Culture

A Korean research team has reported important findings that could potentially improve the performance of retinal prostheses creating artificial vision for blind individuals. The Korea Institute of Science and Technology (KIST) announced that a research team led by Dr. Maesoon Im of the Center for BioMicrosystems, Brain Science Institute had found retinal neural signals arising from electric stimulation are altered depending on disease progression in mice affected by outer retinal degeneration. This research was done in collaboration with the lab of Professor Shelley Fried at Harvard Medical School, Massachusetts General Hospital.

Retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration, primarily destroy photoreceptor cells, which convert light into electrochemical signals, leading to profound vision loss. Currently, there are no available cure for these diseases.

Fortunately, retinal ganglion cells are known to survive those conditions, making "artificial vision" available. An array of microelectrodes can be implanted at the back of the eyeball so that electric pulses applied by those microelectrodes can stimulate ganglion cells to transmit visual neural signals to the brain again. This is the basic working principle of retinal prosthetic devices. Although several retinal prostheses have been commercialized, one of problems preventing broad application has been a huge performance variation across patients due to unidentified reason.

The KIST research team had delved into the potential source of the performance variation and has found the level of disease progression may be critical. They designed a longitudinal study and performed experiments using mice at various stages of retinal degeneration. Those mice lost their vision gradually due to a genetic mutation which is similar to people with retinitis pigmentosa . The researchers recorded electrically-evoked neural activities of retinal ganglion cells from animals at varying ages and tried to correlate those artificial vision signals to the disease progression. They uncovered that both the magnitude and the consistency of the electrically-evoked responses diminished as retinal degeneration advanced.

The response consistency is particularly important for retinal prostheses because they periodically refresh artificial visual percepts using repetitive electrical stimuli. For example, when a retinal prostheses user stares at a letter "K" repeating electrical stimuli need to create neural signals representing "K." Otherwise, i.e. if the response consistency is too low, the electrical stimuli might transmit neural signals meaning different letters such as "L," "R," or "S,", thus making the prosthetic user difficult to correctly interpret what he or she is seeing. The KIST study suggests it is likely to be the case in severly degenerate retinas. Throughout a seriese of experiments to assess the degree of similarities across different neural signals arising from repeated electrical stimuli of a same condition, they found that the response consistency considerably declined with the progressing retinal degeneration while normal retinas showed high consistencies.

Dr. Young-Jun Yoon and Dr. Jae-Ik Lee, the lead authors of the study, said, "Even if a user fixes his/her gaze, their degenerate retina is likely to keep transmitting considerably different neural signals to the brain across repeats of electric stimuli. Probably, it may have caused poor perception of electrically-evoked artificial vision."

"Retinal degenerative diseases exhibit different patterns of progression across patients. Our results suggest that it is crucial to carefully select candidate patients of retinal implants by thorough examinations assesing the progression level of each patient's retinal degeneration," said Dr. Maesoon Im. "We are studying hardware and software approaches for the improved quality of artificial vision for patients at the late-stage degeneration."

When the eye isn't getting enough oxygen in the face of common conditions like premature birth or diabetes, it sets in motion a state of frenzied energy production that can ultimately result in blindness, and now scientists have identified new points where they may be able to calm the frenzy and instead enable recovery.

In this high-energy environ, both the endothelial cells that will form new blood vessels in the retina -- which could improve oxygen levels -- and nearby microglia -- a type of macrophage that typically keeps watch over the retina -- prefer glycolysis as a means to turn glucose into their fuel.

Medical College of Georgia scientists have shown that in retinal disease, the excessive byproducts of this inefficient fuel production system initiate a crescendo of crosstalk between these two cell types. The talk promotes excessive inflammation and development of the classic mass of leaky, dysfunctional capillaries that can obstruct vision and lead to retinal detachment, says Dr. Yuqing Huo, director of the Vascular Inflammation Program at MCG's Vascular Biology Center.

The major byproduct of glycolysis is lactate, which also can be used as a fuel, for example, by our muscles in a strenuous workout. Microglia also need some lactate from the endothelial cells. But in disease, the lactate is in definite oversupply, which instead supports this destructive conversation between cells, says Huo, corresponding author of the study in the journal Science Translational Medicine.

"This is a major problem in our country, loss of vision because of compromised oxygen for a variety of reasons," says Dr. Zhiping Liu, postdoctoral fellow in Huo's lab and the study's first author. "We hope this additional insight into how that process destroys vision, will enable us to find better ways to intervene," Liu says.

In a low-oxygen environ, endothelial cells produce not only a lot of lactate, but also factors that encourage nearby microglia to be more active, and to use glycolysis to get more active, Huo says.

In reality, microglia don't need the encouragement because they already also seem to prefer this method of energy production. But the extra lactate sent their way does spur them to produce even more energy and consequently even more lactate, Huo says.

The normally supportive immune cells also start overproducing inflammation-promoting factors like cytokines and growth factors that promote blood vessel growth or angiogenesis, which, in a vicious loop, further turns up glycolysis by the endothelial cells, which are now inclined to proliferate excessively.

"The reciprocal interaction between macrophages and (endothelial cells) promotes a feed-forward relationship that strongly augments angiogenesis," they write.

The destructive bottom line is termed pathological angiogenesis, a major cause of irreversible blindness in people of all ages, the scientists say, with problems like diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration.

"Our eyes clearly do not have sufficient oxygen, and they end up trying to generate more blood vessels through this process called pathological angiogenesis, which is really hard to control," Huo says.

The excessive sprouting and proliferation of endothelial cells is central to the destruction, and glycolysis is central to their sprouting and proliferation but the exact mechanisms that trigger all the glycolysis and crosstalk between endothelial cells and microglia have been unknown, they write.

"In all these conditions, there is something wrong with the tissue that causes the blood vessels to not behave properly," says coauthor Dr. Ruth B. Caldwell, cell biologist in the Vascular Biology Center. "It's a bad state," she says, which they want to help normalize.

As they are finding more about how the conversation goes bad between these two cells, they are seeing new logical points to do that. When they knock out the most potent activator of glycolysis, called Pfkfb3, from the microglia, lactate production clearly goes down and the cells no longer aid production of dysfunctional capillaries. Conversely, expression of both the messenger RNA that enables production of Pfkfb3 and lactate are significantly higher in the cells when oxygen levels are low.

Agents that stop these cells' over-the-top use of glycolysis could be good therapeutic approaches, they say. Blocking excessive lactate production could be another. Stopping the microglia from lapping up too much lactate also significantly suppresses pathological angiogenesis in their lab studies. Agents that normalize endothelial cell growth might work as well.

While genetic manipulation was used for much of their lab work to date, the scientists are now looking at chemicals that might work at these various points. A problem is that many drugs that suppress glycolysis have numerous unwanted effects, so they are working to more selectively intervene. They note that since the use of glycolysis by macrophages is critical to support of a healthy immune response, localized inhibition should yield the desired response without affecting the immune response.

Current treatments for abnormal blood vessel development and related leaking and swelling include suppressing vascular endothelial growth factor, or anti-VEGF, which, as the name implies, is a key factor in endothelial cell growth, may require ongoing injections in the eye and gets decent results in conditions like diabetic retinopathy. But anti-VEGF therapy really does not facilitate repair, says Caldwell. The scientists have early evidence their intervention strategies may, because they intervene earlier and help normalize the "bad" environment. "We get repair and restoration," Caldwell says.

Huo and his colleagues are among those who have shown that glycolysis is critical to the sprouting of endothelial cells and that mice lacking Pfkfb3 have impaired angiogenesis.

Endothelial cells, which line all our blood vessels, are one of the first things laid down when we make new blood vessels. In the retina, they start making tiny tunnels that ideally will become well-functioning capillaries, blood vessels so small that a single red blood cell may have to fold up just to get through. These thin-skinned blood vessels are the point where oxygen, fluid and nutrients are provided to body tissue, then blood gets routed back through the venous system to the heart where the process starts anew.

Endothelial cells grow accustomed to glycolysis when they are helping make our bodies in the early, no-oxygen days during development, Huo says.

The usual job of microglia includes keeping an eye out for invaders, like a virus, and keeping connections between nerves, called synapses, trimmed up.

A team of medical researchers has found that in human milk, pasteurisation inactivates the virus that causes COVID-19, confirming milk bank processes have been safe throughout the pandemic, and will remain safe going forward, too.

The study - published this month in the Journal of Paediatrics and Child Health - was a partnership between UNSW and a multidisciplinary team from Australian Red Cross Lifeblood Milk.

There are five human milk banks in Australia. As the COVID-19 pandemic evolves, these milk banks continue to provide donated breast milk to preterm babies who lack access to their mother's own milk. Donors are screened for diseases, and milk is tested and pasteurised to ensure that it is safe for medically fragile babies.

"While there is no evidence that the virus can be transmitted through breast milk, there is always a theoretical risk," says Greg Walker, lead author and PhD candidate in Professor Bill Rawlinson's group at UNSW Medicine.

"We've seen in previous pandemics that pasteurised donor human milk (PDHM) supplies may be interrupted because of safety considerations, so that's why we wanted to show that PDHM remains safe."

For this study, the team worked in the Kirby Institute's PC3 lab to experimentally infect small amounts of frozen and freshly expressed breast milk from healthy Lifeblood Milk donors.

"We then heated the milk samples - now infected with SARS-CoV-2 - to 63?C for 30 minutes to simulate the pasteurisation process that occurs in milk banks, and found that after this process, they did not contain any infectious, live virus," Mr Walker says.

"Our findings demonstrate that the SARS-CoV-2 virus can be effectively inactivated by pasteurisation."

The researchers say their experiments simulated a theoretical worst-case scenario.

"The amount of virus we use in the lab is a lot higher than what would be found in breast milk from women who have COVID-19 - so we can be really confident in these findings," Mr Walker says.

Dr Laura Klein, Research Fellow and Lifeblood Milk senior study author, explains that the purpose of the research was to provide evidence behind what people already expected.

"Pasteurisation is well known to inactivate many viruses, including the coronaviruses that cause SARS and MERS," she says.

"These findings are also consistent with a recent study that reported SARS-CoV-2 is inactivated by heat treatment in some contexts."

Kirby Institute researcher and study co-author, Associate Professor Stuart Turville, says this work was a first.

"We've been working in real time to grow and make tools against this new pathogen, which has been an exponential learning curve for everyone involved. This work and many others that are continuing in the PC3 lab tell us how we can be safe at the front line working with this virus in the real world."

Cold storage doesn't inactivate the virus

The researchers also tested if storing SARS-CoV-2 in human milk at 4°C or -30°C would inactivate the virus - the first time a study has assessed the stability of experimentally infected SARS-CoV-2 in human milk under common storage conditions.

"We found that cold storage did not significantly impact infectious viral load over a 48-hour period," Mr Walker says.

"While freezing the milk resulted in a slight reduction in the virus present, we still recovered viable virus after 48 hours of storage."

The researchers say the fact that SARS-CoV-2 was stable in refrigerated or frozen human milk could help inform guidelines around safe expressing and storing of milk from COVID-19 infected mothers.

"For example, we now know that it is particularly important for mothers with COVID-19 to ensure their expressed breast milk does not become contaminated with SARS-CoV-2," Dr Klein says.

"But it's also important to note that breastfeeding is still safe for mothers with COVID-19 - there is no evidence to suggest that SARS-CoV-2 can be transmitted through breastmilk."

Donated breast milk is recommended by the World Health Organisation when mother's own milk is not available to reduce the risks of some health challenges premature babies can face. Lifeblood Milk has provided donor milk to over 1500 babies born premature in 11 NICUs across New South Wales, South Australia, and Queensland since launching in 2018.

Uncertainties in the evolutionary tree of birds and their closest relatives have impeded deeper understanding of early flight in theropods, the group of dinosaurs that includes birds. To help address this, an international study led by HKU Research Assistant Professor Dr. Michael Pittman (Vertebrate Palaeontology Laboratory, Division of Earth and Planetary Science & Department of Earth Sciences) and co-first-authored by his former Postdoctoral Fellow Dr. Rui Pei (now an Associate Professor at the Institute of Vertebrate Paleontology and Paleoanthropology, Beijing), produced an updated evolutionary tree of early birds and their closest relatives to reconstruct powered flight potential, showing it evolved at least three times. Many ancestors of the closest bird relatives neared the thresholds of powered flight potential, suggesting broad experimentation with wing-assisted locomotion before flight evolved. The ten-man five-country team published their findings in the prestigious high-profile journal Current Biology.

"Our revised evolutionary tree supports the traditional relationship of dromaeosaurid ("raptors") and troodontid theropods as the closest relatives of birds. It also supports the status of the controversial anchiornithine theropods as the earliest birds," said Dr. Pei. With this improved evolutionary tree, the team reconstructed the potential of bird-like theropods for power flight, using proxies borrowed from the study flight in living birds. The team found that the potential for powered flight evolved at least three times in theropods: once in birds and twice in dromaeosaurids. "The capability for gliding flight in some dromaeosaurids is well established so us finding at least two origins of powered flight potential among dromaeosaurids is really exciting," said Dr. Pittman. Crucially, the team found that many ancestors of bird relatives neared the thresholds of powered flight potential. "This suggests that theropod dinosaurs broadly experimented with the use of their feathered wings before flight evolved, overturning the paradigm that this was limited to a much more exclusive club," added Dr. Pittman.

This study is the latest in the Vertebrate Palaeontology Laboratory's long-term research into the evolution of early birds and their closest relatives (see Notes). Asked about future plans, Dr. Pittman replied: "We have helped to better constrain the broader functional landscape of theropods just before flight evolved and in its earliest stages. We plan to now focus on the dromaeosaurids and early birds that we have shown to have the potential for powered flight to improve our understanding of what it took to fly and why."

LA JOLLA--(August 10, 2020) While your skeleton helps your body to move, fine skeleton-like filaments within your cells likewise help cellular structures to move. Now, Salk researchers have developed a new imaging method that lets them monitor a small subset of these filaments, called actin.

"Actin is the most abundant protein in the cell, so when you image it, it's all over the cell," says Uri Manor, director of Salk's Biophotonics Core facility and corresponding author of the paper. "Until now, it's been really hard to tell where individual actin molecules of interest are, because it's difficult to separate the relevant signal from all the background."

With the new imaging technique, the Salk team has been able to home in on how actin mediates an important function: helping the cellular "power stations" known as mitochondria divide in two. The work, which appeared in the journal Nature Methods on August 10, 2020, could provide a better understanding of mitochondrial dysfunction, which has been linked to cancer, aging, and neurodegenerative diseases.

Mitochondrial fission is the process by which these energy-generating structures, or organelles, divide and multiply as part of normal cellular maintenance; the organelles divide not only when a cell itself is dividing, but also when cells are under high amounts of stress or mitochondria are damaged. However, the exact way in which one mitochondrion pinches off into two mitochondria has been poorly understood, particularly how the initial constriction happens. Studies have found that removing actin from a cell entirely, among many other effects, leads to less mitochondrial fission, suggesting a role for actin in the process. But destroying all the actin causes so many cellular defects that it's hard to study the protein's exact role in any one process, the researchers say.

So, Manor and his colleagues developed a new way to image actin. Rather than tag all the actin in the cell with fluorescence, they created an actin probe targeted to the outer membrane of mitochondria. Only when actin is within 10 nanometers of the mitochondria does it attach to the sensor, causing the fluorescence signal to increase.

Rather than see actin scattered haphazardly around all mitochondrial membranes, as they might if there were no discrete interactions between actin and the organelles, Manor's team saw bright hotspots of actin. And when they looked closely, the hotspots were located at the same locations where another organelle called the endoplasmic reticulum crosses the mitochondria, previously found to be fission sites. Indeed, as the team watched actin hotspots light up and disappear over time, they discovered that 97 percent of mitochondrial fission sites had actin fluorescing around them. (They speculate that there was also actin at the other 3 percent of fission sites, but that it wasn't visible).

"This is the clearest evidence I've ever seen that actin is accumulating at fission sites," says Cara Schiavon, co-first author of the paper and a joint postdoctoral fellow in the labs of Uri Manor and Salk Professor Gerald Shadel. "It's much easier to see than when you use any other actin marker."

By altering the actin probe so that it attached to the endoplasmic reticulum membrane rather than the mitochondria, the researchers were able to piece together the order in which different components join the mitochondrial fission process. The team's results suggest that the actin attaches to the mitochondria before it reaches the endoplasmic reticulum. This lends important insight towards how the endoplasmic reticulum and mitochondria work together to coordinate mitochondrial fission.

In additional experiments described in a pre-print manuscript available on bioRxiv, Manor's team also reports that the same accumulation of endoplasmic reticulum-associated actin is seen at the sites where other cellular organelles--including endosomes, lysosomes and peroxisomes--divide. This suggests a broad new role for a subset of actin in organelle dynamics and homeostasis (physiological equilibrium).

In the future, the team hopes to look at how genetic mutations known to alter mitochondrial dynamics might also affect actin's interactions with the mitochondria. They also plan to adapt the actin probes to visualize actin that's close to other cellular membranes.

"This is a universal tool that can now be used for many different applications," says Tong Zhang, a light microscopy specialist at Salk and co-first author of the paper. "By switching out the targeting sequence or the nanobody, you can address other fundamental questions in cell biology."

"We're in a golden age of microscopy, where new instruments with ever higher resolution are always being invented; but in spite of that there are still major limitations to what you can see," says Manor. "I think combining these powerful microscopes with new methods that select for exactly what you want to see is the next generation of imaging."

Connections with friends and family are key to helping communities adapt to the devastating impact of climate change on their homes and livelihoods, a new study shows.

The research found people are more empowered to respond when they see others doing the same.

Scientists analysed how an island community in Papua New Guinea of around 700 people coped with the impact of encroaching sea-levels and dwindling fish stocks. The study, published in the journal Nature Climate Change, examined the actions households took to deal with these impacts.

Lead author Dr Michele Barnes, from the ARC Centre of Excellence for Coral Reef Studies (Coral CoE), said: "We found their actions were related to their social networks, the ways they are connected to other people within the community."

"To cope with the impacts of climate change, existing practices or behaviours can be tweaked--this is adaptation. However, in some cases this won't be enough, and people need to enact more fundamental changes--transformation."

"In our case, adaptation included things like building sea walls to protect existing land use," said co-author Dr Jacqueline Lau, from Coral CoE and WorldFish. "And transformation involved developing alternative food and income sources away from fish and fishing-related activities."

Essentially both sets of actions are necessary to combat the impacts of climate change. Dr Barnes says influence within social networks is what encouraged this: the households more socially connected to others taking action were more likely to do the same.

"It may be a situation of 'like-attracts-like' where households with particular mindsets are more socially connected to similar households," Dr Barnes said. "Another explanation is that households were influencing each other's actions. It's likely a combination of the two," she said.

The authors also found household connections with the marine environment played an important role in determining the responses to climate impacts.

"Climate change and other human impacts rapidly degrade coral reef ecosystems and alter the composition of reef fish communities," said co-author Professor Nick Graham, of Lancaster University in the UK.

"The adaptation of coastal communities is becoming essential. Our research highlights that interacting with and learning from the marine environment is one mechanism through which this adaptation can be achieved," he said.

Dr Barnes says the policies and programs seeking to reduce vulnerability to climate change often focus on building up material assets or creating infrastructure.

"Our research emphasises a broader set of factors can play an important part in the actions communities end up taking," she said.

Albert Einstein once said, "I see my life in terms of music." Perhaps inspired by his words, scientists at the Center for Self-assembly and Complexity (CSC), within the Institute for Basic Science (IBS, South Korea) now see chemical reactions in the presence of music. The IBS research team has reported that audible sound can control chemical reactions in solution by continuously supplying energy sources into the interface between air and the solution. The sound-controlled air-liquid chemical interactions "painted" intriguing and aesthetic patterns on the surface and bulk of the solution. "The Pied Piper of Hamelin tells the mythological story of a pied piper who lured rats away from the city of Hamelin by enchanting them with the music from his magical pipe. With music working like a fuel for such artistic control in chemistry, our study has shown that even synthetic molecules can exhibit life-like behavior - listening and following a musical track," says Dr. Rahul Dev Mukhopadhyay, the co-first and -corresponding author of the study.

Music (or audible sound with a frequency range of 20 to 20,000 Hz) in fact finds useful applications in various fields, such as boosting plant cultivation or livestock breeding and even for therapeutic purposes. Ultrasound (greater than 20,000 Hz) has long been used as an essential tool in medical diagnosis. However, audible sound has rarely been associated with chemical reactions due to its low energy. Previous studies have usually focused only on its effect on the movement of water surface.

In this study, the IBS research team has gone further than that. They hypothesized that sound-generated water waves may fuel chemical reactions between air and liquid. "In fact, one aspect of a climate change study is about how CO2 concentration in the ocean changes depending on the movement of ocean waves. In retrospect, it makes sense that a wavy ocean is a more suitable condition for CO2 to be absorbed in the ocean than a still ocean. Our study has revealed the function of audible sound as a source for controlling chemical reactions, which occurs all around us, but has not been noticed till now," explains Dr. HWANG Ilha, the co-first and -corresponding author of the study.

In their experimental set-up, the water was placed on a Petri dish and positioned on top of a speaker. When sound was played through the speaker, different surface wave patterns were generated - depending on the frequency and the amplitude of the audible sound source and the geometry of the vessel. To see how this vibrating air-water interphase controls the dissolution of atmospheric gases like oxygen or carbon dioxide into water, the researchers used O2-sensitive methyl viologen (MV2+/MV+* ) redox couple and CO2-sensitive pH indicator bromothymol blue (BTB).

Organic molecule methyl viologen is normally colorless or white, but turns deep blue upon chemical reduction. When a blue-colored solution of reduced methyl viologen in a Petri dish was exposed to air with sound playing, some regions of the solution slowly turned colorless. The sound waves generates oscillation of the fluid, prompting a streaming effect, and the solution underwent a distinct observable color change due to the gradual dissolution of atmospheric oxygen. Those not affected by the streaming retained their blue color. In the absence of sound, the uncontrolled dissolution of oxygen and natural convection currents of chemicals in solution resulted in a random pattern, which was different each time over the repetition of the same experiment. However, when the same solution was exposed to low frequency sounds below 90 Hz, very interesting and aesthetic patterns were generated. More specifically, two counter-rotating vortices emerged in blue and white contrast in the presence of 40 Hz sound. The same pattern repeated in the same condition during subsequent cycles.

The experiment indicates the reaction with oxygen, which is determined whether the solution is colorless or blue. In other words, by applying sound to a solution, the researchers could control the local molecular concentrations of oxygen in different regions that compose the same solution. Just like the surface waves, the patterns vary according to the frequency of the applied sound as well as the shape of the dish (Figure 1, Middle). The patterns also exhibited self-healing behavior, i.e., they recover their original pattern structure after being manually disturbed.

This concept was further extended to the dissolution of carbon dioxide gas using a pH indicator (bromothymol blue, BTB). BTB has a blue color in basic conditions (pH over 7.6), green color in neutral conditions (pH 6.0 to 7.6), and a yellow color in acidic conditions (pH under 6.0). Sound assisted dissolution of carbon dioxide in water turns it acidic due to the formation of carbonic acid. Therefore, when a blue-colored basic solution of BTB is exposed to carbon dioxide, the solution gradually turns green and eventually changes to yellow. During this process, if the solution is exposed to audible sound, a three-colored pattern having two vortices was generated (Figure 1, Bottom). Interestingly, the pattern represents the coexistence of acidic, neutral, and basic domains in a solution. "Our study visualized a chemical environment that is partitioned into different molecular environments without any physical barrier, resembling cellular microenvironments. This is a novel discovery that may replace the common sense belief that the pH of a solution is uniform throughout all of the vessel," notes Dr. Hwang.

Extending the concept beyond simple molecules, the researchers utilized their strategy to program the organization of organic molecules within solution. In all cases, the sound generated organic aggregate patterns were obtained transiently and maintained only in presence of a steady supply of chemical fuel, which may be either a reducing agent or a base. This type of behavior is generally exhibited by intracellular biochemical processes which are maintained with a steady supply of fuels or energy currencies, such as adenosine-5'-triphosphate (ATP) or guanosine-5'-triphosphate (GTP). Prof. Kimoon Kim, Director of the IBS Center for Self-assembly and Complexity, who supervised the overall research, added, "This is the first study to show that it is possible to control and visualize chemical reactions using audible sound. In the near future, we may further expand the scope of use of audible sound from chemistry to other fields, such as physics, fluid mechanics, chemical engineering and biology."

Animal behaviour scientists from the University of Lincoln, UK, have discovered that filling your home with appeasing pheromones could be the key to a happy household where both dogs and cats are living under the same roof.

The new research, led by Professor Daniel Mills and Dr Miriam Prior, explored the effects of two different pheromone products on cat-dog interactions in homes where owners could see room for improvement in their pets' relationships.

Their new scientific paper is now available to read online via the journal Frontiers in Veterinary Science.

The results show that both products used - Feliway Friends, which emits pheromones that are calming for cats, and Adaptil, which does the same for dogs - both had a positive impact on the interactions between cats and dogs living in the same home.

Over a six week period, both products led to a notable decrease in undesirable interactions - such as dog chasing cat, cat hiding from dog, cat and dog staring at each other, and dog barking at cat. Users of Adaptil even observed a significant increase in some desirable behaviours - friendly greetings between cat and dog, and time spent relaxing in the same room.

"Although we are all aware of the perceived tensions between cats and dogs, we believe this is the first study of its kind to explore the use of pheromone products to improve the relationship when the two species are living in the same household," explained Professor Mills, Professor of Veterinary Behavioural Medicine in Lincoln's School of Life Sciences.

"Seven per cent of households in the UK own both a cat and a dog, which represents a large number of pet owners and their animals living with potentially stressful animal relationships on a day-to-day basis. Many cat and dog owners report that their animals are comfortable in each other's' company, but where this isn't the case, a poor relationship between a resident cat and dog can have serious consequences for the welfare of individual animals. There may be an unacceptable level of social stress or restricted access to key resources such as food, water or suitable toilet areas. There will also be increased stress for the remainder of the family (both human and animal), and potential risks of injury due to conflict."

It has also been reported that a problematic relationship between a new pet and an existing pet is one of the main reasons for cats and dogs being taken to shelters for rehoming.

The pet owners involved in this new scientific trial reported weekly on the frequency of 10 specific undesirable interactions and seven specific desirable interactions between their cats and dogs. They were split into two groups; one group using Feliway Friends and the other using Adaptil, with the pheromones supplied in unlabelled packaging and randomly assigned by an independent staff member such that neither the participants nor the researchers knew which product was being trialled in each household until after the statistics had been collected.

The researchers were aware that in many households, the comfortability of the cat seems to have a stronger influence over the quality of the cat-dog relationship. It could therefore be seen as surprising that it was the product releasing dog pheromones which was seen to increase specific desirable interactions.

Miriam, a Lincoln-based vet who undertook the work as part of her postgraduate degree in Clinical Animal Behaviour at the University of Lincoln, said: "While it might be expected that Feliway Friends would be more effective in multi-species homes given the apparently stronger contribution of the cat's comfortability to the quality of the cat-dog relationship, this did not appear to be the case. Our results might be explained by the behaviour of the dog being the primary determinant of the cat's quality of interaction with it.

"We would like to investigate this further to really tease out the effects of these pheromone products individually and also to investigate their use in combination with each other. We suggest that Adaptil may have had such a beneficial effect because a more relaxed dog may be less likely to disturb the cat (e.g. by chasing it), resulting in a cat that is less stressed and more willing to form some form of social bond with the dog."

Leipzig/Halle. Human changes to the environment have been linked to widespread pollinator declines. New research published in Nature Communications shows that intensive land use will further decrease pollination and reproductive success of wild plants, especially of those plants that are highly specialized in their pollination. An international team of scientists led by researches from the German Centre for Integrative Biodiversity Research (iDiv), Martin Luther University Halle-Wittenberg (MLU) and the Helmholtz Centre for Environmental Research (UFZ) performed a global data analysis that provided conclusive evidence of the links of human land use and pollination of plants.

Plants provide resources including food and shelter to all other living organisms on earth. Most plants need pollinators to reproduce, which is why mounting research showing widespread pollinator declines is concerning. Despite concerns we are facing a pollination crisis, we do not know which types of plants will be most affected by pollinator declines and under which conditions declines in plant reproductive success are to be expected.

Changes in land-use are the leading threat to plants and pollinators. However, different groups of pollinators may have different responses to changes in land-use. For example, some farming practises may increase honeybee abundance on the one hand but reduce the abundance of other pollinators such as wild bees and butterflies on the other hand. Dr Joanne Bennett, who led the research as a postdoctoral researcher at iDiv and MLU and is now working at the University of Canberra, said: "Plants and their pollinators have evolved relationships over millions of years . Humans are now changing these relationships in just a few years."

A global data set on land use and pollen limitation

To determine if land use effects pollen limitation, an international team of researchers set out to compile a global dataset that quantified the degree to which pollenation limits plant reproductive success. For this, they analysed thousands of published pollen supplementation experiments - experiments that estimate the magnitude of pollen limitation by comparing the number of seeds produced by naturally pollinated flowers with flowers receiving hand supplemented pollen. Joanne Bennett said: "If naturally pollinated plants produce less fruits or seeds than plants that have received additional pollen by hand then the reproduction of that plant population is limited - this is called pollen limitation. In this way, pollen limitation experiments provide an unparalled opportunity to link plant reproductive function to the health of pollination services."

It was almost 20 years ago when Prof Dr Tiffany Knight, Alexander von Humboldt professor at MLU and head of the Spatial Interaction Ecology research group at iDiv and UFZ, started to compile the first data sets. Supported by iDiv's synthesis centre sDiv, Knight and Bennett took the project to a new level by forming a group of 16 experts from all over the world to expand the dataset and generate new ideas. The researchers started with 1,000 experiments on 306 plant species from Europe and North America. To date, it includes data from over 2,000 experiments and more than 1,200 plants and has a more global distribution. Tiffany Knight said: "One of the most rewarding components of this research has been the collaboration with the international team, and the inclusion of studies published in languages other than English."

Specialists and plants in intensely used landscape highly pollen limited

Ultimately, this data allowed for a global meta-analysis, which showed that wild plants in intensely used landscapes, such as urban areas, are highly pollen limited. The researchers found that plants that are specialized in their pollination are particularly at risk of pollen limitation, but this varies across the different land-use types and is based on which pollinator taxa they are specialized on. For example, plants specialized on bees were less pollen limited in agriculturally managed lands than those specialized on other pollinator types. This could be because domesticated honey bees support the pollination of wild plants in these lands.

The results show conclusively that intensive land use is linked to lower plant reproductive success due to lower pollination success. This suggests that future land-use change will decrease the pollination and reproductive success of plants, and can cause plant communities to become more dominated by species that are generalized in their pollination.

Tiny factories float inside our cells and provide them with almost all the energy they need: the mitochondria. Their effectiveness decreases when we get older, but also when we face many diseases such as diabetes, cancer or Parkinson's. This is why scientists are increasingly interested in how they work. At EPFL, a team has developed a protocol to measure their activity live in living animals. Described in Nature Chemical Biology, the method relies on the molecule responsible for the firefly's bioluminescence. In the most literal sense of the word, this study sheds light on how mitochondria work.

Mitochondria are almost like cells within the cell. Like their host, they have a membrane that protects their genetic material and, above all, filters exchanges with the outside. The difference in electrical charge between the inside and the outside of the mitochondria, called "membrane potential", allow certain molecules to go through, while other ramain at bay.

As between the two poles of a used electric battery, the membrane potential of the mitochondria can sometimes drop. For scientists, this is an unmistakable clue that its functions are impaired.

We know how to measure the phenomenon on cultured cells. But until now, you couldn't really see it on live animals. "Cell cultures are not very effective in studying diseases linked to mitochondria", explains Elena Goun, professor at EPFL and lead author of the article: "Cancer or diabetes involve complex exchanges between various types of cells, therefore we need animal models. "

Elena Goun and her colleagues have found a way to study the phenomenon in live mice. They use animals that are genetically modified to express luciferase - an enzyme that produces light when combined with another compound called luciferin. This is how fireflies sometimes light up our summer evenings.

Scientists have developed two molecules that, when injected into the rodent, pass into the mitochondria, where they activate a chemical reaction. The mitochondria then produce luciferin and eject it outwards. Luciferin combines with luciferase in the mice's cells and produce light.

"In a completely darkened room, you can see the mice glowing, just like fireflies," says Elena Goun.

Researchers need only measure light intensity to get a clear picture of how well the mitochondria are functioning. When they function less well, their membrane lets in less chemical compounds. The production of luciferin decreases, and therefore the luminosity too.

To demonstrate the potential of their method, the researchers carried out several experiments. For example, they observed that older rodents produce significantly less light. This drop in light reflects a drop in the activity of mitochondria - their membrane potential is much lower than in younger rodents. We know that age causes a decrease in the activity of mitochondria, but this is the first time that the phenomenon has been accurately measured directly in living animals.

The team also tested a chemical known to rejuvenate mitochondria: nicotinamide riboside. This molecule is non-toxic and commercially available as a dietary supplement. Mice given this compound produced more light, a sign of increased mitochondrial activity.

The researchers were also able to measure the same phenomenon in animal models of cancer. This could be of great help for anticancer drug research. In addition, they also successfully demonstrated monitoring of mitochondria membrane potential in cells of brown adipose tissue, rich in mitochondria. Its stimulation could help cure certain forms of obesity.

The method described by Elena Goun is primarily intended for scientists who want to better understand the role of mitochondria and who need an animal model. The field of application is wide: diabetes, oncology, aging, nutrition, neurogenerative diseases... "Our process can measure varying degrees of mitochondria activity, and not just an on / off signal", explains Elena Goun. "It is extremely sensitive - much more than a PET scan - affordable and easy to implement.

With the rise of genomic sequencing, health technology companies are promising parents they can detect rare metabolic disorders in newborns who, despite a healthy appearance, may need immediate treatment.

Now, scientists from UC San Francisco, UC Berkeley and Tata Consultancy Services are offering the first comprehensive assessment of how sequencing stacks up to the older screening technology, tandem mass spectrometry (MS/MS), that California uses to analyze the blood spots taken at birth for rare disorders, known as inborn errors of metabolism. They found that, when used alone, sequencing comes up short, missing some sick babies, while flagging many healthy ones for unnecessary follow-up testing. But sequencing can still be useful in cases that look suspicious but were not clearly identified by MS/MS.

"There has been a lot of publicity about universal sequencing for newborns," said Jennifer Puck, MD, professor of pediatrics at UC San Francisco and co-senior author of the study, published Aug. 10, 2020, in Nature Medicine. "But claims that sequencing is the key to health have been made without the support of rigorous studies."

Accuracy is essential when it comes to newborn screening. If cases are missed, seriously ill babies will go without prompt treatment for diseases that require urgent attention, such as phenylketonuria (PKU), which causes cognitive impairment when left untreated. But referring healthy babies for expert care is wasteful and puts families through unnecessary stress.

This study used a technique called whole-exome sequencing to look for mutations in 78 genes that are known to be involved in the 48 metabolic disorders for which every California newborn is screened. These diseases are rare, affecting about 150 of the estimated half a million babies born each year in California, and there are no signs when babies are born that they are going to get sick.

Since screening is meant for asymptomatic individuals, in this case newborns, it's very different from using sequencing as a diagnostic aid for patients with a medical problem that has already been detected.

"All of the prior studies of the utility of exome sequencing have started with a patient already in front of a doctor--in other words, a patient with a problem," Puck said. "You start with a clue in hand, a person with a particular difficulty, and you're trying to see if there's an underlying genetic reason for that. When you switch to screening mode, you don't have any clues. Most newborns look perfectly healthy."

Inborn metabolic disorders provided a unique opportunity to benchmark the performance of whole-exome sequencing, because it could be compared with California's well-established newborn screening program, which has been using MS/MS since 2005. These disorders have been well studied, and they are known to be caused by changes in a limited set of genes, most of which have been identified. So when they embarked on the study, the team had expected that sequencing technology might do better than the state's MS/MS screening method.

The state's current method looks for clues in babies' blood that something is wrong. The team found that the dried blood spots, which are taken at birth and then stored, could be used years later to analyze DNA. This provided a comprehensive view of nearly all the babies born in California with inborn errors of metabolism--about 1,334 of the nearly 4.5 million babies who were born in the period under study, from July of 2005 to December of 2013.

The team found that the standard MS/MS screening found 99 percent of babies with metabolic disorders, with a false positive rate of just 0.2 percent. But whole-exome sequencing would have found only 88 percent, missing about 160 of the 1,334 California babies who were ultimately diagnosed with metabolic disorders, while incorrectly identifying about 8,000 babies each year as being in need of urgent evaluation by a metabolic disease specialist.

The scientists said the shortcomings of the sequencing approach could have several causes.

"These are well-studied single-gene conditions, but that does not mean we have found all the genes associated with them," said first author Aashish Adhikari, PhD, a member of UCSF's Institute for Human Genetics and UC Berkeley's Department of Plant and Microbial Biology. "Additional genes could be involved, as well as additional biological and environmental factors that may limit our ability to predict disease from DNA sequences alone."

Another problem is that these diseases are so rare that scientists haven't had many sequences to examine. Also, California's newborns are from highly diverse genetic backgrounds, with many variants that have never before been analyzed, since previous studies have emphasized people of Northern European ancestry. To analyze these new variants and predict their impact, the team had to develop a special computational pipeline.

But if whole-exome sequencing has limited use as a standalone primary screen, the study demonstrated that it still can be used to make a definitive diagnosis in cases where MS/MS showed something might be wrong, but doctors were unsure of what it was. And sequencing may yet prove useful in identifying newborns with treatable conditions that current screening methods cannot find.

"If the current mass spectrometry testing comes out unclear, sequencing could reveal a gene variant that solves the mystery," said Steven Brenner, PhD, professor at UC Berkeley, a member of UCSF's Institute for Human Genetics, and co-senior author of the study. "Sequencing to screen additional carefully vetted disorders could enable timely treatment of some children with conditions that presently go unrecognized until it's too late for optimal intervention."

(Boston)-- Although macrophages (cells involved in the detection and destruction of bacteria and other harmful organisms as well as dead cells) are classified as immune cells functioning in the activation and resolution of tissue inflammation, it is now clear that they are critically involved in a variety of disease processes, such as chronic inflammatory diseases, tumor growth and metastasis and tissue fibrosis.

For the first time, researchers from Boston University School of Medicine (BUSM) have characterized the origins, gene expression and diverse functions of resident macrophages in normal skeletal muscle. The findings they believe will provide a knowledge base for future studies of the roles of skeletal muscle resident macrophages in skeletal muscle diseases such as muscular dystrophies as well as muscular injuries such as muscle trauma.

People frequently suffer muscle injuries caused by accidents or sports, while others develop muscle diseases such as muscular dystrophies that display prominent muscle inflammation. Duchenne muscular dystrophy is the most common genetic muscle disease. It causes severe disability and premature death caused by breathing and heart muscle weakness. Currently, the disease has no cure.

"Macrophages are important effectors and regulators of muscle inflammation, fibrosis and regeneration. Our findings build a knowledge base for future studies of resident macrophages in skeletal muscle development, injury repair and diseases with prominent muscle inflammation," explained corresponding author Lan Zhou, MD, PhD, professor of neurology at BUSM. "Understanding their respective origins, tissue-specific characteristics and disease-related functions is absolutely essential to harness their therapeutic potential."

Zhou and her team used experimental models to allow macrophage lineage tracing and performed bone marrow transplant experiments to study the origins of skeletal muscle resident macrophages. They also performed single cell-based transcriptome analyses to analyze subsets of skeletal muscle resident macrophages and their functions.

In a publication in Nature Communications last Friday, NIOZ scientists Nina Dombrowski and Anja Spang and their collaboration partners describe a previously unknown phylum of aquatic Archaea that are likely dependent on partner organisms for growth while potentially being able to conserve some energy by fermentation. In contrast to initial analyses, this study shows that the new phylum is part of a group of Archaea that are believed to mainly comprise symbionts. Further, the study yields new insights into the diversity and evolutionary history of the Archaea.

Archaea make up one of the main divisions of life, next to the Bacteria and the Eukaryotes, the latter of which comprise for example fungi, plants and animals. Archaea are a large group of microorganisms that live in all habitats on Earth ranging from soils and sediments to marine and freshwater environments as well as from human-made to host-associated habitats including the gut. In turn, Archaea are now thought to play a major role in biogeochemical nutrient cycles.

In a publication in Nature Communications last Friday, evolutionary microbiologists Nina Dombrowski and Anja Spang from the Royal Netherlands Institute of Sea Research (NIOZ) describe a previously unknown archaeal lineage (phylum). The authors named them the Undinarchaeota, in reference to the female water spirit or nymph Undina. For the study, Dombrowski and Spang cooperated with partners from Bristol University, the University of Queensland and the Australian National University.

Diverse symbionts and parasites

Because of their great resemblance to Bacteria, Archaea were only described as a separate lineage about 40 years ago and were not studied intensely until very recently, when it became possible to sequence DNA directly from environmental samples and to reconstruct genomes from uncultivated organisms. This field of genetic research, generally referred to as metagenomics (Figure 1), has not only revealed that microbial life including the Archaea is much more diverse than originally thought, but also provided data needed to shed light on the function of these microbes in their environments.

The newly described Undinarchaeota were discovered in genetic material from marine (Indian, Mediterranean and Atlantic ocean) and aquifer (Rifle aquiver, Colorado River) environments. The authors could show that they belong to a very diverse and until recently unknown group of so-called DPANN archaea. Members of the DPANN include organisms with very small genomes and limited metabolic capabilities, which suggests that these organisms depend on other microbes for growth and survival1,2,3. In fact, the few so far cultivated DPANN archaea are obligate symbionts or parasites that cannot live on their own4.

"In line with this, the Undinarchaeota seem to lack several anabolic pathways, indicating that they are, too, depend on various metabolites from so far unknown partner organisms", says research leader Anja Spang. "However, Undinarchaeota seem to have certain metabolic pathways that lack in some of the most parasitic DPANN archaea and may be able to conserve energy by fermentation."

Complex evolutionary history

While DPANN have only been discovered recently, it becomes increasingly clear that they are widespread and that representatives inhabit all thinkable environments on Earth. Yet, little is known about their evolutionary and ecological role. "In some way, some of the DPANN archaea resemble viruses, needing a host organism, likely other archaea or bacteria, for survival", says Spang. "However, and in contrast to viruses, we currently know very little about the DPANN archaea and how they affect food webs and host evolution. It is also unclear whether DPANN are an ancient archaeal lineage that resembles early cellular life or have evolved later or in parallel with their hosts."

With their study, the authors could shed more light on the complex evolution of Archaea. "Our work revealed that many DPANN archaea frequently exchange genes with their hosts, which makes it very challenging to reconstruct their evolutionary history", says first author Nina Dombrowski. Tom Williams (Bristol University) adds: "However, we could show that DPANN have probably evolved in parallel with their hosts over a long evolutionary time scale, by identifying and studying those genes that were inherited from parent-to-offspring instead of having been transferred between host and symbiont".

Role in marine biogeochemical cycles

Spang expects that certain DPANN including the Undinarchaeota, may be important for biogeochemical nutrient cycles within the oceans and sediments. "One reason that DPANN were discovered relatively recently, is that they were not retained on the filters originally used for concentrating cells from environmental samples due to their small cell sizes." But since their discovery, DPANN turned out to be much more widespread than originally anticipated. Chris Rinke from the University of Queensland: "Prospective research on the Undinarchaeota and other DPANN archaea will be essential to obtain a better understanding of marine biogeochemical cycles and the role symbionts play in the transformation of organic matter."

These questions drive some of the prospective projects of Anja Spang. In particular, in collaboration with their NIOZ colleagues Laura Villanueva, Pierre Offre and Julia Engelmann, the authors of the publication Anja Spang and Nina Dombrowski have just sequenced new DNA from water samples from the Black Sea, revealing that Undinarchaeota are present in almost all anoxic depth layers of this basin. Spang says: "These data are a gold mine for the future exploration of the ecology and evolution of these potentially symbiotic Archaea, allowing us to identify their interaction partners and to unravel further secrets about the biology of the Undinarchaeota."

The world's 'best of the last' tropical forests are at significant risk of being lost, according to a paper released today in Nature Ecology and Evolution. Of these pristine forests that provide key services--including carbon storage, prevention of disease transmission and water provision--only a mere 6.5 percent are formally protected.

In the study, the United Nations Development Programme (UNDP), the National Aeronautics and Space Administration (NASA), Wildlife Conservation Society and scientists from eight leading research institutions--including professor Scott Goetz, research professor Patrick Jantz and research associate Pat Burns of Northern Arizona University' School of Informatics, Computing, and Cyber Systems--identified significant omissions in international forest conservation strategies. Current global targets focus solely on forest extent and fail to acknowledge the importance of forest intactness, or structural condition, creating a critical gap in action to safeguard ecosystems essential for human and planetary well-being.

New targets that recognize forest quality are urgently needed to safeguard the Earth's precious humid tropical forests. Of the 1.9 million hectares of humid tropical forests globally, the study advocated for new protections in 41 percent of these areas, active restoration in 7 percent and reduction of human pressure in 19 percent to promote coordinated strategies to sustain forests of high ecological value.

"By serving as a convener to bring together the world's best scientists with governments, UNDP plays a critical role in ensuring that cutting-edge research is relevant for the development of key international agreements and implementation at the national level," commented Haoliang Xu, UN Assistant Secretary-General and UNDP Director of Bureau for Policy and Programme Support.

Collaborating with UNDP Country Offices and key stakeholders in Brazil, Colombia, Costa Rica, the Democratic Republic of the Congo, Ecuador, Indonesia, Peru, and Viet Nam, researchers mapped the location of high-quality forests using recently developed high-resolution maps of forest structure and human pressure across the global humid tropics.

The paper reveals that the Earth's humid tropical forests, only half of which have high ecological integrity, are largely limited to the Amazon and Congo Basins. The vast majority of these forests have no formal protection and, given recent rates of loss, are at significant risk.

With the rapid disappearance of these 'best of the last' forests at stake, the paper provides a policy-driven framework for their conservation and restoration, recommending locations to maintain protections, add new protections, restore forest structure, and mitigate human pressure.

The coming year is a so-called 'super year' for biodiversity, in which the world will agree on a new deal for nature that will shape global action for the next 30 years. Countries will also have a final chance to revise their contributions to reduce carbon emissions before the Paris Climate Agreement goes into effect. Both these milestones will impact efforts to advance the nature-based Sustainable Development Goals of the 2030 Agenda.

"The work reported in this paper is the result of a long process assessing the condition of the world's tropical forests," said Goetz, a co-author of the paper. "The breakthrough here was being able to use spaceborne satellite data to provide the first robust estimates of the structural condition of forests in three dimensions, not just forest canopy cover."

"Advances in earth observation instruments and methodologies developed by NASA and partner institutions, coupled with the use of incredibly powerful computing systems like NAU's Monsoon and Google Earth Engine, enabled a near-global mapping of tropical forest quality. We synthesized the best available earth observation datasets to map the changing condition of the Earth's tropical forests, finding that only 6.5 percent of the highest quality tropical forests are formally protected. We hope that the conservation strategies proposed as part of this international effort will be a step towards conserving high quality forests and restoring those that have been degraded," said Burns.

"Every year, research reveals new ways that old, structurally complex forests contribute to biodiversity, carbon storage, water resources, and many other ecosystem services. That we can now map such forests in great detail is an important step forward in efforts to conserve them," said Jantz.

Army researchers developed a reinforcement learning approach that will allow swarms of unmanned aerial and ground vehicles to optimally accomplish various missions while minimizing performance uncertainty.

Swarming is a method of operations where multiple autonomous systems act as a cohesive unit by actively coordinating their actions.

Army researchers said future multi-domain battles will require swarms of dynamically coupled, coordinated heterogeneous mobile platforms to overmatch enemy capabilities and threats targeting U.S. forces.

The Army is looking to swarming technology to be able to execute time-consuming or dangerous tasks, said Dr. Jemin George of the U.S. Army Combat Capabilities Development Command's Army Research Laboratory.

"Finding optimal guidance policies for these swarming vehicles in real-time is a key requirement for enhancing warfighters' tactical situational awareness, allowing the U.S. Army to dominate in a contested environment," George said.

Reinforcement learning provides a way to optimally control uncertain agents to achieve multi-objective goals when the precise model for the agent is unavailable; however, the existing reinforcement learning schemes can only be applied in a centralized manner, which requires pooling the state information of the entire swarm at a central learner. This drastically increases the computational complexity and communication requirements, resulting in unreasonable learning time, George said.

In order to solve this issue, in collaboration with Prof. Aranya Chakrabortty from North Carolina State University and Prof. He Bai from Oklahoma State University, George created a research effort to tackle the large-scale, multi-agent reinforcement learning problem. The Army funded this effort through the Director's Research Award for External Collaborative Initiative, a laboratory program to stimulate and support new and innovative research in collaboration with external partners.

The main goal of this effort is to develop a theoretical foundation for data-driven optimal control for large-scale swarm networks, where control actions will be taken based on low-dimensional measurement data instead of dynamic models.

The current approach is called Hierarchical Reinforcement Learning, or HRL, and it decomposes the global control objective into multiple hierarchies - namely, multiple small group-level microscopic control, and a broad swarm-level macroscopic control.

"Each hierarchy has its own learning loop with respective local and global reward functions," George said. "We were able to significantly reduce the learning time by running these learning loops in parallel."

According to George, online reinforcement learning control of swarm boils down to solving a large-scale algebraic matrix Riccati equation using system, or swarm, input-output data.

The researchers' initial approach for solving this large-scale matrix Riccati equation was to divide the swarm into multiple smaller groups and implement group-level local reinforcement learning in parallel while executing a global reinforcement learning on a smaller dimensional compressed state from each group.

Their current HRL scheme uses a decupling mechanism that allows the team to hierarchically approximate a solution to the large-scale matrix equation by first solving the local reinforcement learning problem and then synthesizing the global control from local controllers (by solving a least squares problem) instead of running a global reinforcement learning on the aggregated state. This further reduces the learning time.

Experiments have shown that compared to a centralized approach, HRL was able to reduce the learning time by 80% while limiting the optimality loss to 5%.

"Our current HRL efforts will allow us to develop control policies for swarms of unmanned aerial and ground vehicles so that they can optimally accomplish different mission sets even though the individual dynamics for the swarming agents are unknown," George said.

George stated that he is confident that this research will be impactful on the future battlefield, and has been made possible by the innovative collaboration that has taken place.

"The core purpose of the ARL science and technology community is to create and exploit scientific knowledge for transformational overmatch," George said. "By engaging external research through ECI and other cooperative mechanisms, we hope to conduct disruptive foundational research that will lead to Army modernization while serving as Army's primary collaborative link to the world-wide scientific community."

The team is currently working to further improve their HRL control scheme by considering optimal grouping of agents in the swarm to minimize computation and communication complexity while limiting the optimality gap.

They are also investigating the use of deep recurrent neural networks to learn and predict the best grouping patterns and the application of developed techniques for optimal coordination of autonomous air and ground vehicles in Multi-Domain Operations in dense urban terrain.

George, along with the ECI partners, recently organized and chaired an invited virtual session on Multi-Agent Reinforcement Learning at the 2020 American Control Conference, where they presented their research findings.