The research, which benefited from a collaboration with experts at the University of Maryland School of Medicine and focused on microglia in the brain and spinal cord, is published today in leading international journal, Science Advances.

Microglia are a unique type of immune cell whose job it is to support nerve cells, defend against invading microbes, clear debris and remove dying nerve cells by engulfing and eating them. Emerging research indicates that microglia can have different functional responses depending on molecular and biochemical changes occurring within these specialised cells.

In fact, various subtypes of microglia can be distinguished based on a property called autofluorescence. This is the tendency of cells to emit light of one colour after they have absorbed light of another, and it occurs because specific substances inside the cells absorb light. The substances stored in specialised cellular compartments include fat molecules, cholesterol crystals, metals and other misfolded proteins.

David Loane, Assistant Professor of Neuroscience in Trinity’s School of Biochemistry and Immunology in TBSI is the lead author of the research. He said:

“As the brain ages, these materials build up inside autofluorescent microglia, which increase their autofluorescence as a result. Unfortunately, this accumulation of cellular debris also makes it harder for the microglia to perform their essential garbage collection tasks in the brain and to prevent neurological injury and neurodegenerative disease.

“In this study we found — in aged animals — that these microglia adopt a unique, dysfunctional state, which has a number of problematic impacts. For example, there is an increase in cellular stress and damage, an accumulation of fats and iron, alterations to metabolic processes and an increase in production of molecules that over-egg the immune response.”

In addition, the scientists demonstrated that autofluorescent microglia and associated inflammation were more pronounced under pathological conditions, such as in genetic risk factor models of Alzheimer’s disease, and — promisingly — were reversed by drug-assisted microglial replacement in aged animals.

Prof Loane added: “Furthermore, environmental exposure to acute traumatic brain injury in animals accelerated the age of onset and tissue-wide distribution autofluorescent microglia by increasing oxidative stress damage in the brain of injured animals.

“As a result, increasing evidence now suggests that the accumulation of autofluorescent microglia contributes to diseases of ageing and neurodegeneration. If these sub-populations of microglia are highly inflammatory and damaging to the brain, then targeting them could be a new strategy for treating aging-related diseases.”

“Finding a nonsurgical treatment for hydrocephalus, given the fact neurosurgery is fraught with tremendous morbidity and complications, has been the holy grail for our field,” says Kristopher Kahle, MD, PhD, a pediatric neurosurgeon at MGH and senior author of the study. “We’ve identified through a genome-wide analytical approach the mechanism that underlies the swelling of the ventricles which occurs after a brain bleed or brain infection in acquired hydrocephalus. We’re hopeful these findings will pave the way for approval of an anti-inflammatory drug to treat hydrocephalus, which could be a game-changer for populations in the U.S. and around the world that don’t have access to surgery.”

Acquired hydrocephalus occurs in about one of every 500 births globally. It is the most common cause of brain surgery in children, though it can affect people at any age. In underdeveloped parts of the world where bacterial infection is the most prevalent form of the disease, hydrocephalus is often deadly for children due to the lack of surgical intervention. Indeed, the only known treatment for acquired hydrocephalus is brain surgery, which involves implantation of a catheter-like shunt to drain fluid from the brain. But about half of all shunts in pediatric patients fail within two years of placement, according to the Hydrocephalus Association, requiring repeat neurosurgical operations and a lifetime of brain surgeries.

By deciphering the unique cellular and molecular biology that occurs within the brain after infection or severe hemorrhage, the MGH-led research team has taken a major step toward nonsurgical, pharmacologic treatment for humans. Pivotal to the process is the choroid plexus, the brain structure that routinely pumps cerebrospinal fluid into the four ventricles of the brain to keep the organ buoyant and injury-free within the skull. An infection or brain bleed, however, can create a dangerous neuroinflammatory response where the choroid plexus floods the ventricles with cerebral spinal fluid and immune cells from the periphery of the brain — a so-called “cytokine storm,” or immune system overreaction, so often seen in COVID-19 infections — swelling the brain ventricles.

“Scientists in the past thought that entirely different mechanisms were involved in hydrocephalus from infection and from hemorrhage in the brain,” explains co-author Bob Carter, MD, PhD, chair of the Department of Neurosurgery at MGH. “Dr. Kahle’s lab found that the same pathway was involved in both types and that it can be targeted with immunomodulators like rapamycin, a drug that’s been approved by the U.S. Food and Drug Administration for transplant patients who need to suppress their immune system to prevent organ rejection.”

MGH researchers are continuing to explore how rapamycin and other repurposed drugs which quell the inflammation seen in acquired hydrocephalus could be turned into an effective drug treatment for patients. “What has me most excited is that this noninvasive therapy could provide a way to help young patients who don’t have access to neurosurgeons or shunts,” emphasizes Kahle. “No longer would a diagnosis of hydrocephalus be fatal for these children.”

Kahle is director of Pediatric Neurosurgery at MGH, and director of the Harvard Center for Hydrocephalus and Neurodevelopmental Disorders. Carter is chief of Neurosurgery Service at MGH and professor of Surgery at Harvard Medical School.

The study was funded by the National Institutes of Health and the Hydrocephalus Association.

In a study published in Physical Review Letters, researchers at Aalto University in Finland and IAS Tsinghua University in China report a new way to predict how quantum systems, such as groups of particles, behave when they are connected to the external environment. Usually, connecting a system such as a quantum computer to its environment creates decoherence and leaks, which ruin any information about what’s happening inside the system. Now, the researchers developed a technique which turns that problem into its a solution.

The research was carried out by Aalto doctoral researcher Guangze Chen under the supervision of Professor Jose Lado and in collaboration with Fei Song from IAS Tsinghua. Their approach combines techniques from two domains, quantum many-body physics and non-Hermitian quantum physics.

Protection from decoherence and leaks

One of the most intriguing and powerful phenomena in quantum systems is many-body quantum correlations. Understanding these and predicting their behaviour is vital because they underpin the exotic properties of key components of quantum computers and quantum sensors. While a lot of progress has been made in predicting quantum correlations when matter is isolated from its environment, doing so when matter is coupled to its environment has so far eluded scientists.

In the new study, the team showed that connecting a quantum device to an external system can be a strength in the right circumstances. When a quantum device is host to so-called non-Hermitian topology, it leads to robustly protected quantum excitations whose resilience stems from the very fact that they are open to the environment. These kinds of open quantum systems can potentially lead to disruptive new strategies for quantum technologies that harness external coupling to protect information from decoherence and leaks.

From idealised conditions to the real world

The study establishes a new theoretical method to calculate the correlations between quantum particles when they are coupled to their environment. ‘The method we developed allows us to solve correlated quantum problems that present dissipation and quantum many-body interactions simultaneously. As a proof of concept, we demonstrated the methodology for systems with 24 interacting qubits featuring topological excitations,’ says Chen.

Professor Lado explains that their approach will help move quantum research from idealised conditions to real-world applications. ‘Predicting the behavior of correlated quantum matter is one of the critical problems for the theoretical design of quantum materials and devices. However, the difficulty of this problem becomes much greater when considering realistic situations in which quantum systems are coupled to an external environment. Our results represent a step forward in solving this problem, providing a methodology for understanding and predicting both quantum materials and devices in realistic conditions in quantum technologies,’ he says.

“We are making those lines glow-in-the-dark so that they are more detectable, so the sensitivity of the test is better,” said Richard Willson, Huffington-Woestemeyer Professor of chemical and biomolecular engineering and professor of biochemical and biophysical sciences, who previously created a COVID smartphone-based app and test kit based on the technology underlying home pregnancy tests.

The first idea for glow-in-the-dark technology sprang from a star pasted on the ceiling of Willson’s young daughter’s bedroom. One night while he was putting her to sleep, he peered at the glow-in-the-dark star and his mind began to wander, applying its principles to science. Within days Willson and his team of students and postdocs was creating a test with glowing nanoparticles made of phosphors, which would make the particles even more detectable and the tests more accurate. Two of the students became the founders of Luminostics (now called Clip Health), a spinoff from the Willson lab).

Now in the Willson lab, the next generation is developing.

“In this new development, there are two tricks. First, we use enzymes, proteins that catalyze reactions, to drive reactions that emit light, like a firefly. Second, we attached those light-emitting enzymes onto harmless virus particles, along with antibodies that bind to COVID proteins,” reports Willson in the Royal Society of Chemistry’s journal Analyst.

The reason these steps are useful is that one antibody on a virus can bind to one COVID target on the test strip and bring along with it many light-emitting enzymes. So, the team gets more light for each target, thus needing fewer targets to see the light, making the test more sensitive.

And while you might be able to read the results with your eye in a very dark room, the Willson team created a little plastic box to exclude light and let a smartphone camera do the reading.

“This is more reproducible and probably more sensitive, and with smartphones you can communicate the results to databases and things like that,” said the paper’s corresponding author Katerina Kourentzi, University of Houston research associate professor of chemical and biomolecular engineering. Jacinta Conrad, Frank M. Tiller Associate Professor of Chemical and Biomolecular Engineering, also from the William A. Brookshire Department of Chemical and Biomolecular Engineering at the University of Houston Cullen College of Engineering, is on team. Others from UH include the first author of the paper Maede Chabi, Binh Vu, Kristen Brosamer, Maxwell Smith and Dimple Chavan.

Willson adds the sensitivity is really excellent, better than essentially any commercial tests, making the technology useful in an array of medical arenas.

“This technology can be used for detecting all kinds of other things, including flu and HIV, but also Ebola and biodefense agents, and maybe toxins and environmental contaminants and pesticides in food,” said Willson.

So truly, the sky — and stars — are the limit.

Researchers are coming to understand that the best performing materials in sustainable energy applications, such as converting sunlight or waste heat to electricity, often use collective fluctuations of clusters of atoms within a much larger structure. This process is often referred to as “dynamic disorder.”

Dynamic disorder

Understanding dynamic disorder in materials could lead to more energy-efficient thermoelectric devices, such as solid-state refrigerators and heat pumps, and also to better recovery of useful energy from waste heat, such as car exhausts and power station exhausts, by converting it directly to electricity. A thermoelectric device was able to take heat from radioactive plutonium and convert it to electricity to power the Mars Rover when there was not enough sunlight.

When materials function inside an operating device, they can behave as if they are alive and dancing — parts of the material respond and change in amazing and unexpected ways. This dynamic disorder is difficult to study because the clusters are not only so small and disordered, but they also fluctuate in time. In addition, there is “boring” non-fluctuating disorder in materials that researchers aren’t interested in because the disorder doesn’t improve properties. Until now, it has been impossible to see the relevant dynamic disorder from the background of less relevant static disorder.

New “camera” has incredibly fast shutter speed of around 1 picosecond

Researchers at Columbia Engineering and Université de Bourgogne report that they have developed a new kind of “camera” that can see the local disorder. Its key feature is a variable shutter speed: because the disordered atomic clusters are moving, when the team used a slow shutter, the dynamic disorder blurred out, but when they used a fast shutter, they could see it. The new method, which they call variable shutter PDF or vsPDF (for atomic pair distribution function), doesn’t work like a conventional camera — it uses neutrons from a source at the U.S. Department of Energy’sOak Ridge National Laboratory (ORNL) to measure atomic positions with a shutter speed of around one picosecond, or a million million (a trillion) times faster than normal camera shutters. The study was published February 20, 2023, by Nature Materials.

“It’s only with this new vsPDF tool that we can really see this side of materials,” said Simon Billinge, professor of materials science and applied physics and applied mathematics. “It gives us a whole new way to untangle the complexities of what is going on in complex materials, hidden effects that can supercharge their properties. With this technique, we’ll be able to watch a material and see which atoms are in the dance and which are sitting it out.”

New theory on stabilizing local fluctuations and converting waste heat to electricity

The vsPDF tool enabled the researchers to find atomic symmetries being broken in GeTe, an important material for thermoelectricity that converts waste heat to electricity (or electricity into cooling). They hadn’t previously been able to see the displacements, or to show the dynamic fluctuations and how quickly they fluctuated. As a result of the insights from vsPDF, the team developed a new theory that shows just how such local fluctuations can form in GeTe and related materials. Such a mechanistic understanding of the dance will help researchers to look for new materials with these effects and to apply external forces to influence the effect, leading to even better materials.

Research team

Billlinge’s co-lead on this work with Simon Kimber, who was at the University of Bourgogne in France at the time of the study. Billinge and Kimber worked with colleagues at ORNL and the Argonne National Laboratory (ANL), also funded by the DOE. The Inelastic neutron scattering measurements for the vsPDF camera were made at ORNL; the theory was done at ANL.

Next steps

Billinge is now working on making his technique easier to use for the research community and applying it to other systems with dynamic disorder. At the moment, the technique is not turn-key, but with further development, it should become a much more standard measurement that could be used on many material systems where atomic dynamics are important, from watching lithium moving around in battery electrodes to studying dynamic processes during water-splitting with sunlight.

The researchers isolated plots within natural ecosystems and separated the plots from accessing plant roots with a plastic barrier (a technique known as ‘root trenching’). Their study included rainforest, as well as both rubber and oil palm plantations in Sumatra, Indonesia. As a comparison, they removed all dead leaves, the main resource of decomposer animals, from other experimental plots. They found that without living roots, animal abundance in the rainforest plots decreases by 42 percent and in plantations by 30 percent. By contrast, removing the dead leaves has almost no effect on the animals in the underlying soil, but decreased the total animal abundance (in the soil and dead leaves) by 60 percent in rainforest and rubber plantations due to physical litter removal. However, the effects of plant litter removal were not observed in oil palm plantations, where litter is very scarce in any case. The study also revealed that living roots are especially important for the smaller soil animals, such as mites and springtails. Interestingly, after adding artificial plastic leaves in oil palm plantations, abundance of some animal groups — such as prostigmata — increased, highlighting that improving habitat structure, for instance by mulching, can promote soil food networks and the services they provide.

“The study provides novel perspectives for the management of the resources provided by plant litter in tropical plantations, fostering soil animal biodiversity. This is important to develop sustainable agricultural landscapes in the tropics,” says Professor Stefan Scheu, head of the Animal Ecology Working Group at the University of Göttingen.

“This study’s findings are significant not only for the conservation of tropical soil biodiversity, but also for the development of global ecosystem models describing carbon cycling in the tropics. We need a better understanding of the complex ecological systems that support life on Earth,” adds Dr Anton Potapov, Soil Biodiversity and Functions at German Centre for Integrative Biodiversity Research (iDiv), Halle-Jena-Leipzig.