Foundation for Applied Molecular Evolution

Gainesville, FL, United States

Foundation for Applied Molecular Evolution

Gainesville, FL, United States
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News Article | April 5, 2016

CU-Boulder Professor Stephen Mojzsis said if early Mars was as barren and cold as it is today, massive asteroid and comet impacts would have produced enough heat to melt subsurface ice. The impacts would have produced regional hydrothermal systems on Mars similar to those in Yellowstone National Park, which today harbor chemically powered microbes, some of which can survive boiling in hot springs or inhabiting water acidic enough to dissolve nails. Scientists have long known there was once running water on Mars, as evidenced by ancient river valleys, deltas and parts of lake beds, said Mojzsis. In addition to producing hydrothermal regions in portions of Mars' fractured and melted crust, a massive impact could have temporarily increased the planet's atmospheric pressure, periodically heating Mars up enough to "re-start" a dormant water cycle. "This study shows the ancient bombardment of Mars by comets and asteroids would have been greatly beneficial to life there, if life was present," said Mojzsis, a professor in the geological sciences department. "But up to now we have no convincing evidence life ever existed there, so we don't know if early Mars was a crucible of life or a haven for life." Published in Earth and Planetary Science Letters, the study was conducted by Mojzsis and Oleg Abramov, a researcher at the U.S. Geological Survey in Flagstaff, Arizona and a former CU-Boulder research scientist under Mojzsis. Much of the action on Mars occurred during a period known as the Late Heavy Bombardment about 3.9 billion years ago when the developing solar system was a shooting gallery of comets, asteroids, moons and planets. Unlike Earth, which has been "resurfaced" time and again by erosion and plate tectonics, heavy cratering is still evident on Mercury, Earth's moon and Mars, Mojzsis said. Mojzsis and Abramov used the Janus supercomputer cluster at the University of Colorado Computing facility for some of the 3-D modeling used in the study. They looked at temperatures beneath millions of individual craters in their computer simulations to assess heating and cooling, as well as the effects of impacts on Mars from different angles and velocities. A single model comprising the whole surface of Mars took up to two weeks to run on the supercomputer cluster, said Mojzsis. The study showed the heating of ancient Mars caused by individual asteroid collisions would likely have lasted only a few million years before the Red Planet - about one and one-half times the distance to the sun than Earth - defaulted to today's cold and inhospitable conditions. "None of the models we ran could keep Mars consistently warm over long periods," said Mojzsis. While Mars is believed to have spent most of its history in a cold state, Earth was likely habitable over almost its entire existence. A 2009 study by Mojzsis and Abramov showed that the Late Heavy Bombardment period in the inner solar system nearly 4 billion years ago did not have the firepower to extinguish potential early life on Earth and may have even given it a boost if it was present. "What really saved the day for Earth was its oceans," Mojzsis said. "In order to wipe out life here, the oceans would have had to have been boiled away. Those extreme conditions in that time period are beyond the realm of scientific possibility." The new Mars study was funded by NASA and the John Templeton Foundation. Mojzsis recently received an $800,000 grant from the Foundation for Applied Molecular Evolution in Alachua, Florida made possible by the Templeton Foundation to better understand early Earth and the beginning of life before about 4 billion years ago. "Studies of Mars provide us with valuable information about our own place in the solar system," he said. "Our next steps are to model similar bombardment on Mercury and Venus to better understand the evolution of the inner solar system and apply that knowledge to studies of planets around other stars." Mojzsis will meet with scientists from the California Institute of Technology and NASA's Jet Propulsion Laboratory in Pasadena next month to discuss possible landing sites and research targets for the upcoming Mars 2020 rover mission. Mars 2020 will carry instruments to seek out past life or present life, hunt for habitable areas and demonstrate technologies for use on future robotic and human missions to Mars. Explore further: Asteroid Attack 4 Billion Years Ago May Have Accelerated Life on Earth More information: Thermal Effects of Impact Bombardments on Noachian Mars, Oleg Abramov & Stephen J. Mojzsis, 2016 May 15, Earth and Planetary Science Letters,

News Article | April 18, 2016

In a 1967 episode of Star Trek, Captain Kirk and crew investigated the mysterious murders of miners on the planet Janus VI. The killer, it turned out, was a rock monster called the Horta. But the Enterprise’s sensors hadn’t registered any signs of life in the creature. The Horta was a silicon-based life-form, rather than carbon-based like living things on Earth. Still, it didn’t take long to determine that the Horta was alive. The first clue was that it skittered about. Spock closed the case with a mind meld, learning that the creature was the last of its kind, protecting its throng of eggs. But recognizing life on different worlds isn’t likely to be this simple, especially if the recipe for life elsewhere doesn’t use familiar ingredients. There may even be things alive on Earth that have been overlooked because they don’t fit standard definitions of life, some scientists suspect. Astrobiologists need some ground rules — with some built-in wiggle room — for when they can confidently declare, “It’s alive!” Among the researchers working out those rules is theoretical physicist Christoph Adami, who watches his own version of silicon-based life grow inside a computer at Michigan State University in East Lansing. “It’s easy when it’s easy,” Adami says. “If you find something walking around and waving at you, it won’t be that hard to figure out that you’ve found life.” But chances are, the first aliens that humans encounter won’t be little green men. They will probably be tiny microbes of one color or another — or perhaps no color at all. Trying to figure out how to recognize those alien microbes, especially if they are very strange, has led scientists to propose some basic criteria for distinguishing living from nonliving things. Many researchers insist that features such as active metabolism, reproduction and Darwinian evolution are de rigueur for any life, including extraterrestrials. Others add the requirement that life must have cells big enough to contain protein-building machines called ribosomes. But such definitions can be overly restrictive. A list of specific criteria for life may give scientists tunnel vision, blinding them to the diversity of living things in the universe, especially in extreme environments, says philosopher of science Carol Cleland of the University of Colorado Boulder. Narrow definitions will “act as blinkers if you run into a form of life that’s very different.” Some scientists, for instance, say viruses aren’t alive because they rely on their host cells to reproduce. But Adami disagrees. “There’s no doubt in my mind that biochemical viruses are alive,” he says. “They don’t carry with them everything they need to survive, but neither do we.” What’s important, Adami says, is that viruses transmit genetic information from one generation to another. Life, he says, is information that replicates. Darwinian evolution should be off the table, too, Cleland says. Humans probably won’t be able to tell at a quick glance whether something is evolving, anyway. “Evolvability is hard to detect,” she says, “because you’ve got a snapshot and you don’t have time to hang around and watch it evolve.” Cell size restrictions may also squeeze minuscule microbes out of consideration as aliens. But a cell too tiny to contain ribosomes may still be big enough if it uses RNA instead of proteins to carry out biochemical reactions, says Steven Benner, an astrobiologist at the Foundation for Applied Molecular Evolution in Alachua, Fla. Cells are thought necessary because they separate one organism from another. But layers of clay could provide the needed separation, Adami suggests. Cleland postulates that life could even exist as networks of chemical reactions that don’t require separation at all. Such fantastical thinking can loosen the grip of rigid criteria limiting scientists’ ability to recognize alien life when they see it. But they will still need to figure out where to look. With the discovery in recent years of more than a thousand exoplanets far beyond the solar system, the odds favoring the existence of extraterrestrial life in the cosmos are better than ever. But even the most powerful telescopes can’t detect microscopic organisms directly. Chances of finding microbial life are much higher if scientists can reach out and touch it, which means looking within our solar system, says mineralogist Robert Hazen, of the Carnegie Institution for Science in Washington, D.C. “You really need a rover down on its hands and knees analyzing chemicals,” Hazen says. Rovers are sampling rocks on Mars (SN: 5/2/15, p. 24) and the Cassini probe has bathed in geysers spewing from Saturn’s icy moon Enceladus (SN: 10/17/15, p. 8). Those mechanical explorers and others in the works may send back signs of life. But those signs are probably going to be subtle, indirect “biomarkers.” It may be surprisingly difficult to tell whether those biomarkers are from animals, vegetables, microbes or minerals, especially at a distance. “We really need to have life be as obvious as possible,” says astrobiologist Victoria Meadows, who heads the NASA Astrobiology Institute’s Virtual Planetary Laboratory at the University of Washington in Seattle. By obvious, she partly means Earth-like and partly means that no chemical or geologic process could have produced a similar signature. Some scientists say life is an “I’ll know it when I see it” phenomenon, says Kathie Thomas-Keprta, a planetary geologist. But life may also be in the eye of the beholder, as Thomas-Keprta knows all too well from studying a Martian meteorite. She was part of a team at the NASA Johnson Space Center in Houston that studied a meteorite designated ALH84001 (discovered in Antarctica’s Allan Hills ice field in 1984). In 1996, a team led by Thomas-Keprta’s late colleague David McKay claimed that carbonate globules embedded in the meteorite resembled microscopic life on Earth. The researchers found large organic molecules with the carbonate, indicating that they formed at the same time. Thomas-Keprta also identified tiny magnetite crystals overlapping the globules that closely resemble crystals formed by “magnetotactic” bacteria on Earth. Such bacteria use chains of the crystals as a compass to guide them as they swim in search of nutrients. The researchers believed that they were looking at fossils of ancient Martians. Other researchers disagreed. The globules and crystals could have formed by chemical or geologic processes, not biology, critics said. Since then, the claim of fossilized Martian life has been widely dismissed. Surely, recognizing something that is still alive, rather than dead and turned to rock, would be much simpler. But don’t bet on it, Cleland says. There may even be strange forms of life on Earth — a shadow biosphere — that people have overlooked. One bit of evidence for shadow terrestrials is “desert varnish,” the dark stains on the sunny sides of rocks in arid areas. Odd, communal life-forms could be sucking energy from the rocks and building the varnish’s hard outer crust, Cleland suggests. Some scientists, for instance, think manganese-oxidizing bacteria or fungi might be responsible for concentrating iron and manganese oxides to create the stains. Unknown microbes may cement the metals with clay and silicate particles to produce the varnish’s shellac. Scientists have tried and failed to re-create desert varnish in the lab using fungi and bacteria. Critics say that varnishes form too slowly — over thousands of years — to be a microbial process and that oxidizing manganese doesn’t generate enough energy to live on. Desert varnish is most likely a product of physical chemistry, they say. But that criticism shows bias, Cleland responds. “We have an assumption that life on Earth has a pace,” she says. Shadow life may grow far more leisurely, making it hard for scientists to classify it as alive. One way to determine whether the varnish has a biological or geologic origin is to measure isotope ratios, Cleland says. Isotopes are forms of elements with differing numbers of neutrons in the nuclei of their atoms. Lighter isotopes, with fewer neutrons, are favored by some biochemical reactions. “Life is lazy,” says Cleland. “It doesn’t want to haul around an extra neutron.” Concentrations of lighter isotopes could signal the handiwork of living organisms, she notes. To find life, and classify it correctly, look for the odd thing out, suggests Hazen, who is looking for messages in minerals. Minerals on Earth are unevenly distributed, he and colleagues have determined. There are 4,933 recognized minerals on the planet. Hazen and colleagues mapped the locations of 4,831 of them and found that 22 percent exist in only one location (SN Online: 12/8/14). Close to 12 percent occur in only two places, the researchers reported last year in The Canadian Mineralogist. One reason for the skewed distribution is that evolving life has used local resources and concentrated them into new minerals. Take for example hazenite, named for Hazen. The phosphate mineral is produced only by microbes living in California’s Mono Lake. Actions of other species in other places on Earth have combined with the planet’s geology to make Earth’s mineralogy unique, Hazen wrote with colleagues last year in Earth and Planetary Science Letters. Finding similarly distorted distributions of minerals on other planets or moons could indicate that life exists, or once existed, there. Hazen has advised NASA on how rovers might identify mineral clues to life on Mars. But determining whether something is unusual might not be as easy as it sounds. Scientists don’t yet know enough about the environment of Mars, Benner says. “Every rover has given us surprises.” He’d like to see a manned fact-finding mission, which he says might lead to a better understanding of the Red Planet and speed up the search for life there. Mars was once wet (SN Online: 10/8/15) and still has occasional running water (SN: 10/31/15, p. 17). That and other mounting evidence that the Red Planet was once capable of supporting life led Benner to hypothesize in 2013 that Mars may have seeded life on Earth. Whether that hypothesis holds may depend on finding Martians, but Benner doesn’t seem worried. “I think I would be surprised now if they don’t find life on Mars,” he says. Once the announcement is made, researchers will begin fighting over whether the Martians are real, he predicts. “It will be a good-natured fight because everybody wants to find life, but everybody is aware of the pitfalls of experiments conducted at a 100-million-mile distance by robots.” Manned missions could easily reach Mars to confirm a find, says Dirk Schulze-Makuch, an astrobiologist at Washington State University in Pullman. “If you have a human with a microscope and the microbe is wiggling and waving back, that’s really hard to refute,” he jokes. But humans and even probes may have a harder time spotting life on more distant or exotic locales, such as the moons of Jupiter and Saturn. Europa, Enceladus and Titan are frigid places barely kissed by the sun’s energetic rays, but that doesn’t mean they are devoid of life, Schulze-Makuch says. ET hunters are particularly attracted to Europa and Enceladus because liquid oceans slosh beneath their icy crusts. Liquid water is thought to be necessary for many of the chemical reactions that could support life, so it’s one of the primary things astronomers look for. But water is actually a terrible solvent for forming complex molecules on which life could be based, Schulze-Makuch says. Instead, he thinks, really alien aliens might have spawned at hot spots deep in the hydrocarbon lakes of Saturn’s biggest moon, Titan. There, “you could make something very intriguing. Whether you can get all the way to life, we don’t know,” he says. If he sent a probe to that moon, he would first look for large macro-molecules similar to the DNA, RNA and proteins that Earth life uses, but with a Titanic twist. He has been studying a natural asphalt lake in Trinidad to learn more about what life in Titan’s lakes might be like. Last July in the journal Life, he and colleagues laid out the physical, chemical and physiological limits that life on Titan would bump up against. Perhaps the biggest challenge for Titanic life is the extreme cold, says chemical engineer Paulette Clancy of Cornell University. Frosty Titan is so cold that methane — a gas on balmy Earth — is a viscous, almost-freezing liquid, and water “would be like a rock,” she says. Under those conditions, organisms with Earth-like chemistry wouldn’t stand a chance. For one thing, the membranes that hold in a cell’s guts on Earth wouldn’t work on Titan. Membranes are made of twin sheets of chainlike molecules each with an oxygen-containing head and a long tail of fatty acids. “On Titan,” says Clancy, “long chains would be a disadvantage because they would be frozen in place,” making membranes brittle. Plus, Titan has no free oxygen to form the molecules’ traditional heads. But Clancy and her Cornell colleagues, chemical engineer James Stevenson and astronomer Jonathan Lunine, simulated experiments under Titan-like conditions. (Molecules that would be stable on Titan would fall apart on Earth, so the researchers had to do computer experiments instead of synthesizing the molecules in a lab.) Short-tailed acrylonitrile molecules with nitrogen-containing heads could spontaneously create stable bubbles called azotosomes, the researchers reported last year in Science Advances. The bubbles are similar to cell membranes. “Azo” is a prefix that denotes a particular configuration of nitrogen atoms in a molecule. It’s also Greek for “without life.” The word’s meaning “would be ironic if life on Titan were based … on nitrogen,” Clancy says. Like desert varnish, life on Titan may have unfamiliar pacing that could prevent Earthlings from determining whether azotosomes or other membranous bubbles found in that moon’s methane oceans actually harbor life. With little solar radiation to stimulate evolution and frigid temperatures to slow chemical reactions, life on Titan may be really poky, Schulze-Makuch says. He imagines that Titanic life-spans may stretch to millions of years, with organisms reproducing or even breathing only once every thousand years. Scientists may need to measure metabolic reactions instead of generation times to determine whether something is living on Saturn’s frigid satellite. Clancy hopes to explore what types of metabolism Titan’s chemistry might allow. Neptune’s icy moon Triton, which is covered in a thin veneer of nitrogen and methane and has nitrogen-spewing geysers, may also be a candidate for new and exciting biochemistry, she says. With so many options out there, Clancy predicts that there are several planets or moons with life on them. “That we have the lock on the way life decided to develop, I think, is unlikely.” Many other researchers are also optimistic that life is out there to find. “I think life is a cosmic imperative,” Hazen says. Someday, astrobiologists may come face-to-face with ET. Maybe they will even recognize it when they see it. This article appears in the April 30, 2016, Science News with the headline, "Will we know ET when we see it?"

Yang Z.,Foundation for Applied Molecular Evolution | Chen F.,Foundation for Applied Molecular Evolution | Chamberlin S.G.,Foundation for Applied Molecular Evolution | Benner S.A.,Foundation for Applied Molecular Evolution
Angewandte Chemie - International Edition | Year: 2010

(Figure Presented) Cleaning up polymerase chain reactions: DNA polymerases are found that copy two additional nucleotide letters (Z and P) in an expanded DNA alphabet to support six-letter polymerase chain reactions (PCR). Incorporated into external primers in a threefold multiplexed PCR, primers containing Z and P gave much cleaner results than standard multiplexed PCR. © 2010 Wiley-VCH Verlag GmbH &. Co. KGaA, Weinheim.

Benner S.A.,Foundation for Applied Molecular Evolution | Kim H.-J.,Foundation for Applied Molecular Evolution | Carrigan M.A.,Foundation for Applied Molecular Evolution
Accounts of Chemical Research | Year: 2012

RNA has been called a "prebiotic chemist's nightmare" because of its combination of large size, carbohydrate building blocks, bonds that are thermodynamically unstable in water, and overall intrinsic instability. However, a discontinuous synthesis model is well-supported by experimental work that might produce RNA from atmospheric CO2, H2O, and N 2. For example, electrical discharge in such atmospheres gives formaldehyde (HCHO) in large amounts and glycolaldehyde (HOCH2CHO) in small amounts. When rained into alkaline aquifers generated by serpentinizing rocks, these substances were undoubtedly converted to carbohydrates including ribose. Likewise, atmospherically generated HCN was undoubtedly converted in these aquifers to formamide and ammonium formate, precursors for RNA nucleobases. Finally, high reduction potentials maintained by mantle-derived rocks and minerals would allow phosphite to be present in equilibrium with phosphate, mobilizing otherwise insoluble phosphorus for the prebiotic synthesis of phosphite and phosphate esters after oxidation.So why does the community not view this discontinuous synthesis model as compelling evidence for the RNA-first hypothesis for the origin of life? In part, the model is deficient because no experiments have joined together those steps without human intervention. Further, many steps in the model have problems. Some are successful only if reactive compounds are presented in a specific order in large amounts. Failing controlled addition, the result produces complex mixtures that are inauspicious precursors for biology, a situation described as the "asphalt problem". Many bonds in RNA are thermodynamically unstable with respect to hydrolysis in water, creating a "water problem". Finally, some bonds in RNA appear to be "impossible" to form under any conditions considered plausible for early Earth.To get a community-acceptable "RNA first" model for the origin of life, the discontinuous synthesis model must be developed. In particular, the model must be refined so that it yields oligomeric RNA from CO2, H2O, and N2 without human intervention. This Account describes our efforts in this direction.Our hypothesis centers on a geological model that synthesizes RNA in a prebiotic intermountain dry valley (not in a marine environment). This valley receives high pH run-off from a watershed rich in serpentinizing olivines and eroding borate minerals. The runoff contains borate-stabilized carbohydrates, formamide, and ammonium formate. As atmospheric CO2 dissolves in the subaerial aquifer, the pH of the aquifer is lowered. In the desert valley, evaporation of water, a solvent with a nucleophilic "background reactivity", leaves behind formamide, a solvent with an electrophilic "background reactivity". As a result, nucleobases, formylated nucleobases, and formylated carbohydrates, including formylated ribose, can form. Well-known chemistry transforms these structures into nucleosides, nucleotides, and partially formylated oligomeric RNA. © 2012 American Chemical Society.

Neveu M.,Foundation for Applied Molecular Evolution
Astrobiology | Year: 2013

This year marks the 50(th) anniversary of a proposal by Alex Rich that RNA, as a single biopolymer acting in two capacities, might have supported both genetics and catalysis at the origin of life. We review here both published and previously unreported experimental data that provide new perspectives on this old proposal. The new data include evidence that, in the presence of borate, small amounts of carbohydrates can fix large amounts of formaldehyde that are expected in an environment rich in carbon dioxide. Further, we consider other species, including arsenate, arsenite, phosphite, and germanate, that might replace phosphate as linkers in genetic biopolymers. While linkages involving these oxyanions are judged to be too unstable to support genetics on Earth, we consider the possibility that they might do so in colder semi-aqueous environments more exotic than those found on Earth, where cosolvents such as ammonia might prevent freezing at temperatures well below 273 K. These include the ammonia-water environments that are possibly present at low temperatures beneath the surface of Titan, Saturn's largest moon.

Benner S.A.,Foundation for Applied Molecular Evolution | Kim H.-J.,Foundation for Applied Molecular Evolution | Yang Z.,Foundation for Applied Molecular Evolution
Cold Spring Harbor Perspectives in Biology | Year: 2012

No community-accepted scientific methods are available today to guide studies on what role RNAplayed in the origin and early evolution of life on Earth. Further, a definition-theory for life is needed to develop hypotheses relating to the "RNA First" model for the origin of life. Four approaches are currently at various stages of development of such a definition-theory to guide these studies. These are (a) paleogenetics, in which inferences about the structure of past life are drawn from the structure of present life; (b) prebiotic chemistry, in which hypotheses with experimental support are sought that get RNA from organic and inorganic species possibly present on early Earth; (c) exploration, hoping to encounter life independent of terran life, which might contain RNA; and (d) synthetic biology, in which laboratories attempt to reproduce biological behavior with unnatural chemical systems. © 2011 Cold Spring Harbor Laboratory Press.

Moussatche P.,Foundation for Applied Molecular Evolution | Lyons T.J.,Foundation for Applied Molecular Evolution
Biochemical Society Transactions | Year: 2012

The steroid hormone progesterone regulates many critical aspects of vertebrate physiology. The nuclear receptor for progesterone functions as a ligand-activated transcription factor, directly regulating gene expression. This type of signalling is referred to as the 'genomic' pathway. Nevertheless, progesterone also stimulates rapid physiological effects that are independent of transcription. This pathway, termed 'nongenomic', is mediated by the mPRs (membrane progesterone receptors). These mPRs belong to a larger class of membrane receptors called PAQRs (progestin and adipoQ receptors), which include receptors for adiponectin in vertebrates and osmotin in fungi. mPRs have been shown to activate inhibitory G-proteins, suggesting that they act as GPCRs (G-protein-coupled receptors). However, PAQRs do not resemble GPCRs with respect to topology or conserved sequence motifs. Instead, they more closely resemble proteins in the alkaline ceramidase family and they may possess enzymatic activity. In the present paper, we highlight the evidence in support of each model and what is currently known for PAQR signal transduction of this non-canonical receptor. ©The Authors Journal compilation ©2012 Biochemical Society.

Kim M.J.,Foundation for Applied Molecular Evolution
Synthetic Communications | Year: 2010

Recently, 2′-C-methyl nucleoside analogues have been reported to exhibit potent anti-hepatitis C virus (HCV) activity through inhibition of HCV RNA replication without significant cytotoxicity. As a part of our continuous efforts of searching for novel antiviral agents, we now report the synthesis of heterobase-modified 2′-C-methyl ribonucleoside analogues. Copyright © Taylor & Francis Group, LLC.

Laos R.,Foundation for Applied Molecular Evolution | Thomson J.M.,Foundation for Applied Molecular Evolution | Benner S.A.,Foundation for Applied Molecular Evolution
Frontiers in Microbiology | Year: 2014

DNA polymerases have evolved for billions of years to accept natural nucleoside triphosphate substrates with high fidelity and to exclude closely related structures, such as the analogous ribonucleoside triphosphates. However, polymerases that can accept unnatural nucleoside triphosphates are desired for many applications in biotechnology. The focus of this review is on nonstandard nucleotides that expand the genetic "alphabet." This review focuses on experiments that, by directed evolution, have created variants of DNA polymerases that are better able to accept unnatural nucleotides. In many cases, an analysis of past evolution of these polymerases (as inferred by examining multiple sequence alignments) can help explain some of the mutations delivered by directed evolution. © 2014 Laos, Thomson and Benner.

Braun W.,University of Texas Medical Branch | Schein C.H.,Foundation for Applied Molecular Evolution
Structure | Year: 2014

In this issue of Structure, Trésaugues and colleagues determined the interaction of membrane-bound phosphoinositides with three clinically significant human inositol polyphosphate 5-phosphatases (I5Ps). A comparison to the structures determined with soluble substrates revealed differences in the binding mode and suggested how the I5Ps and apurinic endonuclease (APE1) activities evolved from the same metal-binding active center. © 2014 Elsevier Ltd.

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