,” Dr Schmieder said.

New Injectable Hydrogel Encourages Regeneration and Improves Functionality After a Heart Attack

 

Microscopic images of pig hearts damaged by heart attack show the growth of new heart muscle tissue (Shown in Red, Figure A) after treatment with an injectable hydrogel compared to a heart left untreated (Figure B, right). Photo credit: Karen Christman, UC San Diego Jacobs School of Engineering.

Microscopic images of pig hearts damaged by heart attack show the growth of new heart muscle tissue (Shown in Red, Figure A) after treatment with an injectable hydrogel compared to a heart left untreated (Figure B, right). Photo credit: Karen Christman, UC San Diego Jacobs School of Engineering.

University of California, San Diego bioengineers have demonstrated in a study in pigs that a new injectable hydrogel can repair damage from heart attacks, help the heart grow new tissue and blood vessels, and get the heart moving closer to how a healthy heart should. The results of the study were published Feb. 20 in Science Translational Medicine and clear the way for clinical trials to begin this year in Europe. The gel is injected through a catheter without requiring surgery or general anesthesia — a less invasive procedure for patients.

 

There are an estimated 785,000 new heart attack cases in the United States each year, with no established treatment for repairing the resulting damage to cardiac tissue. Lead researcher Karen Christman, a professor in the Department of Bioengineering at the UC San Diego Jacobs School of Engineering, said the gel forms a scaffold in damaged areas of the heart, encouraging new cell growth and repair. Because the gel is made from heart tissue taken from pigs, the damaged heart responds positively, creating a harmonious environment for rebuilding, rather than setting off a chain of adverse immune system defenses.

UC San Diego bioengineers demonstrated in a study in pigs that a new injectable hydrogel gets hearts moving more like they should -- as measured by the Global Wall Motion Index (GWMI) -- in hearts following heart attack. After a heart attack, the score was elevated; however, for pigs that were treated with the hydrogel, this index score dropped back closer to normal. Chart: Karen Christman, UC San Diego Jacobs School of Engineering.

“While more people today are initially surviving heart attacks, many will eventually go into heart failure,” said Christman.  “Our data show that this hydrogel can increase cardiac muscle and reduce scar tissue in the region damaged by the heart attack, which prevents heart failure. These results suggest this may be a novel minimally invasive therapy to prevent heart failure after a heart attack in humans.”

The hydrogel is made from cardiac connective tissue that is stripped of heart muscle cells through a cleansing process, freeze-dried and milled into powder form, and then liquefied into a fluid that can be easily injected into the heart. Once it hits body temperature, the liquid turns into a semi-solid, porous gel that encourages cells to repopulate areas of damaged cardiac tissue and to improve heart function, according to Christman. The material is also biocompatible; animals treated with the hydrogel suffered no adverse affects such as inflammation, lesions or arrhythmic heart beating, according to safety experiments conducted as part of the study. Further tests with human blood samples showed that the gel had no affect on the blood’s clotting ability, which underscores the biocompatibility of the treatment for use in humans.

San Diego-based startup, Ventrix, Inc., which Christman co-founded, has licensed the technology for development and commercialization. Christman also serves on the company’s board. “We are excited and encouraged by the results of the study leading to a novel regenerative medicine solution for cardiac repair. The technology offers the potential for a longer and better quality of life for millions of heart attack sufferers,” said Adam Kinsey, the CEO of Ventrix.