Thursday, October 1, 2009

BUILDING A COMPLETE METABOLIC MODEL

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Investigators at Burnham Institute for Medical Research (Burnham), University of California, San Diego (UC San Diego), The Scripps Research Institute (TSRI), Genomics Institute of the Novartis Research Foundation (GNF) and other institutions have constructed a complete model, including three dimensional protein structures, of the central metabolic network of the bacterium Thermotoga maritima (T. maritima).

This is the first time scientists have developed such a comprehensive model of a metabolic network overlaid with an atomic resolution of network proteins. The analysis of the model, among others, highlights the important role of a small number of essential protein shapes, lending new insights into the evolution of protein networks and the functions within these networks. The study was published in the journal Science on September 18.

Combining biochemical studies, structural genomics and computer modeling, the researchers deciphered the shapes, functions and interactions of 478 proteins that make up T. maritima's central metabolism. The team also found connections between these proteins and 503 unique metabolites in 562 intracellular and 83 extracellular metabolic reactions.

"We have built an actual three dimensional model of every protein in the central metabolic system," said Adam Godzik, Ph.D., director of Burnham's Bioinformatics and Systems Biology program. "We got the whole thing. This is analogous to sequencing an entire genome."

With this data, scientists can simulate metabolism simultaneously on a biochemical and molecular level. This information has the promise to expand computer modeling to allow investigators to simulate the interactions between proteins and various compounds in an entire system. Furthermore, the procedure developed in this study could be applied to study many other organisms, including humans. It could potentially help identify both positive and adverse drug reactions before pre-clinical and clinical trials. The research may also have applications in energy research, as bacteria like T. maritima can be engineered to more efficiently produce hydrogen, a key source of clean energy.

"In addition to the systematic analysis of interacting components, the next challenge is addressing the levels or scales of biological organization, ranging from molecules to an individual and even to populations," said co-author John C. Wooley, Ph.D., of UC San Diego's Center for Research in Biological Systems and the California Institute for Telecommunications and Information Technology. "This work, by including both functional and architectural details, takes that first step and provides a novel, enriched view of the complexity of life."

Researchers were surprised by the degree of structural conservation within the network. Of the 478 proteins, with 714 domains, there were only 182 distinct folds. This supports the hypothesis that nature uses existing shapes, slightly modified, to perform new tasks.

The team used genomic, metabolic, and structural reconstruction to determine the network down to the atomic level. They then classified metabolic reactions based on whether they were similar, connected or unrelated and found that enzymes that catalyze similar reactions have a higher probability of having similar folds. In addition, using a reductive evolution simulation approach, they uncovered the absolutely essential proteins to support a minimal viable network.

"We were able to put together the information from the network biology as well as the protein structural biology," said co-author Bernhard Palsson, Ph.D., a UC San Diego bioengineering professor who leads the Systems Biology Research Group. "This is the first time this has been accomplished. We are in a position to study microorganisms in much greater detail, including those that are important in health care and those that are of environmental concern."

Burnham Institute for Medical Research (Burnham)

SCIENTISTS PINPOINT PROTEIN LINK TO FAT STORAGE

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A protein found present in all cells in the body could help scientists better understand how we store fat.

Researchers at the University of Edinburgh have found that the protein invadolysin, which is essential for healthy cell division, is present in lipid droplets – the parts of cells used to store fat.

The study also found that lower levels of invadolysin were linked to reduced amounts of fat deposits.

The findings, published in the Journal of Cell Science, could ultimately help scientists to better understand obesity-related complications, which can include diabetes, blood clotting and heart disease.

Professor Margarete Heck, at the University's Centre for Cardiovascular Science, said: "The presence of this protein in lipid droplets may suggest that it has a role in obesity. What we would like to understand is whether its presence is related to obesity, and if so, whether the protein's activity aggravates obesity and its consequences. Understanding its role will help us to better understand how the body stores fat."

Invadolysin was first identified by Professor Heck's laboratory in fruit flies. The latest study looked at the protein in human cells, pinpointing its presence in the part of cells used to store fat.

The researchers also found that when invadolysin was absent in fruit fly larvae, fat storage was impaired.

Further studies will look at how the protein affects metabolism to better understand its role in obesity-related disorders.

University of Edinburgh

REPTILES STOOD UPRIGHT AFTER MASS EXTINCTION

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Reptiles changed their walking posture from sprawling to upright immediately after the end-Permian mass extinction, the biggest crisis in the history of life that occurred some 250 million years ago and wiped out 90% of all species.

In a detailed study of 460 fossil tracks of reptiles from below and above the extinction boundary, Tai Kubo and Professor Mike Benton from the University of Bristol have found that before the Permian extinction all the reptiles moved with their arms and legs held sideways in a sprawling posture, just like salamanders and lizards do today.

After the mass extinction, the medium-sized and large reptiles of the subsequent Triassic period, walked with their legs tucked underneath their bodies, just like modern mammals.

Professor Benton said “Dinosaurs – and later the mammals – owe their success to being upright. An upright animal, like an elephant or a Diplodocus, can also be very large because its weight passes directly through the pillar-like legs to the ground. In addition, other upright animals, such as monkeys, could use their arms for climbing or gathering food.”

Walking upright can have great advantages – it means the stride can be longer and the animal can move with much less stress on the knee and elbow joints. Upright walking was the key to the success of the dinosaurs, which originated 25 million years after the great end-Permian crisis. The first dinosaurs were all bipeds and they also became very large. Sprawlers cannot become too big or their legs collapse.

Up to now, the transition from a sprawling to an upright posture was seen as long-term, possibly lasting some 20-30 million years, but the new evidence suggests that the event was much more rapid, and was perhaps initiated by the mass extinction crisis.

This new understanding shifts the evolutionary assumptions as well. “If the replacement of sprawlers by upright animals had been a long drawn-out affair, then we’d be looking at some process of competitive replacement,” said Professor Benton.

“As it is, the new footprint evidence suggests a more dramatic pattern of replacement, where the sprawling animals that dominated Late Permian ecosystems nearly all died out, and the new groups that evolved after the crisis were upright. Any competitive interactions were compressed into a short period of time.”

(Photo: Jim Robins)

University of Bristol

HOT MICROBES CAUSE GROUNDWATER CLEANUP RETHINK

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CSIRO researchers have discovered that micro-organisms that help break down contaminants under the soil can actually get too hot for their own good.

While investigating ways of cleaning up groundwater contamination, scientists examined how microbes break down contaminants under the soil’s surface and found that subsurface temperatures associated with microbial degradation can become too hot for the microbes to grow and consume the groundwater contaminants.

This can slow down the clean up of the groundwater and even continue the spread of contamination.

The new findings mean that researchers now have to rethink the way groundwater remediation systems are designed.

“Although increasing the flow of air would reduce temperatures and overcome these limitations a fine balance needs to be struck as the injected air can generate hazardous vapours that overwhelm the micro-organisms leading to unwanted atmospheric emissions at the ground surface,” Mr Johnston said. CSIRO Water for a Healthy Country Flagship scientist Mr Colin Johnston, who is based in Perth, Western Australia, said the researchers were investigating how temperatures below the soil’s surface could be used as an indicator of the microbial degradation process associated with biosparging.

Biosparging is a technique that injects air into polluted groundwater to enhance the degradation of contaminants.

The contaminants are ‘food’ to the microbes and the oxygen in the air helps the microbes unlock the energy in the food so that they metabolise and grow, consuming more contaminants and stopping the spread of the contamination.

“Observations of diesel fuel contamination showed that, at 3.5 metres below the ground surface, temperatures reached as high as 47 °C,” Mr Johnston said.

“This is close to the 52 °C maximum temperature tolerated by the community of micro-organisms that naturally live in the soil at this depth and within the range where the growth of the community was suppressed.”

The growth of the soil’s micro-organism community can also be helped by adding nutrients.

However computer modelling confirmed that any attempts to further increase degradation of the contamination through the addition of nutrients had the potential to raise temperatures above the maximum for growth.

“Although increasing the flow of air would reduce temperatures and overcome these limitations a fine balance needs to be struck as the injected air can generate hazardous vapours that overwhelm the micro-organisms leading to unwanted atmospheric emissions at the ground surface,” Mr Johnston said.

“This would be particularly so for highly volatile compounds such as gasoline.

“It appears that prudent manipulation of operating conditions and appropriate timing of nutrient addition may help limit temperature increases.”

Mr Johnston said further research was required to better understand the thermal properties in the subsurface as well as the seasonal effects of rainfall infiltration and surface soil heating.

(Photo: Willem van Aken)

Commonwealth Scientific and Industrial Research Organization (CSIRO)

FRICTION DIFFERENCES OFFER NEW MEANS FOR MANIPULATING NANOTUBES

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Nanotubes and nanowires are promising building blocks for future integrated nanoelectronic and photonic circuits, nanosensors, interconnects and electro-mechanical nanodevices. But some fundamental issues remain to be resolved—among them, how to position and manipulate the tiny tubes.

Publishing in the journal Nature Materials, researchers from four different institutions report measuring different friction forces when a carbon nanotube slides along its axis compared to when it slides perpendicular to its axis. This friction difference has its origins in soft lateral distortion of the tubes when they slide in the transverse direction.

The findings not only could provide a better understanding of fundamental friction issues, but from a more practical standpoint, offer a new tool for assembling nanotubes into devices and clarify the forces acting on them. Asymmetries in the friction could potentially also be used in sorting nanotubes according to their chirality, a property that is now difficult to measure with other means.

When an atomic force microscope (AFM) tip is scanned transversely across a multi-walled carbon nanotube, the amount of friction measured is twice as much as when the same tube is scanned longitudinally, along the length of the tube. The researchers attribute this difference to what they call “hindered rolling”—additional effort required to overcome the nanotube’s tendency to roll as the AFM tip strokes across it rather than along it.

“Because the energy required to move in one direction is twice as much as required to move in the other direction, this could be an easy way to control the assembly of carbon nanotubes for nanoelectronics, sensors and other applications,” said Elisa Riedo, co-author of the study and an associate professor in the School of Physics at the Georgia Institute of Technology. “To assemble nanotubes on a surface, you need to know how they interact and what force is needed to move them.”

The combined theoretical and experimental study was supported by the U.S. Department of Energy. Other institutions contributing to the project include the International Centre for Theoretical Physics, International School for Advanced Studies and CNR Democritos Laboratory—all in Trieste, Italy—and the University of Hamburg in Germany. The paper was published in advance online on September 13 by the journal Nature Materials.

Carbon nanotubes have exceptional thermal, mechanical and electrical properties that have generated considerable interest since they were first reported in 1991. Though friction has been studied before in nanotubes, this research is the first to provide detailed information about the frictional forces at work in both the longitudinal and transverse directions when the tubes interact with an AFM tip.

Friction is one of the oldest problems in physics and one of the most important to everyday life. It is estimated that the losses in the U.S. economy due to friction total about 6 percent of the gross national product. Friction is even more important to micro-electromechanical systems (MEMS) and nanoscale devices because these smaller systems are more affected by surface forces than large systems.

“As systems become smaller and smaller, it becomes more important to understand how to address friction,” said Riedo. “Surface forces can prevent micro and nano systems from operating at all.”

Experimentally, the researchers scanned an atomic force microscope tip longitudinally along a series of multiwalled carbon nanotubes held stationary on a substrate. They also conducted a series of similar scans in the transverse direction. The researchers applied a consistent force on the AFM tip in both scanning directions, and relied on powerful Van der Waals forces to hold tubes in place on the substrate.

“When you scan a nanotube transversely, you are probing something very different,” said Riedo. “You are also probing additional dissipation modes due to a kind of swaying motion in which energy is also dissipated through movement of the nanotube as it alters its cross section.”

The experiment showed that greater forces were required to move the tip in the transverse direction. Using molecular dynamics simulations, collaborators Erio Tosatti and Xiaohua Zhang at the International Centre for Theoretical Physics, International School for Advanced Studies and CNR Democritos Laboratory analyzed the phenomenon to understand what was happening.

“In principle, there seems to be no reason why the frictional forces required to move the AFM tip would be different in one direction,” Riedo noted. “But the theory confirmed that this ‘hindered rolling’ and soft mode movement of the nanotubes are the sources of the higher friction when the tip moves transversely.”

Because the nanotube-tip system is so simple, it offers an ideal platform for studying basic friction principles, which are important to all moving systems.

“This kind of system gives you the opportunity to explore friction using an ideal experiment so you can really probe the energy dissipation mechanism,” Riedo explained. “The system is so simple that you can distinguish between the dissipation mechanisms, which you can’t usually do well in macro-scale systems.”

Based on the molecular dynamics simulations, Riedo and Tosatti believe that the friction anisotropy will be very different in chiral nanotubes versus non-chiral—left-to-right symmetric—nanotubes.

“Because of the chirality, the tip moves in a screw-like fashion, creating hindered rolling even for longitudinal sliding,” Tosatti said. “Thus, the new measuring technique may suggest a simple way to sort the nanotubes; among the next steps in the research will be to show experimentally that this can be done.”

In addition to the researchers already mentioned, co-authors for this paper include Christian Klinke at the Institute of Physical Chemistry at the University of Hamburg, and Marcel Lucas and Ismael Palaci at Georgia Tech.

“Understanding the basic mechanism of friction in carbon nanotubes will help us in designing devices with them in the future,” Riedo added. “We have shown an anisotropy in the friction coefficient of carbon nanotubes in the transverse and longitudinal directions, which has its origin in the soft lateral distortion of tubes when the tip-tube contact is moving in the transverse direction. Our findings could help in developing better strategies for chirality sorting, large-scale self-assembling of nanotubes on surfaces, and designing nanotube adhesives and nanotube-polymer composite materials.”

(Photo: Christian Klinke, University of Hamburg)

SCIENTISTS CREATE FIRST COMPLETE IMAGE OF HIMALAYAN FAULT, SUBDUCTION ZONE

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An international team of researchers has created the most complete seismic image of the Earth’s crust and upper mantle beneath the rugged Himalaya Mountains, in the process discovering some unusual geologic features that may explain how the region has evolved.

Their findings, published in the journal Science, help explain the formation of the world’s largest mountain range, which is still growing.

The researchers discovered that as the Indian and Eurasian tectonic plates collide, the Indian lower crust slides under the Tibetan crust, while the upper mantle peels away from the crust and drops down in a diffuse manner.

“The building of Tibet is not a simple process,” said John Nabelek, an Oregon State University geophysicist and lead author on the Science study. “In part, the mountain building is similar to pushing dirt with a bulldozer except in this case, the Indian sediments pile up into a wedge that is the lesser Himalayan mountains.

“However, an important component of the mass transfer from the upper crust of India to the Himalayas also occurs at depth through viscous processes, while the lower crust continues sliding intact farther north under the Tibet plateau,” Nabelek added.

The findings are important because there has not been clear scientific consensus on the boundaries and processes for that region’s tectonic plates. In fact, the piecemeal images gathered by previous research have led to a series of conflicting models of the lithospheric structure and plate movement.

In this study, the international research team – called Hi-CLIMB (Himalayan-Tibetan Continental Lithosphere during Mountain Building) – was able to create new in-depth images of the Earth’s structure beneath the Himalayas.

The interface between the subducting Indian plate and the upper Himalayan and Tibetan crust is the Main Himalayan thrust fault, which reaches the surface in southern Nepal, Nabelek said. The new images show it extends from the surface to mid-crustal depths in central Tibet, but the shallow part of the fault sticks, leading to historically devastating mega-thrust earthquakes.

“The deep part is ductile,” Nabelek said, “and slips in a continuous fashion. Knowing the depth and geometry of this interface will advance research on a variety of fronts, including the interpretation of strain accumulation from GPS measurements prior to large earthquakes.”

Nabelek, an associate professor in OSU’s College of Oceanic and Atmospheric Sciences, said the lower part of the Indian crust slides about 450 kilometers under the southern Tibetan plate and the mantle appears to shear off and break into sub-parallel segments.

The researchers found evidence that subduction in the fault zone has been occurring from both the north and south sides – likely at different times in its geologic history.

In this project, funded primarily by the National Science Foundation, the researchers deployed and monitored about 230 seismic stations for a period of three years, cutting across 800 kilometers of some of the most remote terrain in the world. The lowest-elevation station was at 12 meters above sea level in Nepal; the highest, nearly 5,500 meters in Tibet. In fact, 30 of the stations were higher than 5,000 meters, or 16,400 feet.

“The research took us from the jungles of Nepal, with its elephants, crocodiles and rhinos, to the barren, wind-swept heights of Tibet in areas where nothing grew for hundreds of miles and there were absolutely no humans around,” Nabelek said. “That remoteness is one reason this region had never previously been completely profiled.”

(Photo: OSU/John Nabelek)

Oregon State University

NEW DATA ILLUMINATES ANTARCTIC ICE CAP FORMATION

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A team of scientists from Bristol, Cardiff and Texas A&M universities braved the lions and hyenas of a small East African village to extract microfossils from rocks which have revealed the level of CO2 in the Earth’s atmosphere at the time of the formation of the ice-cap.

Geologists have long speculated that the formation of the Antarctic ice-cap was caused by a gradually diminishing natural greenhouse effect. The study’s findings, published in Nature online, confirm that atmospheric CO2 started to decline about 34 million years ago, during the period known to geologists as the Eocene - Oligocene climate transition, and that the ice sheet began to form about 33.5 million years ago when CO2 in the atmosphere reached a tipping point of around 760 parts per million (by volume).

The new findings will add to the debate around rising CO2 levels in the Earth’s atmosphere as the world’s attention turns to the UN Climate Conference in Copenhagen which opens later this year.

Dr Gavin Foster from the University of Bristol and a co-author on the paper said: “By using a rather unique set of samples from Tanzania and a new analytical technique that I developed, we have, for the first time, been able to reconstruct the concentration of CO2 across the Eocene-Oligocene boundary – the time period about 33.5 million years ago when ice sheets first started to grow on Eastern Antarctica. “

Professor Paul Pearson from Cardiff University’s School of Earth and Ocean Sciences, who led the mission to the remote East Africa village of Stakishari said: “About 34 million years ago the Earth experienced a mysterious cooling trend. Glaciers and small ice sheets developed in Antarctica, sea levels fell and temperate forests began to displace tropical-type vegetation in many areas.

“The period culminated in the rapid development of a continental-scale ice sheet on Antarctica, which has been there ever since. We therefore set out to establish whether there was a substantial decline in atmospheric carbon dioxide levels as the Antarctic ice sheet began to grow.”

Co-author Dr Bridget Wade from Texas A&M University Department of Geology and Geophysics added: “This was the biggest climate switch since the extinction of the dinosaurs 65 million years ago.

“Our study is the first to provide a direct link between the establishment of an ice sheet on Antarctica and atmospheric carbon dioxide levels and therefore confirms the relationship between carbon dioxide levels in the atmosphere and global climate.”

The team mapped large expanses of bush and wilderness and pieced together the underlying local rock formations using occasional outcrops of rocks and stream beds. Eventually they discovered sediments of the right age near a traditional African village called Stakishari. By assembling a drilling rig and extracting hundreds of meters of samples from under the ground they were able to obtain exactly the piece of Earth's history they had been searching for.

(Photo: Bristol U.)

Bristol University

OCEAN ACIDIFICATION: IMPACT ON KEY ORGANISMS OF OCEANIC FAUNA

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In addition to global warming, carbon dioxide emissions cause another, less well-known but equally serious and worrying phenomenon: ocean acidification. Researchers in the Laboratoire d'Océanographie at Villefranche (LOV) (CNRS / UPMC) have just demonstrated that key marine organisms, such as deep-water corals and pteropods (shelled pelagic mollusks) will be profoundly affected by this phenomenon during the years to come. Two studies have been published in the journal Biogeosciences.

Since 1800, one third of anthropogenic CO2 emissions has been absorbed by the oceans, corresponding to an annual uptake of one ton of CO2 per person. This massive absorption has allowed to partly mitigate climate change but it has also caused a major disruption to the chemistry of seawater. Indeed, this absorbed CO2 causes an acidification of the oceans and, at the current rate of emissions, it is estimated that their pH will fall by 0.4 units between now and 2100. This corresponds to a 3-fold increase of the mean acidity of the oceans, which is unprecedented during the past 20 million years. The LOV team, led by Jean-Pierre Gattuso, studied the impact of such a reduction in pH on calcifying organisms. Pteropods (pelagic marine mollusks) and deep-water corals, both playing essential roles in their respective ecosystems, live in areas that will be among the first to be affected by ocean acidification.

The pteropod Limacina helicina thus has an important part to play in the food chain and functioning of the Arctic marine ecosystem. Its calcium carbonate shell provides vital protection. However, the LOV study has shown that the shell of this mollusk develops at a rate that is 30% slower when it is kept in seawater with the characteristics anticipated in 2100. An even more marked reduction (50%) has been measured in the cold-water coral Lophelia pertusa. While tropical coral reefs are built by a large number of species, coral communities in cold waters are constructed by one or two species but provide shelter for many others. A reduction in the growth of reef-building corals due to ocean acidification may therefore threaten the very existence of these biological structures.

These first results raise major concerns about the future of pteropods, deep-water corals and the organisms that depend on them for nutrition or habitat. Research programs such as EPOCA, coordinated by CNRS, are planning new studies on other marine organisms and ecosystems. They are carrying out long-term experiments to study the combined impact of ocean acidification and other parameters that will also be modified during the decades to come, such as temperature and nutrient concentrations.

Ocean acidification can only be controlled by limiting future atmospheric levels of CO2. Negotiations aimed at reducing greenhouse gas emissions (COP 15) are under way and should be finalized in Copenhagen next December. These negotiations must take account not only of increased temperature but also of the acidic nature of CO2 which, once absorbed by the oceans, will have potentially dramatic effects on numerous marine organisms and ecosystems.

(Photo: S. Comeau, LOV)

MIT

THE AFRICAN ORIGIN OF ANTHROPOID PRIMATES CALLED INTO QUESTION

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Well-preserved craniodental fossil remains from two primate species have been discovered during excavations at an Algerian site. They reveal that the small primate Algeripithecus, which is 50 million years old and until now was considered as the most ancient African anthropoid, in fact belonged to another group, that of the crown strepsirhines.

This research was carried out by a team of French researchers from the Institut des Sciences de l'Evolution (Université de Montpellier/CNRS), working with Algerian paleontologists from the universities of Tlemcen, Oran and Jijel. The resulting publication, published online on the website of the Proceedings of the Royal Society B (Biological Sciences) on September 9, 2009, reopens the debate on the African origin of anthropoids, the group to which humans and apes belong.

In 1992, fossilized remains of the small primate Algeripithecus were discovered in the Algerian Sahara. Fifty million years old, weighing just 75 g and known to paleontologists thanks to the remains of two molars, this primate was considered to be the most ancient anthropoid of the African continent. The discovery of Algeripithecus was thus a major contribution to the hypothesis under which Africa was the cradle of anthropoid primates, a group to which humans and apes all belong. The existence of another primate, the Azibius, has been known for longer. This is one of the most ancient African representatives of the crown strepsirhines, another primate group that today is represented by the lemurs of Madagascar, the galagos of Central Africa and the loris of Southern Asia.

At the Glib Zegdou site in north-eastern Algeria, a French team from the Institut des Sciences de l'Evolution in Montpellier (Université de Montpellier/CNRS), working in collaboration with Algerian scientists, recently exhumed cranial and dental fragments from both Algeripithecus and Azibius. They included some nearly complete mandibles. These remains displayed a certain number of traits typical of the crown strepsirhines, notably an adaptation to nocturnal activity and the putative presence of a "toothcomb" in the lower toothrow. The paleontologists concluded that Algeripithecus, like its close relative Azibius, did not in fact belong to the family of anthropoid primates but was very probably one of the most ancient representatives in Africa of the crown strepsirhines.

In Egypt, the presence of more than a dozen fossilized anthropoid primates dating from 30 to 38 million years ago had long been known. This recent Franco-Algerian discovery thus advances the first true appearance of anthropoid primates on the African continent by more than 15 million years. With its major consequences on the evolutionary history of African anthropoid primates, this observation further strengthens the alternative hypothesis of an Asiatic origin for anthropoids. Furthermore, this paleontologic research reveals a hitherto unsuspected diversity and great antiquity of the first crown strepsirhines in Africa.

(Photo: Rodolphe Tabuce, CNRS)

Centre National de la Reserche Scientifique

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