Blood Mystery Solved

You probably know your blood type: A, B, AB or O. You may even know if you’re Rhesus positive or negative. But how about the Langereis blood type? Or the Junior blood type? Positive or negative? Most people have never even heard of these.

Yet this knowledge could be “a matter of life and death,” says University of Vermont biologist Bryan Ballif.

While blood transfusion problems due to Langereis and Junior blood types are rare worldwide, several ethnic populations are at risk, Ballif notes. “More than 50,000 Japanese are thought to be Junior negative and may encounter blood transfusion problems or mother-fetus incompatibility,” he writes.

With skilled handling of this mass spectrometer, Bryan Ballif unraveled the mystery of two little-understood blood types. Now he's looking for more. 

Photo: Joshua Brown

But the molecular basis of these two blood types has remained a mystery — until now.

In the February issue of Nature Genetics, Ballif and his colleagues report on their discovery of two proteins on red blood cells responsible for these lesser-known blood types.

Ballif identified the two molecules as specialized transport proteins named ABCB6 and ABCG2.

“Only 30 proteins have previously been identified as responsible for a basic blood type,” Ballif notes, “but the count now reaches 32.”

The last new blood group proteins to be discovered were nearly a decade ago, Ballif says, “so it’s pretty remarkable to have two identified this year."

Both of the newly identified proteins are also associated with anticancer drug resistance, so the findings may also have implications for improved treatment of breast and other cancers.
Cross-border science

As part of the international effort, Ballif, assistant professor in the biology department, used a mass spectrometer at UVM funded by the Vermont Genetics Network. With this machine, he analyzed proteins purified by his longtime collaborator, Lionel Arnaud at the French National Institute for Blood Transfusion in Paris, France.

Ballif and Arnaud, in turn, relied on antibodies to Langereis and Junior blood antigens developed by Yoshihiko Tani at the Japanese Red Cross Osaka Blood Center and Toru Miyasaki at the Japanese Red Cross Hokkaido Blood Center.

After the protein identification in Vermont, the work returned to France. There Arnaud and his team conducted cellular and genetic tests confirming that these proteins were responsible for the Langereis and Junior blood types. “He was able to test the gene sequence,” Ballif says, “and, sure enough, we found mutations in this particular gene for all the people in our sample who have these problems."
Transfusion troubles

Beyond the ABO blood type and the Rhesus (Rh) blood type, the International Blood Transfusion Society recognizes twenty-eight additional blood types with names like Duffy, Kidd, Diego and Lutheran. But Langereis and Junior have not been on this list. Although the antigens for the Junior and Langereis (or Lan) blood types were identified decades ago in pregnant women having difficulties carrying babies with incompatible blood types, the genetic basis of these antigens has been unknown until now.

Therefore, “very few people learn if they are Langereis or Junior positive or negative,” Ballif says.

“Transfusion support of individuals with an anti-Lan antibody is highly challenging,” the research team wrote in Nature Genetics, “partly because of the scarcity of compatible blood donors but mainly because of the lack of reliable reagents for blood screening.” And Junior-negative blood donors are extremely rare too. That may soon change.

With the findings from this new research, health care professionals will now be able to more rapidly and confidently screen for these novel blood group proteins, Ballif wrote in a recent news article. "This will leave them better prepared to have blood ready when blood transfusions or other tissue donations are required," he notes.

“Now that we know these proteins, it will become a routine test,” he says.
A better match

This science may be especially important to organ transplant patients. “As we get better and better at transplants, we do everything we can to make a good match,” Ballif says. But sometimes a tissue or organ transplant, that looked like a good match, doesn’t work — and the donated tissue is rejected, which can lead to many problems or death.

“We don’t always know why there is rejection,” Ballif says, “but it may have to do with these proteins.”

The rejection of donated tissue or blood is caused by the way the immune system distinguishes self from not-self. “If our own blood cells don’t have these proteins, they’re not familiar to our immune system,” Ballif says, so the new blood doesn’t “look like self” to the complex cellular defenses of the immune system. “They’ll develop antibodies against it,” Ballif says, and try to kill off the perceived invaders. In short, the body starts to attack itself.

“Then you may be out of luck,” says Ballif, who notes that in addition to certain Japanese populations, European Gypsies are also at higher risk for not carrying the Langereis and Junior blood type proteins.

“There are people in the United States who have these challenges too,” he says, “but it’s more rare.”
Other proteins

Ballif and his international colleagues are not done with their search. “We’re following up on more unknown blood types,” he says. “There are probably on the order of 10 to 15 more of these unknown blood type systems — where we know there is a problem but we don’t know what the protein is that is causing the problem.”

Although these other blood systems are very rare, “if you’re that one individual, and you need a transfusion," Ballif says, "there’s nothing more important for you to know.”

Contacts and sources:
Joshua Brown
University of Vermont

NYC To Be Submerged As Storm Of The Century Becomes Storm Of The Decade

As the Earth's climate changes, the worst inundations from hurricanes and tropical storms could become far more common in low-lying coastal areas, a new study suggests. Researchers from Princeton University and the Massachusetts Institute of Technology found that regions such as the New York City metropolitan area that currently experience a disastrous flood every century could instead become submerged every one or two decades.

The researchers report in the journal Nature Climate Change that projected increases in sea level and storm intensity brought on by climate change would make devastating storm surges — the deadly and destructive mass of water pushed inland by large storms — more frequent. Using various global climate models, the team developed a simulation tool that can predict the severity of future flooding an area can expect.

The researchers used New York City as a test case and found that with fiercer storms and a 3-foot rise in sea level due to climate change, "100-year floods" — a depth of roughly 5.7 feet above tide level that occurs roughly once a century — could more likely occur every three to 20 years. What today are New York City's "500-year floods" — or waters that reach more than 9 feet deep — could, with climate change, occur every 25 to 240 years, the researchers wrote.

The research is not only the first to examine the future intensity of storm surges, but also to offer a tool for estimating an area's vulnerability, said co-author Michael Oppenheimer, the Albert G. Milbank Professor of Geosciences and International Affairs at Princeton.

"Coastal managers in cities like New York make daily decisions about costly infrastructure that would be affected by such storms. They need a reliable indicator of the risk," he said.

"Our modeling approach is designed as a key step in this direction," Oppenheimer said. "As the world warms, risks will increase across a variety of fronts, and the threat to coastal infrastructure in the face of an already-rising sea level and potentially stronger hurricanes could be one of the most costly unless we are able to anticipate and reduce vulnerability."

Credit: Princeton University and MIT

Simulations by researchers from Princeton University and the Massachusetts Institute of Technology revealed that projected increases in sea level and storm intensity brought on by climate change could make devastating storm surges more frequent. Using the New York City area as a model, the researchers found that floods experienced every century could instead occur every one or two decades. The worst simulated flood (left) was a 15.5-foot storm surge at Manhattan's Battery (black star) that stemmed from a high-intensity storm (black line) moving northeast and very close to the city. A weaker but larger northwest-bound storm (right) that was further from the city would result in floodwater nearly 15 feet deep as its strongest winds pushed water toward the Battery. The colored contours represent the maximum surge height, from 0 (blue) to 5 (violet) meters. (Image by Ning Lin)

Lead author Ning Lin, a postdoctoral fellow at MIT, said that knowing the frequency of storm surges may help urban and coastal planners design seawalls and other protective structures. Lin, who received her Ph.D. from Princeton in 2010, began the project at Princeton then continued it at MIT; the current report is based on her work at MIT.

"When you design your buildings or dams or structures on the coast, you have to know how high your seawall has to be," said Lin, noting that Manhattan's seawalls now stand a mere 5 feet high. "You have to decide whether to build a seawall to prevent being flooded every 20 years."

Lin and Oppenheimer worked with study co-authors Kerry Emanuel, an MIT atmospheric science professor, and Erik Vanmarcke, a Princeton professor of civil and environmental engineering. Lin, Vanmarcke and Emanuel also co-wrote a 2010 report on the project published in the Journal of Geophysical Research that was based on Lin's work at Princeton.

Carol Friedland, an assistant professor of construction management and industrial engineering at Louisiana State University, sees the latest results as a useful tool to inform coastal design — particularly, she notes, as most buildings are designed with a 60- to 120-year "usable lifespan."

"The physical damage and economic loss that result from storm surge can be devastating to individuals, businesses, infrastructure and communities," Friedland said. "For current coastal community planning and design projects, it is essential that the effects of climate change be included in storm-surge predictions."

The researchers ran a total of 45,000 storm simulations for the New York City region under two scenarios: current climate conditions from 1981 to 2000 based on observed data and four global climate models; and projected climate conditions for the years 2081 to 2100 based on the four climate models, as well as future carbon dioxide output as predicted by the Intergovernmental Panel on Climate Change (IPCC). Oppenheimer is a longtime participant in the IPCC.

Storms in the simulations occurred within a 125-mile (200-kilometer) radius of the Battery, at the southern tip of Manhattan, and generated a maximum wind speed of at least 50 miles per hour. Hurricanes are classified as having a maximum wind speed of at least 74 miles per hour.

Once the researchers simulated storms in the region, they then simulated the resulting storm surges using three different methods, including one used by the National Hurricane Center (NHC). In the days or hours before a hurricane hits land, the NHC uses a storm-surge model to predict the risk and extent of flooding from the impending storm. Such models, however, have not been used to evaluate multiple simulated storms under a scenario of climate change.

Again, the group compared results from multiple methods: one from the NHC that simulates storm surges quickly, though coarsely; another method that generates more accurate storm surges, though more slowly; and a method in between, developed by Lin and her colleagues, that estimates relatively accurate surge floods, relatively quickly.

The researchers found that the frequency of massive storm surges would go up in proportion to an increase in more violent storms and a rise in sea level, the researchers reported. They noted that climate models predict that the sea level around New York City could rise by 1.5 to nearly 5 feet by the end of the 21st century.

Flooding was amplified by the storm's wind direction and proximity to the city. The worst simulated flood, a 15.5-foot storm surge at Manhattan's Battery, stemmed from a high-intensity storm moving northeast and very close to the city. On the other hand, a weaker but larger northwest-bound storm that was further from the city resulted in floodwater nearly 15 feet deep as its strongest winds pushed water toward the Battery.

Floods of this magnitude outstrip the most devastating storm surges in the city's recorded history, Lin said. The worst accompanied the 1821 Norfolk and Long Island hurricane, which packed winds of 135 miles per hour and is one of only four hurricanes known to have made landfall in New York City since pre-Columbian times.

"The highest [surge flood] was 3.2 meters [10.4 feet], and this happened in 1821," Lin said. "That's the highest water level observed in New York City's history, which is like a present 500-year event."

The study was published online Feb. 14 by the journal Nature Climate Change, and was supported by the U.S. National Oceanic and Atmospheric Administration, and the Princeton Environmental Institute through a fellowship from the Program in Science, Technology and Environmental Policy based in Princeton's Woodrow Wilson School of Public and International Affairs.


Contacts and sources:
Morgan Kelly 
Princeton University
Jennifer Chu of MIT contributed to this story.

Earth Siblings Can Be Different! Chemical Clues On The Formation Of Planetary Systems

The study of the photospheric stellar abundances of the planet-host stars is the key to understanding how protoplanets form, as well as which protoplanetary clouds evolve planets and which do not. These studies, which have important implications for models of giant planet formation and evolution, also help us to investigate the internal and atmospheric structure and composition of extrasolar planets.

In this study the 55Cnc planetary system has been analyzed: the Earth sibling in this system presents a very different chemical structure.

 

Credit: NASA

Theoretical studies suggest that C/O and Mg/Si, are the most important elemental ratios in determining the mineralogy of terrestrial planets, and they can give us information about the composition of these planets. The C/O ratio controls the distribution of Si among carbide and oxide species, while Mg/Si gives information on the silicate mineralogy. In 2010 Bond et al. (2010b) carried out the first numerical simulations of planet formation in which the chemical composition of the proto-planetary cloud was taken as an input parameter. Terrestrial planets were found to form in all the simulations with a wide variety of chemical compositions so these planets might be very different from the Earth.

Delgado Mena et al. (2010) have carried out the first detailed and uniform study of C, O, Mg and Si abundances for 61 stars with detected planets and 270 stars without detected planets from the homogeneous high-quality unbiased HARPS GTO sample. They found mineralogical ratios quite different from those in the Sun, showing that there is a wide variety of planetary systems which are unlike the Solar System. Many planetary-host stars present a Mg/Si value lower than 1, so their planets will have a high Si content to form species such as MgSiO3. This type of composition can have important implications for planetary processes like plate tectonics, atmospheric composition and volcanism.

'There could be billions of Earthlike planets in the Universe but a great majority of them may have a totally different internal and atmospheric structure. Building planets in chemically non-solar environments (which are very common in the Universe) may lead to the formation of strange worlds, very different from the Earth! The amount of radioactive and some refractory elements (especially Si) may have drastic implications for planetary processes such as plate tectonics and volcanic activity,' concludes Garik Israelian.

The latest numerical simulations have shown that a wide range of extrasolar terrestrial planet bulk compositions are likely to exist. Planets simulated as forming around stars with Mg/Si ratios less than 1 are found to be Mg-depleted (compared to the Earth), consisting of silicate species such as pyroxene and various types of feldspars. Planetary carbon abundances also vary in accordance with the host stars' C/O ratio. The predicted abundances are in keeping with observations of polluted white dwarfs (expected to have accreted their inner planets during their previous red giant stage).

'The observed variations in the key C/O and Mg/Si ratios for known planetary host stars implies that a wide variety of extrasolar terrestrial planet compositions are likely to exist, ranging from relatively "Earthlike" planets to those that are dominated by C, such as graphite and carbide phases (e.g. SiC, TiC),' Delgado Mena stresses.

The results of Delgado Mena et al. (2010) were used in this study as they are the first to determine the abundance of all of the required elements in a completely internally consistent manner, using high quality spectra and an identical approach for all stars and elements, for a large sample of both host and non-host stars.

The chemical and dynamical simulations were combined by assuming that each embryo retains the composition of its formation location and contributes the same composition to the simulated terrestrial planet. The innermost terrestrial planets (located within ∼0.5 AU from the host star) contain a significant amount of the refractory elements Al and Ca (∼47% of the planetary mass). Planets forming beyond ∼0.5 AU from the host star contain steadily less Al and Ca with increasing distance. One planetary system, 55 Cnc, has a C/O ratio above 1 (C/O = 1.12). This system produced carbon-enriched "Earthlike" planets. All of the terrestrial planets considered in this work have compositions dominated by O, Fe, Mg and Si, most of these elements being delivered in the form of silicates or metals (in the case of iron). However, important differences between those planets forming in systems with C/O < 0.8 (HD17051, HD19994) and those with C/O > 0.8 (55Cnc) have been found.

'We are working hard to decrease abundance measurement errors and make the results of theoretical models and numerical simulations more reliable,' comments González Hernández, 'There is much work to be done'.

The members of the research team are: Garik Israelian and Jonay González Hernández (IAC), Elisa Delgado Mena and N. Santos (University of Porto, Portugal), and J. Carter-Bond and D. O'Brien (Planetary Science Institute, Tucson, Arizona). These results will be reported in The Astrophysical Journal Letters.

Contacts and sources:
Garik Israelian
Instituto de Astrofísica de Canarias (IAC)