Mount Merapi on Java is among the most dangerous volcanoes in the world. Geoscientists have usually used seismic measurements which illustrate underground movements when warning the population of a coming eruption in time.

An international team including scientists from the Technical University of Munich (TUM) has now found another indication for an upcoming eruption in the lava from the peak of Mount Merapi: The uppermost layer of stone, the “plug dome,” becomes impermeable for underground gases before the volcano erupts.

“Our investigations show that the physical properties of the plug dome change over time,” says Prof. H. Albert Gilg from the TUM Professorship for Engineering Geology . “Following an eruption the lava is still easily permeable, but this permeability then sinks over time. Gases are trapped, pressure rises and finally the plug dome bursts in a violent explosion.”

Mount Merapi as a model volcano

Using six lava samples, one from an eruption of Mount Merapi in 2006, the others from the 1902 eruption — the researchers were able to ascertain alterations in the stone. Investigation of pore volumes, densities, mineral composition and structure revealed that permeability dropped by four orders of magnitude as stone alteration increased. The cause is newly formed minerals, in particular potassium and sodium aluminum sulfates which seal the fine cracks and pores in the lava.

The cycle of destruction

Computer simulations confirmed that the reduced permeability of the plug dome was actually responsible for the next eruption. The models show that a stratovolcano like Mount Merapi undergoes three phases: First, after an eruption when the lava is still permeable, outgassing is possible; in the second phase the plug dome becomes impermeable for gases, while at the same time the internal pressure continuously increases; in the third phase the pressure bursts the plug dome.

Photographs of Mount Merapi from the period before and during the eruption of May 11, 2018 support the three-phase model: The volcano first emitted smoke, then seemed to be quiet for a long time until the gas found an escape and shot a fountain of ashes kilometers up into the sky.

“The research results can now be used to more reliably predict eruptions,” says Gilg. “A measurable reduction in outgassing is thus an indication of an imminent eruption.”

Mount Merapi is not the only volcano where outgassing measurements can help in the timely prediction of a pending eruption. Stratovolcanoes are a frequent source of destruction throughout the Pacific. The most famous examples are Mount Pinatubo in the Philippines, Mount St. Helens in the western USA and Mount Fuji in Japan.

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“This molecule is interesting because it builds different structures depending on the conditions when it reaches the bifurcation point of its synthesis,” said Professor Shuichi Hiraoka from the Department of Basic Science. Hiraoka’s research interests are about how molecules put themselves together, including DNA in living cells or micelles, found in both nature and the cosmetics industry.

The bifurcation point is a “fork in the road” of the chemical synthesis pathway where the same precursor molecules can connect in two different ways to eventually form different final structures. In the present reaction, the precursors take different paths depending on the presence or absence of a third molecule.

The precursor molecules are palladium metal atoms and an organic molecule — 1,4-bis(3-pyridyloxy)benzene — made from three rings that can easily swing between an S-shape and C-shape orientation.

The third molecule whose presence or absence influences which path the precursors take is a negatively charged anion molecule (either nitrate or triflate).

In the presence of the anion, the organic molecule takes the C-shape and one at a time, four of those C’s link together into two O-rings, locking the anion in a spherical cage. Two palladium atoms latch the four C’s together at the top and bottom of the cage.

If the anion is absent, the organic molecule swings into the S-shape and connects together with other S-shaped molecules using the palladium atoms as links. Eventually, they form flat sheets about 4 nanometers thick and up to 5 micrometers in diameter.

However, when researchers add the anion to the completed sheet, the molecules will slowly rearrange themselves into the cage formation.

“The sheet is demonstrating some very primitive qualities of a so-called smart material — one that can sense and respond to its environment. This shift from the micrometer-sized sheets to the nanometer-sized cages is a very dramatic structural change,” said Hiraoka.

The research team hopes that their work to understand the fundamental chemical properties of these molecules will lead to the possibility of designing molecules that can self-assemble and independently reorganize depending on environmental conditions.

Paths depend on thermodynamics and kinetics

The sheet and cage formations are more chemically stable in different ways. The cage formation is more thermodynamically stable, meaning it would require energy to move out of that formation. The sheet is more kinetically stable than the cage, meaning the molecules are slow to change position. Researchers are excited to have developed an artificial system that contains the complexities of these different stabilities.

“Complicated natural self-assembly reactions in living systems often have kinetic control,” explains Hiraoka.

Proteins in living organisms are usually kinetically trapped to stay in their healthy formations even though it would be more thermodynamically stable to aggregate into useless clumps.

In the artificial system that Hiraoka’s research team studied, when the precursor molecules form cages, the molecules stay in that final position because it is the lowest thermodynamic energy arrangement.

“The reaction in the early stage to form the cage is very fast, which tells us that the anion is acting as a kinetic template for the precursors to form the cage,” said Hiraoka.

However, the reaction to form the sheet proceeds more slowly and researchers say that the molecules become kinetically trapped in the sheet formation without the presence of the anion to provide a template that pulls them into the cage formation.

Researchers plan to continue studying how the self-assembly pathway is controlled and how to manipulate the influence of the kinetic effect and thermodynamic stability.

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Traumatic brain injuries affect 2 million Americans each year and cause cell death and inflammation in the brain. People who experience a head injury often suffer from lifelong memory loss and can develop epilepsy.

In the study, the UCI team transplanted embryonic progenitor cells capable of generating inhibitory interneurons, a specific type of nerve cell that controls the activity of brain circuits, into the brains of mice with traumatic brain injury. They targeted the hippocampus, a brain region responsible for learning and memory.

The researchers discovered that the transplanted neurons migrated into the injury where they formed new connections with the injured brain cells and thrived long term. Within a month after treatment, the mice showed signs of memory improvement, such as being able to tell the difference between a box where they had an unpleasant experience from one where they did not. They were able to do this just as well as mice that never had a brain injury. The cell transplants also prevented the mice from developing epilepsy, which affected more than half of the mice who were not treated with new interneurons.

“Inhibitory neurons are critically involved in many aspects of memory, and they are extremely vulnerable to dying after a brain injury,” said Robert Hunt, PhD, assistant professor of anatomy and neurobiology at UCI School of Medicine who led the study. “While we cannot stop interneurons from dying, it was exciting to find that we can replace them and rebuild their circuits.”

This is not the first time Hunt and his team has used interneuron transplantation therapy to restore memory in mice. In 2018, the UCI team used a similar approach, delivered the same way but to newborn mice, to improve memory of mice with a genetic disorder.

Still, this was an exciting advance for the researchers. “The idea to regrow neurons that die off after a brain injury is something that neuroscientists have been trying to do for a long time,” Hunt said. “But often, the transplanted cells don’t survive, or they aren’t able to migrate or develop into functional neurons.”

To further test their observations, Hunt and his team silenced the transplanted neurons with a drug, which caused the memory problems to return.

“It was exciting to see the animals’ memory problems come back after we silenced the transplanted cells, because it showed that the new neurons really were the reason for the memory improvement,” said Bingyao Zhu, a junior specialist and first author of the study.

Currently, there are no treatments for people who experience a head injury. If the results in mice can be replicated in humans, it could have a tremendous impact for patients. The next step is to create interneurons from human stem cells.

“So far, nobody has been able to convincingly create the same types of interneurons from human pluripotent stem cells,” Hunt said. “But I think we’re close to being able to do this.”

Jisu Eom, an undergraduate researcher, also contributed to this study. Funding was provided by the National Institutes of Health.

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A successful pest

In an earlier study, Christelle Robert and Matthias Erb from the Institute of plant sciences (IPS) at the University of Bern elucidated one of the strategies that underlies the success of the western corn rootworm. Maize plants store certain defense substances, so-called benzoxazinoids, in their roots. These substances are harmful to many pests. However, the western corn rootworm has developed a strategy to detoxify these substances. The larvae of the corn rootworm thus become resistant against the plant’s own defense. Even worse — the larvae store the benzoxazinoids in their bodies and in turn, use them for self-defense against their own enemies, including parasitic roundworms (entomopathogenic nematodes). The fact that the western corn rootworm has found a defense strategy against nematodes is of particular importance, as the nematodes are used as biological control agents against this pest.

“Considerable successes have already been achieved in the field using nematodes; efficiency-increasing measures could further boost this approach,” explains Matthias Erb, Professor for Biotic Interactions at the IPS. “Against this background, we asked ourselves the question: If pests such as the western corn rootworm can become immune against plant defense substances, could beneficial organisms such as entomopathogenic nematodes do the same?”

Breeding beneficial organisms for pest control

The researchers compared nematodes from areas in which the western corn rootworm is present with nematodes from areas where it is absent. “We found that nematodes from infested areas are resistant against benzoxazinoids, unlike nematodes from other areas,” says Xi Zhang, who worked on the project as a PhD student. In the lab, the researchers were able to observe that nematodes which were exposed to the the western corn rootworm became resistant to plant defense substances within just a few generations. “The speed of this adaptation surprised us,” says Zhang.

The results of the study, which was published in the journal PNAS, are particularly relevant for biological pest control. “Beneficial insects like nematodes, which are resistant against plant defense substances, can keep the insect pests that accumulate these substances from the plant at bay,” explains study co-author Ricardo Machado. This trait can be acquired very quickly through targeted selection and is thus a promising breeding target. “We expect that many other beneficial organisms could be improved by focusing on their capacity to resist plant defense compounds,” says Machado.

In the next stage, researchers are targeting the symbiotic bacteria of the nematodes to make them resistant against benzoxazinoids, and to test the improved biological control agents in the field. “This is a next step to bring our research closer to agricultural application,” says Machado.

Plant defense compounds shape food chains

In the research project, funded by the Swiss National Science Foundation (SNSF), the researchers relied on a combined approach of behavioral ecology, analytical chemistry and plant genetics. The findings illustrate the importance of plant defense compounds such as benzoxazinoids for the evolution and dynamics of food chains. “The arms race between plants and herbivores is often viewed as a motor of the chemical and biological diversity of these two groups,” says study co-author Christelle Robert. “Our study indicates that plant defense compounds may influence the evolution of entire food chains.”

As part of the interfaculty research cooperation “One Health” at the University of Bern (see box), the researchers have recently started to investigate how benzoxazinoids affect the health of animals and humans. “The integration of our findings into the central agricultural food chain is a fascinating expansion of our work with a lot of potential,” says Matthias Erb.

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“We’ve used telemedicine in pediatric cardiology for physician-to-physician communications for years at Children’s National, thanks to cardiologists like Dr. Craig Sable,” says Ashraf Harahsheh, M.D., cardiologist at Children’s National Hospital and senior author of the study. “But this is the first time we’ve really had the appropriate technology to speak directly to patients and their families in their homes instead of requiring an in-person visit.”

“We developed it [telemedicine] into a primary every day component of reading echocardiograms around the region and the globe,” says Craig Sable, M.D., associate chief of cardiology at Children’s National. “Telemedicine has enabled doctors at Children’s National to extend our reach to improve the care of children and avoid unnecessary transport, family travel and lost time from work.”

Participants in the virtual visit pilot study were previously established patients with hyperlipidemia, hypercholesterolemia, syncope, or who needed to discuss cardiac testing results. The retrospective sample included 18 families who met the criteria and were open to the virtual visit/telehealth follow up option between 2016 and 2019. Six months after their virtual visit, none of the participants had presented urgently with a cardiology issue. While many (39%) had additional visits with cardiology scheduled as in person, none of those subsequent in- person visits were a result of a deficiency related to the virtual visit.

“There are many more questions to be answered about how best to appropriately use technology advances that allow us to see and hear our patients without requiring them to travel a great distance,” adds Dr. Harahsheh. “But my team and I were encouraged by the results of our small study, and by the anecdotal positive reviews from families who participated. We’re looking forward to determining how we can successfully and cost-effectively implement these approaches as additional options for our families to get the care they need.”

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Professor Denise Doolan from James Cook University’s Australian Institute of Tropical Health and Medicine (AITHM) was part of an international team that narrowed down the malaria proteins and disease-fighting antibodies that could be used to develop a vaccine against severe malaria.

She said according to the latest figures from the World Health Organisation, there were 219 million cases of malaria worldwide in 2017, leading to an estimated 435,000 deaths.

“What makes this work so difficult is the particular survival strategy of the malaria parasite in the human body. It grows within blood cells and inserts proteins into the surface of the blood cell so it sticks to the walls of blood vessels,” Professor Doolan said.

“But it changes these proteins to escape from immune responses, and every strain has a different set of proteins, making the identification of vaccine targets extraordinarily hard.”

The team of collaborators — involving JCU, the Walter and Eliza Hall Institute of Medical Research (WEHI) at Deakin University, and malaria experts from Papua New Guinea, France and the USA — collected hundreds of PfEMP1 proteins from malaria strains from children in PNG who had been naturally infected by the disease, made a custom protein microarray of those strains, and then examined serum samples to identify which of the many PfEMP1 variants were associated with protection.

The research team managed to pinpoint which antibodies were most effective in fighting the most severe forms of malaria.

Associate Professor Alyssa Barry, who leads the Systems Epidemiology of Infection unit within the Deakin School of Medicine, said the findings from the project were a major step towards developing a viable vaccine for the disease.

“It’s the first time anyone has shown this — for years, researchers have thought that developing a malaria vaccine based on PfEMP1 would be virtually impossible, because the proteins are just so diverse,” Associate Professor Barry said.

“It’s similar to the flu vaccine, where you have to keep adjusting and updating it as the virus strains evolve from year to year. Malaria is even more diverse than influenza — one village in a country such as PNG could contain thousands of possible malaria strains. But in malaria-endemic areas, children who are repeatedly infected develop immunity to severe malaria by the time they’re about two years old, so we know antimalarial immunity is possible, and it can develop after exposure to only a few strains.”

Associate Professor Barry said while immunity to milder forms of malaria presented a “formidable obstacle,” immunity to severe malaria targets only a small subset of proteins that have many similarities between strains — making the essential components for a vaccine much easier to identify.

“Using genomic sequencing, we collected PfEMP1 proteins from different strains of malaria, measured antibodies to those proteins and then used machine learning to identify the protective antibody — the biomarker of immunity — that protects kids against disease,” she said.

“We were able to identify these antibodies by monitoring for patterns of disease, following the children in PNG for 16 months to determine which of them were susceptible to the more severe forms of the disease, and those who were protected and only experienced milder forms of the disease.

“It’s been a long road, and has involved a large team, but it’s a major step forward, and this provides hope that creating a vaccine might be possible.”

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In iNPH, the circulation of cerebrospinal fluid (CSF) is disturbed for an unknown reason, leading to a slightly elevated brain pressure and dilation of the brain ventricles. Symptoms of NPH include gait deviations, impaired short-term memory and urinary incontinence. Patients with iNPH often have changes in brain that are related to Alzheimer’s disease.

The study followed patients with iNPH after they had received treatment for their disease. They were treated with shunt surgery, in which excessive CSF is led from the brain ventricles to the abdominal cavity by using a CSF shunt. Shunted NPH patients who had undergone brain tissue biopsy in connection with their surgery were selected for the study. The objective of the biopsy was to detect changes that are indicative of Alzheimer’s disease.

During the follow-up, the researchers found that up to one in five patients with NPH were later diagnosed with Alzheimer’s disease. At the end of the follow-up, patients with NPH were more frequently diagnosed with Alzheimer’s disease than the general population. The researchers were able to predict the development of Alzheimer’s disease, with moderate accuracy, by using patient-specific DSI. The data used in DSI included the patient’s pre-surgery symptom profile, brain tissue samples and brain MRI images.

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