Caffeine boosts enzyme that could protect against dementia

Indiana University scientists have identified 24 compounds that increase the brain's production of the enzyme NMNAT2, which helps prevent the formation of these tangles associated with neurodegenerative disorders such as Alzheimer's disease.

A study by Indiana University researchers has identified 24 compounds -- including caffeine -- with the potential to boost an enzyme in the brain shown to protect against dementia.

The protective effect of the enzyme, called NMNAT2, was discovered last year through research conducted at IU Bloomington. The new study appears today in the journal Scientific Reports.

"This work could help advance efforts to develop drugs that increase levels of this enzyme in the brain, creating a chemical 'blockade' against the debilitating effects of neurodegenerative disorders," said Hui-Chen Lu, who led the study. Lu is a Gill Professor in the Linda and Jack Gill Center for Biomolecular Science and the Department of Psychological and Brain Sciences, a part of the IU Bloomington College of Arts and Sciences.

Previously, Lu and colleagues found that NMNAT2 plays two roles in the brain: a protective function to guard neurons from stress and a "chaperone function" to combat misfolded proteins called tau, which accumulate in the brain as "plaques" due to aging. The study was the first to reveal the "chaperone function" in the enzyme.

Misfolded proteins have been linked to neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, as well as amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig's disease. Alzheimer's disease, the most common form of these disorders, affects over 5.4 million Americans, with numbers expected to rise as the population ages.

To identify substances with the potential to affect the production of the NMNAT2 enzyme in the brain, Lu's team screened over 1,280 compounds, including existing drugs, using a method developed in her lab. A total of 24 compounds were identified as having potential to increase the production of NMNAT2 in the brain.

One of the substances shown to increase production of the enzyme was caffeine, which also has been shown to improve memory function in mice genetically modified to produce high levels of misfolded tau proteins.

Lu's earlier research found that mice altered to produce misfolded tau also produced lower levels of NMNAT2.

To confirm the effect of caffeine, IU researchers administered caffeine to mice modified to produce lower levels of NMNAT2. As a result, the mice began to produce the same levels of the enzyme as normal mice.

Another compound found to strongly boost NMNAT2 production in the brain was rolipram, an "orphaned drug" whose development as an antidepressant was discontinued in the mid-1990s. The compound remains of interest to brain researchers due to several other studies also showing evidence it could reduce the impact of tangled proteins in the brain.

Other compounds shown by the study to increase the production of NMNAT2 in the brain -- although not as strongly as caffeine or rolipram -- were ziprasidone, cantharidin, wortmannin and retinoic acid. The effect of retinoic acid could be significant since the compound derives from vitamin A, Lu said.

An additional 13 compounds were identified as having potential to lower the production of NMNAT2. Lu said these compounds are also important because understanding their role in the body could lead to new insights into how they may contribute to dementia.

Read more at Science Daily

Survival instinct, not family bonds, weave massive spider colonies together

The spiders studied for this research build webs that require a lot of silk, making the rainy conditions of the lowland tropical rainforest too adverse for them to live alone.

Spiders will live in groups if environmental conditions make it too difficult for single mothers to go it alone, new research shows.

It is rare for spiders to live in groups. The arachnids studied for this research build webs that require a lot of silk, making the rainy conditions of the lowland tropical rainforest too adverse for them to live alone. The findings dispute a long-held belief that social groups form merely so individuals can help their kin. Instead it suggests difficult environmental conditions may be the reason why some species live in cooperative social groups and others don't.

"In all species, family members are closely related, but only in some do they band together to raise each others' offspring," said Leticia Avilés, a professor of zoology at UBC and senior author of the study. "By living in groups, the spiders can occupy spaces that they wouldn't otherwise be able to, thus helping us understand why animals evolve to be social species."

Avilés pointed to other animals to support this theory including penguins who are only able to survive extreme cold and winter storms by huddling together. She said this theory could also help explain why single-celled organisms merged together to form more complicated multicellular organisms in our evolutionary history.

For this research, Avilés and graduate student Catherine Hoffman spent time in Ecuador to study Anelosimus spiders and the habitats in which they occur. At higher elevations, where conditions are mild, Anelosimus tend to live in small colonies containing a single family, whereas lower down in the rainforest, where rains are strong and predation high, they live in colonies of hundreds to thousands.

The researchers took spiders living in single-family groups from the higher elevation and transplanted them to the rainforest below to measure how predators and rainfall affected how the spiders lived. They protected some groups from ant predators and others from heavy rainfall that damages their webs. They found that it was these environmental conditions that forced spiders to form larger colonies to help one another.

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Fault system off San Diego, Orange, Los Angeles counties could produce magnitude 7.3 earthquake

In 2013, Scripps research vessel New Horizon towed a hydrophone array to map the bathymetry of the Newport-Inglewood/Rose Canyon fault zone.

A fault system that runs from San Diego to Los Angeles is capable of producing up to magnitude 7.3 earthquakes if the offshore segments rupture and a 7.4 if the southern onshore segment also ruptures, according to an analysis led by Scripps Institution of Oceanography at the University of California San Diego.

The Newport-Inglewood and Rose Canyon faults had been considered separate systems but the study shows that they are actually one continuous fault system running from San Diego Bay to Seal Beach in Orange County, then on land through the Los Angeles basin.

"This system is mostly offshore but never more than four miles from the San Diego, Orange County, and Los Angeles County coast," said study lead author Valerie Sahakian, who performed the work during her doctorate at Scripps and is now a postdoctoral fellow with the U.S. Geological Survey. "Even if you have a high 5- or low 6-magnitude earthquake, it can still have a major impact on those regions which are some of the most densely populated in California."

The study, "Seismic constraints on the architecture of the Newport-Inglewood/Rose Canyon fault: Implications for the length and magnitude of future earthquake ruptures," appears in the American Geophysical Union's Journal of Geophysical Research.

The researchers processed data from previous seismic surveys and supplemented it with high-resolution bathymetric data gathered offshore by Scripps researchers between 2006 and 2009 and seismic surveys conducted aboard former Scripps research vessels New Horizon and Melville in 2013. The disparate data have different resolution scales and depth of penetration providing a "nested survey" of the region. This nested approach allowed the scientists to define the fault architecture at an unprecedented scale and thus to create magnitude estimates with more certainty.

They identified four segments of the strike-slip fault that are broken up by what geoscientists call stepovers, points where the fault is horizontally offset. Scientists generally consider stepovers wider than three kilometers more likely to inhibit ruptures along entire faults and instead contain them to individual segments -- creating smaller earthquakes. Because the stepovers in the Newport-Inglewood/Rose Canyon (NIRC) fault are two kilometers wide or less, the Scripps-led team considers a rupture of all the offshore segments is possible, said study co-author Scripps geologist and geophysicist Neal Driscoll.

The team used two estimation methods to derive the maximum potential a rupture of the entire fault, including one onshore and offshore portions. Both methods yielded estimates between magnitude 6.7 and magnitude 7.3 to 7.4.

The fault system most famously hosted a 6.4-magnitude quake in Long Beach, Calif. that killed 115 people in 1933. Researchers have found evidence of earlier earthquakes of indeterminate size on onshore portions of the fault, finding that at the northern end of the fault system, there have been between three and five ruptures in the last 11,000 years. At the southern end, there is evidence of a quake that took place roughly 400 years ago and little significant activity for 5,000 years before that.

Driscoll has recently collected long sediment cores along the offshore portion of the fault to date previous ruptures along the offshore segments, but the work was not part of this study.

In addition to Sahakian and Driscoll, study authors include Jayne Bormann, Graham Kent, and Steve Wesnousky of the Nevada Seismological Laboratory at the University of Nevada, Reno, and Alistair Harding of Scripps. Southern California Edison funded the research at the direction of the California Energy Commission and the California Public Utilities Commission.

Read more at Science Daily

Species appears to evolve quickly enough to endure city temperatures

Acorn ants evolve quickly to adjust to living in heat-trapping cities. The capability that may prove essential to enduring other sources of rising temperatures, such as climate change.

The speed at which a tiny ant evolves to cope to its warming city environment suggests that some species may evolve quickly enough to survive, or even thrive, in the warmer temperatures found within cities, according to a new study by researchers at Case Western Reserve University.

Evolution is often thought of as a process that takes millennia, but urban acorn ants collected in Cleveland have taken no more than 100 years to adjust to their heat-trapping home of asphalt and concrete steeped with waste heat from cars and buildings -- although their tolerance to cold was reduced.

The researchers' findings are published online in the Biological Journal of the Linnean Society.

"Ants are an indicator species, and by comparing the physiologies of urban versus rural ants, we can get an idea of whether ants and other cold-blooded animals will be able to cope with the temperature changes associated with urbanization and other sources of warming like global climate change," said Sarah Diamond, assistant professor of biology at Case Western Reserve and the study's lead author.

Diamond worked with Ryan Martin, assistant professor of biology, research associates Lacy Chick and Stephanie Strickler, and PhD student Abe Perez.

Cities tend to be a couple of degrees warmer than surrounding rural areas. To determine whether animals evolve or simply adjust to added warmth, the research team collected and compared acorn ants from the city and nearby rural land.

The acorn ant (Temnothorax curvispinosus) is widespread and important for decomposing organic material in urban and rural environments across the United States. This species of ant is smaller than a cookie crumb; an entire colony of 250 can fit in a single acorn.

The researchers collected colonies from within the city of Cleveland and as far as 28 miles east from the Holden Arboretum in suburban Kirtland, Ohio, to study in Diamond's lab.

To isolate evolutionary change from short-term acclimation, groups of rural and city ants were raised in warmer city temperatures for about 10 weeks. Other groups from both locations were raised in cooler rural temperatures for 10 weeks.

Tests of thermal tolerance showed all the ants acclimated.

"They're very plastic," Martin said. "But ants collected from city habitats retained their higher heat tolerance and loss of cold tolerance compared to rural ants, regardless of whether they were born and reared under warm or cool temperatures."

Martin and Diamond believe the Cleveland ants evolved as the city became and remained highly urban during the last 100 years. Because egg-laying queen ants live from five to 15 years, the evolution to heat tolerance likely took no more than 20 generations, the researchers estimated.

With temperatures predicted to rise at least a couple of degrees Celsius over the next century, "Global data suggests that the acclimation response won't be enough to respond to climate change, but some species, like the acorn ants, may evolve quickly enough," Diamond said.

Read more at Science Daily

Study shows how skates, rays and sharks sense electrical fields

This is an Ampullary bundle with afferent nerve.

Sharks, rays and skates can hunt for prey hidden in the sandy sea floor by "listening" for faint traces of bioelectricity -- they can literally sense their prey's heart beating. The basic anatomy of the electro-sensory organs that accomplish this feat has been known for decades, but the biological mechanisms -- how electrosensory cells pick up faint electrical signs of life -- has remained a puzzle.

Now, in a new study published online in Nature, researchers at UC San Francisco have cracked the mystery of the electrosensory organ of Leucoraja erinacea, commonly called the little skate, in a series of experiments that traced the mechanisms of electrosensation all the way from genes to cell physiology to behavior.

"Skates and sharks have some of the most sensitive electroreceptors in the animal world," said David Julius, PhD, professor and chair of physiology at UCSF and senior author of the new study. "Understanding how this works is like understanding how proteins in the eye sense light -- it gives us insight into a whole new sensory world."

In their study, the researchers first isolated electrosensory cells from skate ampullary organs, which mediate electrosensation, and then performed sensitive recordings that revealed two ionic currents -- a voltage-sensitive calcium current that admits calcium ions into the cell in response to electrical disturbances and a calcium-sensitive potassium current alters the normal electrical properties of the cell. These currents interact with one another to set up an electrical oscillation in the cells' membranes that is exquisitely sensitive to outside electrical disturbances. This oscillation acts almost like an amplifier to enable the skate to detect the tiny electrical perturbations produced by the electrical field of a prey organism.

Gene expression experiments -- which required researchers to functionally annotate the skate genome -- confirmed the identity of two particular subtypes of calcium and potassium channels (called the CaV1.3 and BK channels respectively) with unique characteristics that enable skates' electrosensory perception. In one experiment, the researchers added targeted mutations to similar ion channel genes from the rat genome to make them more like the skate channels -- experiments in lab dishes showed that these changes conferred electrical properties on the rat channels that made them work like those from skate electrosensory cells.

Finally, the researchers demonstrated the behavioral importance of these channels for skate electrosensation: they placed live skates in tanks with an electrical source hidden under a layer of sand and showed that while normal skates spent much of their time orienting towards and investigating the quadrant of the tank with the hidden electrical signal, skates with these key ion channels blocked by drugs appeared unaware of the simulated meal just inches away.

The findings not only reveal new insights about how skates and sharks find their dinners, but could reveal new information about our own biology, the researchers say. Remarkably, the skate's electrosensory system is evolutionarily related to the mammalian auditory system, and there are many similarities between the skate's electrosensory organs and the "hair cells" of the inner ear responsible for sensitive hearing in mammals.

"Versions of the same ion channels with subtly different electrical properties are similarly important in our ears," said Nicholas Bellono, PhD, a postdoctoral researcher in the Julius lab and co-lead author of the new study. "So understanding exactly how small differences in these channels affect electrical function could be important for better understanding the auditory system."

Read more at Science Daily

Cold extermination: One of greatest mass extinctions was due to an ice age and not to Earth's warming

Permian-Triassic boundary in shallow marine sediments, characterised by a significant sedimentation gap between the black shales of Permian and dolomites of Triassic age. This gap documents a globally-recognised regression phase, probably linked to a period of a cold climate and glaciation.

Earth has known several mass extinctions over the course of its history. One of the most important happened at the Permian-Triassic boundary 250 million years ago. Over 95% of marine species disappeared and, up until now, scientists have linked this extinction to a significant rise in Earth temperatures. But researchers from the University of Geneva (UNIGE), Switzerland, working alongside the University of Zurich, discovered that this extinction took place during a short ice age which preceded the global climate warming. It's the first time that the various stages of a mass extinction have been accurately understood and that scientists have been able to assess the major role played by volcanic explosions in these climate processes. This research, which can be read in Scientific Reports, completely calls into question the scientific theories regarding these phenomena, founded on the increase of CO2 in the atmosphere, and paves the way for a new vision of Earth's climate history.

Teams of researchers led by Professor Urs Schaltegger from the Department of Earth and Environmental Sciences at the Faculty of Science of the UNIGE and by Hugo Bucher, from the University of Zürich, have been working on absolute dating for many years. They work on determining the age of minerals in volcanic ash, which establishes a precise and detailed chronology of Earth's climate evolution. They became interested in the Permian-Triassic boundary, 250 million years ago, during which one of the greatest mass extinctions ever took place, responsible for the loss of 95% of marine species. How did this happen? for how long marine biodiversity stayed at very low levels?

A technique founded on the radioactive decay of uranium.

Researchers worked on sediment layers in the Nanpanjiang basin in southern China. They have the particularity of being extremely well preserved, which allowed for an accurate study of the biodiversity and the climate history of the Permian and the Triassic. "We made several cross-sections of hundreds of metres of basin sediments and we determined the exact positions of ash beds contained in these marine sediments," explained Björn Baresel, first author of the study. They then applied a precise dating technique based on natural radioactive decay of uranium, as Urs Schaltegger added: "In the sedimentary cross-sections, we found layers of volcanic ash containing the mineral zircon which incorporates uranium. It has the specificity of decaying into lead over time at a well-known speed. This is why, by measuring the concentrations of uranium and lead, it was possible for us to date a sediment layer to an accuracy of 35,000 years, which is already fairly precise for periods over 250 million years." Ice is responsible for mass extinction

By dating the various sediment layers, researchers realised that the mass extinction of the Permian-Triassic boundary is represented by a gap in sedimentation, which corresponds to a period when the sea-water level decreased. The only explanation to this phenomenon is that there was ice, which stored water, and that this ice age which lasted 80,000 years was sufficient to eliminate much of marine life. Scientists from the UNIGE explain the global temperature drop by a stratospheric injection of large amounts of sulphur dioxide reducing the intensity of solar radiation reaching the surface of Earth. "We therefore have proof that the species disappeared during an ice age caused by the activity of the first volcanism in the Siberian Traps," added Urs Schaltegger. This ice age was followed by the formation of limestone deposits through bacteria, marking the return of life on Earth at more moderate temperatures. The period of intense climate warming, related to the emplacement of large amounts of basalt of the Siberian Traps and which we previously thought was responsible for the extinction of marine species, in fact happened 500,000 years after the Permian-Triassic boundary.

Read more at Science Daily

Underwater mountains help ocean water rise from abyss

A map of a seamount in the Arctic Ocean created by gathering data with a multibeam echo sounder. Researchers have found that such topographic features can trap deep waters and produce turbulence.

At high latitudes, such as near Antarctica and the Arctic Circle, the ocean's surface waters are cooled by frigid temperatures and become so dense that they sink a few thousand meters into the ocean's abyss.

Ocean waters are thought to flow along a sort of conveyor belt that transports them between the surface and the deep in a never-ending loop. However, it remains unclear where the deep waters rise to the surface, as they ultimately must. This information would help researchers estimate how long the ocean may store carbon in its deepest regions before returning it to the surface.

Now scientists from MIT, Woods Hole Oceanographic Institution (WHOI), and the University of Southampton in the U.K. have identified a mechanism by which waters may rise from the ocean's depths to its uppermost layers. Their results are published in the journal Nature Communications.

Through numerical modeling and observations in the Southern Ocean, the team found that topographic features such as seamounts, ridges, and continental margins can trap deep waters from migrating to flatter, calmer parts of the ocean. The underwater chasms and cliffs generate turbulent flows, similar to wind that whips between a city's skyscrapers. The longer water is trapped among these topographic features, the more it mixes with upper layers of the ocean, swirling its way back toward the surface.

"In the abyssal ocean, you have 4,000-meter sea mountains and very deep troughs, up and down, and these topographic features help create turbulence," says Raffaele Ferrari, the Cecil and Ida Green Professor of Oceanography in MIT's Department of Earth, Atmospheric and Planetary Sciences. "What seems to be emerging is that water comes back up from the abyss by spending a lot of time in these places where turbulence is really strong."

Knowing there are hotspots where deep waters return to the surface may help scientists identify regions where carbon, once absorbed from the atmosphere and stored deep in the ocean, rises and is released back to the atmosphere.

"The general understanding is that abyssal waters take few to several thousand years to resurface," says lead author and MIT postdoc Ali Mashayek. "If a considerable amount of such upwelling occurs rapidly along sloped boundaries, continental margins, and mid-ocean ridges, then the timescale of recycling of abyssal waters can be shorter."

Ferrari and Mashayek's co-authors are Sophia Merrifield, an MIT graduate student; Jim Ledwell and Lou St. Laurent of WHOI; and Alberto Naveira Garabato of the University of Southampton.

The power of 10 light bulbs

In cold polar regions, the amount of water that continually sinks to the deep ocean is estimated to be "about 107 cubic meters per second -- 50 times the transport of the Amazon River," Ferrari says.

In 1966, acclaimed oceanographer Walter Munk addressed the puzzle of how all this deep water returns to the surface, proposing that small-scale ocean turbulence may drive heavy, deep water to mix and rise. This turbulence, he posited, takes the form of breaking internal gravity waves that travel between water layers of different densities, below the ocean's surface.

Munk calculated the mixing power that would have to be generated by breaking internal gravity waves to bring all the ocean's deep water back up to the surface. The number, Ferrari says, is equivalent to "about 10 light bulbs per cubic kilometer of the ocean."

Since then, oceanographers have identified limited areas, such as seamounts and ridges, that create turbulence similar to what Munk theorized.

"But if you summed those few places up, you didn't seem to come up to the number you needed to bring all that water back up," Ferrari says.

Making passage

In February 2009, collaborators from WHOI deployed a tracer in the Southern Ocean, about 1,000 miles west of Drake Passage, as part of a project called DIMES (Diapycnal and Isopycnal Mixing Experiment in the Southern Ocean) to analyze the mixing of ocean waters.

"They released a blob of dye, like a drop of milk in a coffee cup, and let the ocean mix it around," Ferrari says.

Over two years, they sampled the tracer at various stations downstream from where it was released, and found that it experienced very little turbulence, or mixing, in parts of the ocean with few topographic features. However, once the tracer crossed Drake Passage, it encountered seamounts and ridges, and "all of a sudden, it started to spread in the vertical quite fast, at three times the rate predicted by Munk," Ferrari says.

What was driving this accelerated mixing? To find out, the team, led by Mashayek, developed a numerical model to simulate the Southern Ocean region -- no small task, as it was unclear whether such a model could have high enough resolution to reproduce a tracer's small-scale movements amid a vast volume of seawater.

"I did some preliminary calculations, back of the envelope estimates, and realized we would have just enough resolution to be able to do it," Mashayek recalls.

A tracer, trapped

The researchers used MIT's general circulation model -- a numerical model designed to study Earth's atmosphere, ocean, and climate -- as their framework, and programmed into it all the external forces that are known to exist in the Southern Ocean, including wind patterns, solar heating, evaporation, and precipitation. They then worked measurements from the DIMES experiment into the model and extrapolated the turbulence across the entire ocean region, given the underlying topography.

The team then placed a tracer in its model at the same location where the real tracer was released into the Southern Ocean, and observed that, indeed, it spread vertically, at the same rate that the researchers observed in the field, proving that the model was representing the real ocean's turbulence.

Looking more closely at their simulations, the researchers observed that regions with topography such as seamounts and ridges were essentially trapping the tracer for long periods of time, buffeting and mixing it vertically, before the tracer escaped and drifted through calmer waters.

The researchers believe the turbulence that occurs in these isolated regions over long periods of time may measure up to the total amount of mixing that Munk initially predicted. This mixing process may thus explain how waters in the deep ocean swell back up to the surface.

Read more at Science Daily

Martian Meteorites Could Reveal Wetter Past on the Red Planet Than Thought

In a twist for Martian meteorite studies, it turns out their mineral composition may show that the Red Planet was wet and possibly habitable in the past. It's the opposite to what researchers thought based on past examinations of meteorites, which hinted at a dry and dusty history.

The findings come from studying a synthetic version of whitlockite, a rare mineral on Earth. The research team ran shock-compression experiments to simulate the conditions that happen when a Martian sample is ejected from Mars into space; a fraction of these meteorites then make their way to Earth, where they fall on the surface and are collected.

Scientists studied the sample using X-ray experiments at Berkeley Lab's Advanced Light Source and at Argonne National Laboratory's Advanced Photon Source. Results show that the whitlockite becomes dehydrated and creates a mineral called merrillite, which has been found many times in Martian meteorites.

"If even a part of merrillite had been whitlockite before, it changes the water budget of Mars dramatically," Oliver Tschauner, co-leader of the study and a research professor in the Department of Geoscience at the University of Nevada, Las Vegas, said in a statement.

If the study proves true of actual Martian meteorites, this would help resolve a discrepancy between meteorite studies and examinations on the planet itself. While meteorite studies showed that Mars was dry, examinations by Martian rovers show abundant evidence of water. Certain minerals (such as hematite) formed in the presence of water. The Curiosity rover has also seen rounded pebbles and other evidence of ancient streambeds.

The Mojave Crater on Mars, which is believed to be the source of some Martian meteorites found on Earth, is pictured here in a rendering produced by the HIRISE camera on NASA's Mars Reconnaissance Orbiter.

From orbit, pictures have shown ancient gullies that were likely worn down by water flow, although other explanations, such as lava, have been proposed as well. In 2015, NASA announced, based on examinations by the Mars Reconnaissance Orbiter, that briny water may even flow today. Features called recurring slope lineae on Mars, which tend to appear in warmer weather, appear consistent with water flow.

Whitlockite contains phosphorous — a needed element for life on Earth — and can also dissolve in water. Since merrillite is found in so many Martian meteorites, the study suggests that habitable conditions for life on Mars were common, at least in the region from where the meteorites came.

"The only missing link now is to prove that (merrillite) had, in fact, really been Martian whitlockite before," Tschauner said. "We have to go back to the real meteorites and see if there had been traces of water."

A key limitation of the study is the origins of Martian meteorites. Many collected on Earth likely came from one region of Mars, and only during a narrow time period: 150-586 million years ago. These meteorites represent samples below the surface that were excavated when an impact on Mars sent them flying off the planet. Because these samples were buried, they are believed to indicate the Martian environment in the more ancient past.

Read more at Discovery News

Painkillers without dangerous side effects

Treating postoperative and chronic inflammatory pain should now be possible without causing side effects. Doing so would substantially improve patient quality of life.

Researchers from Charité -- Universitätsmedizin Berlin have discovered a new way of developing painkillers. The team of researchers used computational simulation to analyze interactions at opioid receptors -- the cell's docking sites for painkillers. When used in an animal model, their prototype of a morphine-like molecule was able to produce substantial pain relief in inflamed tissues. However, healthy tissues remained unaffected, suggesting that the severe side effects currently associated with these types of painkillers might be avoided. This research has been published in the current issue of the journal Science.

Opioids are a class of strong pain killers. They are mainly used to treat pain associated with tissue damage and inflammation, such as that caused by surgery, nerve damage, arthritis or cancer. Common side effects associated with their use include drowsiness, nausea, constipation and dependency and, in some cases, respiratory arrest. "By analyzing drug-opioid receptor interactions in damaged tissues, as opposed to healthy tissues, we were hoping to provide useful information for the design of new painkillers without harmful side effects," explains Prof. Dr. Christoph Stein, Head of the Department of Anesthesiology and Surgical Critical Care Medicine on Campus Benjamin Franklin. In cooperation with PD Dr. Marcus Weber from the Zuse Institute Berlin, and with the help of innovative computational simulations, the researchers were able to analyze morphine-like molecules and their interactions with opioid receptors. They were able to successfully identify a new mechanism of action, which is capable of producing pain relief only in the desired target tissues -- those affected by inflammation.

Treating postoperative and chronic inflammatory pain should now be possible without causing side effects. Doing so would substantially improve patient quality of life. The study's first authors, Dr. Viola Spahn and Dr. Giovanna Del Vecchio, explain: "In contrast to conventional opioids, our NFEPP-prototype appears to only bind to, and activate, opioid receptors in an acidic environment. This means it produces pain relief only in injured tissues, and without causing respiratory depression, drowsiness, the risk of dependency, or constipation." After designing and synthesizing the drug prototype, the researchers subjected it to experimental testing. Using computer modeling, the researchers simulated an increased concentration of protons, thereby mimicking the acidic conditions found in inflamed tissues. "We were able to show that the protonation of drugs is a key requirement for the activation of opioid receptors," conclude the authors. Their findings, which may also apply to other types of pain, may even find application in other areas of receptor research. Thereby, the benefits of improved drug efficacy and tolerability are not limited to painkillers, but may include other drugs as well.

From Science Daily

'Super-deep' diamonds may hold new information about Earth's interior

Earth's interior and the location of super-deep diamonds.

Researchers at Tohoku University believe that it is possible for natural diamonds to form at the base of Earth's mantle. The formation of such "super-deep" diamonds was simulated using high-pressure and high-temperature experiments by the Japanese research team, led by Fumiya Maeda.

Diamonds are evidence that carbon exists deep in Earth. Most natural diamonds are formed around the depth of 200km. But it's been suggested that some extremely rare diamonds come from as deep as 400km. Such diamonds are called "super-deep" diamonds, and researchers are hoping that they may offer new clues about the deep interior of Earth.

This is because natural diamonds often contain mineral inclusions in their crystals, and these inclusions can reveal the conditions of the environment where the diamonds were formed. The hardness of the diamonds also make them good capsules as they can protect the inclusions from contamination or breakdown when they are brought to Earth's surface.

Although super-deep diamonds can provide good samples to help understand Earth's deep interior, researchers say they are still uncertain of the real depth and the formation process of these diamonds.

Results of their experiment show that super-deep diamonds can form through the reaction of Mg-carbonate and silica minerals. The reaction may occur in cold plates which descend all the way to the base of the mantle.

Details of actual diamond formation in such a deep part of Earth has so far, never been reported. But researchers plan to combine their recent experimental model with observation and analysis, in the hopes of getting information from natural diamonds that would provide further knowledge about our planet.

This study was published in Nature Publishing Group's Scientific Reports.

From Science Daily