From Hot Springs to HIV, Same Protein Complexes Are Hijacked to Promote Viruses

Scanning electron micrograph of Sulfolobus solfataricus cells infected with STIV, showing pyramid-like structures on the surface of the cell (Credit: Montana State University)

June 10, 2013 — Biologists from Indiana University and Montana State University have discovered a striking connection between viruses such as HIV and Ebola and viruses that infect organisms called archaea that grow in volcanic hot springs. Despite the huge difference in environments and a 2 billion year evolutionary time span between archaea and humans, the viruses hijack the same set of proteins to break out of infected cells.

In eukaryotes -- the group that includes plants and animals -- and in archaea -- micro-organisms with no defined nucleus in their cellular construction -- viruses co-opt a group of important protein complexes called the Endosomal Sorting Complexes Required for Transport, or ESCRT.

The researchers were studying Sulfolobus turreted icosahedral virus, or STIV, which infects Sulfolobus solfataricus, a species of archaea called a thermophile that can be found in volcanic springs, such those in Yellowstone National Park. Thermophiles are micro-organisms that survive in extremely hot environments. The researchers found that, as with a range of viruses that infect humans, STIV is also dependent upon its host's ESCRT machinery to complete its life cycle.

"The new work yields insight into the evolution of the relationship between hosts and viruses and, more importantly, presents us with a new and simple model system to study how viruses can hijack and utilize cellular machineries," said Stephen D. Bell, professor in the IU Department of Molecular and Cellular Biochemistry and Department of Biology. Bell is co-lead author on the paper that appears today in early online editions of the Proceedings of the National Academy of Sciences.

The researchers looked for interactions between STIV and ESCRT proteins by using a technique in molecular biology called two-hybrid screening, which identifies binding interactions between two proteins or a protein and a DNA molecule. After finding two examples where viral proteins (the major capsid protein B345 and the viral protein C92) interacted with ESCRT proteins (SSO0619 and SSO0910), epiflouresence microscopy and transmission electron microscopy were used to determine exactly where ESCRT protein components localized in STIV-infected cells.

Epiflouresence microscopy uncovered spots of the ESCRT protein Vps4 in STIV-infected S. solfataricus cells, while no Vps4 was found after similar analysis in uninfected cells. In testing with transmission electron microscopy, the researchers identified Vps4 localized in the seven-sided pyramid-like structures that form in the membrane of S. solfataricus prior to viruses causing cell breakdown when the viral protein C92 expressed. No localization of Vps4 was found in similar cells where C92 was repressed.

The work shows that Vps4 is recruited to viral budding sites -- those seven-sided pyramid-like structures -- in the S. solfataricus thermophile. Significantly, other scientists have shown that the Vps4 protein of the eukaryotic ESCRT machinery localizes to the HIV budding site in humans.

"We believe the ESCRT machinery plays two roles in STIV biology. First, by virtue of interaction between the viral B345 protein and the host protein SSO0619, ESCRT aids in the construction of the STIV viral particles," Bell said. "Second, the strong association we find between the pyramid structures formed by C92 and ESCRT's Vps4 protein allows us to hypothesize that the ESCRT machinery plays a vital role in opening those pyramid exit structures that then leads to cell disruption and the release of viral progeny."

Just as the ESCRT machinery in plants and animals plays a key role in cell division, Bell's lab has previously shown that the same is true for that similar yet less-complicated ESCRT complex in archaea. Also of importance, Bell added, is that the ESCRT apparatus both in eukaryotes and in archaea like S. solfataricus is co-opted by viruses.

"These parallels support the idea that the cellular ESCRT is ancient and that it is likely to have evolved prior to archaea and eukarya separating to become different domains of life," Bell said.

Scientists date archaea back to 3.7 billion years, while the oldest eukaryote fossils date back to 1.7 billion years.

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Journal Reference:

1. Jamie C. Snyder, Rachel Y. Samson, Susan K. Brumfield, Stephen D. Bell, and Mark J. Young. Functional interplay between a virus and the ESCRT machinery in Archaea. PNAS, June 10, 2013 DOI:10.1073/pnas.1301605110

Bridge Species Drive Tropical Engine of Biodiversity

David Jablonski, the William R. Kenan Jr. Professor in Geophysical Sciences, is presenting new evidence that most evolutionary lineages started in the tropics and expanded outward in a process driven by what he and his colleagues call “bridge species.” (Credit: NASA Visible Earth)

June 10, 2013 — Although scientists have known since the middle of the 19th century that the tropics are teeming with species while the poles harbor relatively few, the origin of the most dramatic and pervasive biodiversity on Earth has never been clear.

New research sheds light on how that pattern came about. Furthermore, it confirms that the tropics have been and continue to be Earth's engine of biodiversity.

By examining marine bivalves (two-shelled mollusks including scallops, cockles and oysters), a model system for large-scale ecological and evolutionary analysis, the study shows that most evolutionary lineages started in the tropics and expanded outward.

"This 'out of the tropics' dynamic is the major process that shapes the latitudinal pattern of biodiversity that we see today on land and sea," said lead author David Jablonski, the William R. Kenan Jr. Professor in Geophysical Sciences at the University of Chicago. His team focuses on marine bivalves because they combine a wealth of important biological patterns with a large but manageable number of living species (about 8,000) and a rich fossil record.

The new research will be published this week in the online Early Edition of the Proceedings of the National Academy of Sciences presents evidence that the "out of the tropics" process is driven mainly by bridge species, a new term referring to evolutionary lineages that straddle the boundary between the tropics and cooler neighboring regions.

"We thought the 'out of the tropics' process would be driven by the formation of new species at the edge of the tropics, but that doesn't seem to be true," Jablonski said. "Whether bridge species really are the conduit, 'out of the tropics' for all those lineages still needs to be confirmed. We'll tackle that next, by examining molecular data on species within these lineages, inside and outside the tropics, to see how they're related."

As with the PNAS study, this follow-up research would require examining data on both fossils and living organisms. "Alas, it's still rare for paleontologists to integrate the fossil record with data on present-day organisms, but for large-scale biodiversity studies like this, it's a very powerful approach, often an essential one," Jablonski said. "Biodiversity is a product of origination, extinction and immigration, and when the fossil record is adequate, as it is with bivalves, it provides the most robust window into the dynamics that produced present-day patterns."

Surprising findings

The new research corroborates the "out of the tropics" model that Jablonski and others introduced in a 2006 publication. In fact, the new research documents this dynamic over the past 12 million years -- even during the Ice Ages, when the temperature differences between the equator and the poles became more severe. That runs counter to the broadly accepted principle of "niche conservatism," which suggests that related species tend to retain the ecological limits of their ancestors, Jablonski said. "Most species we studied do adhere to that principle, but the ones that do not are crucial to the deployment of biodiversity on Earth."

There are many such bridge species but each evolutionary lineage generally has only one or two. Therefore, bridge species are widespread in an evolutionary sense but rare in terms of overall biodiversity, according to the research. And the fossil record shows that most of today's bridge species started as tropical species. "Somehow they left their tropical cradle, adapting to the colder temperatures and more variable climates of the temperate zones," said Jablonski. "It's impressive that they apparently expanded their ability to tolerate these harsher conditions."

Another surprise is that the most widespread species of bivalves are not the ones with the broadest temperature tolerances. Rather, they are often the ones with limited temperature tolerances that have specialized on temperatures that are the most widespread. "This is important because broad geographic range is one of the most reliable estimates of the extinction-resistance of a species," Jablonski said. "What surprised us is that the most widespread temperatures -- and therefore many of the most widespread bivalve species -- occur in the tropics."

Homo sapiens is even more impressive than the bridge species in this study, he added. Humans have not only immigrated out of the tropics but throughout Earth. Only a handful of marine species range all the way from equator to poles, Jablonski has found, but humans are as widespread as any species known today. "As a species we're pretty extinction-resistant, but even widespread tropical species may be at risk today," said Jablonski.

As research on both living and fossil species has shown, broad geographic ranges buffer species from extinction when pressures are local, such as from hurricanes, pollution or overexploitation. But when -- for marine species -- those pressures alter global ocean temperatures, circulation patterns or chemistry, a broad geographic range is less likely to help, Jablonski said.

"That's what happened at the end-Cretaceous mass extinction 65 million years ago, and that could be looming today."

Other co-authors from UChicago are Christina L. Belanger (now at South Dakota School of Mines and Technology), Sarah K. Berke (now at Siena College), Shan Huang, Andrew Z. Krug (now at Flint Hill School), and Adam Tomasovych (now at Slovak Academy of Sciences). Kaustuv Roy, University of California, San Diego; and James W. Valentine, University of California, Berkeley, are also co-authors.

Funding: The National Science Foundation's Sedimentary Geology & Paleobiology and Systematic Biology Programs; NASA's Exobiology Program; the John Simon Guggenheim Foundation; and University of California Faculty Research Awards.

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The above story is reprinted from materials provided byUniversity of Chicago. The original article was written by Greg Borzo.

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Journal Reference:

1. David Jablonski et al. Out of the Tropics, but how? Fossils, bridge species, and thermal ranges in the dynamics of the marine latitudinal diversity gradient.PNAS, 2013

High Sugar Intake Linked to Low Dopamine Release in Insulin Resistant Patients

These images show that insulin-sensitive (normal) subjects had significantly higher dopamine release in the brain's reward regions compared with insulin-resistant subjects when both groups were given a sugary drink prior to the scans. The lower response of the insulin-resistant subjects may play a role in abnormal eating behavior and possibly increase their potential for developing diabetes. (Credit: Gene-Jack Wang, MD)

June 10, 2013 — Using positron emission tomography (PET) imaging of the brain, researchers have identified a sweet spot that operates in a disorderly way when simple sugars are introduced to people with insulin resistance, a precursor to type 2 diabetes. For those who have the metabolic syndrome, a sugar drink resulted in a lower-than-normal release of the chemical dopamine in a major pleasure center of the brain. This chemical response may be indicative of a deficient reward system, which could potentially be setting the stage for insulin resistance. This research could revolutionize the medical community's understanding of how food-reward signaling contributes to obesity, according to a study presented at the Society of Nuclear Medicine and Molecular Imaging's 2013 Annual Meeting.

"Insulin resistance is a significant contributor to obesity and diabetes," said Gene-Jack Wang, MD, lead author of the study and Professor of Radiology at Stony Brook University and researcher at the U.S. Department of Energy's Brookhaven National Laboratory in Upton, N.Y. "A better understanding of the cerebral mechanisms underlying abnormal eating behaviors with insulin resistance would help in the development of interventions to counteract the deterioration caused by overeating and subsequent obesity. We suggest that insulin resistance and its association with less dopamine release in a central brain reward region might promote overeating to compensate for this deficit."

An estimated one-third of Americans are obese, according to the U.S. Centers for Disease Control and Prevention. The American Diabetes Association estimates that about 26 million Americans are living with diabetes and another 79 million are thought to be prediabetic, including those with insulin resistance.

The tendency to overeat may be caused by a complex biochemical relationship, as evidenced by preliminary research with rodents. Dr. Wang's research marks the first clinical study of its kind with human subjects.

"Animal studies indicated that increased insulin resistance precedes the lack of control associated with pathological overeating," said Wang. "They also showed that sugar ingestion releases dopamine in brain regions associated with reward. However, the central mechanism that contributes to insulin resistance, pathological eating and weight gain is unknown."

He continued, "In this study we were able to confirm an abnormal dopamine response to glucose ingestion in the nucleus accumbens, where much of the brain's reward circuitry is located. This may be the link we have been looking for between insulin resistance and obesity. To test this, we gave a glucose drink to an insulin-sensitive control group and an insulin-resistant group of individuals and we compared the release of dopamine in the brain reward center using PET."

In this study, a total of 19 participants-including 11 healthy controls and eight insulin-resistant subjects-consumed a glucose drink and, on a separate day, an artificially sweetened drink containing sucralose. After each drink, PET imaging with C-11 raclopride-which binds to dopamine receptors-was performed. Researchers mapped lit-up areas of the brain and then gauged striatal dopamine receptor availability (which is inversely related to the amount of natural dopamine present in the brain). These results were matched with an evaluation in which patients were asked to document their eating behavior to assess any abnormal patterns in their day-to-day lives. Results showed agreement in receptor availability between insulin-resistant and healthy controls after ingestion of sucralose. However, after patients drank the sugary glucose, those who were insulin-resistant and had signs of disorderly eating were found to have remarkably lower natural dopamine release in response to glucose ingestion when compared with the insulin-sensitive control subjects.

"This study could help develop interventions, i.e., medication and lifestyle modification, for early-stage insulin-resistant subjects to counteract the deterioration that leads to obesity and/or diabetes," said Wang. "The findings set a path for future clinical studies using molecular imaging methods to assess the link of peripheral hormones with brain neurotransmitter systems and their association with eating behaviors."

Scientific Paper 29: Gene-Jack Wang, Radiology, Stony Brook University; Jean Logan, Elena Shumay, Joanna Fowler, Bioscience, Brookhaven National Laboratory, Upton, NY; Antonio Convit, Psychiatry, New York University, New York, NY; Tomasi Dardo, Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Upton, NY; Nora Volkow, National Institute on Drug Abuse, Bethesda, MD, "Peripheral insulin resistance affects brain dopaminergic signaling after glucose ingestion," SNMMI's 60th Annual Meeting, June 8-12, 2013, Vancouver, British Columbia.

The study was conducted at the U.S. Department of Energy's Brookhaven National Laboratory and supported by the National Institutes of Health and Brookhaven Lab. The PET Radiotracer Imaging technology used in the study was developed with the support of the DOE Office of Science. The imaging program is part of a Stony Brook University clinical research center, which also supports the research.

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Unfrozen Mystery: H2O Reveals a New Secret

A fragment of the crystal structure of the new ice is shown where the oxygen atoms are blue and the molecular hydrogen atoms pink. Hydrogen atoms that have been pulled off the water molecules are colored gold. These appear to locate in polyhedral voids in the oxygen lattice (one of which is shaded light grey). Previously, these voids were believed to remain even after the water molecule breaks up at enormous pressures. (Credit: Image is provided courtesy of Oak Ridge National Laboratory)

June 10, 2013 — Using revolutionary new techniques, a team led by Carnegie's Malcolm Guthrie has made a striking discovery about how ice behaves under pressure, changing ideas that date back almost 50 years. Their findings could alter our understanding of how the water molecule responds to conditions found deep within planets and could have implications for energy science.

Their work is published in theProceedings of the National Academy of Sciences.

When water freezes into ice, its molecules are bound together in a crystalline lattice held together by hydrogen bonds. Hydrogen bonds are highly versatile and, as a result, crystalline ice reveals a striking diversity of at least 16 different structures.

In all of these forms of ice, the simple H2O molecule is the universal building block. However, in 1964 it was predicted that, under sufficient pressure, the hydrogen bonds could strengthen to the point where they might actually break the water molecule apart. The possibility of directly observing a disassociated water molecule in ice has proven a fascinating lure for scientists and has driven extensive research for the last 50 years. In the mid-1990s several teams, including a Carnegie group, observed the transition using spectroscopic techniques. However, these techniques are indirect and could only reveal part of the picture.

A preferred method is to "see" the hydrogen atoms-or protons-directly. This can be done by bouncing neutrons off the ice and then carefully measuring how they are scattered. However, applying this technique at high enough pressures to see the water molecule dissociate had simply not been possible in the past. Guthrie explained that: "you can only reach these extreme pressures if your samples of ice are really small. But, unfortunately, this makes the hydrogen atoms very hard to see."

The Spallation Neutron Source was opened at Oak Ridge National Laboratory in Tennessee in 2006, providing a new and intensely bright supply of neutrons. By designing a new class of tools that were optimized to exploit this unrivalled flux of neutrons, Guthrie and his team-Carnegie's Russell Hemley, Reinhard Boehler, and Kuo Li, as well as Chris Tulk, Jamie Molaison, and António dos Santos of Oak Ridge National Laboratory-have obtained the first glimpse of the hydrogen atoms themselves in ice at unprecedented pressures of over 500,000 times atmospheric pressure.

"The neutrons tell us a story that the other techniques could not," said Hemley, director of Carnegie's Geophysical Laboratory. "The results indicate that dissociation of water molecules follows two different mechanisms. Some of the molecules begin to dissociate at much lower pressures and via a different path than was predicted in the classic 1964 paper."

"Our data paint an altogether new picture of ice," Guthrie commented. "Not only do the results have broad consequences for understanding bonding in H2O, the observations may also support a previously proposed theory that the protons in ice in planetary interiors can be mobile even while the ice remains solid."

And this startling discovery may prove to be just the beginning of scientific discovery. Tulk emphasized "being able to 'see' hydrogen with neutrons isn't just important for studies of ice. This is a game-changing technical breakthrough. The applications could extend to systems that are critical to societal challenges, such as energy. For example, the technique can yield greater understanding of methane-containing clathrate hydrates and even hydrogen storage materials that could one day power automobiles."

The group is part of Energy Frontier Research in Extreme Environments (EFree), an Energy Frontier Research Center headquartered at Carnegie's Geophysical Laboratory.

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Martian Clay Contains Chemical Implicated in the Origin of Life, Astrobiologists Find

Electron microscope image showing the 700-million-year-old Martian clay veins containing boron (100 µm = one tenth of a millimeter). (Credit: Image courtesy of Institute for Astronomy at the University of Hawaii at Manoa)

June 10, 2013 — Researchers from the University of Hawaii at Manoa NASA Astrobiology Institute (UHNAI) have discovered high concentrations of boron in a Martian meteorite. When present in its oxidized form (borate), boron may have played a key role in the formation of RNA, one of the building blocks for life.

The work was published on June 6 inPLOS ONE.

The Antarctic Search for Meteorites team found the Martian meteorite used in this study in Antarctica during its 2009-2010 field season. The minerals it contains, as well as its chemical composition, clearly show that it is of Martian origin.

Using the ion microprobe in the W. M. Keck Cosmochemistry Laboratory at UH, the team was able to analyze veins of Martian clay in the meteorite. After ruling out contamination from Earth, they determined boron abundances in these clays are over ten times higher than in any previously measured meteorite.

"Borates may have been important for the origin of life on Earth because they can stabilize ribose, a crucial component of RNA. In early life RNA is thought to have been the informational precursor to DNA," said James Stephenson, a UHNAI postdoctoral fellow.

RNA may have been the first molecule to store information and pass it on to the next generation, a mechanism crucial for evolution. Although life has now evolved a sophisticated mechanism to synthesize RNA, the first RNA molecules must have been made without such help. One of the most difficult steps in making RNA nonbiologically is the formation of the RNA sugar component, ribose. Previous laboratory tests have shown that without borate the chemicals available on the early Earth fail to build ribose. However, in the presence of borate, ribose is spontaneously produced and stabilized.

This work was born from the uniquely interdisciplinary environment of UHNAI. The lead authors on the paper, Stephenson, an evolutionary biologist, and Lydia Hallis, a cosmochemist who is also a UHNAI postdoctoral fellow, first came up with the idea over an after-work beer. "Given that boron has been implicated in the emergence of life, I had assumed that it was well characterized in meteorites," said Stephenson. "Discussing this with Dr. Hallis, I found out that it was barely studied. I was shocked and excited. She then informed me that both the samples and the specialized machinery needed to analyze them were available at UH."

On our planet, borate-enriched salt, sediment and clay deposits are relatively common, but such deposits had never previously been found on an extraterrestrial body. This new research suggests that when life was getting started on Earth, borate could also have been concentrated in deposits on Mars.

The significance goes beyond an interest in the red planet, as Hallis explains: "Earth and Mars used to have much more in common than they do today. Over time, Mars has lost a lot of its atmosphere and surface water, but ancient meteorites preserve delicate clays from wetter periods in Mars' history. The Martian clay we studied is thought to be up to 700 million years old. The recycling of the Earth's crust via plate tectonics has left no evidence of clays this old on our planet; hence Martian clays could provide essential information regarding environmental conditions on the early Earth."

The presence of ancient borate-enriched clays on Mars implies that these clays may also have been present on the early Earth. Borate-enriched clays such as the ones studied here may have represented chemical havens in which one of life's key molecular building blocks could form.

UHNAI is a research center that links the biological, chemical, geological, and astronomical sciences to better understand the origin, history, distribution, and role of water as it relates to life in the universe.

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The above story is reprinted from materials provided byInstitute for Astronomy at the University of Hawaii at Manoa.

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Journal Reference:

1. James D. Stephenson, Lydia J. Hallis, Kazuhide Nagashima, Stephen J. Freeland. Boron Enrichment in Martian Clay. PLoS ONE, 2013; 8 (6): e64624 DOI:10.1371/journal.pone.0064624