Bacteria may help frogs attract mates

Adult female (left) and calling male of Boana prasina.

Brazilian scientists have discovered that the strong odor released by some amphibian species is produced by bacteria and that attracting a mate is one of its purposes. The bacteria in question are a noteworthy example of symbiosis as they assist in the animal's mating process. A paper recounting the discovery of this role of microorganisms isolated from the skin of frogs has been published in the journal Proceedings of the National Academy of Sciences (PNAS).

"Frogs emit a pungent odor. Sometimes a particular species can be recognized by its scent, but until now, the function of this odor was unknown. It was typically assumed to be an aposematic smell, meaning a chemical warning sign that served to repel predators, as in the case of skunks [Mephitis mephitis] among mammals, for example," said Célio Haddad, a professor at São Paulo State University's Rio Claro Bioscience Institute (IBRC-UNESP) in Brazil and a coauthor of the article.

According to Haddad, who is also affiliated with the university's Aquaculture Center (CAUNESP) in Jaboticabal, this hypothesis was considered plausible because many amphibian species, especially when poisonous, are brightly colored, and this serves as a visual alert to frighten predators. "We thought odor might play a similar role among anurans [frogs and toads]," he said.

The new study resulted from the postdoctoral research of Argentinean biologist Andrés Eduardo Brunetti, supervised by Professor Norberto Peporine Lopes. Conducted at the University of São Paulo's Ribeirão Preto School of Pharmaceutical Sciences (FCFRP-USP), the research was supported by FAPESP.

"The importance and originality of Brunetti's research is that for the first time it shows a pronounced difference in the odors emitted by frogs of opposite sexes," Haddad said. "No other studies of anurans have ever described this type of behavior. The results suggest that the odor serves to permit mutual recognition between males and females of the same species for mating purposes."

The research was also supported by the FAPESP Research Program on Biodiversity Characterization, Conservation, Restoration and Sustainable Use (BIOTA-FAPESP) and by the University of São Paulo (USP), the National Council for Scientific and Technological Development (CNPq) and Brazil's Coordination for the Improvement of Higher Education Personnel (CAPES).

"In anurans, you often see different species sharing a lake or marsh. In such places, there are 30 male frogs for every female of the same species on average. The question is how the females recognize males of their own species among a multitude of males belonging to several species while they're all vocalizing at the same time," Brunetti said.

"It's well-known that the function of the call of anuran males is to attract females and that every species has a characteristic song. Our findings suggest that odor appears to play a similar role, serving as an olfactory signal that enables females to recognize males of their own species."

Biologists were also unaware of a difference in the scents of male and female frogs. Brunetti discovered this difference during his research, whose primary goal was to understand the chemical composition of the volatile components emitted by the skin of various frog species.

His working hypothesis suggested that smell was a chemical warning sign that served to repel predators. To verify the hypothesis, Brunetti conducted field surveys at several sites in São Paulo state and Rio de Janeiro state, collecting specimens of the tree frog Boana prasina.

"It's very hard to collect females in the wild. Initially, we managed to collect only males. When we noticed what appeared to be a sexual difference in their odors, I went into the field again with the specific aim of capturing females for comparison," he said.

"During my doctoral research at the Argentinian Natural Science Museum in Buenos Aires, while investigating the volatile compounds in two other frog species, I discovered that the secretions were made up of a blend of 35 to 42 compounds in nine different chemical classes. We then realized that some of the compounds had the specific signature of compounds produced by bacteria."

Brunetti came to Brazil to investigate whether the selected tree frogs had skin bacteria that produced the characteristic odor of each species, and if so, which compounds they produced. His laboratory research proceeded on two fronts: analysis of the volatile compounds released by the skin of these frogs and identification of the bacteria on their skin.

Brunetti and colleagues used gas chromatography and mass spectrometry to analyze the diversity of the volatile components secreted by the skin of B. prasina. They found that adult males and females secrete a blend of 60-80 compounds, including alcohols, aldehydes, alkenes, ethers, ketones, methoxypyrazines, terpenes and thioethers.

The compounds were exactly the same in both males and females, but the researchers were surprised to find a pronounced sexual difference in the levels of methoxypyrazines, terpenes, and thioethers.

"These three components were responsible for the difference between males and females. Thioethers and methoxypyrazines are typically produced by microorganisms," Brunetti said.

They decided to determine whether microorganisms were the source of these compounds in B. prasina. To do so, they isolated, cultivated and identified bacteria associated with the skin of these frogs and analyzed their volatile components.

No fewer than 128 different components were detected. Analysis of each component revealed that four methoxypyrazines present in males and females were produced by a single bacterium of the genus Pseudomonas.

In B. prasina, Brunetti discovered, methoxypyrazines were much more abundant in females than in males. Two of the four types of methoxypyrazines were measured at higher levels in females, while two were found at higher levels in males.

Symbiotic relationship

"The interesting thing about Pseudomonas sp. is that these bacteria live on the skin of males and females, where they metabolize the same volatile compounds but at different levels of concentration according to the sex of the host," Brunetti said.

The levels of methoxypyrazine measured in these frogs, he added, suggest the existence of a complex mechanism of metabolic interactions that creates a different environment on the skin of males and females, favoring the synthesis of characteristic methoxypyrazines in each sex.

"These frogs and bacteria have a symbiotic relationship. In exchange for the service provided by the bacteria, entailing sexual differentiation by scent, the frogs provide an environment -- their own skin -- on which the bacteria can proliferate," he explained.

The function of this sexual difference in methoxypyrazine levels is unknown. "However, we assume that the difference in scent helps male frogs of this species recognize females of the same species in places inhabited by other frog species," Brunetti said.

"We know that many anurans use visual communication [bright skin colors] to repel predators as well as acoustic communication [vocalization] to attract female mates. Perhaps B. prasina uses a form of olfactory communication for the same purpose."

Brunetti will attempt to confirm this hypothesis in future research. If correct, it will have major repercussions. "Only one anuran, in Madagascar, is currently known to communicate by odor. Among amphibians, salamanders, which are distant relatives of anurans, are known to use this form of communication," Haddad said.

Read more at Science Daily

Unique diversity of the genetic history of the Iberian Peninsula revealed by dual studies

Excavation work in progress at the site of Balma Guilanyà.

An international team of researchers have analyzed ancient DNA from almost 300 individuals from the Iberian Peninsula, spanning more than 12,000 years, in two studies published today in Current Biology and Science. The first study looked at hunter-gatherers and early farmers living in Iberia between 13,000 and 6000 years ago. The second looked at individuals from the region during all time periods over the last 8000 years. Together, the two papers greatly increase our knowledge about the population history of this unique region.

The Iberian Peninsula has long been thought of as an outlier in the population history of Europe, due to its unique climate and position on the far western edge of the continent. During the last Ice Age, Iberia remained relatively warm, allowing plants and animals -- and possibly people -- who were forced to retreat from much of the rest of Europe to continue living there. Similarly, over the last 8000 years, Iberia's geographic location, rugged terrain, position on the Mediterranean coast and proximity to North Africa made it unique in comparison to other parts of Europe in its interactions with other regions. Two new studies, published concurrently in Current Biology and Science, analyze a total of almost 300 individuals who lived from about 13,000 to 400 years ago to give unprecedented clarity on the unique population history of the Iberian Peninsula.

Iberian hunter-gatherers show two ancient Paleolithic lineages

For the paper in Current Biology, led by researchers at the Max Planck Institute for the Science of Human History, researchers analyzed 11 hunter-gatherers and Neolithic individuals from Iberia. The oldest newly analyzed individuals are approximately 12,000 years old and were recovered from Balma Guilanyà in Spain.

Earlier evidence had shown that, after the end of the last Ice Age, western and central Europe were dominated by hunter-gatherers with ancestry associated with an approximately 14,000-year-old individual from Villabruna, Italy. Italy is thought to have been a potential refuge for humans during the last Ice Age, like Iberia. The Villabruna-related ancestry largely replaced earlier ancestry in western and central Europe related to 19,000-15,000-year-old individuals associated with what is known as the Magdalenian cultural complex.

Interestingly, the findings of the current study show that both lineages were present in Iberian individuals dating back as far as 19,000 years ago. "We can confirm the survival of an additional Paleolithic lineage that dates back to the Late Ice Age in Iberia," says Wolfgang Haak of the Max Planck Institute for the Science of Human History, senior author of the study. "This confirms the role of the Iberian Peninsula as a refuge during the Last Glacial Maximum, not only for fauna and flora but also for human populations."

This suggests that, far from being replaced by Villabruna-related individuals after the last Ice Age, hunter-gatherers in Iberia in fact already had ancestry from Magdalenian- and Villabruna-related sources. The discovery suggests an early connection between two potential refugia, resulting in a genetic ancestry that survived in later Iberian hunter-gatherers.

"The hunter-gatherers from the Iberian Peninsula carry a mix of two older types of genetic ancestry: one that dates back to the Last Glacial Maximum and was once maximized in individuals attributed to Magdalenian culture and another one that is found everywhere in western and central Europe and had replaced the Magdalenian lineage during the Early Holocene everywhere except the Iberian Peninsula," explains Vanessa Villalba-Mouco of the Max Planck Institute for the Science of Human History, first author of the study.

The researchers hope that ongoing efforts to decipher the genetic structure of late hunter-gatherer groups across Europe will help to even better understand Europe's past and, in particular, the assimilation of a Neolithic way of life brought about by expanding farmers from the Near East during the Holocene.

Ancient DNA from individuals spanning the last 8000 years helps clarify the history and prehistory of the Iberian Peninsula

The paper published in Science focuses on slightly later time periods, and traces the population history of Iberia over the last 8000 years by analyzing ancient DNA from a huge number of individuals. The study, led by Harvard Medical School and the Broad Institute and including Haak and Villalba-Mouco, analyzed 271 ancient Iberians from the Mesolithic, Neolithic, Copper Age, Bronze Age, Iron Age and historical periods. The large number of individuals allowed the team to make more detailed inferences about each time period than previously possible.

The researchers found that during the transition to a sedentary farming life-style, hunter-gatherers in Iberia contributed subtly to the genetic make-up of newly arriving farmers from the Near East. "We can see that there must have been local mixture as the Iberian farmers also carry this dual signature of hunter-gatherer ancestry unique to Iberia," explains Villalba-Mouco.

Between about 2500-2000 BC, the researchers observed the replacement of 40% of Iberia's ancestry and nearly 100% of its Y-chromosomes by people with ancestry from the Pontic Steppe, a region in what is today Ukraine and Russia. Interestingly, the findings show that in the Iron Age, "Steppe ancestry" had spread not only into Indo-European-speaking regions of Iberia but also into non-Indo-European-speaking ones, such as the region inhabited by the Basque. The researchers' analysis suggests that present-day Basques most closely resemble a typical Iberian Iron Age population, including the influx of "Steppe ancestry," but that they were not affected by subsequent genetic contributions that affected the rest of Iberia. This suggests that Basque speakers were equally affected genetically as other groups by the arrival of Steppe populations, but retained their language in any case. It was only after that time that they became relatively isolated genetically from the rest of the Iberian Peninsula.

Additionally, the researchers looked at historical periods, including times when Greek and later Roman settlements existed in Iberia. The researchers found that beginning at least in the Roman period, the ancestry of the peninsula was transformed by gene flow from North Africa and the eastern Mediterranean. They found that Greek and Roman settlements tended to be quite multiethnic, with individuals from the central and eastern Mediterranean and North Africa as well as locals, and that these interactions had lasting demographic as well as cultural impacts.

Read more at Science Daily

Bernese Mars camera CaSSIS returns spectacular images

The image shows a panchromatic channel image of the InSight landing site on Mars. The image shows an area of about 2.25 km x 2.25 km in the Elysium Planitia region. The original image had a scale of about 4.5 m per pixel, and has been stretched by a factor of two for display purposes. The resulting resolution of this image is 5-6 m/pixel. The positions of the InSight lander itself, the blast marks from the retro rockets used during landing, the heatshield and the backshell of the entry descent and landing system are marked. The original image had a scale of about 4.5 m per pixel, and has been expanded to 2.25 m/pixel for display purposes.

ExoMars is a space mission of the European Space Agency (ESA) in cooperation with the Russian space agency Roskosmos. ExoMars stands for exobiology on Mars: for the first time since the 1970s, active research is being conducted into life on Mars. So called trace gases including methane and their sources are being detected by the Trace Gas Orbiter (TGO) while the ExoMars programme as a whole (combining TGO with a rover, Rosalind Franklin, due to launch next year) will investigate how the water and the geochemical environment has changed with time.

The Colour and Stereo Surface Imaging System (CaSSIS) on board the ExoMars Trace Gas Orbiter (TGO) was developed by an international team led by Prof. Nicolas Thomas of the Center for Space and Habitability (CSH) at the University of Bern. The TGO launched three years ago today, on 14 March 2016. It arrived at Mars on 19 October that year, and spent over a year demonstrating the aerobraking technique needed to reach its science orbit, starting its prime mission at the end of April 2018.

Hello, InSight

Amongst a new showcase of images from CaSSIS is an image of NASA's InSight lander -- the first time a European instrument has identified a lander on the Red Planet. InSight arrived on Mars on 26 November 2018 to study the interior of the planet. Images of the lander have already been returned by NASA's Mars Reconnaissance Orbiter, these are the first images from TGO.

The panchromatic image was captured by CaSSIS on 2 March 2019, and covers an area of about 2.25 x 2.25 km. At that time, InSight was hammering a probe into the surface in order to measure heat coming from inside the planet. The CaSSIS view shows InSight as a slightly brighter dot in the centre of the dark patch produced when the lander fired its retro rockets just before touchdown in the Elysium Planitia region of Mars, and disturbed the surface dust. The heat shield released just before landing can also be seen on the edge of a crater, and the backshell used to protect the lander during descent is also identified.

"The TGO is being used to relay data from InSight to Earth," says Nicolas Thomas, CaSSIS Principal Investigator, from the University of Bern. "Because of this function, to avoid uncertainties in communications, we had not been able to point the camera towards the landing site so far -- we had to wait until the landing site passed directly under the spacecraft to get this image."

CaSSIS is expected to provide additional support to the InSight team by observing the surface of Mars in the surrounding area. If the seismometer picks up a signal, the source might be a meteorite impact. One of CaSSIS's tasks will be to help search for the impact site, which will allow the InSight team to better constrain the internal properties of Mars near the landing site.

The image of InSight also demonstrates that CaSSIS will be able to take pictures of the future ExoMars mission. The mission comprises a rover -- named Rosalind Franklin -- together with a surface science platform, and is due to be launched in July 2020, arriving at Mars in March 2021. TGO will also act as the data relay for the rover.

Science showcase

Also released today is a selection of images capturing the impressive science capabilities of CaSSIS, ranging from high-resolution views of curious surface features and images that highlight the diversity of minerals on the surface, to 3D stereo views and digital terrain models. The images have been produced by teams from the University of Bern, the University of Arizona, and INAF-Padova.

The images selected include detailed views of polar layered deposits, the dynamic nature of dunes, and the surface effects of converging dust devils. The stereo images bring the scenes alive by providing an extra insight into elevation differences, which is essential for deciphering the history in which different layers and deposits were laid down.

Colour-composite images are processed to better highlight the contrast of surface features. Combined with data from other instruments, this allows scientists to trace out regions that have been influenced by water, for example. These images can also be used to help guide surface exploration missions and provide broader regional context for landers and rovers.

"The InSight landing site image is just one of many really high quality images that we have been receiving. The ones in the ESA Gallery represent some of the best from recently. The digital terrain models also look really nice," said Nicolas Thomas.

"This stunning image showcase really demonstrates the scientific potential we have with TGO's imaging system," says Håkan Svedhem, ESA's TGO project scientist. "Over the course of the mission we'll be able to investigate dynamic surface processes, including those that might also help to constrain the atmospheric gas inventory TGO's spectrometers are analysing, as well as characterise future landing sites." ?

Support of the SERI / Swiss Space Office

CaSSIS is a project of the University of Bern and funded through the Swiss Space Office via the European Space Agency's PRODEX programme. The instrument hardware development was also supported by the Italian Space Agency (ASI), INAF/Astronomical Observatory of Padova, and the Space Research Center (CBK) in Warsaw.

It must be noted that, for all instruments developed in Switzerland and under the lead of the University of Bern, significant work and/or supplies have come from Swiss industry. The PRODEX programme under which scientific instruments or sub-systems are provided requires an industrial share of at least 50% of the overall project. This condition enables a knowledge- and technology transfer from and to industry and provides the Swiss workplace with a structural and competitive advantage -- this includes spill over effects to the non-space sector of the involved companies.

Swiss contributions to ESA programmes enable swiss scientists and industry to participate in selected missions.

Bernese space exploration: working together with the world's elite for 50 years

When viewed in terms of figures, Bernese space exploration reveals an impressive balance sheet: Instruments have flown into the upper atmosphere and ionosphere with rockets 25 times (1967-1993), into the stratosphere on balloon flights 9 times (1991-2008), 33 instruments have accompanied space probes on their missions, and a satellite has been built (CHEOPS, start of the 2nd half of 2019).

Read more at Science Daily

Tectonics in the tropics trigger Earth's ice ages

Over the last 540 million years, as the Earth's tectonic plates have shifted, MIT researchers have found that periods of major tectonic activity (orange lines) in the tropics (green belt) were likely triggers for ice ages during those same periods.

Over the last 540 million years, the Earth has weathered three major ice ages -- periods during which global temperatures plummeted, producing extensive ice sheets and glaciers that have stretched beyond the polar caps.

Now scientists at MIT, the University of California at Santa Barbara, and the University of California at Berkeley have identified the likely trigger for these ice ages.

In a study published in Science, the team reports that each of the last three major ice ages were preceded by tropical "arc-continent collisions" -- tectonic pileups that occurred near the Earth's equator, in which oceanic plates rode up over continental plates, exposing tens of thousands of kilometers of oceanic rock to a tropical environment.

The scientists say that the heat and humidity of the tropics likely triggered a chemical reaction between the rocks and the atmosphere. Specifically, the rocks' calcium and magnesium reacted with atmospheric carbon dioxide, pulling the gas out of the atmosphere and permanently sequestering it in the form of carbonates such as limestone.

Over time, the researchers say, this weathering process, occurring over millions of square kilometers, could pull enough carbon dioxide out of the atmosphere to cool temperatures globally and ultimately set off an ice age.

"We think that arc-continent collisions at low latitudes are the trigger for global cooling," says Oliver Jagoutz, an associate professor in MIT's Department of Earth, Atmospheric, and Planetary Sciences. "This could occur over 1-5 million square kilometers, which sounds like a lot. But in reality, it's a very thin strip of Earth, sitting in the right location, that can change the global climate."

Jagoutz' co-authors are Francis Macdonald and Lorraine Lisiecki of UC Santa Barbara, and Nicholas Swanson-Hysell and Yuem Park of UC Berkeley.

A tropical trigger

When an oceanic plate pushes up against a continental plate, the collision typically creates a mountain range of newly exposed rock. The fault zone along which the oceanic and continental plates collide is called a "suture." Today, certain mountain ranges such as the Himalayas contain sutures that have migrated from their original collision points, as continents have shifted over millenia.

In 2016, Jagoutz and his colleagues retraced the movements of two sutures that today make up the Himalayas. They found that both sutures stemmed from the same tectonic migration. Eighty million years ago, as the supercontinent known as Gondwana moved north, part of the landmass was crushed against Eurasia, exposing a long line of oceanic rock and creating the first suture; 50 million years ago, another collision between the supercontinents created a second suture.

The team found that both collisions occurred in tropical zones near the equator, and both preceded global atmospheric cooling events by several million years -- which is nearly instantaneous on a geologic timescale. After looking into the rates at which exposed oceanic rock, also known as ophiolites, could react with carbon dioxide in the tropics, the researchers concluded that, given their location and magnitude, both sutures could have indeed sequestered enough carbon dioxide to cool the atmosphere and trigger both ice ages.

Interestingly, they found that this process was likely responsible for ending both ice ages as well. Over millions of years, the oceanic rock that was available to react with the atmosphere eventually eroded away, replaced with new rock that took up far less carbon dioxide.

"We showed that this process can start and end glaciation," Jagoutz says. "Then we wondered, how often does that work? If our hypothesis is correct, we should find that for every time there's a cooling event, there are a lot of sutures in the tropics."

Exposing Earth's sutures

The researchers looked to see whether ice ages even further back in Earth's history were associated with similar arc-continent collisions in the tropics. They performed an extensive literature search to compile the locations of all the major suture zones on Earth today, and then used a computer simulation of plate tectonics to reconstruct the movement of these suture zones, and the Earth's continental and oceanic plates, back through time. In this way, they were able to pinpoint approximately where and when each suture originally formed, and how long each suture stretched.

They identified three periods over the last 540 million years in which major sutures, of about 10,000 kilometers in length, were formed in the tropics. Each of these periods coincided with each of three major, well-known ice ages, in the Late Ordovician (455 to 440 million years ago), the Permo-Carboniferous (335 to 280 million years ago), and the Cenozoic (35 million years ago to present day). Importantly, they found there were no ice ages or glaciation events during periods when major suture zones formed outside of the tropics.

"We found that every time there was a peak in the suture zone in the tropics, there was a glaciation event," Jagoutz says. "So every time you get, say, 10,000 kilometers of sutures in the tropics, you get an ice age."

He notes that a major suture zone, spanning about 10,000 kilometers, is still active today in Indonesia, and is possibly responsible for the Earth's current glacial period and the appearance of extensive ice sheets at the poles.

This tropical zone includes some of the largest ophiolite bodies in the world and is currently one of the most efficient regions on Earth for absorbing and sequestering carbon dioxide. As global temperatures are climbing as a result of human-derived carbon dioxide, some scientists have proposed grinding up vast quantities of ophiolites and spreading the minerals throughout the equatorial belt, in an effort to speed up this natural cooling process.

But Jagoutz says the act of grinding up and transporting these materials could produce additional, unintended carbon emissions. And it's unclear whether such measures could make any significant impact within our lifetimes.

Read more at Science Daily

With single gene insertion, blind mice regain sight

Adeno-associated viruses (AAV) engineered to target specific cells in the retina can be injected directly into the vitreous of the eye to deliver genes more precisely than can be done with wild type AAVs, which have to be injected directly under the retina. UC Berkeley neuroscientists have taken AAVs targeted to ganglion cells, loaded them with a gene for green opsin, and made the normally blind ganglion cells sensitive to light.

It was surprisingly simple. University of California, Berkeley, scientists inserted a gene for a green-light receptor into the eyes of blind mice and, a month later, they were navigating around obstacles as easily as mice with no vision problems. They were able to see motion, brightness changes over a thousandfold range and fine detail on an iPad sufficient to distinguish letters.

The researchers say that, within as little as three years, the gene therapy -- delivered via an inactivated virus -- could be tried in humans who've lost sight because of retinal degeneration, ideally giving them enough vision to move around and potentially restoring their ability to read or watch video.

"You would inject this virus into a person's eye and, a couple months later, they'd be seeing something," said Ehud Isacoff, a UC Berkeley professor of molecular and cell biology and director of the Helen Wills Neuroscience Institute. "With neurodegenerative diseases of the retina, often all people try to do is halt or slow further degeneration. But something that restores an image in a few months -- it is an amazing thing to think about."

About 170 million people worldwide live with age-related macular degeneration, which strikes one in 10 people over the age of 55, while 1.7 million people worldwide have the most common form of inherited blindness, retinitis pigmentosa, which typically leaves people blind by the age of 40.

"I have friends with no light perception, and their lifestyle is heart-wrenching," said John Flannery, a UC Berkeley professor of molecular and cell biology who is on the School of Optometry faculty. "They have to consider what sighted people take for granted. For example, every time they go to a hotel, each room layout is a little different, and they need somebody to walk them around the room while they build a 3D map in their head. Everyday objects, like a low coffee table, can be a falling hazard. The burden of disease is enormous among people with severe, disabling vision loss, and they may be the first candidates for this kind of therapy."

Currently, options for such patients are limited to an electronic eye implant hooked to a video camera that sits on a pair of glasses -- an awkward, invasive and expensive setup that produces an image on the retina that is equivalent, currently, to a few hundred pixels. Normal, sharp vision involves millions of pixels.

Correcting the genetic defect responsible for retinal degeneration is not straightforward, either, because there are more than 250 different genetic mutations responsible for retinitis pigmentosa alone. About 90 percent of these kill the retina's photoreceptor cells -- the rods, sensitive to dim light, and the cones, for daylight color perception. But retinal degeneration typically spares other layers of retinal cells, including the bipolar and the retinal ganglion cells, which can remain healthy, though insensitive to light, for decades after people become totally blind.

In their trials in mice, the UC Berkeley team succeeded in making 90 percent of ganglion cells light sensitive.

Isacoff, Flannery and their UC Berkeley colleagues will report their success in an article appearing online March 15 in Nature Communications.

'You could have done this 20 years ago'

To reverse blindness in these mice, the researchers designed a virus targeted to retinal ganglion cells and loaded it with the gene for a light-sensitive receptor, the green (medium-wavelength) cone opsin. Normally, this opsin is expressed only by cone photoreceptor cells and makes them sensitive to green-yellow light. When injected into the eye, the virus carried the gene into ganglion cells, which normally are insensitive to light, and made them light-sensitive and able to send signals to the brain that were interpreted as sight.

"To the limits that we can test the mice, you can't tell the optogenetically-treated mice's behavior from the normal mice without special equipment," Flannery said. "It remains to be seen what that translates to in a patient."

In mice, the researchers were able to deliver the opsins to most of the ganglion cells in the retina. To treat humans, they would need to inject many more virus particles because the human eye contains thousands of times more ganglion cells than the mouse eye. But the UC Berkeley team has developed the means to enhance viral delivery and hopes to insert the new light sensor into a similarly high percentage of ganglion cells, an amount equivalent to the very high pixel numbers in a camera.

Isacoff and Flannery came upon the simple fix after more than a decade of trying more complicated schemes, including inserting into surviving retinal cells combinations of genetically engineered neurotransmitter receptors and light-sensitive chemical switches. These worked, but did not achieve the sensitivity of normal vision. Opsins from microbes tested elsewhere also had lower sensitivity, requiring the use of light-amplifying goggles.

To capture the high sensitivity of natural vision, Isacoff and Flannery turned to the light receptor opsins of photoreceptor cells. Using an adeno-associated virus (AAV) that naturally infects ganglion cells, Flannery and Isacoff successfully delivered the gene for a retinal opsin into the genome of the ganglion cells. The previously blind mice acquired vision that lasted a lifetime.

"That this system works is really, really satisfying, in part because it's also very simple," Isacoff said. "Ironically, you could have done this 20 years ago."

Isacoff and Flannery are raising funds to take the gene therapy into a human trial within three years. Similar AAV delivery systems have been approved by the FDA for eye diseases in people with degenerative retinal conditions and who have no medical alternative.

It can't possibly work

According to Flannery and Isacoff, most people in the vision field would question whether opsins could work outside their specialized rod and cone photoreceptor cells. The surface of a photoreceptor is decorated with opsins -- rhodopsin in rods and red, green and blue opsins in cones -- that are embedded in a complicated molecular machine. A molecular relay -- the G-protein coupled receptor signaling cascade -- amplifies the signal so effectively that we are able to detect single photons of light. An enzyme system recharges the opsin once it has detected the photon and becomes "bleached." Feedback regulation adapts the system to very different background brightnesses. And a specialized ion channel generates a potent voltage signal. Without transplanting this entire system, it was reasonable to suspect that the opsin would not work.

But Isacoff, who specializes in G protein-coupled receptors in the nervous system, knew that many of these parts exist in all cells. He suspected that an opsin would automatically connect to the signaling system of the retinal ganglion cells. Together, he and Flannery initially tried rhodopsin, which is more sensitive to light than cone opsins.

To their delight, when rhodopsin was introduced into the ganglion cells of mice whose rods and cones had completely degenerated, and who were consequently blind, the animals regained the ability to tell dark from light -- even faint room light. But rhodopsin turned out to be too slow and failed in image and object recognition.

They then tried the green cone opsin, which responded 10 times faster than rhodopsin. Remarkably, the mice were able to distinguish parallel from horizontal lines, lines closely spaced versus widely spaced (a standard human acuity task), moving lines versus stationary lines. The restored vision was so sensitive that iPads could be used for the visual displays instead of much brighter LEDs.

"This powerfully brought the message home," Isacoff said. "After all, how wonderful it would be for blind people to regain the ability to read a standard computer monitor, communicate by video, watch a movie."

These successes made Isacoff and Flannery want to go a step farther and find out whether animals could navigate in the world with restored vision. Strikingly, here, too, the green cone opsin was a success. Mice that had been blind regained their ability to perform one of their most natural behaviors: recognizing and exploring three-dimensional objects.

They then asked the question, "What would happen if a person with restored vision went outdoors into brighter light? Would they be blinded by the light?" Here, another striking feature of the system emerged, Isacoff said: The green cone opsin signaling pathway adapts. Animals that were previously blind adjusted to the brightness change and could perform the task just as well as sighted animals. This adaptation worked over a range of about a thousandfold -- the difference, essentially, between average indoor and outdoor lighting.

"When everyone says it will never work and that you're crazy, usually that means you are onto something," Flannery said. Indeed, that something amounts to the first successful restoration of patterned vision using an LCD computer screen, the first to adapt to changes in ambient light and the first to restore natural object vision.

The UC Berkeley team is now at work testing variations on the theme that could restore color vision and further increase acuity and adaptation.

Read more at Science Daily

Study uncovers genetic switches that control process of whole-body regeneration

DNA structure

When it comes to regeneration, some animals are capable of amazing feats -- if you cut the leg off a salamander, it will grow back. When threatened, some geckos drop their tails as a distraction, and regrow them later.

Other animals take the process even further. Planarian worms, jellyfish, and sea anemones can actually regenerate their entire bodies after being cut in half.

Led by Assistant Professor of Organismic and Evolutionary Biology Mansi Srivastava, a team of researchers is shedding new light on how animals pull off the feat, and uncovered a number of DNA switches that appear to control genes for whole-body regeneration. The study is described in a March 15 paper in Science.

Using three-banded panther worms to test the process, Srivastava and Andrew Gehrke, a post-doctoral fellow working in her lab, found that a section of non-coding DNA controls the activation of a "master control gene" called early growth response, or EGR. Once active, EGR controls a number of other processes by switching other genes on or off.

"What we found is that this one master gene comes on...and that's activating genes that are turning on during regeneration," Gehrke said. "Basically, what's going on is the non-coding regions are telling the coding regions to turn on or off, so a good way to think of it is as though they are switches."

For that process to work, Gehrke said, the DNA in the worms' cells, which is normally tightly folded and compacted, has to change, making new areas available for activation.

"A lot of those very tightly packed portions of the genome actually physically become more open, because there are regulatory switches in there that have to turn genes on or off," he said. "So one of the big findings in this paper is that the genome is very dynamic and really changes during regeneration as different parts are opening and closing."

But before Gehrke and Srivastava could understand the dynamic nature of the worm's genome, they had to assemble its sequence -- no simple feat in itself.

"That's a big part of this paper -- we're releasing the genome of this species, which is important because it's the first from this phylum," Srivastava said. "Until now there had been no full genome sequence available."

And it's also noteworthy, she said, because the three banded panther worm represents a new model system for studying regeneration.

"Previous work on other species helped us learn many things about regeneration," she said. "But there are some reasons to work with these new worms, one of which is that they're in an important phylogenetic position, so the way they're related to other animals...allows us to make statements about evolution.

"The other reason is they're really great lab rats," she continued. "I collected them in the field in Bermuda a number of years ago during my post-doc, and since we've brought them into the lab they're amenable to a lot more tools than some other systems."

And while those tools can demonstrate the dynamic nature of the genome during regeneration -- Gehrke was able to identify as many as 18,000 regions that change -- what's important she said is how much meaning he was able to derive from studying them.

The results, she said, show that EGR acts like a power switch for regeneration -- once it is turned on, other processes can take place, but without it, nothing happens.

"We were able to decrease the activity of this gene and we found that if you don't have Egr, nothing happens," Srivastava said. "The animals just can't regenerate. All those downstream genes won't turn on, so the other switches don't work, and the whole house goes dark, basically."

While the study reveals new information about how the process works in worms, it also may help explain why it doesn't work in humans.

"It turns out that Egr, the master gene, and the other genes that are being turned on and off downstream are present in other species, including humans," Gehrke said.

"The reason we called this gene in the worms Egr is because when you look at its sequence, it's similar to a gene that's already been studied in humans and other animals," Srivastava said. "If you have human cells in a dish and stress them, whether it's mechanically or you put toxins on them, they'll express Egr right away.

"But the question is: If humans can turn on Egr, and not only turn it on, but do it when our cells are injured, why can't we regenerate?" Srivastava said. "The answer may be that if EGR is the power switch, we think the wiring is different. What EGR is talking to in human cells may be different than what it is talking to in the three-banded panther worm, and what Andrew has done with this study is come up with a way to get at this wiring. So we want to figure out what those connections are, and then apply that to other animals, including vertebrates that can only do more limited regeneration."

Going forward, Srivastava and Gehrke said, they hope to investigate whether the genetic switches activated during regeneration are the same as those used during development and to continue working to better understand the dynamic nature of the genome.

"Now that we know what the switches are for regeneration, we are looking at the switches involved in development, and whether they are the same," Srivastava said. "Do you just do development over again, or is a different process involved?"

The team is also working on understanding the precise ways that EGR and other genes activate the regeneration process, both for three-banded panther worms, and for other species as well.

In the end, Srivastava and Gehrke said, the study highlights the value not only in understanding the genome, but understanding all of the genome -- the non-coding as well as the coding portions.

"Only about two percent of the genome makes things like proteins," Gehrke said. "We wanted to know: What is the other 98 percent of the genome doing during whole-body regeneration? People have known for some time that many DNA changes that cause disease are in non-coding regions...but it has been underappreciated for a process like whole-body regeneration.

"I think we've only just scratched the surface," he continued. "We've looked at some of these switches, but there's a whole other aspect of how the genome is interacting on a larger scale, not just how pieces open and close, and all of that is important for turning genes on and off, so I think there are multiple layers of this regulatory nature."

"It's a very natural question to look at the natural world and think, if a gecko can do this why can't I," Srivastava said. "There are many species that can regenerate, and others that can't, but it turns out if you compare genomes across all animals, most of the genes that we have are also in the three banded panther worm...so we think that some of these answers are probably not going to come from whether or not certain genes are present, but from how they are wired or networked together, and that answer can only come from the noncoding portion of the genome."

Read more at Science Daily

Changes in rat size reveal habitat of 'Hobbit' hominin

This is a graphic image of the Liang Bua rat species used in the study.

A study of rat body sizes shifting over time gives a glimpse into the habitat of the mysterious hominin Homo floresiensis -- nicknamed the "Hobbit" due to its diminutive stature.

The Journal of Human Evolution is publishing the study, based on an analysis of thousands of rodent bones, mainly fore- and hind-limbs, from an Indonesian cave where H. floresiensis was discovered in 2003. The results indicate that the local habitat was mostly open grasslands more than 100,000 years ago, but began shifting rapidly to a more closed environment 60,000 years ago.

"Our paper is the first that we know of to use the leg bones of rats in this way to interpret ecological change through time, and it provides new evidence for the local environment during the time of Homo Floresiensis," says Elizabeth Grace Veatch, a PhD candidate at Emory University and a first author of the study.

H. floresiensis stood only about 3 feet 6 inches tall and was known to have lived about 190,000 to 50,000 years ago on the oceanic island of Flores in eastern Indonesia. The tiny hominin shared the island with animals that could have come from the pages of a Tolkien novel, including giant Komodo dragons, six-foot-tall storks, vultures with a six-foot wingspan, and pygmy Stegodons -- herbivores that looked like small elephants with swooping, oversized tusks.

It was the rats, however, that most interested Veatch.

Murids, as the rat family is known, are more taxonomically diverse than any other mammal group and are found in nearly every part of the world. "They exhibit an incredible range of behaviors occupying many different ecological niches," Veatch says. "And because small mammals are typically sensitive to ecological shifts, they can tell you a lot about what's going on in an environment."

The study was based on remains recovered from the limestone cave known as Liang Bua, where partial skeletons of H. floresiensis have been found, along with stone tools and the remains of animals -- most of them rats. In fact, out of the 275,000 animal bones identified in the cave so far, 80 percent of them are from rodents.

Veatch came to Emory to work with paleoanthropologist Jessica Thompson, a leading expert in using taphonomy -- the study of what happens to bones after an organism dies -- to learn more about the evolution of the human diet. Although Thompson has now moved to Yale University, she continues to mentor Veatch in her graduate studies at Emory.

Veatch became part of the Liang Bua project while doing an internship with the Human Origins Program of the Smithsonian Institution's National Museum of Natural History. Her mentor there was paleoanthropologist Matthew Tocheri (now with Lakehead University in Ontario) who shares first-authorship of the current paper with Veatch.

"Matthew asked me if I wanted to analyze some rat bones and I said, 'Sure,'" Veatch recalls. "I had no idea what I was getting into."

The study encompassed about 10,000 of the Liang Bua rat bones. The remains spanned five species with distinct sizes, from the mouse-sized Rattus hainaldi up to the housecat-sized Papagomys armandvillei -- commonly known as the Flores giant rat. After categorizing the bones, the researchers could then directly link them to both species and environmental types.

While rats can adjust to new environments, the morphologies of different species tend to be adaptive to their preferred environment. For example, the habitat of the medium-sized Komodomys rintjanus, included in the study, is primarily open grasslands intermittent with patches of forest. In contrast, the tiny R. hainaldi and the giant P. armandvillei both prefer more closed or semi-closed forested habitats.

Tracking the relative abundances of the different rat species over time indicated that the local ecology was mostly open grassland 100,000 years ago, transitioning to a more-closed, forested habitat around 60,000 years ago. That is around the same time that skeletal elements belonging to Homo floresiensis, the pygmy Stegodon, giant storks, vulture and Komodo dragons disappear from Liang Bua.

"The evidence suggests that Homo floresiensis may have preferred more open habitats where they may have been a part of this scavenging guild of Stegodons, storks and vultures," Veatch says. "We think that when the habitat changed, becoming more forested, Homo floresiensis probably left the Liang Bua area, tracking these animals to more open habitats elsewhere on the island."

Many more mysteries remain regarding H. floresiensis, Veatch says, and the Liang Bua rat bones may help solve some of them.

One key question is whether H. floresiensis hunted small game.

"Our early ancestors adapted to consuming large amounts of big game through hunting or scavenging -- or both," Veatch says. "Big game undoubtedly became a critical food source, resulting in numerous social and physiological adaptations, including social cooperation and brain expansion. It's much less known, however, what role small-game hunting may have played in our early evolution -- if any at all."

Liang Bua, she says, offers an ideal opportunity to study what a small-brained hominin, like H. floresiensis, might hunt if it had both sources of big game, like the Stegodon, and small game, like the giant Flores rat and other rat species.

Veatch is conducting field studies at the Liang Bua site, including running experiments to determine how difficult it would be to capture wild Flores rats. She is also doing research at the Pusat Penelitian Arkeologi Nasional (ARKENAS) Museum in the Indonesian capital of Jakarta where many of the bones from the cave site are now stored. She is analyzing a large sample of the bones to determine if any have cut marks -- indicating butchering with tools -- or pitted marks that would indicate they were digested by owls or other raptors that may have deposited them in the cave.

Read more at Science Daily

Wolves lead, dogs follow -- and both cooperate with humans

Wolves cooperate with humans, but they take the lead.

Human social life would be unthinkable without cooperation. The frequency and complexity with which humans cooperate with each other are extraordinary, if not unique. To better understand the evolution of this outstanding human skill, researchers have proposed dogs (Canis familiaris) as a good model of human cooperation.

The wolf inside dogs makes the difference

A recent study by Vetmeduni Vienna, published in the journal Scientific Reports, shows that the ability to work with people lies not so much within dogs themselves but in the "wolf within the dog" -- that is to say, in very specific behavioural characteristics that dogs share with wolves. The study tested the extent to which dogs and grey wolves collaborate with humans in order to solve certain tasks. The findings show that both dogs and wolves cooperate intensively with humans and are equally successful, although the animals attain their goals in different ways.

Wolves show more initiative

Especially in one point the two closely related animals show significantly different forms of behaviour. In their cooperation with human partners, dogs follow the behaviour of the humans while wolves lead the interaction: they are more independent. Study director Friederike Range from the Konrad Lorenz Institute at Vetmeduni Vienna says, "The detailed analysis of the cooperative interactions revealed interesting differences between wolves and dogs. It shows that, while wolves tend to initiate behaviour and take the lead, dogs are more likely to wait and see what the human partner does and follow that behaviour."

Differences in behaviour due to domestication

Based on the results of the study, the researchers propose that in the course of domestication dogs were selected for breeding because of their higher submissive tendencies (deferential behaviour hypothesis). According to this hypothesis, this helped minimize conflicts over resources and ensured the safe coexistence and cooperation in which humans lead and dogs follow.

Teamwork counts for wolves

Forming the background to the study are certain fundamental considerations in the field of behavioural science. As humans and dogs have been exposed to similar environmental pressures, this could conceivably represent a case of convergent evolution. Some research suggests that dogs acquired specific predispositions for cooperative interactions during the domestication process due to reduced aggression and increased tolerance. Against this background, better cooperation with humans would be expected in dogs than in wolves. However, wolves are a highly cooperative species, working together to raise the young, hunt and defend their territory.

Early socialization with humans is crucial

The research team led by Friederike Range therefore hypothesized that dogs did not develop any new traits during domestication, but rather that the collaborative skills of their common ancestors -- wolves -- form the basis for the evolution of dog-human cooperation (canine cooperation hypothesis). In contrast to the hypotheses of other scientists, the researchers from Vetmeduni Vienna therefore did not assume that dogs will outperform wolves when cooperating with humans. As Friederike Range says, "Based on the canine cooperation hypothesis, we expected that wolves would cooperate with humans as well as dogs if early and intensive socialization is given." The present study fully confirms this assumption.

Read more at Science Daily

Wild African ape reactions to novel camera traps

Chimpanzees (left), gorillas (center) and bonobos (right) notice novel objects in their natural environments, but react to them differently.

An international team of researchers from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, analyzed video from remote camera-trap devices placed in ape-populated forests throughout Africa to see how wild apes would react to these unfamiliar objects. Responses varied by species, and even among individuals within the same species, but one thing was consistent throughout: the apes definitely noticed the cameras.

"Our goal was to see how chimpanzees, bonobos, and gorillas react to unfamiliar objects in the wild since novel object experiments are often used in comparative psychology research, and we wanted to know if there were any differences among the three great apes," says Ammie Kalan, a primatologist at the Max Planck Institute for Evolutionary Anthropology. "We were specifically surprised by the differences in reactions we observed between the chimps and bonobos. Since they're sister species and share a lot of the same genetic makeup, we expected them to react similarly to the camera, but this wasn't the case."

"The chimpanzees were overall uninterested in the camera traps -- they barely seemed to notice their presence and were generally unbothered by them," Kalan says. "Yet the bonobos appeared to be much more troubled by camera traps; they were hesitant to approach and would actively keep their distance from them."

Individuals within a species reacted differently to the cameras as well. For example, apes living in areas with more human activity, such as near research sites, can get desensitized to unfamiliar items and become indifferent toward such encounters in the future. However, another member of the same species who has had less exposure to strange or new items, might be more interested in them. The age of the ape plays a similar role. "Younger apes would explore the camera traps more by staring at them for longer periods of time," Kalan says. "Like human children, they need to take in more information and learn about their environment. Being curious is one way of doing that."

The range of responses shown by the apes, and the complex differences both between species and within a single species, demonstrates a need for scientists to consider how animals will respond to the presence of unfamiliar monitoring equipment in their natural habitats. "The within and between species variation in behavior towards the unfamiliar items might be problematic when trying to collect accurate monitoring data," Kalan says. "To curb this effect, it would be worth having a familiarization period, where the wild animals can get used to the new items."

Read more at Science Daily

Sea otters' tool use leaves behind distinctive archaeological evidence

Wild sea otter at Bennett Slough Culverts opening mussels using emergent anvil stone.

An international team of researchers has analyzed the use by sea otters of large, shoreline rocks as "anvils" to break open shells, as well as the resulting shell middens. The researchers used ecological and archaeological approaches to identify patterns that are characteristic of sea otter use of such locations. By looking at evidence of past anvil stone use, scientists could better understand sea otter habitat use.

Sea otters are an especially captivating marine mammal, well known for their use of rocks to break open shells. Sea otters are estimated to have once numbered between 150,000-300,000 individuals and their range stretched from Baja California, Mexico, around the northern Pacific Rim to Japan. Their numbers were dramatically reduced by the fur trade. In California, the southern sea otter population was reduced to around 50 individuals, but a massive conservation effort has resulted in increasing their numbers to around 3000 today. However, the southern sea otter is still considered threatened.

Sea otters are unique for being the only marine mammal to use stone tools. They often use rocks to crack open shells while floating on their back, and also sometimes use stationary rocks along the shoreline as "anvils" to crack open mollusks, particularly mussels. A joint project including the Max Planck Institute for the Science of Human History, the Monterey Bay Aquarium and the University of California, Santa Cruz, among others, has resulted in a first-of-its-kind interdisciplinary study published in Scientific Reports, combining ten years of observations of sea otters with archaeological methods to analyze sea otter use of such anvil stones, also known as emergent anvils.

Sea otter use of anvil stones leaves distinctive wear and shell middens that are characteristic of sea otters

Researchers spent ten years between 2007-2017 observing sea otters consuming mussels at the Bennett Slough Culverts site in California. Their analysis identified that mussels were the most common prey eaten at the site and were the only prey for which the sea otters used stationary anvil stones. The sea otters used such stones for about 20% of the mussels they consumed.

Interestingly, careful analysis of the stationary anvil stones using archaeological methods showed that their use resulted in a recognizable damage pattern that was distinguishable from what would be caused by human use. For example, the sea otters preferentially struck the mussels against points and ridges on the rocks, and struck the rocks from a position in the water, rather than from the land or from on top of the rock.

Consistent damage pattern on broken mussel shells indicates probable "pawedness" in sea otters

In addition to the stones themselves, the researchers also carefully analyzed the mussel shells left around the stationary anvils. The researchers took a random sample of the shell fragments from these shell middens, which likely contained as many as 132,000 individual mussel shells. They found an extremely consistent damage pattern, with the two sides of the mussel shell still attached, but a diagonal fracture running through the right side of the shell.

"The shell breakage patterns provide a novel way to distinguish mussels broken by sea otter pounding on emergent anvils from those broken by humans or other animals," explains Natalie Uomini of the Max Planck Institute for the Science of Human History. "For archaeologists who excavate past human behavior, it is crucial to be able to distinguish the evidence of sea otter food consumption from that of humans."

In combination with analysis of videos they took of the otters using the anvils, researchers could see that the otters held the shells evenly in both paws, but when striking the shell against the anvil tended to have their right paw slightly on top. Though the total number of otters observed was small, these results suggest that otters may exhibit handedness, or "pawedness," as do humans and many other mammals.

Potential for archaeological investigations of past sea otter behavior

The researchers hope that the study will be useful for archaeologists working with coastal populations, as a way to distinguish between human and sea otter use of rocks and consumption of marine resources. Additionally, the research could be helpful in future studies of the geographic spread of stationary anvil use throughout the former sea otter range, and how far into the past this behavior extends.

"Our study suggests that stationary anvil use can be detected in locations previously inhabited by sea otters. This information could help to document past sea otter presence and diet in locations where they are currently extirpated," explains Jessica Fujii of the Monterey Bay Aquarium.

Read more at Science Daily

Secrets of early life revealed from less than half a teaspoon of blood

A global team of scientists have mapped the developmental pathway of a newborn's life for the first time. The research, published in Nature Communications, could transform our understanding of health and disease in babies.

Co-led by the MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine, the new study included lifting the lid on what genes are turned on, what proteins are being made and what metabolites are changing in the first seven days of human life.

Newborn babies are the most vulnerable population when it comes to infectious disease. Establishing key pathways in early development could help measure the impact of factors such as diet, disease and maternal health, as well as key interventions like vaccines.

The study was conducted by the Expanded Program on Immunization Consortium (EPIC) research team, which includes MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine, Boston Children's Hospital, the University of British Columbia, and the Papua New Guinea Institute of Medical Research.

The first week of a newborn's life is a time of rapid biological change as the baby adapts to living outside the womb, suddenly exposed to new bacteria and viruses, yet surprisingly little is known about these early changes. One of the biggest challenges in gathering data on newborn development has been sourcing a large enough blood sample for comprehensive profiling from a tiny newborn. The team overcame this with pioneering laboratory techniques applied on less than half a teaspoon of blood.

By using sophisticated software and new approaches they integrated different kinds of measurements to interpret the complex data derived from the precious samples. Thousands of changes over the first week of life were found including in gene expression and components involved in immunity.

Senior author Beate Kampmann, Professor of Paediatric Infection and Immunity from the London School of Hygiene & Tropical Medicine and Director of its Vaccine Centre, said: "Up to two thirds of newborn deaths can be prevented if effective health measures are provided at birth and during the first week of life. Of the 5.4 million under-five child deaths per year, about half occur during the neonatal period, i.e. the first month of life.

"Knowledge about key developmental processes during our earliest days remains sparse, but this study plugs some of those crucial gaps. This work is particularly important for vaccine research. Newborns have very limited protection from infection in early life and there is an urgent need to optimise protective measures, including vaccines, used in this age group."

Working closely with local communities, the research team recruited newborns in a health centre in The Gambia, West Africa. They took blood samples from the babies on the day of birth, and then again either on day one, three or seven.

The samples were processed in the collaborating laboratories in Africa and North America, where the researchers discovered dramatic molecular changes driven by development. The findings were then validated in a second group of Australasian newborns. The two independent cohorts were found to have common, highly dynamic developmental trajectories, suggesting that the changes do not occur at random, but instead follow an age-specific pathway.

Prof Kampmann said: "The MRC Unit in The Gambia has carried out important studies in newborns for a long time in order to optimize the use of vaccines. Given our excellent community relations and infrastructure, we were ready to partner with our collaborators to apply the new tools of systems biology to very small blood samples. We wanted to establish this work in a real world situation in order to gain insight into immune development in a setting where new interventions can have the biggest impact on newborn survival."

Ofer Levy, Director of the Precision Vaccines Program at Boston Children's Hospital and a senior author on the paper, said: "Most infections in the world occur early in life, and newborns have the greatest susceptibility and the worst outcomes. This work provides a valuable window into health and disease in the first week of life. Our exciting findings allows us to ask bigger questions about the differences between different populations and the impact of biomedical interventions such as vaccines on development.

"Currently, most vaccines are developed by trial and error. We seek deep molecular insight into vaccine function in early life so we can better develop infant vaccines for the future. We demonstrated that it's possible to recruit newborns in a resource-poor setting, obtain small amounts of their blood, process it, ship it, conduct systems biology assays and integrate the results -- turning big data into knowledge."

Going forward, the EPIC team is currently investigating the impact of different vaccines on this early developmental trajectory in a larger cohort in The Gambia and Papua New Guinea.

Read more at Science Daily

ALMA observes the formation sites of solar-system-like planets

You can see two concentric rings where planets may be forming.

Researchers have spotted the formation sites of planets around a young star resembling our Sun. Two rings of dust around the star, at distances comparable to the asteroid belt and the orbit of Neptune in our Solar System, suggest that we are witnessing the formation of a planetary system similar to our own.

The Solar System is thought to have formed from a cloud of cosmic gas and dust 4.6 billion years ago. By studying young planetary systems forming around other stars, astronomers hope to learn more about our own origins.

Tomoyuki Kudo, an astronomer at the National Astronomical Observatory of Japan (NAOJ), and his team observed the young star DM Tau using the Atacama Large Millimeter/submillimeter Array (ALMA). Located 470 light-years away in the constellation Taurus, DM Tau is about half the mass of the Sun and estimated to be three to five million years old.

"Previous observations inferred two different models for the disk around DM Tau," said Kudo. "Some studies suggested the radius of the ring is about where the Solar System's asteroid belt would be. Other observations put the size out where Neptune would be. Our ALMA observations provided a clear answer: both are right. DM Tau has two rings, one at each location."

The researchers found a bright patch in the outer ring. This indicates a local concentration of dust, which would be a possible formation site for a planet like Uranus or Neptune.

"We are also interested in seeing the details in the inner region of the disk, because the Earth formed in such an area around the young Sun," commented Jun Hashimoto, a researcher at the Astrobiology Center, Japan. "The distribution of dust in the inner ring around DM Tau will provide crucial information to understand the origin of planets like Earth."

From Science Daily

Prehistoric Britons rack up food miles for feasts near Stonehenge

Stonehenge.

Archaeologists have unearthed evidence of the earliest large-scale celebrations in Britain -- with people and animals travelling hundreds of miles for prehistoric feasting rituals.

The study, led by Dr Richard Madgwick of Cardiff University, is the most comprehensive to date and examined the bones of 131 pigs, the prime feasting animals, from four Late Neolithic (c. 2800-2400BC) complexes. Serving the world-famous monuments of Stonehenge and Avebury, the four sites -- Durrington Walls, Marden, Mount Pleasant and West Kennet Palisade Enclosures -- hosted the very first pan-British events, feasts that drew people and animals from across Britain.

The results show pig bones excavated from these sites were from animals raised as far away as Scotland, North East England and West Wales, as well as numerous other locations across the British Isles. The researchers believe it may have been important for those attending to contribute animals raised locally at their homes.

Before now, the origins of people that took part in rituals at these megalithic monuments and the extent of the population's movements at the time have been long-standing enigmas in British prehistory.

Dr Richard Madgwick, of the School of History, Archaeology and Religion, said: "This study demonstrates a scale of movement and level of social complexity not previously appreciated."

"These gatherings could be seen as the first united cultural events of our island, with people from all corners of Britain descending on the areas around Stonehenge to feast on food that had been specially reared and transported from their homes."

Representing great feats of engineering and labour mobilisation, the Neolithic henge complexes of southern Britain were the focal point for great gatherings in the third millennium BC. Pigs were the prime animal used in feasting and they provide the best indication of where the people who feasted at these sites came from as almost no human remains have been recovered.

Using isotope analysis, which identifies chemical signals from the food and water that animals have consumed, the researchers were able to determine geographical areas where the pigs were raised. The study offers the most detailed picture yet of the degree of mobility across Britain at the time of Stonehenge.

Dr Madgwick said: "Arguably the most startling finding is the efforts that participants invested in contributing pigs that they themselves had raised. Procuring them in the vicinity of the feasting sites would have been relatively easy.

"Pigs are not nearly as well-suited to movement over distance as cattle and transporting them, either slaughtered or on the hoof, over hundreds or even tens of kilometres, would have required a monumental effort.

"This suggests that prescribed contributions were required and that rules dictated that offered pigs must be raised by the feasting participants, accompanying them on their journey, rather than being acquired locally."

Read more at Science Daily

Astronomers discover 83 supermassive black holes in the early universe

Astronomers from Japan, Taiwan and Princeton University have discovered 83 quasars powered by supermassive black holes in the distant universe, from a time when the universe was less than 10 percent of its present age. In this photograph taken by the Hyper-Suprime Camera on the Subaru Telescope on Maunakea, light shines from one of the most distant quasars known, powered by a supermassive black hole lying 13.05 billion light-years away from Earth. The other objects in the field are mostly stars in our Milky Way or galaxies along the line of sight.

Astronomers from Japan, Taiwan and Princeton University have discovered 83 quasars powered by supermassive black holes in the distant universe, from a time when the universe was less than 10 percent of its present age.

"It is remarkable that such massive dense objects were able to form so soon after the Big Bang," said Michael Strauss, a professor of astrophysical sciences at Princeton University who is one of the co-authors of the study. "Understanding how black holes can form in the early universe, and just how common they are, is a challenge for our cosmological models."

This finding increases the number of black holes known at that epoch considerably, and reveals, for the first time, how common they are early in the universe's history. In addition, it provides new insight into the effect of black holes on the physical state of gas in the early universe in its first billion years. The research appears in a series of five papers published in The Astrophysical Journal and the Publications of the Astronomical Observatory of Japan.

Supermassive black holes, found at the centers of galaxies, can be millions or even billions of times more massive than the sun. While they are prevalent today, it is unclear when they first formed, and how many existed in the distant early universe. A supermassive black hole becomes visible when gas accretes onto it, causing it to shine as a "quasar." Previous studies have been sensitive only to the very rare, most luminous quasars, and thus the most massive black holes. The new discoveries probe the population of fainter quasars, powered by black holes with masses comparable to most black holes seen in the present-day universe.

The research team used data taken with a cutting-edge instrument, "Hyper Suprime-Cam" (HSC), mounted on the Subaru Telescope of the National Astronomical Observatory of Japan, which is located on the summit of Maunakea in Hawaii. HSC has a gigantic field-of-view -- 1.77 degrees across, or seven times the area of the full moon -- mounted on one of the largest telescopes in the world. The HSC team is surveying the sky over the course of 300 nights of telescope time, spread over five years.

The team selected distant quasar candidates from the sensitive HSC survey data. They then carried out an intensive observational campaign to obtain spectra of those candidates, using three telescopes: the Subaru Telescope; the Gran Telescopio Canarias on the island of La Palma in the Canaries, Spain; and the Gemini South Telescope in Chile. The survey has revealed 83 previously unknown very distant quasars. Together with 17 quasars already known in the survey region, the researchers found that there is roughly one supermassive black hole per cubic giga-light-year -- in other words, if you chunked the universe into imaginary cubes that are a billion light-years on a side, each would hold one supermassive black hole.

The sample of quasars in this study are about 13 billion light-years away from the Earth; in other words, we are seeing them as they existed 13 billion years ago. As the Big Bang took place 13.8 billion years ago, we are effectively looking back in time, seeing these quasars and supermassive black holes as they appeared only about 800 million years after the creation of the (known) universe.

It is widely accepted that the hydrogen in the universe was once neutral, but was "reionized" -- split into its component protons and electrons -- around the time when the first generation of stars, galaxies and supermassive black holes were born, in the first few hundred million years after the Big Bang. This is a milestone of cosmic history, but astronomers still don't know what provided the incredible amount of energy required to cause the reionization. A compelling hypothesis suggests that there were many more quasars in the early universe than detected previously, and it is their integrated radiation that reionized the universe.

"However, the number of quasars we observed shows that this is not the case," explained Robert Lupton, a 1985 Princeton Ph.D. alumnus who is a senior research scientist in astrophysical sciences. "The number of quasars seen is significantly less than needed to explain the reionization." Reionization was therefore caused by another energy source, most likely numerous galaxies that started to form in the young universe.

The present study was made possible by the world-leading survey ability of Subaru and HSC. "The quasars we discovered will be an interesting subject for further follow-up observations with current and future facilities," said Yoshiki Matsuoka, a former Princeton postdoctoral researcher now at Ehime University in Japan, who led the study. "We will also learn about the formation and early evolution of supermassive black holes, by comparing the measured number density and luminosity distribution with predictions from theoretical models."

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Hubble's dazzling display of 2 colliding galaxies

Located in the constellation of Hercules, about 230 million light-years away, NGC 6052 is a pair of colliding galaxies.

Located in the constellation of Hercules, about 230 million light-years away, NGC 6052 is a pair of colliding galaxies. They were first discovered in 1784 by William Herschel and were originally classified as a single irregular galaxy because of their odd shape. However, we now know that NGC 6052 actually consists of two galaxies that are in the process of colliding. This particular image of NGC 6052 was taken using the Wide Field Camera 3 on the NASA/ESA Hubble Space Telescope.

A long time ago gravity drew the two galaxies together into the chaotic state we now observe. Stars from within both of the original galaxies now follow new trajectories caused by the new gravitational effects. However, actual collisions between stars themselves are very rare as stars are very small relative to the distances between them (most of a galaxy is empty space). Eventually the galaxies will fully merge to form a single, stable galaxy.

Our own galaxy, the Milky Way, will undergo a similar collision in the future with our nearest galactic neighbor, the Andromeda galaxy. However, this is not expected to happen for around 4 billion years.

This object was previously observed by Hubble with its old Wide Field and Planetary Camera 2 (WFPC2). That image was released in 2015.

From Science Daily

Meet India's starry dwarf frog, lone member of newly discovered ancient lineage

The starry dwarf frog is an expert hider. Plunging into leaf litter at the slightest disturbance, it has successfully evaded attention for millions of years -- until now.

The thumbnail-sized species was discovered in India's Western Ghats, one of the world's "hottest" biodiversity hotspots. Scientists have named the frog Astrobatrachus kurichiyana for its constellation-like markings and the indigenous people of Kurichiyarmala, the hill range where it was found.

But A. kurichiyana is not only a new species to science. It's the sole member of an ancient lineage, a long branch on the frog tree of life that researchers have classified as a new subfamily, Astrobatrachinae.

"This is an oddball frog -- it has no close sister species for maybe tens of millions of years," said David Blackburn, the associate curator of herpetology at the Florida Museum of Natural History. "With frogs, there are still ancient lineages out there awaiting discovery. This gives us one more puzzle piece to think about deep time."

Dark brown with a bright orange underbelly and speckled with pale blue dots, the frog camouflages well in wet leaf litter, and only a few individuals have been found.

"The coloration was the first thing that stood out to me, these starry patterns with a blue tinge," said Seenapuram Palaniswamy Vijayakumar, lead author of the species description and now a postdoctoral fellow at George Washington University. "We hadn't seen anything like this before."

But the starry dwarf frog nearly got overlooked in the crush of new species that Vijayakumar and his then-doctoral supervisor Kartik Shanker were finding on a series of expeditions to the Western Ghats, a 1,000-mile-long mountain range along India's southwestern coast.

Vijayakumar and Shanker, associate professor at the Indian Institute of Science, had designed a meticulous study, covering multiple elevations, habitats and hill ranges to record and map the region's frogs, lizards and snakes.

"When we started sampling, we realized we were digging up a huge treasure," Vijayakumar said. "This was one among 30 species we captured one night, and while I took photos of it, none of us paid much attention to it."

The next morning, on a chilly, wet stroll over the grasslands -- watching the ground for leeches -- Vijayakumar spotted another of the unusually patterned frogs.

"I picked it up and said, 'Hey, this is the same guy I photographed in the night,'" he said. "As a greedy researcher, I kept it, but at that point in time, it wasn't too exciting for me. I didn't realize it would become so interesting."

Years passed before Vijayakumar and Shanker could turn their attention to the unknown frog species and assemble a research team to describe it. Alex Pyron, the Robert F. Griggs associate professor of biology at George Washington University and now Vijayakumar's adviser, analyzed the frog's genetics, and Florida Museum associate scientist Edward Stanley CT scanned the frog, revealing its skeleton and other internal features.

Thanks to CT technology, the starry dwarf frog could traverse more than 8,700 miles from Pune, India, to Blackburn's computer monitor in Gainesville, Florida, in a matter of minutes.

"I've never physically seen this species we've put all this effort into describing," Blackburn said. "Once specimens are digitized, it really doesn't matter where they are. The strengths that Ed and I could contribute to the team -- comparative anatomy -- were things we were able to do digitally."

Blackburn and Stanley could instantly compare the starry dwarf frog's bone structure to other frog species from the Western Ghats that have been imaged as part of the openVertebrate project, known as oVert, an initiative to scan 20,000 vertebrates from museum collections.

"We have this deep bench of CT data that makes collections amassed over hundreds of years instantaneously available, not just to researchers, but to anyone with a computer," Stanley said.

The team found that A. kurichiyana's closest relatives are the family Nyctibatrachidae, a group of nearly 30 species native to India and Sri Lanka. But their last common ancestor could date back tens of millions of years.

"These frogs are relics. They persisted so long. This lineage could have been knocked off at any point in time," Vijayakumar said. "Irrespective of who we are, we should be celebrating the very fact that these things exist."

Scientists have found many ancient lineages of frogs in the Western Ghats, whose biodiversity stems from its history and distinct geography. India, once part of Africa, split from Madagascar about 89 million years ago and drifted northeast, eventually colliding with the Asian mainland and giving rise to the Himalayas. But its long isolation as an island provided fertile ground for the evolution of new life forms and may have sheltered species that disappeared elsewhere. This is especially true of the Western Ghats, which is much like a network of islands, Vijayakumar said. The elevated region has been cross-sectioned into separate hill ranges by millions of years of erosion and climatic changes.

"It's a perfect scenario for cooking up new species," he said.

One question he and Blackburn are interested in exploring further is whether peninsular India's frogs are the descendants of African ancestors or whether they first originated in Asia and then moved south.

Finding ancient lineages like Astrobatrachinae can help fill in in the region's distant biological past, but the starry dwarf frog maintains many mysteries of its own. Researchers still do not know its life cycle, the sound of its call or whether the species is threatened or endangered.

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From Stone Age chips to microchips: How tiny tools may have made us human

The iconic, tear-drop shaped hand axe, which filled a human palm, required a large toolkit to produce (left), in contrast to a toolkit for tiny flakes.

Anthropologists have long made the case that tool-making is one of the key behaviors that separated our human ancestors from other primates. A new paper, however, argues that it was not tool-making that set hominins apart -- it was the miniaturization of tools.

Just as tiny transistors transformed telecommunications a few decades ago, and scientists are now challenged to make them even smaller, our Stone Age ancestors felt the urge to make tiny tools. "It's a need that we've been perennially faced with and driven by," says Justin Pargeter, an anthropologist at Emory University and lead author of the paper. "Miniaturization is the thing that we do."

The journal Evolutionary Anthropology is publishing the paper -- the first comprehensive overview of prehistoric tool miniaturization. It proposes that miniaturization is a central tendency in hominin technologies going back at least 2.6 million years.

"When other apes used stone tools, they chose to go big and stayed in the forests where they evolved," says co-author John Shea, professor of anthropology at Stony Brook University. "Hominins chose to go small, went everywhere, and transformed otherwise hostile habitats to suit our changing needs."

The paper reviews how stone flakes less than an inch in length -- used for piercing, cutting and scraping -- pop up in the archeological record at sites on every continent, going back to some of the earliest known stone tool assemblages. These small stone flakes, Pargeter says, were like the disposable razor blades or paperclips of today -- pervasive, easy to make and easily replaced.

He identifies three inflection points for miniaturization in hominin evolution. The first spike occurred around two million years ago, driven by our ancestors' increasing dependence on stone flakes in place of nails and teeth for cutting, slicing and piercing tasks. A second spike occurred sometime after 100,000 years ago with the development of high-speed weaponry, such as the bow and arrow, which required light-weight stone inserts. A third spike in miniaturization occurred about 17,000 years ago. The last Ice Age was ending, forcing some humans to adapt to rapid climate change, rising sea levels and increased population densities. These changes increased the need to conserve resources, including the rocks and minerals needed to make tools.

A native of South Africa, Pargeter co-directs field work in that country along its rugged and remote Indian Ocean coastline and nearby inland mountains. He is also a post-doctoral fellow in Emory University's Center for Mind, Brain and Culture and the Department of Anthropology's Paleolithic Technology Laboratory. The lab members actually make stone tools to better understand how our ancestors learned these skills, and how that process shaped our evolution. The lab's director, Dietrich Stout, focuses on hand axes, dating back more than 500,000 years. These larger tools are considered a turning point in human biological and cognitive evolution, due to the complexity involved in making them.

Pargeter's work on tiny tools adds another facet to the investigation of human evolution. "He's exploring what may have led to the compulsion to produce these tiny instruments -- essentially the relationship between the tools and the human body, brain and the probable uses of the tools," Stout says.

When looking for a PhD thesis topic, Pargeter first focused on collections of larger implements, considered typical of the Stone Age tool kit. He pored over artifacts from a South African site called Boomplaas that were being held in storage at the Iziko Museum in Cape Town. As he rummaged through a bag labelled as waste -- containing small flakes thought to be left over from making larger tools -- something caught his eye. A sliver of crystal quartz looked like it had been shaped using a highly technical method called pressure flaking.

"It was diminutive, about the size of a small raisin, and weighed less than half a penny," he recalls. "You could literally blow it off your finger."

Pargeter examined the flake under a magnifying glass. He noticed it had a distinctive, stair-step fracture on its tip that previous experimental research showed to be associated with damage caused in hunting.

"It suddenly occurred to me that archeologists may have missed a major component of our stone tool record," Pargeter says. "In our desire to make 'big' discoveries we may have overlooked tiny, but important, details. A whole technology could lay hidden behind our methods, relegated to bags considered waste material."

So how to interpret the use of a tool so tiny that you could easily blow it off your finger?

Pargeter began thinking of this question in terms of the age of the flake -- about 17,000 years -- and the environment at the time. The last Ice Age was ending and massive melting of ice at the poles caused the global sea-level to rise. In parts of South Africa, the rising oceans swallowed an area the size of Ireland. As the coastal marshes and grasslands disappeared -- along with much of the game and aquatic life -- the hunter-gatherers living there fled inland to sites like Boomplaas, currently located about 80 kilometers inland. The mountains around Boomplaas provided permanent springs and other dependable freshwater sources.

The climate, however, was less predictable, with sudden shifts in temperature and rainfall. Vegetation was shifting dramatically, temperatures were rising and large mammals were increasingly scarce. Archaeology from Boomplaas shows that people ate small game like hares and tortoises. These small animals would have been easy to catch, but they provided limited nutritional packages.

"These are low-reward food sources, indicating a foraging stress signal," Pargeter says. "Boomplaas might have even served as a type of refugee camp, with groups of hunter-gatherers moving away from the coast, trying to survive in marginal environments as resources rapidly depleted and climate change ratcheted up."

Arrow points a little less than an inch across were already in the archaeological literature, but the Boomplaas crystal quartz flake was half that size. In order to bring down an animal, Pargeter hypothesized, the Boomplaas flake would need poison on its tip -- derived either from plants or insects -- and a high-speed delivery system, such as a bow and arrow.

Pargeter used his own extensive knowledge of prehistoric tool-making and archaeology to hypothesize that the tiny flake could have been hafted, using a plant-based resin, onto a link shaft, also likely made of a plant-based material, such as a reed. That link shaft, about the length of a finger, would in turn fit onto a light arrow shaft.

"The link shaft goes into the animal, sacrificing the small blade, but the arrow shaft pops out so you can retain this more costly component," he says. "Our ancestors were masters of aerodynamics and acted like engineers, rather than what we think of as 'cave people.' They built redundancy into their technological systems, allowing them to easily repair their tools and to reduce the impact of errors."

Our ancestors were also connoisseurs of the type of fine-grained rocks needed for tool-making.

Supplies of such vital toolmaking raw materials, however, were likely diminished as the rising oceans consumed land and people became more crowded together, driving them to more carefully conserve what they could find on the landscape.

As paleoanthropologists are faced with more than three million years of hominin "stuff," one of the perennial questions they keep seeking to answer is, what makes us humans unique? "We've typically said that tool use makes us human, but that's kind of buckled under," Pargeter says, as evidence of tool use by other animals accumulates.

Macaques, for example, use rocks to smash apart oysters. Chimpanzees use rocks as hammers and anvils to crack nuts and they modify sticks to dig and fish for termites. These tools, however, are large. "The hands of other primates are not evolved for repeated fine manipulation in high-force tasks," Pargeter says. "We've evolved a unique precision grip that ratchets up our ability for miniaturized technology."

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