Tuesday, December 22, 2020

Melody of an Alpine summit falling apart

Seismometers listen to the resonance vibration of the Hochvogel, Allgäu

GFZ GEOFORSCHUNGSZENTRUM POTSDAM, HELMHOLTZ CENTRE

Research News

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IMAGE: ACROSS THE SUMMIT OF THE 2592-METRE-HIGH HOCHVOGEL IN THE ALLGÄU REGION OF GERMANY, A DANGEROUS CRACK IS GAPING AND GROWING. THE SOUTHERN SIDE OF THE MOUNTAIN THREATENS TO SLIDE INTO... view more 

CREDIT: TU MÜNCHEN

The entire summit of the 2592 metres high Hochvogel is sliced by a five metres wide and thirty metres long fracture. It continues to open up by up to half a centimetre per month. Throughout the years, the southern side of the mountain has already subsided by several meters; and at some point it will fail, releasing up to 260,000 cubic meters of limestone debris down into the Hornbach Valley in Austria. Such a volume would roughly correspond to 260 family houses. When this will happen is hard to predict by conventional methods. Researchers of the Helmholtz Centre Potsdam - German Research Centre for Geosciences and the Technical University of Munich have approached this question by seismic sensors. The devices record the subtle vibration of the peak: similar to a violin string which is pulled more or less does the pitch of the summit change as it becomes stressed, an effect that allows unique insight to the preparation phase of an upcoming rock slide. Thus, also a timely warning should become possible - even if human dwellings are not threatened directly at this site. The study has recently been published in the journal Earth Surface Processes and Landforms.

Rock slope failures shape the landscape

Large rock slope failures happen again and again. They play a central role in the long-term evolution of landscapes. And they are of fundamental interest in land use planning and hazard aspects. However, because they occur suddenly and then proceed at high speed, such mass movements are difficult to study. In general, it is clear that mechanical load or temperature fluctuations build up stress inside the rock, which is then released in processes of disintegration: cracks evolve on different spatial scales. At some point, the structure has become unstable enough to ultimately break apart. While the failure phase has already been well studied, there are still considerable knowledge gaps regarding their longer-term precursors. One reason is that the installation of permanent measurement equipment in high mountains is difficult and costly. The other reason is that long-term monitoring has so far often been carried out using remote sensing data or sensors that collect only point data. None of these approaches has been able to record the processes inside a rock volume at sufficient temporal and spatial detail, continuously and in a larger spatial context.

To understand when and why the instable rock mass at the Hochvogel becomes mobile, in 2018 researchers around Michael Dietze of the GFZ had deployed a network of six seismometers at the summit, each at a distance of thirty to forty meters from each other. For several months, the sensors have recorded the frequency with which the mountain swings back and forth. The vibrations are caused by wind and numerous small excitations of the Earth's surface, and the summit's frequency is determined by factors such as temperature, rock stress and material weakening.


CAPTION

Around the 5-metre-wide and 30-metre-long crack, the researchers led by Michael Dietze of the GFZ have installed a network of six seismometers, which they use to eavesdrop on the Alpine peak as it breaks.

CREDIT

TU Munich


New monitoring method with seismometers

During the summer of 2018, the researchers were able to measure a recurring sawtooth-like frequency pattern: Over a period of five to seven days, it rose repeatedly from 26 to 29 Hertz, only to drop back to its original value within less than two days. The increase in frequency is caused by stress increase within the rock mass. As the frequency drops, the sensors also recorded an increased rate of crack signals, as they are known to happen when rock is being torn apart. This cyclic increase and decrease of stress by jerky movement is also called stick slip motion. It is a typical precursor of large mass movements. The decisive factor here is that the closer this event comes, the shorter the observed cycles become, making them an important hazard indicator.

"With the help of the seismic approach, we can now for the first time sense, record and process this cyclical phenomenon continuously and almost at real time", says Michael Dietze, post-doctoral researcher in the Geomorphology Section at GFZ. He collaborates with colleagues from the Technical University of Munich in the AlpSenseBench project, which focuses on instrumentation of further Alpine peaks to study progressive rock instability evolution.

Dietze estimates that the new seismic approach is still a fair bit from becoming a routine application: "We have currently shown the proof of concept, so to speak, and now the results have to be repeated elsewhere". From a technical point of view, that shouldn't be too difficult, Dietze believes. And with the increased activity on the many more peaks in the Alps, there are also plenty of areas of application.

Outlook: Role of water and ice in the fissures

In the course of their measurements, which - with interruptions due to lightning strikes - extended from July to October, the researchers made another interesting discovery: While the sawtooth-like build-up and release of stress was clearly visible in the first few months after snow melt, it disappeared in late summer of the drought year 2018. Apparently, the summit ran short in an essential lubricant during the summer: water. By then, only a diurnal up and down of the summit's vibration frequency played a role: during the cold night hours the rock contracts, fissures become larger and the connection to the solid rock becomes less rigour, resulting in a decreasing vibration frequency. In turn, the heat of the sun lets the rock mass expand, closing small fissures and thus causing a rise of the vibration frequency.

Over a period of two more years, the researchers will now investigate how these dirurnal and longer period cycles interact and how the chilly winters will affect the deep, water filled crevices that cut the Hochvogel. This includes investigating the consequences of rock mass activity at the summit for the south facing hillslope by a larger seismic network that stretches down towards the Hornbachtal. Settlements in that valley will not be threatened by mass wasting along the slopes, but the access of the peak from this area has already been closed years ago due to an imminent rockfall risk.


CAPTION

The researchers observe a characteristic sawtooth pattern in the frequency of the mountain (top): it rises with the stress in the rock and drops again after days. In the process, seismic signals are registered (bottom), which occur when rock cracks open. If the cycles become shorter, a mass break-up is approaching. This is also a danger indicator.

CREDIT

Dietze/GFZ

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Related Instagram Story: Michael Dietze from the GFZ reports on his measurement campaign in summer 2018 https://www.instagram.com/p/CJDo2CYsRmU/


QUATUM ALCHEMY

Scientists and philosopher team up, propose a new way to categorize minerals

A diamond lasts forever, but that doesn't mean all diamonds have a common history

CARNEGIE INSTITUTION FOR SCIENCE

Research News

Washington, DC-- A diamond lasts forever, but that doesn't mean all diamonds have a common history.

Some diamonds were formed billions of years ago in space as the carbon-rich atmospheres of dying stars expanded and cooled. In our own planet's lifetime, high-temperatures and pressures in the mantle produced the diamonds that are familiar to us as gems. 5,000 years ago, a large meteorite that struck a carbon-rich sediment on Earth produced an impact diamond.

Each of these diamonds differs from the others in both composition and genesis, but all are categorized as "diamond" by the authoritative guide to minerals--the International Mineralogical Association's Commission on New Minerals, Nomenclature and Classification.

For many physical scientists, this inconsistency poses no problem. But the IMA system leaves unanswered questions for planetary scientists, geobiologists, paleontologists and others who strive to understand minerals' historical context.

So, Carnegie's Robert Hazen and Shaunna Morrison teamed up with CU Boulder philosophy of science professor Carol Cleland to propose that scientists address this shortcoming with a new "evolutionary system" of mineral classification--one that includes historical data and reflects changes in the diversity and distribution of minerals through more than 4 billion years of Earth's history.

Their work is published by the Proceedings of the National Academy of Sciences.

"We came together from the very different fields of philosophy and planetary science to see if there was a rigorous way to bring the dimension of time into discussions about the solid materials that compose Earth," Hazen said.

The IMA classification system for minerals dates to the 19th century when geologist James Dwight Dana outlined a way to categorize minerals on the basis of unique combinations of idealized compositions of major elements and geometrically idealized crystal structure.

"For example, the IMA defines quartz as pure silicon dioxide, but the existence of this idealized version is completely fictional," said Morrison. "Every specimen of quartz contains imperfections--traces of its formation process that makes it unique."

This approach to the categorization system means minerals with distinctly different historical origins are lumped together--as with the example of diamonds--while other minerals that share a common causal history are split apart.

"The IMA system is typical," said lead author Cleland, explaining that most classification systems in the natural sciences, such as the periodic table of the elements, are time independent, categorizing material things "solely on the basis of manifest similarities and differences, regardless of how they were produced or what modifications they have undergone."

For many researchers, a time-independent system is completely appropriate. But this approach doesn't work well for planetary and other historically oriented geosciences, where the emphasis is on understanding the formation and development of planetary bodies.

Differences in a diamond or quartz crystal's formative history are critical, Cleland said, because the conditions under which a sample was formed and the modifications it has undergone "are far more informative than the mere fact that a crystal qualifies as diamond or quartz."

She, Hazen, and Morrison argue that what planetary scientists need is a new system of categorizing minerals that includes historical "natural kinds."

Biology faced an analogous issue before Darwin put forward his theory of evolution. For example, lacking an understanding of how organisms are historically related through evolutionary processes, 17th century scholars debated whether bats are birds. With the advent of Darwin's work in the 19th century, however, biologists classified them separately on evolutionary grounds, because they lack a common ancestor with wings.

Because a universal theory of "mineral evolution" does not exist, creating such a classification system for the geosciences is challenging. Hazen, Morrison, and Cleland's proposed solution is what they call a "bootstrap" approach based on historically revelatory, information-rich chemical, physical, and biological attributes of solid materials. This strategy allows scientists to build a historical system of mineral kinds while remaining agnostic about its underlying theoretical principles.

"Minerals are the most durable, information-rich objects we can study to understand our planet's origin and evolution," Hazen said. "Our new evolutionary approach to classifying minerals complements the existing protocols and offers the opportunity to rigorously document Earth's history."

Morrison concurred, adding: "Rethinking the way we classify minerals offers the opportunity to address big, outstanding scientific mysteries about our planet and our Solar System, through a mineralogical lens. In their imperfections and deviations from the ideal, minerals capture the story of what has happened to them through deep time--they provide a time machine to go back and understand what was happening on our planet and other planets in our solar system millions or billions of years ago."

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The Carnegie Institution for Science (carnegiescience.edu) is a private, nonprofit organization headquartered in Washington, D.C., with three research divisions on both coasts of the U.S. Since its founding in 1902, the Carnegie Institution has been a pioneering force in basic scientific research. Carnegie scientists are leaders in plant biology, developmental biology, astronomy, materials science, global ecology, and Earth and planetary science.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Nanoplastics alter intestinal microbiome and threaten human health

NANOPLASTICS ARE SMALLER THAN MICROBEADS

UNIVERSITAT AUTONOMA DE BARCELONA

Research News

IMAGE

IMAGE: NANOPLASTICS (IN GREEN) INSIDE A ZEBRA FISH CELL view more 

CREDIT: UAB/CREAF

We live in a world invaded by plastic. Its role as a chemically stable, versatile and multi-purpose fostered its massive use, which has finally translated into our current situation of planetary pollution. Moreover, when plastic degrades it breaks into smaller micro and nanoparticles, becoming present in the water we drink, the air we breathe and almost everything we touch. That is how nanoplastics penetrate the organism and produce side effects.

A revised study led by the Universitat Autónoma de Barcelona (UAB), the CREAF and the Centre for Environmental and Marine Studies (CESAM) at the University of Aviero, Portugal, and published in the journal Science Bulletin, verifies that the nanoplastics affect the composition and diversity of our intestinal microbiome and that this can cause damage to our health. This effect can be seen in both vertebrates and invertebrates, and has been proved in situations in which the exposure is widespread and prolonged. Additionally, with alteration of the gut microbiome come alterations in the immune, endocrine and nervous system and therefore, although not enough is known about the specific physiological mechanisms, the study alerts that stress to the gut microbiome could alter the health of humans.

The health effects of being exposed to nanoplastics was traditionally evaluated in aquatic animals such as molluscs, crustaceans and fish. Recent in vitro analyses, using cell cultures of fish and mammals, has allowed scientists to analyse the changes in gene expression associated with the presence of nanoplastics from a toxicological viewpoint. The majority of neurological, endocrine and immunological tracts in these vertebrates are very similar to those of humans, and therefore authors warn that some of the effects observed in these models could also be applied to humans. Understanding and analysing the process through which these plastic fragments penetrate the organism and harm it is fundamental, as is determining precisely the amount and typology of nanoplastics polluting the environment. For this reason, researchers highlight not only the need to further study the specific mechanisms and effects on human cell models, but also unify analysis methodologies in order to conduct correct measurements of the quantity of nanoplastics present in different ecosystems.

Mariana Teles, researcher at the UAB, in collaboration with other researchers such as Josep Peñuelas, CSIC lecturer at the CREAF, comments that "this article does not aim to raise the alarm, but it does seek to warn about the fact that plastic can be found in almost everything surrounding us, it does not disintegrate and we are constantly exposed to it. At the moment, we can only speculate on the long-term effects this can have on human health, although we already have evidence in several studies describing hormonal and immune alterations in fish exposed to nanoplastics, and which could be applied to humans".

Invasive and Toxic

The study presents the main environmental sources through which nanoplastics enter the human body and summarises how they are able to penetrate the body: by ingesting them, occasionally inhaling them, and very rarely by being in contact with human skin.

Once they are ingested, up to 90% of the plastic fragments that reach the intestine are excreted. However, one part is fragmented into nanoplastics which are capable, due to their small size and molecular properties, to penetrate the cells and cause harmful effects. The study establishes that alterations in food absorption have been described, as well as inflammatory reactions in the intestinal walls, changes in the composition and functioning of the gut microbiome, effects on the body's metabolism and ability to produce, and lastly, alterations in immune responses. The article alerts about the possibility of a long-term exposure to plastic, accumulated throughout generations, could give way to unpredictable changes even in the very genome, as has been observed in some animal models.

The team in which Mariana Teles (Evolutive Immunology Group, IBB-UAB) is member also recently published a second article analysing the effects of nanoplastics in fish. The study, which is the result of Irene Brandts' PhD thesis directed by Nerea Roher, was published in Environmental Science: Nano and analyses the consequences of being exposed to nanoplastics to the immune system of a zebrafish (a small tropical fish widely used as a model organism for research). The scientists conclude that the nanoplastics can accumulate both in the cells and in the embryos of the zebrafish, additionally causing changes in the levels of genes relevant to the correct functioning of the animal's immune system. Despite this fact, the capacity of zebrafish embryos to survive a bacterial infection was not affected by the exposure to nanoplastics. The team of researchers nonetheless defend the need to continue research in this field, given that the presence of microplastics and nanoplastics in our ecosystems is an extremely crucial environmental issue which needs answers in order to understand how far-reaching any possible consequences may be.

Responsible usage

The review study acknowledges that different techniques are being tested to eliminate nanoplastics from the water, such as filtration, centrifugation and flocculation of wastewater, and the treatment of rainwater. Although the results are promising, they are limited to treating larger particles of plastics, and therefore until date no effective solution has been found for the elimination of nanoplastics from the environment.

"To solve this problem of plastic pollution, human routines must change and policies should be based on informed decisions on the known risks and available alternatives. Individual actions such as the use of more environmentally-friendly products and an increase in recycling indexes are important", Mariana Teles comments.

"The authorities can promote these pro-environmental actions through economic stimuli, such as tax benefits for reusing plastic as industrial raw material, as well as bottle deposit schemes for consumers", researchers recommend.


Under Antarctica's ice, Weddell seals produce ultrasonic vocalizations

University of Oregon-led study identifies nine types of sound outside the range of human hearing

UNIVERSITY OF OREGON

Research News

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IMAGE: UNIVERSITY OF OREGON EVOLUTIONARY BIOLOGIST PAUL CZIKO LOOKS OVER THE UNDERWATER CAMERA DURING A DIVE AT THE NATIONAL SCIENCE FOUNDATION-FUNDED MCMURDO OCEANOGRAPHIC OBSERVATORY. THE OBSERVATORY, COMPLETED IN 2017, IS LOCATED... view more 

CREDIT: PHOTO BY HENRY KAISER

EUGENE, Ore. -- Dec. 21, 2020 -- Weddell seals are chirping, whistling and trilling under Antarctica's ice at sound frequencies that are inaudible to humans, according to a research team led by University of Oregon biologists.

Two years of recordings at a live-streaming underwater observatory in McMurdo Sound have captured nine types of tonal ultrasonic seal vocalizations that reach to 50 kilohertz. Humans hear in the sonic range of 20 to 20,000 hertz, or 20 kilohertz.

The discovery is detailed in a paper published online Dec. 18 ahead of print the Journal of the Acoustical Society of America.

Weddell seals (Leptonychotes weddelii), the world's southernmost-ranging mammal, thrive under the continent's sea ice, using their large teeth to create air holes. They can dive to 600 meters in search of prey and remain submerged for 80 minutes. Researchers had first identified 34 seal call types at sonic frequencies in 1982, tying the sounds to social interactions.

The study's lead author Paul Cziko, a visiting research professor in the UO's Institute of Ecology and Evolution, began recording the seals' sonic-ranged vocalizations in 2017 after completing the installation of the McMurdo Oceanographic Observatory. Workers at McMurdo Station, he said, often fell asleep listening to broadcasts of the seals' sonic sounds coming from below.

"The Weddell seals' calls create an almost unbelievable, otherworldly soundscape under the ice," Cziko said. "It really sounds like you're in the middle of a space battle in 'Star Wars,' laser beams and all."

Over the next two years, the observatory's broadband digital hydrophone - more sensitive than equipment used in earlier recordings - picked up the higher-frequency vocalizations during passive monitoring of the seals.

"We kept coming across these ultrasonic call types in the data," said co-author Lisa Munger, a marine biologist who studies marine mammal acoustics and a career instructor in the UO's Clark Honors College. "Finally, it dawned on us that the seals were actually using them quite regularly."

The nine new call types were composed of single or multiple vocal elements having ultrasonic fundamental frequencies. Eleven elements, including chirps, whistles and trills, were above 20 kHz. Two exceeded 30 kHz and six were always above 21 kHz. One whistle reached 44.2 kHz and descending chirps in another call type began at about 49.8 kHz. Harmonics, or the overtones, of some vocalizations exceeded 200 kHz.

"It was really surprising that other researchers previously had, in effect, missed a part of the conversation," said Cziko, who earned a doctorate in evolutionary biology from the UO in 2014.

What the ultrasonic vocalizations mean in the Weddell seals' repertoire is unknown. The seals are among 33 species of fin-footed mammals grouped as pinnipeds. Until now, pinnipeds, which also include sea lions and walruses, were believed to vocalize only at sonic levels.

It could be, Cziko said, that the seals produce the sounds simply to "stand out over all the lower-frequency noise, like changing to a different channel for communicating."

Or, the researchers noted, the ultrasonic vocalizations may be used for echolocation, a biological sonar that dolphins, toothed whales and bats use to navigate in limited visibility to avoid obstacles and locate friends or prey.

"The possibility of seals using some kind of echolocation has really been discounted over the years," Cziko said. "We actually had a lot of somewhat heated discussions in our group about whether or how the seals use these ultrasonic sounds for echolocation-like behaviors."

It is not known how Weddell seals navigate and find prey during the months of near absolute darkness in the Antarctic winter. The study provides no evidence for echolocation.

"We'd like to know who is producing the ultrasonic calls -- males, females, juveniles, or all of the above," Munger said. "And how are the seals using these sounds when they're out in deeper water, looking for fish? We need to record in more places to be able to correlate sounds with behaviors."

CAPTION

Two Weddell seals relax atop the sea ice at McMurdo Sound, Antarctica. A University of Oregon-led research team has discovered that Weddell seals produce nine types of vocalizations at sound frequencies that are inaudible to humans.

CREDIT

Photo by Elliott Devries


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Nick Santos of the Center for Information Technology Research in the Interest of Society at the University of California, Merced, and John Terhune, professor emeritus at the University of New Brunswick in Saint John, Canada, were co-authors. Santos engineered the data-collection pipelines for the observatory.

The National Science Foundation primarily supported the research through a grant to Cziko and Arthur L. DeVries, professor emeritus at the University of Illinois at Urbana-Champaign who has conducted research since 1961 in Antarctica. DeVries discovered the biological antifreeze that allows fish to survive in seawater at temperatures at and just below freezing.

Related Links, including to videos and images:

McMurdo Oceanographic Observatory: https://moo-antarctica.net/

About Paul Cziko: http://www.paulcziko.net/

About Lisa Munger: https://honors.uoregon.edu/lisa-munger

UO Institute of Ecology and Evolution: https://ie2.uoregon.edu/

Opening a Window on Life Under Antarctica: https://around.uoregon.edu/antarctica

The research group's video summary of the study: https://youtu.be/jmZ8uLwyxIo

The new ultrasonic call types: https://youtu.be/bqk4nOcbxnY

Observatory recording of a seal ultrasonic call: https://youtu.be/NE-sNx1R2L4

Photos of the observatory and Weddell seals: https://www.dropbox.com/sh/nycl0muisi0xvyx/AACe36NHa5G5P_xUAkkAjD0ga?dl=0

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by c

 

CRISPR helps researchers uncover how corals adjust to warming oceans

The revolutionary, Nobel Prize-winning technology can be deployed to guide conservation efforts for fragile reef ecosystems

CARNEGIE INSTITUTION FOR SCIENCE

Research News

Baltimore, MD-- The CRISPR/Cas9 genome editing system can help scientists understand, and possibly improve, how corals respond to the environmental stresses of climate change. Work led by Phillip Cleves--who joined Carnegie's Department of Embryology this fall--details how the revolutionary, Nobel Prize-winning technology can be deployed to guide conservation efforts for fragile reef ecosystems.

Cleves' research team's findings were recently published in two papers in the Proceedings of the National Academy of Sciences.

Corals are marine invertebrates that build extensive calcium carbonate skeletons from which reefs are constructed. But this architecture is only possible because of a mutually beneficial relationship between the coral and various species of single-celled algae that live inside individual coral cells. These algae convert the Sun's energy into food using a process called photosynthesis and they share some of the nutrients they produce with their coral hosts--kind of like paying rent.

Coral reefs have great ecological, economic, and aesthetic value. Many communities depend on them for food and tourism. However, human activity is putting strain on coral reefs including warming oceans, pollution, and acidification and that affects this symbiotic relationship.

"In particular, increasing ocean temperatures can cause coral to lose their algae, a phenomenon called bleaching, because the coral takes on a ghostly white look in the absence of the algae's pigment," Cleves explained. "Without the nutrients provided by photosynthesis, the coral can die of starvation."

In 2018, Cleves headed up the team that demonstrated the first use of the CRISPR/Cas9 genome editing on coral. Now, his teams used CRISPR/Cas9 to identify a gene responsible for regulating coral's response to heat stress.

Working first in the anemone Aiptasia, one team--including Stanford University's Cory Krediet, Erik Lehnert, Masayuki Onishi, and John Pringle--identified a protein, called Heat Shock Factor 1 (HSF1), which activates many genes associated with the response to heat stress. Anemones are close coral relatives that have similar symbiotic relationships with photosynthetic algae, but they grow faster and are easier to study. These traits make Aiptasia a powerful model system to study coral biology in the lab.

Then another Cleves-led team--including Stanford University's Amanda Tinoco and John Pringle, Queensland University of Technology's Jacob Bradford and Dimitri Perrin, and Line Bay of the Australian Institute of Marine Science (AIMS)--used CRISPR/Cas9 to create mutations in the gene that encodes HSF1 in the coral Acropora millepora, demonstrating its importance for coping with a warming environment. Without a functioning HSF1 protein, the coral died rapidly when the surrounding water temperature increased.

"Understanding the genetic traits of heat tolerance of corals holds the key to understanding not only how corals will respond to climate change naturally but also balancing the benefits, opportunities and risks of novel management tools," said Bay, who is the AIMS principal research scientist and head of its Reef Recovery, Restoration and Adaptation team.

Added Cleves: "Our work further demonstrates how CRISPR/Cas9 can be used to elucidate aspects of coral physiology that can be used to guide conservation. This time we focused on one particular heat tolerance gene, but there are so many more mechanisms to reveal in order to truly understand coral biology and apply this knowledge to protecting these important communities."

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Funding for the Acropora research was provided by The Simons Foundation and the Australian Institute of Marine Science.

Coral collection was conducted under permit from GBRMPA and experimental work undertaken under the approval of the AIMS Institutional Biosafety Committee.

Funding for the Aiptasia study was provided by the Gordon and Betty Moore Foundation, the Simons Foundation, and the U.S. National Science Foundation.

This work used the Genome Sequencing Service Center of the Stanford Center for Genomics and Personalized Medicine supported by grant awards from the U.S. National Institutes of Health

The Carnegie Institution for Science (carnegiescience.edu) is a private, nonprofit organization headquartered in Washington, D.C., with three research divisions on both coasts of the U.S.. Since its founding in 1902, the Carnegie Institution has been a pioneering force in basic scientific research. Carnegie scientists are leaders in plant biology, developmental biology, astronomy, materials science, global ecology, and Earth and planetary science.

The far-reaching effects of mutagens on human health

ARIZONA STATE UNIVERSITY

Research News

IMAGE

IMAGE: MICHAEL LYNCH IS THE DIRECTOR OF THE BIODESIGN CENTER FOR MECHANISMS OF EVOLUTION AND PROFESSOR AT ASU'S SCHOOL OF LIFE SCIENCES. view more 

CREDIT: THE BIODESIGN INSTITUTE AT ARIZONA STATE UNIVERSITY

In order to survive, flourish and successfully reproduce, organisms rely on a high degree of genetic stability. Mutagenic agents, which can threaten the integrity of the genetic code by causing mutations in DNA, pose a serious risk to human health. They have long been implicated in a range of genetically inherited afflictions, as well as cancer, aging and neurodegenerative diseases like Alzheimer's.

It now appears that mutagenic threats to a cell's subtle machinery may be far more widespread than previously appreciated. In a new study, Michael Lynch and his colleagues demonstrate that DNA mutation itself may represent only a fraction the health-related havoc caused by mutagens.

The study highlights the ability of mutagenic compounds to also affect the process of transcription, during which a DNA sequence is converted (or transcribed) to mRNA, an intermediary stage preceding translation into protein.

The research findings, (which highlight mutagenic transcription errors in yeast, worms, flies and mice), suggest that the harmful effects of mutagens on transcription are likely much more pervasive than previously appreciated--a fact that may have momentous implications for human health.

"Our results have the potential to completely transform the way we think about the consequences of environmental mutagens," Lynch says.

Professor Lynch is the director of the Biodesign Center for Mechanisms in Evolution and a researcher in ASU's School of Life Sciences.

The research results appear in the current issue of the journal PNAS.

Cells under threat

Due to their important role in disease processes, mutagenic compounds have long been a topic of intensive scientific study. Such agents include sunlight and other sources of radiation, chemotherapeutics, toxic byproducts of cellular metabolism, or chemicals present in food and water.

Mutagens can inflict damage to the DNA, which can later snowball when cells divide, and DNA replication multiplies these errors. Such mutations, if not corrected through DNA proofreading mechanisms, can be passed to subsequent generations and depending on the location at which they appear along the human DNA strand's three billion letter code may seriously impact health, in some cases, with lethal results.

But even if repaired prior to replication, transiently damaged DNA can also interfere with transcription--the process of producing RNA from a DNA sequence. This can happen when RNA polymerase, an enzyme that moves along a single strand of DNA, producing a complementary RNA strand, reads a mutated sequence of DNA, causing an error in the resulting RNA transcript.

Because RNA transcripts are the templates for producing proteins, transcription errors can produce aberrant proteins harmful to health or terminate protein synthesis altogether. It is already known that even under the best of conditions, transcript error rates are orders of magnitude higher than those at the DNA level.

RNA: a string of errors?

While the existence of transcription errors has long been recognized, their quantification has been challenging. The new study describes a clever technique for ferreting out transcription errors caused by mutagens and separating these from experimental artifacts--mutations caused during library preparation of RNA transcripts through processes of reverse-transcription and sequencing.

The method described involves the use of massively parallel sequencing technology to identify only those errors in RNA sequence directly caused by the activity of a mutagen. The results demonstrate that at least some mutagenic compounds are potent sources of both genomic mutations and abundant transcription errors.

The circular sequencing assay outlined in the study creates redundancies in the reverse-transcribed message, providing a means of proofreading the resultant linear DNA. In this way, researchers can confirm that the transcription errors observed are a result of the mutagen's effects on transcription and not an artifact of sample preparation.

The DNA molecule has been shown to be particularly vulnerable to a class of mutagens known as alkylating agents. One of these, known as MNNG, was used to inflict transcriptional errors on the four study organisms. The effects observed were dose-dependent, with higher levels of mutagen causing a corresponding increase in transcriptional errors.

Hidden mistakes may be costly to health

Transcription errors differ from mutations in the genome in at least one vital respect. While DNA replication during cell division acts to amplify mutations to the genome, transcription errors can accumulate in non-dividing cells, with a single mutated DNA template giving rise to multiple abnormal RNA transcripts.

The full effects of these transcription errors on human health remain largely speculative because they have not been amenable to study until now. Using the new technique, researchers can mine the transcriptome--the full library of a living cell's RNA transcripts, searching for errors caused by mutagens.

While the new research offers hope for a more thorough understanding of the relationship between various mutagens and human health, it is also a cautionary tale. A preoccupation with mutational defects in DNA sequence may have blinded science to the potential effects of agents that result in transcription errors without leaving permanent traces in the genome.

This fact raises the possibility that a broad range of environmental factors as well as chemicals and foods deemed safe for human consumption are in need of careful reevaluation based on their potential for producing transcriptional mutagenesis. Further, transcriptional errors in both dividing and non-dividing cell types are likely key players in the complex processes of physical aging 

Beyond changing DNA itself, mutagens also cause errors in gene transcription

The discovery that toxic stressors can cause errors in gene transcription opens new avenues of research on diseases such as Alzheimer's and Parkinson's and sheds light on the potential role of the "transcriptome" in aging.

UNIVERSITY OF SOUTHERN CALIFORNIA

Research News

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IMAGE: ASSISTANT PROFESSOR MARC VERMULST view more 

CREDIT: USC/STEPHANIE KLEINMAN

Exposure to mutagens, or mutation-causing agents, can not only bring about changes in DNA but also appear to induce errors when genes are transcribed to make proteins, which may be an important factor in age-related diseases.

USC Leonard Davis School of Gerontology Assistant Professor Marc Vermulst and colleagues made the discovery by using state-of-the-art circle sequencing techniques to determine how frequently molecules called RNA polymerases make mistakes when they read (or "transcribe") our DNA. RNA polymerases transcribe DNA to make temporary copies of genes, which are then used to build all of the proteins required to keep us alive and healthy.

Transcription errors vastly outnumber DNA mutations

Vermulst compared our cells to a busy kitchen, teeming with hundreds of chefs that are all making dishes out of a single recipe book. Because it's so busy, they cannot take the recipe book with them when an order comes in. So instead they send the kitchen staff to the recipe book to read the recipes as carefully as possible and then bring the instructions to the chefs. Our cells work in a very similar manner. When an "order" for a protein comes in, RNA polymerases are sent to our genome (or in other words, our recipe book), to make a temporary copy of a gene. That temporary copy is then brought to the chefs, who cook the protein just like the message they received dictates. In this example, transcription errors could be an incorrect amount or ingredient that wasn't properly recorded by the person jotting down the recipe.

"The molecule doing the reading and writing is what's introducing the errors, even if the DNA itself isn't mutated," he explained.

To demonstrate that a mutagen - an agent that can cause a genetic mutation - can induce these errors, Vermulst and his team exposed yeast cells to the chemical N-Methyl-N?-nitro-N-nitrosoguanidine (MNNG), then screened for transcription errors. The cells exposed to MNNG displayed many more transcription errors than the unexposed cells, and in addition, the rate of transcription errors vastly outnumbered the rate of DNA mutations. The team confirmed similar results when the experiments were repeated in cells from the worm species C. elegans, fruit fly D. melanogaster and mice.

DNA mutations occur when the genome is inaccurately copied during cell division, leaving the newly formed cells with a mistake in their DNA. However, a few types of cells, including neurons and muscle cells, rarely divide in adults. These cells all still need to transcribe proteins, which means that harmful errors within these cells are much more likely to arise from transcription, Vermulst explained.

"There are a hundredfold more transcription errors being made for every DNA mutation that eventually arises," he said.

A possible role in several diseases

The genes that code for a protein not only instruct which amino acids to put in what order but also control the specific shape into which the finished protein folds itself. Transcription errors often cause proteins to misfold into a dysfunctional shape, which can result in clusters, or plaques, of nonfunctioning proteins that hinder healthy cell function. This raises questions of how these errors may play roles in diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS) and others, Vermulst said.

In future research, Vermulst is pushing for more investigation into whether other substances known to cause DNA mutations also affect transcription, as well as if there are any substances previously thought of as safe that may be in fact inducing transcription errors.

"This is potentially a really important finding in the context of genetic toxicology: a new mechanism by which all these molecules - from exposures in our environment or from our lifestyle choices - can result in pathology," he said. "There could potentially be molecules that we're eating and drinking that are deemed safe because they don't result in any genetic changes, but do result in transcription errors, that have gone completely unnoticed because nobody had a tool to see whether or not that was happening."

He also hopes that the research will make new links between established pillars of aging research - DNA damage, mitochondrial dysfunction, oxidative species and others - and connect them in a mechanistic way to detrimental outcomes such as Alzheimer's, Parkinson's and cancer. It may also help identify sources of the symptoms in DNA repair deficiency disorder, in which patients are unable to repair damage to their genome properly and often results in accelerated aging or increased cancer risk.

While recent years have seen increased interest in the "transcriptome" - the entirety of what is transcribed from a genome - Vermulst wants to focus on the accuracy of what's being transcribed and not just the amount of each protein produced. He hopes this quality-over-quantity approach offers new insight into the fundamental processes of diseases.

"If you've done the same thing a hundred times and you don't get a solution for your problem, it might be something that you've overlooked," he said. "So we're trying to find this something else."

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Vermulst's co-corresponding author for the study was Michael Lynch of Arizona State University, and first author was Clark Fritsch of the University of Pennsylvania. Other coauthors included Berenice Benayoun, Prakroothi S. Danthi, Eric McGann, Jessica LaGosh and Claire Chung of the USC Leonard Davis School; Jean-Francois Gout of Mississippi State University; Suraiya Haroon, Atif Towheed, Yuanquan Song and Douglas Wallace of the Children's Hospital of Philadelphia; Xinmin Zhang of BioInfoRx, Inc.; and Stephen Simpson and Kelley Thomas of the University of New Hampshire.

The study, "Genome-wide surveillance of transcription errors in response to genotoxic stress," appeared online in Proceedings of the National Academy of Sciences on December 21, 2020. This research was supported by the National Institute on Aging Award R01AG054641 and American Federation for Aging Research young investigator award in Alzheimer's disease to Vermulst; the Multidisciplinary University Research Initiative Awards W911NF-09-1-0444 from the US Army Research Office and NIH Award R35-GM122566-01 to Lynch; and Environmental Toxicology Training Grant T32ES019851 by the National Institute of Environmental Health Sciences to Fritsch.


Deep, slow-slip action may direct largest earthquakes and their tsunamis

PENN STATE

Research News

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IMAGE: MAP OF THE CASCADIA SUBDUCTION ZONE. view more 

CREDIT: PUBLIC DOMAIN

Megathrust earthquakes and subsequent tsunamis that originate in subduction zones like Cascadia -- Vancouver Island, Canada, to northern California -- are some of the most severe natural disasters in the world. Now a team of geoscientists thinks the key to understanding some of these destructive events may lie in the deep, gradual slow-slip behaviors beneath the subduction zones. This information might help in planning for future earthquakes in the area.

"What we found was pretty unexpected," said Kirsty A. McKenzie, doctoral candidate in geoscience, Penn State.

Unlike the bigger, shallower megathrust earthquakes that move and put out energy in the same direction as the plates move, the slow-slip earthquakes' energy may move in other directions, primarily down.

Subduction zones occur when two of the Earth's plates meet and one moves beneath the other. This typically creates a fault line and some distance away, a line of volcanoes. Cascadia is typical in that the tectonic plates meet near the Pacific coast and the Cascade Mountains, a volcanic range containing Mount St. Helens, Mount Hood and Mount Rainier, forms to the east.

According to the researchers, a megathrust earthquake of magnitude 9 occurred in Cascadia in 1700 and there has not been a large earthquake there since then. Rather, slow-slip earthquakes, events that happen deeper and move very short distances at a very slow rate, happen continuously.

"Usually, when an earthquake occurs we find that the motion is in the direction opposite to how the plates have moved, accumulating that slip deficit," said Kevin P. Furlong, professor of geosciences, Penn State. "For these slow-slip earthquakes, the direction of movement is directly downward in the direction of gravity instead of in the plate motion directions."

The researchers have found that areas in New Zealand, identified by other geologists, slow slip the same way Cascadia does.

"But there are subduction zones that don't have these slow-slip events, so we don't have direct measurements of how the deeper part of the subducting plate is moving," said Furlong. "In Sumatra, the shallower seismic zone, as expected, moves in the plate-motion direction, but even though there are no slow-slip events, the deeper plate movement still appears to be primarily controlled by gravity."

Slow-slip earthquakes occur at a deeper depth than the earthquakes that cause major damage and earth-shaking events, and the researchers have analyzed how this deep slip may affect the timing and behavior of the larger, damaging megathrust earthquakes.

"Slow-slip earthquakes rupture over several weeks, so they are not just one event," said McKenzie. "It's like a swarm of events."

According to the researchers, in southern Cascadia, the overall plate motion is about an inch of movement per year and in the north by Vancouver Island, it is about 1.5 inches.

"We don't know how much of that 30 millimeters (1 inch) per year is accumulating to be released in the next big earthquake or if some movement is taken up by some non-observable process," said McKenzie. "These slow-slip events put out signals we can see. We can observe the slow-slip events going east to west and not in the plate motion direction."

Slow-slip events in Cascadia occur every one to two years, but geologists wonder if one of them will be the one that will trigger the next megathrust earthquake.

The researchers measure surface movement using permanent, high-resolution GPS stations on the surface. The result is a stair step pattern of loading and slipping during slow-slip events. The events are visible on the surface even though geologists know they are about 22 miles beneath the surface. They report their results in Geochemistry, Geophysics, Geosystems.

"The reason we don't know all that much about slow-slip earthquakes is they were only discovered about 20 years ago," said Furlong. "It took five years to figure out what they were and then we needed precise enough GPS to actually measure the motion on the Earth's surface. Then we had to use modeling to convert the slip on the surface to the slip beneath the surface on the plate boundary itself, which is bigger."

The researchers believe that understanding the effects of slow-slip earthquakes in the region at these deeper depths will allow them to understand what might trigger the next megathrust earthquake in the area. Engineers want to know how strong shaking in an earthquake will be, but they also want to know the direction the forces will be in. If the difference in direction of slow-slip events indicates a potential change in behavior in a large event, that information would be helpful in planning.

"More fundamentally, we don't know what triggers the big earthquake in this situation," said McKenzie. "Every time we add new data about the physics of the problem, it becomes an important component. In the past, everyone thought that the events were unidirectional, but they can be different by 40 or 50 degrees."

While the slow-events in Cascadia are shedding light on potential megathrust earthquakes in the area and the tsunamis they can trigger, Furlong thinks that other subduction zones may also have similar patterns.

"I would argue that it (differences in direction of motion) is happening in Alaska, Chile, Sumatra," said Furlong. "It is only in a few that we see the evidence of it, but it may be a universal process that has been missed. Cascadia exhibits it because of the slow-slip events, but it may be fundamental to subduction zones."

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Also working on this project was Matthew W. Herman, assistant professor of geology, California State University, Bakersfield.

The National Science Foundation supported this work.