Did The Ancient Maya Have Parks? (Archeology)

A first-of-its-kind DNA analysis finds trees and wild vegetation grew around reservoirs in Tikal

The ancient Maya city of Tikal was a bustling metropolis and home to tens of thousands of people.

The city comprised roads, paved plazas, towering pyramids, temples and palaces and thousands of homes for its residents, all supported by agriculture.

Now researchers at the University of Cincinnati say Tikal’s reservoirs — critical sources of city drinking water — were lined with trees and wild vegetation that would have provided scenic natural beauty in the heart of the busy city.

UC researchers developed a novel system to analyze ancient plant DNA in the sediment of Tikal’s temple and palace reservoirs to identify more than 30 species of trees, grasses, vines and flowering plants that lived along its banks more than 1,000 years ago. Their findings painted a picture of a lush, wild oasis.

“Almost all of the city center was paved. That would get pretty hot during the dry season,” said paleoethnobotanist David Lentz, a professor of biology in UC’s College of Arts and Sciences and lead author of the study.

“So it would make sense that they would have places that were nice and cool right along the reservoir,” he said. “It must have been beautiful to look at with the water and trees and a welcome place for the kings and their families to go.”

The study was published in the Nature journal Scientific Reports.

An aerial view of Tikal using light detection and ranging technology.
An aerial view using light detection and ranging or LIDAR shows the ancient layout of the city center at Tikal. Graphic/Scientific Reports

Lentz and his research team offered four hypotheses about what, if any, plants might have grown along the all-important reservoirs: Did the Maya grow crops such as maize or squash there? Or did they plant fruit trees like those found at a similar reservoir at Mexico’s Purron Dam?

Maybe they lined the reservoirs with cattails in keeping with their nickname people of the reeds? Lentz noted that water lilies often adorn ancient Maya paintings.

“Throughout Maya iconography, water lilies represent continuity between the water world and the above world,” Lentz said. “It was part of their mythology.”

But researchers found little evidence to support any of these hypotheses. Instead, they found evidence bolstering a fourth idea: that the Maya allowed the embankments to remain undisturbed forest. This would have helped to prevent erosion and provided medicinal or edible plants and fruits.

Having a sacred grove adjacent to the sacred spring and pool at the heart of the city was an extremely potent symbol — kind of like parts of the cosmos in miniature.

 — Nicholas Dunning, UC geography professor

Researchers found evidence of a variety of plants living along the aquifers, including trees like cabbage bark and ramón that tower 100 feet high. Lentz said ramón is a dominant rainforest species in Guatemala.

“Why you would find ramón around the reservoir is a curiosity. The answer is they left this forest intact,” Lentz said. “Tikal has a harsh climate. It’s pretty tough to survive when you don’t get rain for five months of the year. This reservoir would have been the font of their lives. So they sometimes would protect these places by not cutting down the trees and preserving a sacred grove.”

Among dozens of plants native to the region, they found evidence of wild onion, fig, wild cherry and two types of grasses. Lentz said grass seeds might have been introduced to the reservoir by visiting waterfowl. Grass would have proliferated at the edges of the reservoirs during dry seasons and droughts.

“Tikal had a series of devastating droughts. As the water levels dropped, they saw blue green algae blooms, which produces toxic substances,” Lentz said. “The droughts were great for the grass but not so much for the forest plants that lived along the reservoir’s banks.”

The pyramids of Tikal rise above the rainforest.
The ancient Maya city of Tikal in Guatemala. Photo/Jimmy Baum/Wikimedia Commons

Were these wild areas the equivalent of a park?

“I think they were. I don’t know how public they would have been,” Lentz said. “This was a sacred area of the city surrounded by temples and palaces. I don’t know if the commoners would have been that welcome.”

Tikal was a flourishing seat of power, religion and trade for Mesoamerica in what is now northern Guatemala, reaching its peak of influence more than 1,200 years ago. Today, the cultural and archaeological site is a scenic national park surrounded by primary rainforest.

But more than 1,000 years ago, the area would have looked dramatically different. Instead of rainforest, the city center would have been surrounded by homes and farm plots of corn, beans and squash needed to support 60,000 people or more. At its peak, Tikal was bigger in population than Wilkes-Barre, Pennsylvania; Atlantic City, New Jersey; or Pensacola, Florida.

Mamey fruit.
UC researchers found ancient DNA from trees such as Pouteria sapota, which produces fruit called mamey. Photo/Peggy Greb/Wikimedia Commons

Given the documented and widespread deforestation that occurred around Tikal during the city’s rise and fall, the presence of an intact forest in the city would have stood out, said Nicholas Dunning, a UC geography professor and study co-author.

“It would not have been much of a park — maybe 50 meters by 50 meters,” Dunning said. “But it would have been in vivid contrast to the surrounding area of the city’s central precinct, which was essentially entirely paved with plaster with many of the buildings colored red.”

The reservoirs would have held significance beyond their value as an important source of water, he said.

“Given that the Maya were a forest culture whose cosmology included many forest elements (for example, certain sacred trees that held up the sky) having a sacred grove adjacent to the sacred spring and pool at the heart of the city was an extremely potent symbol — kind of like parts of the cosmos in miniature,” Dunning said. “On the other hand, ancient Maya cities as a whole were very green.”

Hog plums.
Hog plum in the cashew family is cultivated for its edible fruit and use in traditional medicine. Photo/SR Shaakib/Wikimedia Commons

Tikal put today’s urban gardens to shame.

“Away from the central precinct of Tikal, most of the land was either managed trees or crops,” Dunning said. “Just about every household complex had significant gardens. A great deal of the food consumed by the residents of Maya cities was probably grown within the city itself or its immediate hinterland. Nothing much like a modern Western city.”

Previously, researchers learned about the crops and wild plants that grew in ancient Tikal by studying ancient pollen or charcoal, Lentz said. For their study, UC turned to next-generation DNA sequencing that can identify plants and animals with even small strands of DNA.

“Typically, high-quality, high-concentration DNA is needed for next-gen work,” UC botanist and study co-author Eric Tepe said. “The Tikal samples were both poor quality and very low concentration.”

Microbiologists Alison Weiss, a professor in UC’s College of Medicine, and Trinity Hamilton, now with the University of Minnesota, took up the task of analyzing ancient microbial DNA from the reservoir’s sediment samples.

Weiss studies pathogenic E. coli and human microbiomes in her lab. Her latest work examined how chemotherapy in cancer patients impairs the protective lining of their digestive systems. But she likes all science, she said, and was eager to accept a new challenge.

“The DNA is ancient so it tends to be degraded with short little sequences,” Weiss said.

With the help of the Florida company Rapid Genomics, UC’s scientists developed a novel probe to select plant DNA in the sediment samples. And they were able to amplify small strands of DNA from chloroplasts, the plant structures where photosynthesis takes place. Then researchers could match the ancient Tikal samples with the DNA of known plant species in much the same way scientists amplify ribosomal DNA to identify species of bacteria.

“The analysis was quite challenging because we were the first to do this,” Weiss said. “Bacterial ribosomal DNA has a database. There was no database for this. We had to take sequences one by one and search the general database to find the best match.”

“This project was a bit of a shot in the dark,” Tepe said. “We half-expected to get no results at all. The fact that we were able to get an idea of the vegetation surrounding the reservoirs at Tikal is, in my opinion, a spectacular success and a proof of concept that we hope to apply to other Mayan sites.”

UC researchers can now study the ancient world in a promising new way.

“We’re delighted we had success,” Weiss said. “It took a long time to figure out how to do it and make sure it wasn’t junk data in, junk data out. Now to be able to learn more about ancient people from these sediment studies is very exciting.”

Featured image at top: UC College of Arts and Sciences biology professor David Lentz stands in front of a pyramid at Tikal in Guatemala. Photo/Provided

Reference: Lentz, D.L., Hamilton, T.L., Dunning, N.P. et al. Environmental DNA reveals arboreal cityscapes at the Ancient Maya Center of Tikal. Sci Rep 11, 12725 (2021). https://doi.org/10.1038/s41598-021-91620-6

Provided by UC Cincinnati

How a Bone Marrow Fat Hormone Controls Metabolism And Bone Cell Development? (Medicine)

A new study reveals how a hormone located in fat cells inside bone marrow helps control the production of bone and fat in response to changing conditions.

An enzyme found in fat tissue in the centre of our bones helps control the production of new bone and fat cells, shows a study in mice published today in eLife.

The findings may help scientists better understand how the body maintains fat stores and bone production in response to changing conditions, such as during aging. They may also suggest new approaches to treating conditions that cause bone loss in older adults.

Fat cells, including those found in the bone marrow, are increasingly recognised as an important part of the body that helps regulate body weight, insulin sensitivity and bone mass. Fat tissue in the bone marrow expands as people age, or when they take certain diabetes medications, and during prolonged fasting.

“This expansion of bone marrow fat is strongly associated with bone loss in mice and humans,” explains lead author Nicole Aaron, PhD, a graduate student at Columbia University Vagelos College of Physicians and Surgeons, New York, US. “But how these changes occur is still not well understood.”

Aaron and her colleagues conducted a series of experiments to explore these processes further. They fed mice a calorie-restricted diet and found that this caused fat in their bone marrow to grow and increased the production of an enzyme called adipsin. The levels of adipsin were also high in mice treated with a diabetes drug called rosiglitazone, which increases bone marrow fat and decreases bone mass. Aging also caused similar changes in the animals.

The team then carried out similar experiments in mice that were genetically engineered to lack adipsin. They found that the animals were resistant to these changes, and had less bone marrow fat and stronger bones. Specifically, these experiments showed that adipsin appears to cause stem cells in the bone marrow to develop into fat cells rather than bone cells.

“Similarly, results from our human studies also revealed that the expansion of bone marrow fat with fasting was associated with a marked increase in adipsin and evidence of bone breakdown,” says author Clifford Rosen, Director of Clinical and Translational Research at Maine Medical Center, Portland, Maine, US. “These findings may help explain the link between expansion of bone marrow fat tissue and bone strength, particularly during aging.”

Drugs that block adipsin are currently being developed to treat people with a form of age-related vision loss. The current study also suggests these drugs might help increase bone mass in older people with diseases such as osteoporosis that cause progressive bone loss.

“There is the potential for these existing treatments to be repurposed to treat and prevent age-related skeletal disorders,” concludes senior author Li Qiang, PhD, Assistant Professor of Pathology and Cell Biology at Columbia University Vagelos College of Physicians and Surgeons. “These treatments could also potentially be targeted to individuals who develop bone loss as a result of eating disorders, such as anorexia, or aging.”

The study, “Adipsin promotes bone marrow adiposity by priming mesenchymal stem cells”, published in elife, DOI: 10.7554/eLife.69209

Provided by Elife

How Pancreatic Cancer Cells Dodge Drug Treatments? (Medicine)

The Takeaway

Pancreatic cancer cells typically rely on a mutant version of the KRAS protein to proliferate. These cancer cells can also survive losing KRAS by activating alternative growth pathways. CSHL scientists discovered a new interaction between mutant KRAS and a protein complex called RSK1/NF1 that may be the source of this adaptive resistance.

Cancer cells can become resistant to treatments through adaptation, making them notoriously tricky to defeat and highly lethal. Cold Spring Harbor Laboratory (CSHL) Cancer Center Director David Tuveson and his team investigated the basis of “adaptive resistance” common to pancreatic cancer. They discovered one of the backups to which these cells switch when confronted with cancer-killing drugs.

KRAS is a gene that drives cell division. Most pancreatic cancers have a mutation in the KRAS protein, causing uncontrolled growth. But, drugs that shut off mutant KRAS do not stop the proliferation. The cancer cells find a way to bypass the blockage and keep on dividing. Derek Cheng, the lead author of the study and a former Medical Scientist Training Program student in the Tuveson lab, compares this process to backup engines on a ship. He says:

“You take away your main engine, you’re kind of on some backup engines. But it’s getting by on those. The ship isn’t sinking yet. It’s still moving at a slower pace. Ultimately what we want to do is sink the ship.”

Image of Pancreatic Cancer Cells
When KRAS (red) is modified to stay in the cytoplasm or center of the cell, as seen in these pancreas cells, the protein does not promote cell division. In pancreatic cancer cells, a mutant form of KRAS stays close to the cell’s outer layer and interacts with nearby proteins to cause the cells to divide far too much. Image: Derek Cheng/Tuveson lab

Tuveson and his team wanted to figure out the “backup engines” in these cancer cells. They used a technique called biotin proximity labeling to identify what other proteins interacted with mutant KRAS. Cheng says, “I basically attach a spray can to my favorite protein, or rather least favorite protein, in this case. And so it attaches biotin, basically spraying biotin ‘paint’ to nearby proteins, and we’re able to analyze it to figure out what proteins were labeled.”

The scientists found “biotin paint” on a protein named RSK1, which is part of a complex that keeps a nearby group of proteins, called RAS proteins, dormant. The scientists were surprised to discover that when they inactivated mutant KRAS, the nearby RSK1 complex stopped working as well. This allowed the RAS proteins to activate and take over the work of the missing mutant KRAS.

Stopping pancreatic cancer cells may require drugs that can simultaneously target multiple molecules. Tuveson hopes to uncover more of the players contributing to adaptation in cancer cells to improve future treatments.


The Lustgarten Foundation, the Cold Spring Harbor Laboratory Association, the V Foundation, the Thompson Foundation, the National Institutes of Health, the Simons Foundation, the National Cancer Institute, the Cold Spring Harbor Laboratory and Northwell Health Affiliation (Project Lazarus)


Cheng, D., et al., “Oncogenic KRAS engages an RSK1/NF1 pathway to inhibit wild-type RAS signaling in pancreatic cancer”Proceedings of the National Academy of Sciences, May 21, 2021. DOI: 10.1073/pnas.2016904118

Featured image: Most pancreatic cancer cells have mutations in the KRAS gene that allow unregulated growth. In this image, the mutant, cancer-causing version of the KRAS protein is stained red in pancreatic cancer cells. KRAS outlines the plasma membrane—the outer layer of the cell. Cell nuclei are stained blue. Cold Spring Harbor Laboratory researchers discovered a new mechanism that might explain how pancreatic cancer cells develop resistance to drug treatments that target the KRAS protein. Image: Derek Cheng/Tuveson lab

Provided by Cold Spring Harbor Laboratory

Ready, Set, Go – How Stem Cells Synchronise to Repair The Spinal Cord in Axolotls (Biology)

The spinal cord is an important component of our central nervous system: it connects the brain with the rest of the body and plays a crucial part in coordinating our sensations with our actions. Falls, violence, disease – various forms of trauma can cause irreversible damage to the spinal cord, leading to paralysis, sometimes even death.

Although many vertebrates, including humans, are unable to recover from a spinal cord injury, some animals stand out. For instance, the axolotl (Ambystoma mexicanum), a salamander from Mexico, has the remarkable ability to regenerate its spinal cord after an injury. When an axolotl’s tail is amputated, neural stem cells residing in the spinal cord are recruited to the injury to rebuild the tail. So far, scientists could only detect this activity a few days after the process had started.

“Four days after amputation, stem cells within about one millimetre of the injury divide three times as fast as the normal rate to regenerate the spinal cord and replace lost neurons,” explains Emanuel Cura Costa, co-first author of the study. “What the stem cells are doing in the first four days after injury was the real mystery.”

To understand what happens in the first moments of spinal cord regeneration, researchers at CONICET, IMP, and TU Dresden teamed up to recreate the process in a mathematical model and test its predictions in axolotl tissue with the latest imaging technologies. Their findings, published in eLife, show that neural stem cells accelerate their cell cycles in a highly synchronised manner, with the activation spreading along the spinal cord.

Regenerating in sync: cells follow the tempo

In the uninjured spinal cord, cells multiply asynchronously: some are actively replicating their DNA before splitting into two cells to sustain growth, while some are simply resting.

The scientists’ model predicted that this could change dramatically upon injury: most cells in the vicinity of the injury would jump to a specific stage of the cell cycle to synchronise and proliferate in unison.

“We developed a tool to track individual cells in the growing spinal cord of axolotls. Different colours label resting and active cells, which allow us to see how far and how fast cell proliferation happens with a microscope,” says Leo Otsuki, postdoc in the lab of Elly Tanaka at the IMP and co-first author of this study. “We were very excited to see the match between the theoretical predictions and the experimental results.”

The way cells multiply in chorus in the regenerating spinal cord is exceptional in animals. How can cells coordinate their efforts over almost one millimetre – 50 times the size of a single cell?

A mystery signal orchestrating regeneration

“Our model made us realise there had to be one or more signals that spread through the tissue from the injury, like a wave, for the area of proliferating cells to expand,” explains Osvaldo Chara, career researcher at CONICET, group leader of SysBio at the Institute of Physics of Liquids and Biological Systems (IFLySIB) and guest professor at Center for Information Services and High Performance Computing (ZIH), Technische Universität Dresden. “This signal might act like a messenger and instruct stem cells to proliferate.”

The researchers suspect that this mystery messenger helps reprogram stem cells to divide rapidly and regrow amputated tissue. Their work pinpoints this signal in space and time, and paves the way to characterise it further.

“Combining mathematical models with our expertise in tissue imaging was key to understanding how the spinal cord starts regenerating,” says Elly Tanaka, senior scientist at the IMP. “The next step is to identify the molecules that promote regeneration of the spinal cord – that could have tremendous therapeutic potential for patients with spinal injuries.”

Featured image: Cross-section of axolotl spinal cord. Neural stem cells in the middle (red and green) line the fluid-filled central canal, nerve fibres are on the outside (yellow). Blue labels cell nuclei. © L. Otsuki/IMP

Original publication

Cura Costa, E., Otsuki, L., Rodrigo Albors, A., Tanaka, E. M., Chara, O.: “Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration”. eLife, 8 June 2021. DOI: https://doi.org/10.7554/eLife.55665.

Provided by Technische Universitat Dresden

Exotic Superconductors: The Secret That Wasn’t There (Physics)

How reproducible are measurements in solid-state physics? New measurements show: An allegedly sensational effect does not exist at all.

A single measurement result is not a proof – this has been shown again and again in science. We can only really rely on a research result when it has been measured several times, preferably by different research teams, in slightly different ways. In this way, errors can usually be detected sooner or later.

However, a new study by Prof. Andrej Pustogow from the Institute of Solid State Physics at TU Wien together with other international research teams shows that this can sometimes take quite a long time. The investigation of strontium ruthenate, a material that plays an important role in unconventional superconductivity, has now disproved an experiment that gained fame in the 1990s: it was believed that a novel form of superconductivity had been discovered. As it now turns out, however, the material behaves very similarly to other well-known high-temperature superconductors. Nevertheless, this is an important step forward for research.

Two particles with coupled spin

Superconductivity is one of the great mysteries of solid-state physics: certain materials lose their electrical resistance completely at low temperatures. This effect is still not fully understood. What is certain, however, is that so-called “Cooper pairs” play a central role in superconductivity.

In a normal metal, electric current consists of individual electrons that collide with each other and with the metal atoms. In a superconductor, the electrons move in pairs. “This changes the situation dramatically,” explains Andrej Pustogow. “It’s similar to the difference between a crowd in a busy shopping street and the seemingly effortless motion of a dancing couple on the dance floor.” When electrons are bound in Cooper pairs, they do not lose energy through scattering and move through the material without any disturbance. The crucial question is: Which conditions lead to this formation of Cooper pairs?

Pyramid shaped crystal in a coil. © TU Wien

“From a quantum physics point of view, the important thing is the spin of these two electrons,” says Andrej Pustogow. The spin is the magnetic moment of an electron and can point either ‘up’ or ‘down’. In Cooper pairs, however, a coupling occurs: in a ‘singlet’ state, the spin of one electron points upwards and that of the other electron points downwards. The magnetic moments cancel each other out and the total spin of the pair is always zero.

However, this rule, which almost all superconductors follow, seemed to be broken by the Cooper pairs in strontium ruthenate (Sr2RuO4). In 1998, results were published that indicated Cooper pairs in which the spins of both electrons point in the same direction (then it is a so-called “spin triplet”). “This would enable completely new applications,” explains Andrej Pustogow. “Such triplet Cooper pairs would then no longer have a total spin of zero. This would allow them to be manipulated with magnetic fields and used to transport information without loss, which would be interesting for spintronics and possible quantum computers.”

This caused quite a stir, not least because strontium ruthenate was also considered a particularly important material for superconductivity research for other reasons: its crystal structure is identical to that of cuprates, which exhibit high-temperature superconductivity. While the latter are deliberately doped with “impurities” to make superconductivity possible, Sr2RuO4 is already superconducting in its pure form.

New measurement, new result

“Actually, we studied this material for a completely different reason,” says Andrej Pustogow. “But in the process, we realised that these old measurements could not be correct.” In 2019, the international team was able to show that the supposedly exotic spin effect was just a measurement artefact: the measured temperature did not match the actual temperature of the sample studied; in fact, the sample studied at the time was not superconducting at all. With this realisation in mind, the superconductivity of the material was now re-examined with great precision. The new results clearly show that strontium ruthenate is not a triplet superconductor. Rather, the properties correspond to what is already known from cuprates.

However, Andrej Pustogow does not find this disappointing: “It is a result that brings our understanding of high-temperature superconductivity in these materials another step forward. The finding that strontium ruthenate shows similar behaviour to cuprates means two things: On the one hand, it shows that we are not dealing with an exotic, new phenomenon, and on the other hand it also means that we have a new material at our disposal, in which we can investigate already known phenomena.” Ultra-pure strontium ruthenate is better suited for this than previously known materials. It offers a much cleaner test field than cuprates.

In addition, one also learns something about the reliability of old, generally accepted publications: “Actually, one might think that results in solid-state physics can hardly be wrong,” says Pustogow. “While in medicine you might have to be satisfied with a few laboratory mice or a sample of a thousand test subjects, we examine billions of billions (about 10 to the power of 19) electrons in a single crystal. This increases the reliability of our results. But that does not mean that every result is completely correct. As everywhere in science, reproducing previous results is indispensable in our field – and so is falsifying them.”

Original publications

The first paper, published in 2019

A. Pustogow et al, Nature volume 574, pages72–75 (2019)., opens an external URL in a new window

The new paper (2021)

A. Chronister et al., PNAS June 22, 2021 118 (25)

Featured image: Experiments in the lab at TU Wien © Tu Wien

Provided by Tu Wien

Scientists Identify Combination of Biological Markers Associated With Severe Dengue (Medicine)

New findings could improve the triage process for patients with dengue and help clinicians determine those who may be at risk of developing moderate to severe disease.

Researchers have identified a combination of biological markers in patients with dengue that could predict whether they go on to develop moderate to severe disease, according to a study published today in eLife.

Biomarkers are used to identify the state or risk of a disease in patients. Examples of biomarkers can include naturally occurring molecules or genes in the vascular, inflammatory or other biological pathways. The new findings could aid the development of biomarker panels for clinical use and help improve triage and risk prediction in patients with dengue.

Dengue is the most common mosquito-borne viral disease to affect humans globally. In 2019, the World Health Organization identified dengue as one of the top 10 threats to global health, with transmission occurring in 129 countries and an estimated 3.9 billion people being at risk.

“While most symptomatic dengue infections are self-limiting, a small number of patients develop complications that usually occur at around four to six days from symptom onset,” explains first author Vuong Nguyen Lam, Researcher and PHD Student at Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam. “Large numbers of patients therefore need regular assessments to identify these complications. The accurate and early identification of such patients, particularly within the first three days of illness, should allow for the appropriate care to be provided.”

The role of blood biomarkers in predicting severe outcomes has been investigated in other studies, but mostly in the later stages of disease progression or at hospital admission. Many of these biomarkers either peak too late in the disease course or have too short a half-life to be clinically useful.

To address this, Vuong and colleagues selected 10 candidate biomarkers from vascular, immunological and inflammatory pathways that are associated with dengue disease pathogenesis. These biomarkers were: VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, and CRP. They were chosen based on their likelihood to be increased during the early stages of disease.

The team then conducted a study using samples and clinical information from a large multi-country observational study called ‘Clinical evaluation of dengue and identification of risk factors for severe disease’ (IDAMS study). Of the 2,694 laboratory-confirmed dengue cases included in the IDAMS study, 38 and 266 cases were classified as severe and moderate dengue, respectively.

For the current study, the researchers selected 281 cases in four countries – Vietnam, Cambodia, Malaysia and El Salvador – as the blood samples from these participants were stored at the OUCRU laboratory. For comparison, the team also selected 556 patients with uncomplicated dengue who shared similar geographies and demographic characteristics.

They measured the participants’ blood biomarkers at two different time points – one during the first three days of illness, and the second following recovery (10–31 days after symptom onset). They found that, during the first three days of illness, higher levels of any of the 10 biomarkers increased a patient’s risk of developing moderate to severe dengue.

They also identified a combination of six biomarkers that was best associated with severe disease in children, and a combination of seven biomarkers that was best associated with severe disease in adults. “This highlights how relationships between biomarkers and clinical outcome can differ between age groups,” Vuong says.

“Together, our findings should assist the development of biomarker panels to help improve future triage and early assessment of dengue patients,” concludes senior author Sophie Yacoub, Dengue Research Group Head at OUCRU. “This would help improve individual patient management and healthcare allocation, which would be of major public health benefit especially in outbreak settings.”

Featured image: Blood samples. Image credit: Public domain

Provided by Elife

The Very Venomous Caterpillar (Biology)

The venom of a caterpillar, native to South East Queensland, shows promise for use in medicines and pest control, Institute for Molecular Bioscience researchers say.

The Doratifera vulnerans is common to large parts of Queensland’s south-east and is routinely found in Toohey Forest Park on Brisbane’s southside.

Dr Andrew Walker has been researching the striking looking caterpillar since 2017.

Venomous caterpillar has strange biology

“We found one while collecting assassin bugs near Toowoomba and its strange biology and pain-causing venom fascinated me,” Dr Walker said.

Unlike The Very Hungry Caterpillar that charmed generations of children around the world, this caterpillar is far from harmless. 

“Its binomial name means ‘bearer of gifts of wounds’,” Dr Walker said.

Caterpillar venom similar to spiders

The caterpillar has spines that inject liquid venom. © University of Queensland

Dr Walker’s research found the caterpillar has venom toxins with a molecular structure similar to those produced by spiders, wasps, bees and ants.

The research also unlocked a source of bioactive peptides that may have uses in medicine, biotechnology or as scientific tools.

“Many caterpillars produce pain-inducing venoms and have evolved biological defences such as irritative hairs, toxins that render them poisonous to eat, spots that mimic snake eyes or spines that inject liquid venoms,” Dr Walker said.

“Previously researchers had no idea what was in the venom or how they induce pain.

Venom with stunning complexity

“We found that the venom is mostly peptides and shows stunning complexity, containing 151 different protein-based toxins from 59 different families.”

The researcher team synthesised 13 of the peptide toxins and used them to show the unique evolutionary trajectory the caterpillar followed to produce pain-inducing venom.

“We now know the amino acid sequences, or the blueprints, of each protein-based toxin,” Dr Walker said.

“This will enable us to make the toxins and test them in diverse ways.”

Credit: Jiayi Jin

Venom which can kill bacteria

Some peptides already produced in the laboratory as part of Dr Walker’s research showed very high potency, with potential to efficiently kill nematode parasites that are harmful to livestock, as well as disease-causing pathogens.

“Our research unlocks a new source of bioactive peptides that may have use in medicine, through an ability to influence biological processes and promote good health,” he said.

Potential for medicines and pesticides

“First, we need to work out what the individual toxins do, to inform us about how they might be used.”

The findings incorporate work from researchers at the CSIRO, Canada’s York University, Austria’s University of Vienna and the Department of Food and Agriculture in the US.

The research is published in the Proceedings of the National Academy of Sciences of the USA.

Featured image: The Doratifera vulnerans is common to large parts of Queensland’s south-east. © Jiayi Jin

Reference: Andrew A. Walker, Samuel D. Robinson, Jean-Paul V. Paluzzi, David J. Merritt, Samantha A. Nixon, Christina I. Schroeder, Jiayi Jin, Mohaddeseh Hedayati Goudarzi, Andrew C. Kotze, Zoltan Dekan, Andy Sombke, Paul F. Alewood, Bryan G. Fry, Marc E. Epstein, Irina Vetter, Glenn F. King, “Production, composition, and mode of action of the painful defensive venom produced by a limacodid caterpillar, Doratifera vulnerans”, PNAS May 4, 2021 118 (18) e2023815118; https://doi.org/10.1073/pnas.2023815118

Provided by University of Queensland

Soft Robots — Smart Elastomers Are Making the Robots of the Future More Touchy-feely (Engineering)

Imagine flexible surgical instruments that can twist and turn in all directions like miniature octopus arms, or how about large and powerful robot tentacles that can work closely and safely with human workers on production lines. A new generation of robotic tools are beginning to be realized thanks to a combination of strong ‘muscles’ and sensitive ‘nerves’ created from smart polymeric materials. A research team led by the smart materials experts Professor Stefan Seelecke and Junior Professor Gianluca Rizzello at Saarland University is exploring fundamental aspects of this exciting field of soft robotics.

In the factory of the future, man and machine will work side-by-side – in harmony, as a team, joining forces whenever necessary – just as if the robot co-worker was made from flesh and blood. While collaborative robots (‘cobots’) are already being deployed in industrial production lines, real hand-in-hand teamwork involving robots and their human counterparts is still some way off. The problem lies in the physical proximity of human co-workers, whose actions – unlike those of a robot – do not follow predictable algorithms. A human worker can become tired or distracted and may act suddenly or even illogically as a result. This has clear implications for safety and explains why the robot arms currently used on production lines are often housed in cages. For anyone who gets too close, things can get dangerous. Typically, industrial robots are large, heavy machines. But they are also powerful, fast and agile and are used for a wide range of operations, like welding, assembling, painting, stacking and lifting. However, the motions that they execute are dictated wholly by the programs that control them. And if someone gets in their way or too close, the consequences can be serious.

The team led by Professor Stefan Seelecke and Junior Professor Gianluca Rizzello of Saarland University and the Center for Mechatronics and Automation Technology (ZeMA) in Saarbrücken are working on new, smart types of robot arms. ‘Our technology is based on smart polymer systems and enables us to create novel soft robotic tools that are lighter, more manoeuvrable and more flexible than the rigid components in use today,’ explains Stefan Seelecke. An accidental shove from one of these robotic arms of the future would be more like being pushed by a human co-worker (and less likely to land you in hospital).

The material used for these new soft robot arms is a special kind of polymer known as a ‘dielectric elastomer’. The Saarbrücken researchers are using this composite material to create artificial muscles and nerves. The special properties of dielectric elastomers make it possible to develop systems inspired by the ingenious designs found in nature. These elastomers can be compressed, but can then be stretched to regain their original shape. ‘We print electrodes onto both sides of the elastomer material. When we apply a voltage, the two electrodes attract each other, compressing the polymer and causing it to expand out sideways,’ says Dr. Gianluca Rizzello, Junior Professor for Adaptive Polymer-Based Systems. The Italian research scientist has been working in Seelecke’s team since 2016. The elastomer can thus be made to contract and relax, just like muscle tissue. ‘We exploit this property when designing our actuators,’ explains Rizzello. By precisely varying the electric field, the engineers can make the elastomer execute high-frequency vibrations or continuously variable flexing motions or even remain still in a particular desired intermediate position.

The researchers then combine a large number of these small ‘muscles’ to create a flexible robot arm. When combined in this way to form a robot tentacle, the interplay between the muscles produces motions that mimic those of an octopus arm that can twist and turn in all directions. Unlike the heavy, rigid robotic limbs currently in use, which, like humans, can only execute motions in certain directions, these new robot tentacles are free to move in almost any direction. Gianluca Rizzello together with his doctoral student Johannes Prechtl recently won the Best Paper Award at the RoboSoft 2021 conference for their work on developing a prototype dielectric-elastomer-based tentacle – just one of the numerous accolades earned by Professor Seelecke’s research team. The team hopes to have the tentacle prototype fully developed in about a year’s time.

When it comes to imparting intelligence into polymeric materials, Gianluca Rizzello is something of an expert. He provides the control unit (i.e. the robot’s ‘brain’) with the input needed to move the arm in an intelligent manner – a highly complex and ambitious task. ‘These systems are significantly more complex than the robot arms in use today. Using artificial intelligence to control polymer-based components is substantially more challenging than controlling conventional mechatronic systems,’ explains Rizzello. As the elastomer muscles also have sensor properties, they can act as the system’s nerves, which means that the robot arm does not need to be equipped with additional sensors. ‘Every distortion of the elastomer, every change in its geometry causes a change in the material’s capacitance, which enables the team to assign a precise electrical capacitance value to any specific deformation of the elastomer. By measuring the capacitance, we know exactly what shape the elastomer has adopted, which allows us to extract sensor data,’ explains Rizzello.

This quantitative data can then be used to precisely model and program the motion of the elastomer arm. The focus of Rizzello’s research work is on developing intelligent algorithms that can train these novel robot tentacles to move and respond in the required manner. ‘We are attempting to uncover which physical properties are responsible for the behaviour of these polymers. The more we know, the more precisely we can design the algorithms to control the elastomer muscles,’ says Dr. Rizzello.

The technology being developed in Saarland will be scalable. It can be used to create miniature tentacles for medical instruments or to make large robot arms for industrial applications. But unlike the heavy robot arms in use today, the robot limbs built from smart elastomers will be far lighter. ‘Our robot arms don’t need to be driven by motors or by hydraulic or pneumatic systems – they can be powered simply by the application of an electric current. The elastomer muscles can also be produced in shapes that meet the requirements of a particular application. And they consume very little electric power. Depending on the capacitance, the electric currents that flow are in the microampere range. This type of soft robot technology has huge promise for the future as it is both energy efficient and cost-effective to manufacture,’ says Stefan Seelecke in summary.

This research is supported by the German Research Foundation (DFG) through the Priority Programme SPP2100 ‘Soft Material Robotic Systems’.

Journal papers

(1) J. Kunze, J. Prechtl, D. Bruch, B. Fasolt, S. Nalbach, P. Motzki, S. Seelecke, and G. Rizzello, “Design, Manufacturing, and Characterization of Thin, Core-Free, Rolled Dielectric Elastomer Actuators,” Actuators, vol. 10, no. 4, p. 69, Mar. 2021 (DOI: 10.3390/act10040069). (2) G. Rizzello, P. Serafino, D. Naso and S. Seelecke, “Towards Sensorless Soft Robotics: Self-Sensing Stiffness Control of Dielectric Elastomer Actuators,” in IEEE Transactions on Robotics, vol. 36, no. 1, pp. 174-188, Feb. 2020, doi: 10.1109/TRO.2019.2944592. (3) “Modeling and Design Optimization of a Rotational Soft Robotic System Driven by Double Cone Dielectric Elastomer Actuators”, Front. Robot. AI, 10 January 2020 DOI: 10.3389/frobt.2019.00150

International conference proceedings

a.o.: J. Prechtl, J. Kunze, D. Bruch, S. Seelecke, and G. Rizzello, “Modeling and Parameter Identification of Rolled Dielectric Elastomer Actuators for Soft Robots,” in Electroactive Polymer Actuators and Devices (EAPAD) XXIII, 2021, p. 115871H (DOI: 10.1117/12.2581019)

Featured image: Imagine flexible surgical instruments that can twist and turn in all directions like miniature octopus arms, or how about large and powerful robot tentacles that can work closely and safely with human workers on production lines. A new generation of robotic tools are beginning to be realized thanks to a combination of strong ‘muscles’ and sensitive ‘nerves’ created from smart polymeric materials. A research team led by the smart materials experts Professor Stefan Seelecke and Junior Professor Gianluca Rizzello at Saarland University is exploring fundamental aspects of this exciting field of soft robotics. The photo shows Gianluca Rizzello with ‘dielectric elastomers.’ The Saarbrücken researchers are using this composite material to create artificial muscles and nerves for use in flexible robot arms. Credit: Oliver Dietze

Provided by Saarland University

Secretin Hormone Induces Satiation by Activating Brown Fat (Medicine)

Researchers from the Turku PET Centre and Technical University of Munich have discovered a new mechanism controlling satiation. According to the recently published study, the hormone secretin induces satiation by activating brown adipose tissue.

Brown adipose tissue is known for its ability to generate heat in response to cold exposure. Its activity has been proven to be connected to normal weight and glucose metabolism as well as lesser risks of cardiovascular diseases. Meals have also been shown to increase the thermogenesis in brown fat, but the significance of this phenomenon has been unclear. 

– Secretin is a hormone secreted into blood circulation by the intestines, and it stimulates the production of peptic juices in the pancreas when we have meals. In our research, we discovered secretin receptors in the brown adipose tissue of healthy people, which suggested that secretin also affects brown fat. Secretin infusions not only increased glucose uptake in brown adipose tissue, but also elevated energy expenditure in the whole body, says Doctoral Candidate, Cardiologist Sanna Laurila from the University of Turku.

Positron emission tomography images showing glucose tracer uptake after placebo and secretin infusions
Positron emission tomography images showing glucose tracer uptake after placebo and secretin infusions. Arrows show the location of brown adipose tissue.

Using magnetic resonance imaging, the researchers discovered that secretin also decreased the activity of the reward system in the brain when the subjects were looking at delicious photos of food. The subjects’ decreased appetite could also be verified with a questionnaire survey, and the time between their meals grew by 40 minutes. 

fMRI images, showing diminished activity of reward circuits
fMRI images, showing diminished activity of reward circuits during a food cue task after secretin infusion. © University of Turku

Brown fat generates great interest from the perspective of weight control because it has the ability to burn fat instead to storing it. However, humans have a relatively small amount of brown fat, which means that the metabolic advantages probably cannot be solely ascribed to increased energy consumption. 

– This newly-confirmed message chain affecting satiation in people can be one of the reasons behind the beneficial metabolic effects of brown fat, sums Professor Pirjo Nuutila

– This study underlines the functional relevance of human brown fat in controlling energy balance as it affects both food intake and energy expenditure, comments Professor Martin Klingenspor from the Technical University of Munich.

The newly-discovered mechanism controlling satiation opens up new opportunities for the research of the development, prevention, and treatment of obesity. Further research is needed to investigate in more detail what kind of role secretin has in metabolic disorders such as metabolic syndrome, obesity, and type 2 diabetes.    

In 2018, researchers from the Technical University of Munich and the Turku PET Centre discovered using mouse models a new mechanism mediated via brown adipose tissue and impacting satiation, and the research results were published in the journal Cell.

The most recent research findings have been published in the journal Nature Metabolism.

Pirjo Nuutila’s research group is part of the InFLAMES Flagship which is a joint initiative of University of Turku and Åbo Akademi University. The goal of the Flagship is to integrate immunological and immunology-related research activities to develop and exploit new diagnostic and therapeutic tools.

Reference: Laurila, S., Sun, L., Lahesmaa, M. et al. Secretin activates brown fat and induces satiation. Nat Metab 3, 798–809 (2021). https://doi.org/10.1038/s42255-021-00409-4

Provided by University of Turku