Enzymes carry out fundamental biological processes such as photosynthesis, nitrogen fixation and respiration, with the help of clusters of metal atoms as “active” sites. But scientists lack basic information about their function because the states thought to be critical to their chemical abilities cannot be experimentally observed.
Now, researchers at Princeton University have reported the first direct observation of the electronic states of iron-sulfur clusters, common to many enzyme active sites. Published on August 31 in the journal Nature Chemistry, the states were revealed by computing the complicated quantum mechanical behavior of the electrons in the clusters.
“These complexes were thought of as impossible to model, due to the complexity of the quantum mechanics,” said Garnet Chan, the A. Barton Hepburn Professor of Chemistry and corresponding author on the paper.
In these systems, the electrons interact strongly with each other, their movements resembling a complicated dance. To reduce the complexity, the researchers drew on a new understanding, gained from fundamental work in quantum information theory, that the motion of the electrons had a special pattern.
“At first glance, the electrons appear to move in a complicated way, but eventually you realize that they only care about what their immediate neighbors are doing, similar to being in a crowded room. This restriction on their behavior leads to important simplifications: the calculations become very difficult rather than impossible — it’s just on the edge of what can be done,” Chan said.
Using their new method, Chan and coworkers found that iron-sulfur clusters possess an order of magnitude more accessible electronic states than previously reported. The researchers suggested that this unusual richness might explain their ubiquity in biological processes.
This finding, that there are many more available electronic states than previously thought, presents many different chemical possibilities. What if these clusters simultaneously used a combination of mechanisms, instead of the accepted chemical idea that there is one distinct electronic pathway, Chan wondered. To test that idea and learn more about the clusters’ behavior, the researchers plan to extend their calculations to observe a chemical transformation in action.
“If you want to understand why iron-sulfur clusters are a ubiquitous biological motif and how we can create even better synthetic analogs, then you need to know what the electrons are doing,” Chan said. “Now we’ve caught a first glimpse as to what they are getting up to.”
This work was supported by the US National Science Foundation (CHE-1265277) and used software developed with the support of OCI-1265278. F.N. and K.S acknowledge financial support from the Max Planck Society, the University of Bonn and the SFB 813 “Chemistry at Spin Centers.”
One of the world’s deadliest mosquitoes sustains its taste for human blood thanks in part to a genetic tweak that makes it more sensitive to human odor, according to new research.
Researchers report in the journal Nature that the yellow fever mosquito contains a version of an odor-detecting gene in its antennae that is highly attuned to sulcatone, a compound prevalent in human odor. The researchers found that the gene, AaegOr4, is more abundant and more sensitive in the human-preferring “domestic” form of the yellow fever mosquito than in its ancestral “forest” form that prefers the blood of non-human animals.
The research also could help in developing better ways to stem the yellow fever mosquito’s appetite for humans, McBride said. The yellow fever mosquito is found in tropical and subtropical areas worldwide and is the principal carrier of yellow fever, the measles-like dengue fever, and the painful infection known as chikungunya. Yellow fever annually kills tens of thousands of people worldwide, primarily in Africa, while dengue fever infects hundreds of millions. The research also suggests a possible genetic root for human preference in other mosquitoes, such as malaria mosquitoes, although that species is genetically very different from the yellow fever mosquito.
“The more we know about the genes and compounds that help mosquitoes target us, the better chance we have of manipulating their response to our odor” McBride said, adding that scent is not the only driver of mosquito behavior, but it is a predominant factor.
The researchers first conducted a three-part series of experiments to establish the domestic yellow fever mosquito’s preference for human scent. Forest and domestic mosquitoes were put into a large cage and allowed to bite either a guinea pig or a researcher’s arm. Then the mosquitoes were allowed to choose between streams of air that had passed over a guinea pig or human arm. Finally, to rule out general mosquito attractants such as exhaled carbon dioxide, mosquitoes were allowed to choose between the scent of nylon sleeves that had been in contact with a human or a guinea pig.
In all three cases, the domestic form of the yellow fever mosquito showed a strong preference for human scent, while the forest form primarily chose the guinea pig. Although domestic mosquitoes would sometimes go for the guinea pig, it happened very rarely, McBride said.
McBride and colleagues then decided to look for differences in the mosquitoes’ antennae, which are equivalent to a human’s nose. They interbred domestic and forest mosquitoes, then interbred their offspring to create a second hybrid generation. The genomes of these second-generation hybrids were so completely reshuffled that when the researchers compared the antennae of the human- and guinea pig-preferring individuals they expected to see only genetic differences linked directly to behavior, McBride said.
The researchers found 14 genes that differed between human- and guinea pig-preferring hybrids — two of them were the odorant receptors Or4 and Or103. Choosing to follow up on Or4, the researchers implanted the gene into fruit-fly neurons. They found that the neurons exhibited a burst of activity when exposed to sulcatone, but no change when exposed to guinea pig odors. McBride plans to further study Or103 and other genes that could be linked to host preference at Princeton.
This work provides insight into how the domestic form of the yellow fever mosquito evolved from its animal-loving ancestor into a human-biting specialist, McBride said. “At least one of the things that happened is a retuning of the ways odors are detected by the antennae,” she said. “We don’t yet know whether there are also differences in how odor information is interpreted by the brain.”
This work was supported in part by the National Institutes of Health (NIDCD grant no. DC012069; NIAID grant no. HHSN272200900039C; and NCATS CTSA award no. 5UL1TR000043); the Swedish Research Council and the Swedish University of Agricultural Science’s Insect Chemical Ecology, Ethology and Evolution initiative; and the Howard Hughes Medical Institute.
Carolyn S. McBride, Felix Baier, Aman B. Omondi, Sarabeth A. Spitzer, Joel Lutomiah, Rosemary Sang, Rickard Ignell, and Leslie B. Vosshall. 2014. Evolution of mosquito preference for humans linked to an odorant receptor. Nature. Article published in print Nov. 13, 2014. DOI: nature13964.3d
A recently launched European satellite could reveal tens of thousands of new planets within the next few years, and provide scientists with a far better understanding of the number, variety and distribution of planets in our galaxy, according to research published today.
Researchers from Princeton University and Lund University in Sweden calculated that the observational satellite Gaia could detect as many as 21,000 exoplanets, or planets outside of Earth’s solar system, during its five-year mission. If extended to 10 years, Gaia could detect as many as 70,000 exoplanets, the researchers report. The researchers’ assessment is accepted in the Astrophysical Journal and was published Nov. 6 in advance-of-print on arXiv, a preprint database run by Cornell University.
Exoplanets will be an important “by-product” of Gaia’s mission, explained first author Michael Perryman, who made the assessment while serving as Princeton’s Bohdan Paczyński Visiting Fellow in the Department of Astrophysical Sciences. Built and operated by the European Space Agency (ESA) and launched in December 2013, Gaia will capture the motion, physical characteristics and distance from Earth — and one another — of roughly 1 billion objects, mostly stars, in the Milky Way galaxy with unprecedented precision. The presence of an exoplanet will be determined by how its star “wobbles” as a result of the planet’s orbit around it.
More important than the numbers of predicted discoveries are the kinds of planets that the researchers expect Gaia to detect, many of which — such as planets with multi-year orbits that pass directly, or transit, in front of their star as seen from Earth — are currently difficult to find, Perryman said. The satellite’s instruments could reveal objects that are considered rare in the Milky Way, such as an estimated 25 to 50 Jupiter-sized planets that orbit faint, low-mass stars known as red dwarfs. Unique planets and systems — such as planets that orbit in the opposite direction of their companions — can inspire years of research, he said.
“It’s not just about the numbers. Each of these planets will be conveying some very specific details, and many will be highly interesting in their own way,” Perryman said. “If you look at the planets that have been discovered until now, they occupy very specific regions of discovery space. Gaia will not only discover a whole list of planets, but in an area that has not been thoroughly explored so far.”
Ultimately, a comprehensive census allows scientists to more accurately determine how many planets and planetary systems exist, the detailed properties of those planets, and how they are positioned throughout the galaxy, Perryman said.
Perryman worked with Joel Hartman, an associate research scholar in Princeton’s astrophysical sciences department, Gáspár Bakos, an associate professor of astrophysical sciences, and Lennart Lindegren, a professor of astronomy at Lund University. Gaia is based on a satellite proposal led by Lindegren and Perryman that was submitted to the ESA in 1993.
Research on exoplanets has increased dramatically in the 15 years since Gaia was accepted by the ESA in 2000. The new estimate is based on a highly detailed model of how stars and planets are positioned in the Milky Way; more accurate details of Gaia’s measurement and data-analysis capabilities; and current estimates of exoplanet distributions, particularly those derived from NASA’s Kepler satellite, which has identified nearly 1,000 confirmed planets and more than 3,000 candidates. Crucial to conducting the assessment is the much-improved knowledge that now exists about distant planets, Perryman said, such as the types of stars that exoplanets orbit.
The first exoplanet was detected in 1995. Nearly 1,900 have since been discovered. Bakos, who focuses much of his research on exoplanets, launched and oversees HATNet (Hungarian-made Automated Telescope Network) and HATSouth, planet-hunting networks of fully automated, small-scale telescopes installed on four continents that scan the sky every night for planets as they transit in front of their parent star. The projects have discovered more than 50 planets since 1999.
“Our assessment will help prepare exoplanet researchers for what to expect from Gaia,” Perryman said. “We’re going to be adding potentially 20,000 new planets in a completely new area of discovery space. It’s anyone’s guess how the field will develop as a result.”
This work was partly supported by the National Science Foundation (grant no. 1108686) and NASA (grant no. NNX13AJ15G).
Michael Perryman, Joel Hartman, Gáspár Bakos and Lennart Lindegren. 2014. Astrometric exoplanet detection with Gaia. Astrophysical Journal. Article first published to the arXiv preprint database: Nov. 6, 2014.
In nature, the right amount of death at the right time might actually help boost a species’ population density, according to new research that could help in understanding animal populations, pest control and managing fish and wildlife stocks.
In a paper in the journal Trends in Ecology and Evolution, a Princeton University researcher and European colleagues conclude that the kind of positive population effect an overall species experiences from a loss of individuals, or mortality, depends on the size and developmental stage of the creatures that die.
If many juveniles perish, more adults are freed up to reproduce, but if more adults die, the number of juveniles that mature will increase because density dependence is relaxed, explained co-author Anieke van Leeuwen, a postdoctoral researcher in Princeton’s Department of Ecology and Evolutionary Biology. Van Leeuwen worked with first author Arne Schröder, a postdoctoral research fellow at the Leibniz-Institute of Freshwater Ecology and Inland Fisheries in Berlin, and Tom Cameron, a lecturer in aquatic community ecology at the University of Essex in the United Kingdom.
This dynamic wherein the loss of individuals in one developmental stage translates to more robust individuals in another stage can be important to managing wildlife, pests or resource stocks, van Leeuwen said. For instance, targeting the adults of an invasive insect could have a counterproductive effect of making more food available to growing larvae, she said.
“It doesn’t matter which developmental stage you target, if you impose mortality on one you will get overcompensation on the opposite end of the size range,” van Leeuwen said. “This effect can be especially advantageous in situations where we want to manage resources we want to harvest. Knowing that there are potential effects that result in an increase in that segment of the population we want to encourage is highly relevant.”
At a certain point, of course, mortality becomes too high and the species as a whole declines, the researchers report.
The researchers compared existing theoretical and experimental work on the effect of mortality on population density to resolve various inconsistencies between the two. Existing mathematical models have predicted this phenomenon, and laboratory and field studies have shown that the effect holds true for a variety of animal species.
Many ecological theories and models, however, have ignored differences in body size and development, and predicted that a modest amount of mortality would result in an increase in the total number of individuals, the researchers wrote. On the other hand, experiments have predominantly shown — along with certain models — that mortality has a positive effect within certain life stages or size classes. The researchers concluded that the overlap of experimental and theoretical data indicates that the benefit of mortality is likely divided by developmental stage. In addition, the number of species in which the phenomenon has been observed makes it commonplace in the natural world.
This work was supported by the Journal of Experimental Biology; the Swedish Research Council and the Leibniz-Institute of Freshwater Ecology and Inland Fisheries; the University of Leeds, the National Environment Research Council (grant no. NE/C510467/1) and the European Commission Intra-European Fellowship (FANTISIZE, #275873); and the National Science Foundation (grant no. 1115838).
Citation: Schröder, Arne, Anieke van Leeuwen, Thomas C. Cameron. 2014. When less is more: Positive population-level effects of mortality. Trends in Ecology and Evolution. Published in November 2014 edition: Vol. 29, issue 11, pp. 614–624. DOI: 10.1016/j.tree.2014.08.006