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Scientists find molecular patterns that may help identify extraterrestrial life

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Upcoming Solar System exploration missions will search for extraterrestrial (ET) life, but ET life may not be like Earth life; a new mass spectrometry analysis technique may allow for process-based ways to find ET life that is compositionally alien

Scientists have begun the search for extraterrestrial life in the Solar System in earnest, but such life may be subtly or profoundly different from Earth-life, and methods based on detecting particular molecules as biosignatures may not apply to life with a different evolutionary history. A new study by a joint Japan/US-based team, led by researchers at the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology, has developed a machine learning technique which assesses complex organic mixtures using mass spectrometry to reliably classify them as biological or abiological.

In season 1, episode 29 (“Operation: Annihilate!”) of Star Trek, which aired in 1966, the human-Vulcan hybrid character Spock made the observation “It is not life as we know or understand it. Yet it is obviously alive; it exists.” This now 55-year old pop-culture meme still makes a point: how can we detect life if we fundamentally don’t know what life is, and if that life is really different from life as we know it?

The question of “Are we alone?” as living beings in the Universe has fascinated humanity for centuries, and humankind has been looking for ET life in the Solar System since NASA’s Viking 2 mission to Mars in 1976. There are presently numerous ways scientists are searching for ET life. These include listening for radio signals from advanced civilisations in deep space, looking for subtle differences in the atmospheric composition of planets around other stars, and directly trying to measure it in soil and ice samples they can collect using spacecraft in our own Solar System. This last category allows them to bring their most advanced chemical analytical instrumentation directly to bear on ET samples, and perhaps even bring some of the samples back to Earth, where they can be carefully scrutinised.

Exciting missions such as NASA’s Perseverance rover will look for life this year on Mars; NASA’s Europa Clipper, launching in 2024, will try to sample ice ejected from Jupiter’s moon Europa, and its Dragonfly mission will attempt to land an “octacopter” on Saturn’s moon Titan starting in 2027. These missions will all attempt to answer the question of whether we are alone.

Mass spectrometry (MS) is a principal technique that scientists will rely on in spacecraft-based searches for ET life. MS has the advantage that it can simultaneously measure multitudes of compounds present in samples, and thus provide a sort of “fingerprint” of the composition of the sample. Nevertheless, interpreting those fingerprints may be tricky.

As best as scientists can tell, all life on Earth is based on the same highly coordinated molecular principles, which gives scientists confidence that all Earth-life is derived from a common ancient terrestrial ancestor. However, in simulations of the primitive processes that scientists believe may have contributed to life’s origins on Earth, many similar but slightly different versions of the particular molecules terrestrial life uses are often detected. Furthermore, naturally occurring chemical processes are also able to produce many of the building blocks of biological molecules. Since we still have no known sample of alien life, this leaves scientists with a conceptual paradox: did Earth-life make some arbitrary choices early in evolution which got locked in, and thus life could be constructed otherwise, or should we expect that all life everywhere is constrained to be exactly the same way it is on Earth? How can we know that the detection of a particular molecule type is indicative of whether it was or was not produced by ET life?

It has long troubled scientists that biases in how we think life should be detectable, which are largely based on how Earth-life is presently, might cause our detection methods to fail. Viking 2 in fact returned odd results from Mars in 1976. Some of the tests it conducted gave signals considered positive for life, but the MS measurements provided no evidence for life as we know it. More recent MS data from NASA’s Mars Curiosity rover suggest there are organic compounds on Mars, but they still do not provide evidence for life. A related problem has plagued scientists attempting to detect the earliest evidence for life on Earth: how can we tell if signals detected in ancient terrestrial samples are from the original living organisms preserved in those samples or derived from contamination from the organisms which presently pervade our planet?

Scientists at the Earth-Life Science Institute at the Tokyo Institute of Technology in Japan and the National High Magnetic Field Laboratory (The National MagLab) in the US decided to address this problem using a combined experimental and machine learning computational approach. The National MagLab is supported by the US National Science Foundation through NSF/ DMR-1644779 and the State of Florida to provide cutting-edge technologies for research. Using ultrahigh-resolution MS (a technique known as Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry (or FT-ICR MS)) they measured the mass spectra of a wide variety of complex organic mixtures, including those derived from abiological samples made in the lab (which they are fairly certain are not living), organic mixtures found in meteorites (which are ~ 4.5 billion-year-old samples of abiologically produced organic compounds which appear to have never become living), laboratory-grown microorganisms (which fit all the modern criteria of being living, including novel microbial organisms isolated and cultured by ELSI co-author Tomohiro Mochizuki), and unprocessed petroleum (or raw natural crude oil, the kind we pump out of the ground and process into gasoline, which is derived from organisms which lived long ago on Earth, providing an example of how the “fingerprint” of known living organisms might change over geological time). These samples each contained tens of thousands of discrete molecular compounds, which provided a large set of MS spectra that could be compared and classified.

In contrast to approaches that use the accuracy of MS measurements to uniquely identify each peak with a particular molecule in a complex organic mixture, the researchers instead aggregated their data and looked at the broad statistics and distribution of signals. Complex organic mixtures, such as those derived from living things, petroleum, and abiological samples present very different “fingerprints” when viewed in this way. Such patterns are much more difficult for a human to detect than the presence or absence of individual molecule types.

The researchers fed their raw data into a computer machine learning algorithm and surprisingly found that the algorithms were able to accurately classify the samples as living or non-living with ~95% accuracy. Importantly, they did so after simplifying the raw data considerably, making it plausible that lower-precision instruments, spacecraft-based instruments are often low power, could obtain data of sufficient resolution to enable the biological classification accuracy the team obtained.

The underlying reasons this classification accuracy is possible to remain to be explored, but the team suggests it is because of the ways biological processes, which modify organic compounds differently than abiological processes, relate to the processes which enable life to propagate itself. Living processes have to make copies of themselves, while abiological processes have no internal process controlling this.

“This work opens many exciting avenues for using ultra-high resolution mass spectrometry for astrobiological applications,” says co-author Huan Chen of the US National MagLab.

Lead author Nicholas Guttenberg adds, “While it is difficult if not impossible to characterise every peak in a complex chemical mixture, the broad distribution of components can contain patterns and relationships which are informative about the process by which that mixture came about or developed. If we’re going to understand complex prebiotic chemistry, we need ways of thinking in terms of these broad patterns – how they come about, what they imply, and how they change – rather than the presence or absence of individual molecules. This paper is an initial investigation into the feasibility and methods of characterisation at that level and shows that even discarding high-precision mass measurements, there is significant information in peak distribution that can be used to identify samples by the type of process that produced them.”

Co-author Jim Cleaves of ELSI adds, “This sort of relational analysis may offer broad advantages for searching for life in the Solar System, and perhaps even in laboratory experiments designed to recreate the origins of life.” The team plans to follow up with further studies to understand exactly what aspects of this type of data analysis allows for such successful classification.

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Reference:

Nicholas Guttenberg1,2,3, Huan Chen4, Tomohiro Mochizuki1, H. James Cleaves II1,5,6,*, Classification of the Biogenicity of Complex Organic Mixtures for the Detection of Extraterrestrial Life, Life, DOI: 10.3390/life11030234

1. Earth-Life Science Institute, Tokyo Institute of Technology, Ookayama, Tokyo 152-8550, Japan

2. Cross Labs, Cross Compass Ltd., 2-9-11-9F Shinkawa, Chuo-ku, Tokyo 104-0033, Japan

3. GoodAI, Na Petynce 213/23b, 169 00 Prague, Czech Republic

4. National High Magnetic Field Laboratory, Florida State University, 1800 East Paul Dirac Drive,
Tallahassee, FL 32310-4005, USA

5. Institute for Advanced Study, 1 Einstein Drive, Princeton, NJ 08540, USA

6. Blue Marble Space Institute of Science, Seattle, WA 98104, USA

More information:

Tokyo Institute of Technology (Tokyo Tech) stands at the forefront of research and higher education as the leading university for science and technology in Japan. Tokyo Tech researchers excel in fields ranging from materials science to biology, computer science, and physics. Founded in 1881, Tokyo Tech hosts over 10,000 undergraduate and graduate students per year, who develop into scientific leaders and some of the most sought-after engineers in industry. Embodying the Japanese philosophy of “monotsukuri,” meaning “technical ingenuity and innovation,” the Tokyo Tech community strives to contribute to society through high-impact research.

The Earth-Life Science Institute (ELSI) is one of Japan’s ambitious World Premiere International research centers, whose aim is to achieve progress in broadly inter-disciplinary scientific areas by inspiring the world’s greatest minds to come to Japan and collaborate on the most challenging scientific problems. ELSI’s primary aim is to address the origin and co-evolution of the Earth and life.

The World Premier International Research Center Initiative (WPI) was launched in 2007 by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to help build globally visible research centers in Japan. These institutes promote high research standards and outstanding research environments that attract frontline researchers from around the world. These centers are highly autonomous, allowing them to revolutionise conventional modes of research operation and administration in Japan.

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Source: https://bioengineer.org/scientists-find-molecular-patterns-that-may-help-identify-extraterrestrial-life/

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Researchers discover unique ‘spider web’ mechanism that traps, kills viruses

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Immunologists at McMaster University have discovered a previously unknown mechanism which acts like a spider web, trapping and killing pathogens such as influenza or SARS-CoV-2, the virus responsible for COVID-19.

The researchers have found that neutrophils, the most abundant white blood cells in the human body, explode when they bind to such pathogens coated in antibodies and release DNA outside of the cell, creating a sticky tangle which acts as a trap.

The findings, published online in the Proceedings of the National Academy of Science, are significant because little is understood about how antibodies neutralize viruses in the respiratory tract.

The discovery has implications for vaccine design and delivery, including aerosol and nasal spray technologies that could help the body head off infections before they have a chance to take hold.

“Vaccines can produce these antibodies that are present in our lungs, which are the first type of antibody to see viruses like flu or COVID-19, which infect our lungs and respiratory tracts,” says the study’s lead author Matthew Miller, an associate professor at McMaster’s Michael G. DeGroote Institute for Infectious Disease Research and Canada’s Global Nexus for Pandemics and Biological Threats. “Mechanisms that can stop the infection at the site where it enters our body can prevent the spread and serious complications.”

By comparison, injectable vaccines are designed to bolster antibodies in the blood, but those antibodies are not as prevalent at the sites where infection begins.

“We should be thinking carefully about next generation COVID-19 vaccines that could be administered in the respiratory tract to stimulate antibodies. We don’t have many candidates right now that are focused on raising the mucosal response,” says Hannah Stacey, a graduate student in the Miller Lab and lead author of the paper, who recently won a major national scholarship from the Canadian Society for Virology for her work on COVID-19.

“If you want a lot of these antibodies that are really abundant in blood, then injections make the most sense, but if you want antibodies that are abundant in the respiratory tract, then a spray or an aerosol makes sense,” she says.

Researchers caution that while the body’s spider-web mechanism has the potential to be hugely beneficial, it can cause harm too, including inflammation and further illness when the web formation is uncontrollable.

They point to the early waves of the pandemic, prior to vaccinations, when these NETs, or neutrophil extracellular traps, were found in some patients’ lungs, and had made their breathing more difficult.

“An immune response that is meant to protect you can end up harming you if it’s not properly controlled,” says Miller. “It’s important to understand the balance of the immune system. If you have a lot of these antibodies before you get infected, they are likely going to protect you, but if the infection itself stimulates a lot of those antibodies it might be harmful.”

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Source: https://bioengineer.org/researchers-discover-unique-spider-web-mechanism-that-traps-kills-viruses/

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Making seawater drinkable in minutes

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According to the World Health Organization, about 785 million people around the world lack a clean source of drinking water. Despite the vast amount of water on Earth, most of it is seawater and freshwater accounts for only about 2.5% of the total. One of the ways to provide clean drinking water is to desalinate seawater. The Korea Institute of Civil Engineering and Building Technology (KICT) has announced the development of a stable performance electrospun nanofiber membrane to turn seawater into drinking water by membrane distillation process.

Membrane wetting is the most challenging issue in membrane distillation. If a membrane exhibits wetting during membrane distillation operation, the membrane must be replaced. Progressive membrane wetting has been especially observed for long-term operations. If a membrane gets fully wetted, the membrane leads to inefficient membrane distillation performance, as the feed flow through the membrane leading to low-quality permeate.

A research team in KICT, led by Dr. Yunchul Woo, has developed co-axial electrospun nanofiber membranes fabricated by an alternative nano-technology, which is electrospinning. This new desalination technology shows it has the potential to help solve the world’s freshwater shortage. The developed technology can prevent wetting issues and also improve the long-term stability in membrane distillation process. A three-dimensional hierarchical structure should be formed by the nanofibers in the membranes for higher surface roughness and hence better hydrophobicity.

The co-axial electrospinning technique is one of the most favorable and simple options to fabricate membranes with three-dimensional hierarchical structures. Dr. Woo’s research team used poly(vinylidene fluoride-co-hexafluoropropylene) as the core and silica aerogel mixed with a low concentration of the polymer as the sheath to produce a co-axial composite membrane and obtain a superhydrophobic membrane surface. In fact, silica aerogel exhibited a much lower thermal conductivity compared with that of conventional polymers, which led to increased water vapor flux during the membrane distillation process due to a reduction of conductive heat losses.

Most of the studies using electrospun nanofiber membranes in membrane distillation applications operated for less than 50 hours although they exhibited a high water vapor flux performance. On the contrary, Dr. Woo’s research team applied the membrane distillation process using the fabricated co-axial electrospun nanofiber membrane for 30 days, which is 1 month.

The co-axial electrospun nanofiber membrane performed a 99.99% salt rejection for 1 month. Based on the results, the membrane operated well without wetting and fouling issues, due to its low sliding angle and thermal conductivity properties. Temperature polarization is one of the significant drawbacks in membrane distillation. It can decrease water vapor flux performance during membrane distillation operation due to conductive heat losses. The membrane is suitable for long-term membrane distillation applications as it possesses several important characteristics such as, low sliding angle, low thermal conductivity, avoiding temperature polarization, and reduced wetting and fouling problems whilst maintaining super-saturated high water vapor flux performance.

Dr. Woo’s research team noted that it is more important to have a stable process than a high water vapor flux performance in a commercially available membrane distillation process. Dr. Woo said that “the co-axial electrospun nanofiber membrane have strong potential for the treatment of seawater solutions without suffering from wetting issues and may be the appropriate membrane for pilot-scale and real-scale membrane distillation applications.”

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The Korea Institute of Civil Engineering and Building Technology (KICT) is a government sponsored research institute established to contribute to the development of Korea’s construction industry and national economic growth by developing source and practical technology in the fields of construction and national land management.

This research was supported by an internal grant (20200543-001) from the KICT, Republic of Korea. The outcomes of this project were published in the international journal, Journal of Membrane Science, a renowned international journal in the polymer science field (IF: 7.183 and Rank #3 of the JCR category) in April 2021.

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Source: https://bioengineer.org/making-seawater-drinkable-in-minutes/

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McIndoe leading $6.2 million innovative research initiative

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Dr. Richard A. McIndoe, bioinformatics expert and associate director of the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia, is leading a dynamic, new $6.2 million federally funded initiative to support highly innovative research ideas in three areas with tremendous impact on health.

This Innovative Science Accelerator, or ISAC, program establishes an expedited but still extensive review process that will enable scientists to pursue some of their most innovative research ideas in diseases of the kidneys; the urinary tract in both sexes as well as the male reproductive organs; and the blood and bone marrow.

“The idea is that ISAC will provide seed funds to investigators who have high-risk, high-reward ideas, and they will get one year of money to try to figure out if their idea is going to work. If it works, they will be able to use the data they generate to apply for a larger grant,” says McIndoe, who wants the new program to be as innovative as the ideas scientists bring to it.

The five-year initiative is a new program of the Division of Kidney, Urologic and Hematologic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

The goal is to move science forward that matters to people’s lives, and the opportunities include giving particularly new scientists experience writing grants, going through the review process and generating findings, McIndoe says.

ISAC will provide scientists an efficient path to secure a one-time $100,000 grant that should ease application for a larger, traditional NIH grant, the gold standard for biomedical research in the U.S., or conversely to acknowledge that their idea does not merit additional pursuit.

Another primary function of ISAC is to host an annual scientific meeting for scientists working in these areas where awardees can present their work, and that will help fuel discussion and collaboration, says McIndoe, Regents’ Professor and Georgia Research Alliance Distinguished Investigator.

High-risk research with high-reward potential often doesn’t get funded in the traditional, highly competitive process of seeking NIH funding, McIndoe says. For example, the 2019 payline for the NIDDK was 13%, which means only 13 of 100 submitted grants get funded.

About half of submitted grants, don’t even make it through the NIH study section manned by experts in the field who do the frontline review of grant proposals, says McIndoe, who at points in his career has sat on more than a half-dozen study sections annually.

As director of ISAC’s coordinating unit, McIndoe will also work with NIH program officers with expertise in the area of interest of an application to identify other experts across the country. He’ll then manage the review process from there, including assigning reviewers and making sure reviews are done on time.

He’ll ensure that the scores and critiques get back to the NIH program officers who also will rank the grant proposals, and that information along with what the ISAC office determines to be a fundable score range will then go to one more group of experts in the field, ISAC’s External Evaluation Committee, and if they agree with the determinations, the decision is made.

Although the review process is extensive, it’s about half of the standard process for submitting for scientists and reviewers alike, starting with a three-page research plan rather than up to a dozen pages for an RO1, the NIH’s oldest grant mechanism, and the application is easier for reviewers to digest, McIndoe says.

The ISAC Working Group recently opted to have three application review times annually to further expedite the process, and applications can be submitted at any time, McIndoe says. Scientists can begin submitting applications this fall, and the first annual meeting likely will be next Spring.

The local ISAC Working Group, which will advise McIndoe on kidney, urologic and hematology research, includes Dr. David Mattson, chair of the MCG Department of Physiology and an established hypertension researcher; Dr. Jennifer Sullivan, pharmacologist and physiologist in the Department of Physiology who is also interim dean of The Graduate School at AU and studies blood pressure regulation and kidney health, with a particular interest in gender differences; and Dr. Betty Pace, pediatric hematologist in the MCG Department of Pediatrics, an established sickle cell physician scientist who leads a federally funded national initiative to inspire the next generation of investigators.

ISAC’s target areas may change annually based on what’s happening in the scientific literature and what experts in respective fields identify as hot topics that need pursuing. The Working Group and the annual meetings will further enable those discussions and decisions.

McIndoe, an expert in managing and analyzing large amounts of data, has already managed two other innovative NIH funding approaches and consequently has a solid infrastructure in place to support this new initiative. For 20 years he has led the Coordinating and Bioinformatics Unit for the Diabetic Complications Consortium to fund shorter-term laboratory and human studies to better understand the complications of diabetes, like heart and kidney disease and vision problems. The consortium began as the Animal Models of Diabetes Complications, which specifically designed and shared good mouse models.

Fifteen years ago he began providing similar services for the Mouse Metabolic Phenotyping Centers, which make the specialized, expensive mouse-testing capabilities of a select number of universities available and affordable to researchers nationwide. Expertise includes things like characterizing mouse metabolism and analyzing blood composition.

Together those NIDDK initiatives, which also hold scientific meetings and support websites to support interested scientific communities, have resulted in thousands of publications that demonstrate new findings and helped scientists secure larger NIH grants. As an example, more than 60% of those receiving a $100,000 grant through the Diabetic Complications Consortium applied for an RO1 and about 25% were successful. “That’s higher than the normal percentage and a goal of these kinds of programs,” McIndoe says. Both those programs are scheduled to phase out next year.

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Source: https://bioengineer.org/mcindoe-leading-6-2-million-innovative-research-initiative/

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Oregon State graduate student sheds light on better way to study reputedly secretive toad

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CORVALLIS, Ore. – Research by a graduate student in Oregon State University’s College of Science has upended the conventional wisdom that for a century has incorrectly guided the study of a toad listed as endangered in part of its range.

Anne Devan-Song used spotlighting – shining a light in a dark spot and looking for eye reflections – to find large numbers of the eastern spadefoot toad. The study illustrates how confirmation bias – a tendency to interpret new information as ratification of existing theories – can hamper discovery and the development of better ones.

Her findings, which show that the toad spends much more time above ground than commonly believed, were published in the Journal of Herpetology.

Known for bright yellow eyes with elliptical pupils and, as the name suggests, a spade on each hind foot, the eastern spadefoot toad ranges from the southeast corner of the United States up the Atlantic Coast to New England. Known scientifically as Scaphiopus holbrooki, it is a species of conservation concern in the northern reaches of its territory.

Devan-Song, a Ph.D. student in integrative biology, grew up in Singapore, where she learned she could search for reptiles and amphibians by spotlighting. In Rhode Island, where she earned a master’s degree and then worked as a university research associate, the eastern spadefoot toad is endangered.

One rainless night while surveying for amphibians during a project in Virginia, Devan-Song’s spotlight detected one eastern spadefoot after another. That surprised her because the toads were thought to be detectable only on a few rainy nights every year, when they emerge from underground burrows to mate in wetlands.

She continued looking for eastern spadefoots and kept finding them on dry nights, including in upland forest locales not close to any damp areas. Spadefoots remain still when spotlighted so it was easy for Devan-Song to approach the eye-shines and positively identify the toads.

“They need to get above ground to hunt for insects and build up energy stores for mating,” she said. “That’s why we were finding them when and where conventional wisdom said we weren’t supposed to be finding them.”

Back in Rhode Island, she tried spotlighting for spadefoots; it took her just 15 minutes to find one. The success led to a 10-night survey in a pair of locations last summer that produced 42 sightings – nearly double the number of eastern spadefoot toad sightings in Rhode Island over the previous seven decades.

Devan-Song also learned that she wasn’t the first to question the notion that the eastern spadefoot was so “secretive” as to almost always avoid detection. As far back as 1944, Devan-Song said, it was suggested in scientific literature that the toad could be found outside of rain-induced migration and breeding aggregations. And in 1955, researchers used spotlighting to detect huge numbers of eastern spadefoots in Florida; the technique subsequently, inexplicably fell into disuse.

“Confirmation bias perpetuated the fallacy of when the eastern spadefoot could be found,” Devan-Song said. “No breeding events or migration occurred during our surveys and we detected thousands of toads in Virginia and dozens in Rhode Island. The majority of those were subadults, a demographic category mainly overlooked in the literature. Progress in learning about the toad, its ecology and its conservation has been greatly hindered by a misconception that persisted even when evidence to the contrary was presented.”

The ease with which many toads could be found during breeding, combined with a lack of data on toads in upland habitats, helped fuel confirmation bias in this case, she said.

“Everyone assumed they were underground most of the time so no one was really looking for them most of the time,” Devan-Song said. “Our research demonstrates that you can detect them year round, though they do remain rare in Rhode Island. But likely not as rare as the scientific community thought.”

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The National Park Service, through a cooperative agreement with the University of Rhode Island, supported this research.

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Source: https://bioengineer.org/oregon-state-graduate-student-sheds-light-on-better-way-to-study-reputedly-secretive-toad/

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