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CLEMSON, South Carolina -- Lions, tigers and ... vampire elephants? Oh, my.

Human-wildlife conflict research has often focused on ways such apex predators as lions, tigers and wolves endanger humans, impact livelihoods and threaten livestock, but a pair of Clemson University researchers has expanded the discussion to include two non-traditional culprits: "vampire elephants" and "ecological zombies."

Better known simply as elephants and hogs than by those macabre monikers, the species are not carnivores traditionally associated with loss of livestock -- nor do they have supernatural powers -- but they can have a similar impact.

New research by Shari Rodriguez and Christie Sampson in the open-access journal PLOS Biology, examines the effects of these less-studied relationships, particularly for feral hogs and elephants, and the potential consequences of excluding these animals from research focused on mitigating wildlife impact on livestock.

"When we deal with livestock issues and human-wildlife conflicts, it's not enough right now to just talk about carnivores," Rodriguez said. "We have to talk about at least hogs and elephants, as well, because there's no reason to reinvent the wheel with (mitigating the impact of) elephants and hogs when we've got a wheel that exists for carnivores that can be applied to at least two other groups of species."

These species can have significant effects on livelihoods by killing young and small livestock and damaging farming infrastructure. They may also affect local communities' perception of the species, which in the case of species of conservation concern, such as elephants, could reduce people's willingness to support conservation initiatives.

Sampson saw the latter scenario -- misconception about a species -- play out right before her eyes during a research trip to Myanmar. An elderly woman had put her store of rice on a platform in a tree to keep it out of the elephants' reach and went to sleep beside it before being killed by what locals believed to be a "vampire elephant."

"She didn't use a tree limb high enough so that, unfortunately, the elephant could reach it," Sampson said. "So the elephant goes to get the rice, takes down the branch, takes her down with it and ends up killing her. When they found the body the next morning, there was no blood because she had been badly injured during the event and lost a great deal into the sandy ground."

It didn't take long for the story to spread that an elephant had killed the woman to drink her blood ... and, as urban legends do, the tall tale spread quickly.

"We heard the story in one village and then we went to an entirely different place and they had the same story that was being passed around -- that a vampire elephant was out killing people to drink their blood," Sampson said. "We tried to tell people, 'They don't eat meat, and they don't drink your blood.' Part of our job is to understand those missing pieces of information for people. Fundamentally, that's not our charge; our charge is the research. But a secondary effect of the research is that we can correct some of those misconceptions as we interact with people and do our work."

But misconceptions can be difficult to dissuade. A couple of years ago when Sampson returned to India, her travel party came across a pile of elephant dung with pieces of human clothing in it. For many locals, the evidence appeared clear: a 'vampire elephant' had claimed another victim.

That was not the case, of course, but it did further underline to the scientists the importance of their research.

"Elephants aren't carnivores, but they still have an effect on people and livestock, and if we can mitigate the conflict to begin with then we don't have issues of 'vampire elephants' or (the belief in) elephants that eat people," Rodriguez said. "If you can mitigate the conflict to begin with, some of these problems will go away."

The publication from Rodriguez and Sampson aims to highlight the importance of including species not traditionally considered in the livestock-protection conversation and finding similarities in how the effects of non-carnivora species can be addressed through the same methodologies as wolves, tigers or lions.

And while vampire elephants don't exist, the threat to livestock is very much real. Both African and Asian elephant species are known to cause livestock injuries and deaths. Livestock owners in elephant ranges perceive elephants as a risk to their livestock, which may reduce their tolerance toward elephants and jeopardize conservation efforts in the area, according to the research.

The Clemson research duo has worked internationally on the topic of human-wildlife conflict with animals such as tigers and elephants, but in the United States, and particularly its Southeast region, feral hogs are much more central to the discussion.

Rodriguez, who serves on the South Carolina Wild Hog Task Force, has often referred to feral hogs as "ecological zombies" because "they will eat anything." The animals are notorious for preying on wildlife and livestock and consuming large amounts of agricultural crops and seeds, sprouts and seedlings, which disrupts reforestation. Their rooting, wallowing and nesting behaviors decrease water quality and promote soil erosion, and they can also spread diseases like pseudorabies and brucellosis, which can spread to humans.

"Though feral hogs may not be of conservation concern, these animals contribute significant losses to farmers' livelihoods. We advocate for the inclusion of noncarnivore species in policies that promote livestock protection because it will allow for better communication regarding effective strategies and more application in the field," the paper reads.

While the scientific community at large had done quite a bit of research on human interactions with apex predators, the scientists realized in reading the existing research it was overlooking a significant portion of the problem it was aimed at addressing.

Rodriguez and Sampson assert that non-predator impact on livestock are a related and equally pressing issue that has received far less attention in the scientific community.

"We ended up writing not a response, but more of an addendum that was a global, larger-scale discussion of how we can prevent wildlife attacks on livestock; herbivores and maybe more non-traditionally considered species should also be part of the conversation because we can learn a lot from the non-carnivore side," Sampson said. "We can learn a lot from them and then we can also share a lot of information to really make a bigger impact overall in the field."

The 'double whammy' of co-occurring insomnia and obstructive sleep apnea (OSA) is a complex problem best managed with non-drug targeted psych interventions, a new Australian study has found.

By following simple new guidelines, people with the concurrent conditions reported great improvement to both their sleep, and their health - with about 50% improvement in global insomnia severity and night-time insomnia after six months.

'Co-Morbid Insomnia and Sleep Apnoea' (COMISA) is a little studied and debilitating disorder which can improve by identifying and treating insomnia separately.

The new Australian study of 145 patients aimed to work out better treatments for 'COMISA' patients who, in the past, have shown poor results from using continuous positive airway pressure (CPAP) therapy, compared to patients who do not report symptoms of insomnia.

As a result, the sleep experts are advising people living with both conditions to be treated first with a targeted, 4-10 week program of cognitive and behavioural therapy for insomnia (CBTi) - before using CPAP machines to reduce the effects of sleep apnoea.

"We found that treating COMISA patients with non-drug CBTi before commencing CPAP significantly improved insomnia symptoms," says lead researcher Dr Alexander Sweetman, from the Adelaide Institute for Sleep Health at Flinders University.

"Importantly, we also found increased use of CPAP therapy by about one hour per night in patients treated with CBTi and CPAP therapy, compared to a group receiving treatment with CPAP alone."

OSA patients - who comprise around 10% of the general population - suffer from frequent airway narrowing events during sleep which leads to a poor quality of sleep and reduced daytime functioning.

About one-third of OSA patients also report clinically significant insomnia symptoms, including long-term difficulties falling asleep at the start of the night, or long awakenings during the night.

The study found the new routine resulted in CBTi patients increasing acceptance of CPAP devices by 87% and increased long-term CPAP use by one hour each night over the first four months.

At six months, combined CBTi and CPAP therapy led to significant improvements of:

52% in global insomnia severity, compared to 35% in the control group,

48% in night-time insomnia complaints, compared to 34%

30% in dysfunctional sleep-related cognitions (compared to 10%).

Heart disease, obesity and depression have been connected to insomnia and sleep apnoea, so getting the best therapies are important to health and wellbeing for millions of people around the world, says co-author Professor Doug McEvoy.

"Long-term cardio-metabolic benefits for patients with COMISA is an important consideration, independent of those debilitating symptoms which can be relieved with the right treatment," Professor McEvoy says.

"This latest study suggests that sleep physicians and clinics should screen for insomnia symptoms and, if present, treat the insomnia with CBTi to improve subsequent acceptance and use of CPAP therapy. This will improve outcomes for both disorders."

Aug. 9, 2019--Certain traits may define a type of obstructive sleep apnea that can be effectively treated with an oral appliance, according to new research published online in the Annals of the American Thoracic Society.

With OSA there are times during sleep when air cannot flow normally into the lungs. The collapse of the soft tissues in the back of the throat or tongue usually causes the airflow obstruction.

Continuous positive airway pressure, or CPAP, is considered the gold standard for preventing the obstruction by blowing air through a mask into the nose and throat. However, many patients have trouble sleeping with CPAP. For these patients, an oral appliance that moves the lower jaw forward to prevent the periods of obstructed airflow is often an alternative.

In "Polysomnographic Endotyping to Select Obstructive Sleep Apnea Patients for Oral Appliances," Ahmad A. Bamagoos and colleagues identify five traits that appear to determine the effectiveness of an oral appliance in treating OSA.

"Sleep apnea is not all the same, but we only recently developed ways to look at a sleep study and determine what traits cause the condition in different patients," said senior author Scott Sands, PhD, assistant professor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston. "Since oral appliances work by improving the collapsibility of the upper airway, patients without really severe collapsibility are more likely to benefit from an oral appliance, while those with sleep apnea caused by other traits, such as exaggerated reflex responses to drops in oxygen levels, are less likely to benefit."

The researchers used their new technology to measure the traits causing sleep apnea through polysomnography, the test used to diagnose sleep apnea. For this study, the researchers analyzed polysomnographic data already gathered from 93 adults (average age: 56) who were diagnosed with moderate to severe OSA.

The authors looked at two traits related to the upper airway: collapsibility and muscle compensation. The researchers found that patients without severe collapsibility benefitted more from the oral appliance than those without this trait. Those with a weaker reflex response of the throat muscles that act to maintain an open airway (lower muscle compensation) also benefitted more than those with a stronger reflex response. Patients with very mild collapsibility, indicating deficits in other traits, responded less well.

The researchers also found that three traits unrelated to the upper airway helped predict those patients who would respond less well to an oral appliance: higher loop gain, lower arousal threshold and higher ventilatory response to arousal.

Loop gain is a measure of how aggressively the brain and lungs respond to falling oxygen and rising carbon dioxide in the blood. Arousal threshold is a measure of how easily a person wakes up from sleep; deeper sleep (higher arousal threshold) promotes better breathing.

Based on these five traits, oral appliances were predicted to be effective in treating sleep apnea in more than half (61 percent) of the participants. Patients in this group experienced a 73 percent reduction in the Apnea-Hypopnea Index, which is the number of breathing pauses per hour lasting 10 seconds or longer. (Apnea means no airflow and hypopnea means reduction in airflow). With an oral appliance, they had just eight apneas/hypopneas per hour.

The other patient group experienced a smaller reduction in the Apnea-Hypopnea Index and had twice the number of breathing pauses remaining with the oral appliance.

The authors said that responses to oral appliances in their study could not be predicted by the severity of sleep apnea or how overweight patients were. "Surprisingly, it didn't seem to matter whether sleep apnea was moderate or very severe," Dr. Sands said. "Oral appliance therapy was remarkably effective in some quite overweight patients with very severe OSA."

Based on these findings, the authors write that, if their results are upheld in future studies, an oral appliance could be considered, along with CPAP, as a first-line therapy for treating a certain type of OSA.

"While CPAP is great for some, there remains a large group of patients who really struggle with it," Dr. Sands said. "For these folks, this study highlights the potential benefit of measuring the underlying causes of their sleep apnea to estimate whether an oral appliance might be an equivalent or better choice over CPAP for the treatment of their sleep apnea."

Dr. Sands added that once the most useful measures for predicting patient outcomes are established, he believes they will be readily incorporated into routine sleep recording systems.

Researchers at the Max Delbrueck Center for Molecular Medicine (MDC) have identified an epigenetic mechanism that appears to strongly influence healthy aging. It's a protein that controls muscle integrity, lifespan and levels of an essential sugar. How does one protein have that much power?

Researchers at MDC's Berlin Institute for Medical Systems Biology (BIMSB) have found a protein that has a significant impact on healthy muscles and lifespan. Animals lacking this protein, called LIN-53, have severe muscle defects, limited motility, and die early compared to animals with the protein.

Dr. Baris Tursun, who leads BIMSB's Gene Regulation and Cell Fate Decision Lab, and his collaborators figured out two specific ways LIN-53 works in roundworms. Their findings, reported in the journal Aging Cell, lay the groundwork for further studies on the human version of the protein.

"Identifying the genetic factors that play a role in linking lifespan and healthspan is key for understanding human health and aging-related diseases such as muscular dystrophy," Tursun said. 

Epigenetic factor

LIN-53 is not just any protein, it is a "histone chaperone," binding to the molecules called histones that long DNA strands tightly wrap around to fit in the cell nucleus. Histone modifications can ultimately turn gene expression levels up or down, affecting an organism's development, function and lifespan. LIN-53 is considered an "epigenetic factor" because by interacting with histones, it can help activate and deactivate genes that can result in heritable traits passed to offspring, but without changing the underlying DNA sequence.

Tursun and his colleagues wanted to understand if this epigenetic factor influences how long an organism lives (lifespan), and how long an organism lives in a healthy state (healthspan). They also wanted to learn if lifespan and healthspan are directly related.

"Usually when we age, we experience aging symptoms accompanied by muscle loss," Tursun said. "Is this all coincidence or is it linked, and if so, how it is linked? Our paper is one of the first to show an epigenetic link."

One factor, two routes

The team of molecular biologists and geneticists investigated LIN-53's role in Caenorhabditis elegans (C. elegans), a worm only 1 millimeter long. Also referred to as a nematode, it is one of the primary model organisms used in aging research because many of its genes are highly conserved, or found, across species.

"It is such a small organism and yet still resembles human tissues, pathways and gene regulation, so we are able to transfer results from the nematode to humans," said Stefanie Müthel, first author of the paper and a postdoctoral researcher at the Myology Lab at the Experimental and Clinical Research Center (ECRC), a joint institution of Charité and the MDC.

When the researchers knocked out the gene for LIN-53, the worms showed reduced ability to move and did not live as long as counterparts with the gene.

This clearly indicated LIN-53 plays role in healthy muscles and lifespan. The team dug further and determined LIN-53 affects muscle development through the molecular complex NuRD, while it affects lifespan through a separate complex, Sin3. The fact that these are distinct pathways, but both involving LIN-53, is particularly intriguing and strongly suggests the importance of LIN-53 as a link between healthspan and lifespan.

"LIN-53 is part of seven different molecular complexes regulating chromatin modification and structure," Müthel said. "I was surprised and excited that we were able to clearly define the complexes important for healthspan and lifespan."

The good sugar

Additional analysis revealed a possible explanation for why LIN-53 is so powerful. Animals without LIN-53 had very low levels of a sugar, called trehalose; it consists of two glucose molecules is known to be essential for normal lifespan in invertebrates. The interaction between LIN-53 and Sin3 affected genes that regulate metabolism, including the production of this sugar. Further research is needed to understand exactly how LIN-53 interacts with both NuRD and Sin3, and inhibits sugar production.

Since the LIN-53 protein is very similar to human protein RBBP4/7, researchers can use insights gained from the microscopic worms to guide where to look for answers to similar questions in humans.

"We all want to age in a healthy manner," Tursun said. "Once we understand the links between aging and all the accompanying detrimental effects, then we can begin to think about how to unlink them." (pet)

EVANSTON, Ill. -- Targeted drug-delivery systems hold significant promise for treating cancer effectively by sparing healthy surrounding tissues. But the promising approach can only work if the drug hits its target.

A Northwestern University research team has developed a new way to determine whether or not single drug-delivery nanoparticles will successfully hit their intended targets -- by simply analyzing each nanoparticle's distinct movements in real time.

By studying drug-loaded gold nanostars on cancer cell membranes, the researchers found that nanostars designed to target cancer biomarkers transited over larger areas and rotated much faster than their non-targeting counterparts. Even when surrounded by non-specifically adhered proteins, the targeting nanostars maintained their distinct, signature movements, suggesting that their targeting ability remains uninhibited.

"Moving forward, this information can be used to compare how different nanoparticle characteristics -- such as particle size, shape and surface chemistry -- can improve the design of nanoparticles as targeting, drug-delivery agents," said Northwestern's Teri Odom, who led the study.

The study published today (Aug. 9) in the journal ACS Nano. Odom is the Charles E. and Emma H. Morrison Professor of Chemistry in Northwestern's Weinberg College of Arts and Sciences.

The medical field has long been searching for alternatives to current cancer treatments, such as chemotherapy and radiation, which harm healthy tissues in addition to diseased cells. Although these are effective ways to treat cancer, they carry risks of painful or even dangerous side effects. By delivering drugs directly into the diseased area -- instead of blasting the whole body with treatment -- targeted delivery systems result in fewer side effects than current treatment methods.

"The selective delivery of therapeutic agents to cancer tumors is a major goal in medicine to avoid side effects," Odom said. "Gold nanoparticles have emerged as promising drug-delivery vehicles that can be synthesized with designer characteristics for targeting cancer cells."

Various proteins, however, tend to bind to nanoparticles when they enter the body. Researchers have worried that these proteins might impede the particles' targeting abilities. Odom and her team's new imaging platform can now screen engineered nanoparticles to determine if their targeting function is retained in the presence of the adhered proteins.

In the journal Science Immunology, researchers from DTU Health Technology and Jacobs University in Bremen have just published their cutting-edge research demonstrating advancement in detection of a certain type of immune cells, called T cells. Improved detection of T cells have several therapeutic implications. For example, in cancer immunotherapy (a therapeutic approach that engage patients own immune cells) characterization of T cells that recognize cancer cells is crucial for tailoring personalized treatment strategies.

T cells are white blood cells of the immune system that have amazing properties: they can detect cancer cells and virus-infected cells in the body, and they even attack and eliminate these. This is why T cells constitute an essential part of the immune response, which patients mount, against tumors and viruses.

When applying immunotherapy an immune response against a tumor takes place, the tumor-fighting T cells in the blood of the patient multiply. To find out how well the immunotherapy is working, scientists and doctors want to check how many tumor-specific T cells a patient has mounted. The tumor-specific T cells are identified by their specific T cell receptor using a colored reagent called an MHC tetramer. Using this reagent, the tumor-specific T cells become visible and can be counted under the microscope or in a high-throughput machine called a flow cytometer.

Super-stable molecule

The MHC proteins of the MHC tetramer reagent were previously difficult to produce due to the inherent instability of the MHC protein, and that used to be a bottleneck in research and diagnosis.

"Whenever a researcher needed MHC tetramers, they had to ask a company to make them, and the process took four to six weeks", explains Prof. Sebastian Springer, Jacobs University Bremen.

"Of course, that created big problems if they had a sick patient they wanted to diagnose, or if they were following a really urgent scientific project. The problem was that every MHC protein contains a little piece of a tumor or virus called a peptide, which varies from one patient to the other, and without the peptide, the MHC protein was unstable and perished quickly, even if it was kept in the fridge, thereby destroying the MHC tetramer."

It is the development and use of a super-stable form of the MHC tetramer reagents that professor Sine Reker Hadrup, DTU Health Technology, and her collaborators at the Jacobs University Bremen in Germany, led by Prof. Sebastian Springer has published in Science Immunology.

With the new invention, MHC molecules can be loaded with peptides instantly, on demand.

"The technology opens a range of new possibilities for tracking disease relevant T cells in patients and to manipulate T cells to specifically fight e.g. cancer" says Sine Reker Hadrup.

Cause for a company

Hadrup and Springer have now co-founded a company named Tetramer Shop to produce and sell this innovative MHC tetramer reagent. The company has already seen significant interest, in its MHC tetramer reagents, from academia and pharma working on T cell immunotherapy as well as from various diagnostic platform companies.

Furthermore, Hadrup and Springer believes that the stabilized form of the MHC protein holds great promise within a new field of personalized T cell therapy, termed precision activated cell therapy, where patients own tumor-specific T cells, in a personalized protocol, are isolated and activated before being used as the therapeutic product.

This use could potentially give rise to yet another company.

What happens in the early days of organ development? How do a small group of cells organize to become a heart, a brain, or a kidney? This critical period of development has long remained the black box of developmental biology, in part because no sensor was small or flexible enough to observe this process without damaging the cells.

Now, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have grown simplified organs known as organoids with fully integrated sensors. These so-called cyborg organoids offer a rare glimpse into the early stages of organ development.

The research was published in Nano Letters.

"I was so inspired by the natural organ development process in high school, in which 3D organs start from few cells in 2D structures. I think if we can develop nanoelectronics that are so flexible, stretchable, and soft that they can grow together with developing tissue through their natural development process, the embedded sensors can measure the entire activity of this developmental process," said Jia Liu, Assistant Professor of Bioengineering at SEAS and senior author of the study. "The end result is a piece of tissue with a nanoscale device completely distributed and integrated across the entire three-dimensional volume of the tissue."

This type of device emerges from the work that Liu began as a graduate student in the lab of Charles M. Lieber, the Joshua and Beth Friedman University Professor. In Lieber's lab, Liu once developed flexible, mesh-like nanoelectronics that could be injected in specific regions of tissue.

Building on that design, Liu and his team increased the stretchability of the nanoelectronics by changing the shape of the mesh from straight lines to serpentine structures (similar structures are used in wearable electronics). Then, the team transferred the mesh nanoelectronics onto a 2D sheet of stem cells, where the cells covered and interwove with the nanoelectronics via cell-cell attraction forces. As the stem cells began to morph into a 3D structure, the nanoelectronics seamlessly reconfigured themselves along with the cells, resulting in fully-grown 3D organoids with embedded sensors.

The stem cells were then differentiated into cardiomyocytes -- heart cells -- and the researchers were able to monitor and record the electrophysiological activity for 90 days.

"This method allows us to continuously monitor the developmental process and understand how the dynamics of individual cells start to interact and synchronize during the entire developmental process," said Liu. "It could be used to turn any organoid into cyborg organoids, including brain and pancreas organoids."

In addition to helping answer fundamental questions about biology, cyborg organoids could be used to test and monitor patient-specific drug treatments and potentially used for transplantations.

Artificial Intelligence engineers should enlist ideas and expertise from a broad range of social science disciplines, including those embracing qualitative methods, in order to reduce the potential harm of their creations and to better serve society as a whole, a pair of researchers has concluded in an analysis that appears in the journal Nature Machine Intelligence.

"There is mounting evidence that AI can exacerbate inequality, perpetuate discrimination, and inflict harm," write Mona Sloane, a research fellow at New York University's Institute for Public Knowledge, and Emanuel Moss, a doctoral candidate at the City University of New York. "To achieve socially just technology, we need to include the broadest possible notion of social science, one that includes disciplines that have developed methods for grappling with the vastness of social world and that helps us understand how and why AI harms emerge as part of a large, complex, and emergent techno-social system."

The authors outline reasons where social science approaches, and its many qualitative methods, can broadly enhance the value of AI while also avoiding documented pitfalls. Studies have shown that search engines may discriminate against women of color while many analysts have raised questions about how self-driving cars will make socially acceptable decisions in crash situations (e.g., avoiding humans rather than fire hydrants).

Sloane, also an adjunct faculty member at NYU's Tandon School of Engineering, and Moss acknowledge that AI engineers are currently seeking to instill "value-alignment"--the idea that machines should act in accordance with human values--in their creations, but add that "it is exceptionally difficult to define and encode something as fluid and contextual as 'human values' into a machine."

To address this shortcoming, the authors offer a blueprint for inclusion of the social sciences in AI through a series of recommendations:

Qualitative social research can help understand the categories through which we make sense of social life and which are being used in AI. "For example, technologists are not trained to understand how racial categories in machine learning are reproduced as a social construct that has real-life effects on the organization and stratification of society," Sloane and Moss observe. "But these questions are discussed in depth in the social sciences, which can help create the socio-historical backdrop against which the...history of ascribing categories like 'race' can be made explicit."

A qualitative data-collection approach can establish protocols to help diminish bias. "Data always reflects the biases and interests of those doing the collecting," the authors note. "Qualitative research is explicit about the data collection, whereas quantitative research practices in AI are not."

Qualitative research typically requires researchers to reflect on how their interventions affect the world in which they make their observations. "A quantitative approach does not require the researcher or AI designer to locate themselves in the social world," they write. "Therefore, does not require an assessment of who is included into vital AI design decision, and who is not."

"As we move onwards with weaving together social, cultural, and technological elements of our lives, we must integrate different types of knowledge into technology development," Sloane and Moss conclude. "A more socially just and democratic future for AI in society cannot merely be calculated or designed; it must be lived in, narrated, and drawn from deep understandings about society."

New Haven, Conn. -- A beautiful landscape painting, a beautiful piano sonata -- art and music are almost exclusively described in terms of aesthetics, but what about math? Beyond useful or brilliant, can an abstract idea be considered beautiful?

Yes, actually -- and not just by mathematicians, reports a new study in Cognition.

Coauthored by a Yale mathematician and a University of Bath psychologist, the study shows that average Americans can assess mathematical arguments for beauty just as they can pieces of art or music. The beauty they discerned about the math was not one-dimensional either: Using nine criteria for beauty -- such as elegance, intricacy, universality, etc. -- 300 individuals had better-than-chance agreement about the specific ways that four different proofs were beautiful.

This inquiry into the aesthetics of mathematics began when study co-author and Yale assistant professor of mathematics Stefan Steinerberger likened a proof he was teaching to a "really good Schubert sonata."

"As it turns out, the Yale students who do math also do a statistically impressive amount of music," said Steinerberger. "Three or four students came up to me afterwards and asked, 'What did you mean by this?' And I realized I had no idea what I meant, but it just sounded sort of right. So, I emailed the psych department."

Yale professor of psychology Woo-Kyoung Ahn replied to Steinerberger and, after further discussion, gave him the name of a psychology graduate student with whom she thought he would get along.

Enter Samuel G.B. Johnson, study co-author and now an assistant professor of marketing at the University of Bath School of Management, who was still completing his Ph.D. in psychology at Yale when he connected with Steinerberger. Johnson studies reasoning and decision making. "A lot of my work is about how people evaluate different explanations and arguments for things," he explained.

Steinerberger said Johnson understood immediately how to design an experiment to test his question of whether we share the same aesthetic sensibilities about math that we do about other modalities, i.e. art and music, and if this would hold true for an average person, not just a career mathematician like himself.

"I had some diffuse notion about this, but Sam immediately got it," said Steinerberger. "It was a match made in heaven."

For the study, they chose four each of mathematical arguments, landscape paintings, and piano sonatas. Because the similarities between math and music have long been noted, Johnson explained, they also wanted to test people using another aesthetic modality -- art in this case -- to see if there's something more universal about the way we judge aesthetics.

Johnson divided the study into three parts. The first task required a sample of individuals to match the four math proofs to the four landscape paintings based on how aesthetically similar they found them; the second required a different sample to do the same but instead comparing the proofs to sonatas; and the third required another unique sample of people to independently rate, on a scale of zero to ten, each of the four artworks and mathematical arguments along nine different criteria plus an overall score for beauty.

They derived these criteria from "A Mathematician's Apology," a 1940 essay by famous mathematician G.H. Hardy, which discusses mathematical beauty. The researchers' nine dimensions elaborated from Hardy's six were: seriousness, universality, profundity, novelty, clarity, simplicity, elegance, intricacy, and sophistication. When Steinerberger and Johnson analyzed the ratings given by participants in part three, they found that for both the artworks and math arguments a high rating for elegance was most likely to predict a high rating for beauty.

The final step was to calculate the "similarity scores" for the participants in group three, which revealed how aesthetically similar they considered each proof and painting were to each other based on
the separate beauty criteria. They then compared these scores to the results from the first group of participants, who were asked to simply match proofs with paintings based on their own intuitive sense of aesthetic similarity -- much like Steinerberger's initial analogy of the proof to a "good Schubert sonata."

When the results came in, Steinerberger and Johnson were surprised but pleased. They were able to take the similarity scores from participants in the third task to predict how the participants would behave in the first task. Participants in the third group agreed about which arguments were elegant and which paintings were elegant while, likewise, participants in the first group tended to match the argument the third group rated as most elegant with the painting they'd rated most elegant.

Laypeople not only had similar intuitions about the beauty of math as they did about the beauty of art but also had similar intuitions about beauty as each other. In other words, there was consensus about what makes something beautiful, regardless of modality.

"I'd like to see our study done again but with different pieces of music, different proofs, different artwork," said Steinerberger. "We demonstrated this phenomenon, but we don't know the limits of it. Where does it stop existing? Does it have to be classical music? Do the paintings have to be of the natural world, which is highly aesthetic?"

While quick to point out that they are not education scholars, both Steinerberger and Johnson see eventual implications of this research for math education, especially at the secondary-school level.

"There might be opportunities to make the more abstract, more formal aspects of mathematics more accessible and more exciting to students at that age," said Johnson, "And that might be useful in terms of encouraging more people to enter the field of mathematics."

"I think if you understand what people consider beautiful in math, then it could give insight into how people understand math in the first place and how they process it," added Steinerberger. "There's also the human implication of the question: How are we actually thinking about things as human beings? I think we have an obligation to collaborate with psychologists on this."

Glioblastoma, a cancer that arises in the brain's supporting glial cells, is one of the worst diagnoses a child can receive. The grade IV, highly malignant tumor aggressively infiltrates healthy brain tissue, and most children die of the disease within one to two years of diagnosis, similar to adults.

"The current approach is surgical removal, radiation, and then some kind of chemotherapy, but there is no chemotherapy that improves survival," says Mariella Filbin, MD, PhD, a pediatric neuro-oncologist at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center. "It's a very vicious tumor that we haven't gotten a handle on."

Filbin co-led a study, published online last week in Cell, that made some surprising discoveries about this poorly understood tumor. Regardless of what genetic mutation causes glioblastoma, it can readily shift among four distinct cell types, each of which may need to be targeted separately.

Profiling a tumor, cell by cell

Usually diagnosed in school-age children, childhood glioblastoma outwardly looks like the adult glioblastoma that killed John McCain, Ted Kennedy, and Beau Biden. But genetically, it is completely different: like many childhood cancers, its various genetic mutations tend to hijack normal pathways of early brain tissue development, which regulate cell functions.

In both children and adults, glioblastoma can take many forms - hence the cancer's full name, glioblastoma multiforme. But it had been thought that within a given patient, all tumor cells are the same.

That turns out not to be true. The tumor is a mosaic.

In a group effort -- "no single lab can do this alone" -- Filbin teamed up with Cyril Neftel in the lab of Mario Suvà, MD, PhD, at Massachusetts General Hospital and the Broad Institute; Julie Laffy in the lab of Itay Tirosh, PhD of the Weizmann Institute of Science; and Toshiro Hara, PhD of the Salk Institute. These researchers, all co-first authors on the paper, analyzed tumors from eight children and 20 adults, going cell by cell.

In all, they profiled more than 24,000 cells, sequencing the RNA of each cell. While DNA is hard-wired, the RNA "transcriptome" is more like software, providing a readout of what genes are turned on and what proteins the cell is making -- revealing what the cell is doing and what state it's in.

Applying novel technologies to these vicious tumors give us an opportunity to understand what drives them at a whole new level that was unthinkable a few years ago.

"If you look at single cells, they're very different from one another," says Filbin. "Some are more immature, stem-like cells, some are differentiating cells, and some are mature cells that are not even dividing anymore."

I'll morph to someone else

The team distinguished four distinct tumor cell types. Each type closely resembled different types of normal developing brain cells: neural progenitor cells, oligodendrocyte progenitor cells, astrocytes, and mesenchymal cells. The proportions of the different cell types varied according to the genetic defect driving the patient's cancer (increased copies of PDGFRA, CDK4 or EGFR, or alterations of NF1). But every patient had all four tumor cell types.

glioblastoma cell types, via single-cell sequencing

Four glioblastoma cell states: Clockwise from lower left: astrocyte-like cells, oligodendrocyte-progenitor-like cells, neural-progenitor-like cells, and mesenchymal-like cells. The lighter/darker tones indicate the strength of each state, with intermediate states shown in the middle. The mesenchymal-like cells are shown interacting with macrophages, indicating that they "talk" with the immune system.

More ominously, the four cell types could all change into each other. The study found that glioblastomas are highly "plastic" -- their cell types readily morphing over time and when exposed to cancer treatments. When the researchers injected any of the four types of patient tumor cells into mice, they all formed tumors containing all four cell types.

"This explains the failures of single-target drugs," says Filbin. "The tumors can 'become' something else and escape our drug therapies -- and it's very easy for them."

Uncovering cancer-cell 'hierarchies'

Recently, Filbin and her colleagues used single-cell RNA sequencing to profile another deadly tumor called diffuse midline glioma, also known as diffuse intrinsic pontine glioma (DIPG). In tumors caused by one specific mutation, they found a rogue immature type of cell that constantly divided and proliferated much like stem cells -- fueling the tumor's spread.

Unlike glioblastoma, DIPG cells seemed to morph in just one direction: a few rogue cells were able to differentiate into more mature cells. That offers a new approach to explore: getting these tumor-propagating cells to mature and become less of a threat. Filbin thinks other tumors might follow this "unidirectional hierarchy."

"The younger the child, the more immature the tumors, and the more unidirectional we think they will be, because they resemble early development so much," she says. "Older children may be more likely to follow a glioblastoma pattern."

Treating glioblastoma: The plot thickens

As for glioblastoma, the new findings indicate a need for combination therapies that target all four tumor states at once. Filbin and her colleagues plan to try different combinations of gene editing approaches and drugs aimed at changing cell state. Such drugs could block molecular pathways that keep tumor cells in an immature state, or target the packaging of DNA into chromatin that determines what RNA is transcribed.

"Applying novel technologies to these vicious tumors give us an opportunity to understand what drives them at a whole new level that was unthinkable a few years ago," says Filbin. "The time is ripe to take these findings and finally translate them into novel therapies."

The brains of Alzheimer's patients who have already developed clinical symptoms contain large clumps of the protein beta-amyloid, known as plaques. Many therapeutic approaches focus on removing plaques, but such attempts have met with only limited success to date.

"It's crucial that we detect and treat the disease much earlier. We therefore focused on hyperactive neurons, which occur at a very early stage - long before patients develop memory loss," explains Professor Arthur Konnerth, Hertie Senior Professor of Neuroscience at the TUM. As a consequence of hyperactivation, connected neurons in the circuits constantly receive false signals, leading to impairments in signal processing.

Together with his doctoral student Benedikt Zott and the entire research team, Konnerth succeeded in identifying the cause and trigger of this early disturbance in the brain. The discovery may open the way to new therapeutic approaches. The study appeared in the journal Science.

Beta-amyloid blocks glutamate re-uptake

Neurons use chemicals called neurotransmitters to communicate with each other. Glutamate, one of the most important of these chemicals, serves to activate connected neurons. Glutamate is released at the connecting site between two neurons, called synapse, and than rapidly removed to allow the transmission of the next signal. This removal involves so-called active pump molecules as well as a passive transport of glutamate along nearby membranes.

The researchers discovered that high concentrations of glutamate persisted too long in the synaptic cleft of hyperactive neurons. This was due to the action of beta-amyloid molecules, which blocked glutamate transport out of the synaptic cleft. The team tested the mechanism using beta-amyloid molecules from patient samples and by using various mouse models obtaining similar results with both approaches.

Indication for treatment strategies at early stages

The team was also intrigued to discover that the neurotransmitter blockade was mediated by an early soluble form of beta-amyloid and not by the plaques. Beta-amyloid occurs initially as a single molecule form, or monomer, and then aggregates to double-molecule forms (dimers) and larger chains resulting, eventually, in plaques. The researchers found that glutamate blockade is caused by the soluble dimers.

"Our data provide clear evidence for a rapid and direct toxic effect of a particular beta-amyloid type, the dimers. We were even able to explain this mechanism," as Benedict Zott, first author of the study, outlined. The researchers now want to use this knowledge to further improve their understanding of the cellular mechanisms of Alzheimer's and, thus, to support the development of strategies for treatment at early stages of the disease.

Green turtles are more likely to swallow plastic that resembles their natural diet of sea grass, new research suggests.

The turtles strongly favour narrow lengths of plastic in natural colours like green and black, rather than debris of other shapes and colours, the study found.

Scientists from the University of Exeter and the Society for the Protection of Turtles (Cyprus) examined the guts of turtles found washed up on beaches in Cyprus.

Plastic was found in all turtles whose full gastrointestinal tract could be examined, with one found to contain 183 pieces.

The study could not determine what, if any, role the plastic had in the turtles' deaths. Most had likely died as a result of interaction with fishing nets.

"Previous research has suggested leatherback turtles eat plastic that resembles their jellyfish prey, and we wanted to know whether a similar thing might be happening with green turtles," said Dr Emily Duncan, of the University of Exeter.

"Sea turtles are primarily visual predators - able to choose foods by size and shape - and in this study we found strong evidence that green turtles favour plastic of certain sizes, shapes and colours.

"Compared to a baseline of plastic debris on beaches, the plastic we found in these turtles suggests they favour threads and sheets that are black, clear or green.

"The sources of this plastic might include things like black bin bags, and fragments from items such as fishing rope and carrier bags."

Duncan is also a National Geographic Explorer and a team member of the "Sea to Souce: Ganges" plastic expedition. She's currently working on similar research on plastic pollution with turtle populations in Australia, supported by a National Geographic Society grant.

The study found smaller turtles tended to contain more plastic, possibly because they are less experienced (and therefore more likely to eat the wrong food) or because diet choices change with age and size.

Of the 34 turtles examined, the scientists were able to examine the full gastrointestinal tracts of 19.

All of these turtles contained plastic, with the number of pieces ranging from three to 183.

"Research like this helps us understand what sea turtles are eating, and whether certain kinds of plastic are being ingested more than others," said Professor Brendan Godley, who leads the Exeter Marine research strategy.

"It's important to know what kinds of plastic might be a particular problem, as well as highlighting issues that can help motivate people to continue to work on reducing overall plastic consumption and pollution."

Stem cells hold the key to wound healing, as they develop into specialised cell types throughout the body - including in teeth.

Now an international team of researchers has found a mechanism that could offer a potential novel solution to tooth repair.

Published today (Friday 9 August) in Nature Communications, the study showed that a gene called Dlk1 enhances stem cell activation and tissue regeneration in tooth healing.

The work was led by Dr Bing Hu from the University of Plymouth's Peninsula Dental School, with collaboration from researchers worldwide.

The science behind the discovery

Dr Hu and his team discovered a new population of mesenchymal stem cells (the stem cells that make up skeletal tissue such as muscle and bone) in a continuously growing mouse incisor model. They showed that these cells contribute to the formation of tooth dentin, the hard tissue that covers the main body of a tooth.

Importantly, the work showed that when these stem cells are activated, they then send signals back to the mother cells of the tissue to control the number of cells produced, through a molecular gene called Dlk1. This paper is the first to show that Dlk1 is vital for this process to work.

In the same report, the researchers also proved that Dlk1 can enhance stem cell activation and tissue regeneration in a tooth wound healing model. This mechanism could provide a novel solution for tooth reparation, dealing with problems such as tooth decay and crumbling (known as caries) and trauma treatment.

Further studies need to take place to validate the findings for clinical applications, in order to ascertain the appropriate treatment duration and dose, but these early steps in an animal model are exciting, as Dr Hu explains.

What the authors say

Dr Hu, who is also part of the University's Institute of Translational and Stratified Medicine (ITSMed), said: "Stem cells are so important, as, in the future, they could be used by laboratories to regenerate tissues that have been damaged or lost due to disease - so it's vital to understand how they work.

"By uncovering both the new stem cells that make the main body of a tooth and establishing their vital use of Dlk1 in regenerating the tissue, we have taken major steps in understanding stem cell regeneration.

"The work has taken place in lab models at this stage, and further work needs to be done before we can bring them in to human use. But it's a really big breakthrough in regenerative medicine that could have huge implications for patients in future."

Professor Christopher Tredwin, Head of Peninsula Dental School and co-author of the paper, said: "We are highly excited by the recent progresses in Dr Bing Hu's group. This new work, together with a recent high-impact paper published in The EMBO Journal (doi: 10.15252/embj.201899845), which is about another type of stem cells in the tooth: epithelial stem cells, puts Plymouth at the front of the world's dental and craniofacial stem cell research and regenerative medicine. We expect those researchers will soon provide dental patients better time and cost-effective solutions to serious tooth problems - from trauma to caries."

MADISON, Wis. -- For nearly 100 years, scientists thought they understood everything there was to know about how metals bend.

They were wrong.

Materials science and engineering researchers at the University of Wisconsin-Madison have demonstrated that the rules of metal-bending aren't so hard and fast after all. They described their findings Aug. 9 in the journal Nature Communications.

Their surprising discovery not only upends previous notions about how metals deform, but could help guide the creation of stronger, more durable materials.

"This creates new opportunities for materials design," says Izabela Szlufarska, a professor of materials science and engineering at UW-Madison. "It adds another parameter we can control to enable strength and ductility."

Ductility is the ability of a metal to bend. Most approaches to increase a metal's strength do so at the expense of flexibility -- and as metals become more resistant to bending, they're more likely to crack under pressure.

However, the researchers' new mechanism for bending might allow engineers to strengthen a material without running the risk of fractures.

It's an advance that holds particular interest for the United States Army, which has an urgent need for strong and durable materials in order to keep troops safe in combat zones.

"Professor Szlufarska has opened up an entirely new area for exploration for structural materials processing and design," said Michael Bakas, synthesis and processing program manager at Army Research Office in the U.S. Army Combat Capabilities Development Command Army Research Laboratory. "By making such a high-impact discovery, Professor Szlufarska has potentially laid the technical foundation for the development of a new generation of advanced structural materials that could eventually be employed in future Army equipment and vehicles."

Engineers typically manipulate the strength of a metal through techniques such as cold working or annealing, which exert their effects through small, yet important, structural irregularities called dislocations.

"Everybody in the metals community knows that dislocations are critical," says Szlufarska.

It's a truism that's held since 1934, when three researchers independently realized that dislocation explained an ages-old paradox: Metals are much easier to bend than their molecular structures -- which typically take the form of regularly repeating three-dimensional grids -- would suggest.

Dislocations are tiny irregularities in the otherwise well-ordered crystal lattice of a metal. They arise from slight mismatches -- picture the pages of a book as rows of atoms, and imagine how the neat stack of paper becomes ever-so-slightly distorted at the spot where someone inserts a bookmark.

Normal metals bend because dislocations are able to move, allowing a material to deform without ripping apart every single bond inside its crystal lattice at once.

Strengthening techniques typically restrict the motion of dislocations. So it was quite a shock when Szlufarska and colleagues discovered that the material samarium cobalt -- known as an intermetallic -- bent easily, even though its dislocations were locked in place.

"It was believed that metallic materials would be intrinsically brittle if dislocation slip is rare," says Hubin Luo, a former staff scientist in Szlufarska's lab now working at Ningbo Institute of Industrial Technology in China. "However, our recent study shows that an intermetallic can be deformed plastically by a significant amount even when the dislocation slip is absent."

Instead, bending samarium cobalt caused narrow bands to form inside the crystal lattice, where molecules assumed a free-form "amorphous" configuration instead of the regular, grid-like structure in the rest of the metal.

Those amorphous bands allowed the metal to bend.

"It's almost like lubrication," says Szlufarska. "We predicted this in simulations, and we also saw the amorphous shear bands in our deformation studies and transmission electron microscopy experiments."

A combination of computational simulations and experimental studies was critical to explaining the perplexing result, which is why Szlufarska and her group were exceptionally suited to crack open the mystery.

"It is often easier to carry out theoretical simulations to explain existing experimental results," says Hongliang Zhang, a UW-Madison postdoctoral scholar. "Here, we first theoretically predicted the existence of shear bands and their role in plasticity in samarium cobalt; these were entirely surprising phenomena. We then confirmed these results experimentally with many different types of experiments to test our theory and to be sure that the predicted phenomenon can be indeed observed in nature."

The researchers plan to search for other materials that might also bend in this peculiar manner. Eventually, they hope to use the phenomenon to tune a material's properties for strength and flexibility.

"This might change the way you look for optimization of material properties," says Szlufarska. "We know it's different, we know it's new, and we think we can use it."

Lack of sleep can be dangerous; it is thought to play a role in up to 30% of all motor vehicle crashes and even implicated in catastrophic events, such as the Chernobyl nuclear disaster (1, 2). As sleepy individuals are often unaware of their performance impairments, there is a critical need for objective measures of deficits due to sleepiness to prevent accidents. New research published today in the The Journal of Physiology shows that a range of eye-movement tests provide a reliable biomarker of individual acute sleep loss. (Learn more in our video: https://www.youtube.com/watch?v=yBXxSqQ0F_U&feature=youtu.be).

The research, conducted at NASA's Ames Research Center in California's Silicon Valley, found that a set of easily-obtainable eye-movement measures could be used to provide a sensitive and reliable tool to detect small neural deficits. Importantly, these measures could even be used to distinguish sleep-related impairment from that due to alcohol or brain injury.

To establish a baseline, the research team had the participants experience two weeks with a regular 8.5 hours per night sleep schedule and abstain from any alcohol, drugs, or caffeine so that they were sure they started the experiment completely well-rested with no sleep debt or disruptions.

They then had the participants spend up to 28 hours awake in the Fatigue Countermeasures Laboratory at NASA Ames, where they tested them periodically throughout the day and night to monitor how their visual and eye-movement performance changed throughout the day-night cycle.

By using state-of-the-art eye movement research techniques, they were able to generate reliable effects showing trends of increasing impairment throughout the night for components of motion perception, such as smooth, continuous tracking eye movements (called pursuit), and effects on the small, episodic, jumping corrective eye movements (called saccades)

The researchers found that when participants were asked to track stimuli with unpredictable onset, direction, speed and starting location, human eye movements were dramatically impaired.

These findings have important implications for individuals who work in jobs requiring vigilant monitoring and precise motor action, such as military personnel, surgeons and truck drivers. These measures could be used in assessing individuals working during the biological night, or following sleep loss.

Lee Stone, senior author on the study said:

"There are significant safety ramifications for workers who may be performing tasks that require precise visual coordination of one's actions when sleep deprived or during night shifts. By looking at a wide variety of components of human eye movements, we could not only detect sleepiness but also distinguish it from other factors, such as alcohol use or brain injury, that we have previously shown cause subtly different deficits in eye movements."