Culture

Networks offer a powerful way to visualize and analyze complex systems. However, depending on the size and complexity of the network, many visualizations are limited. Protein interactions in the human body constitute such a complex system that can hardly be visualized. Jörg Menche, Adjunct Principal Investigator at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Professor at the University of Vienna and research group leader at Max Perutz Labs (Uni Wien/MedUni), and his team developed an immersive virtual reality (VR) platform that solves this problem. With the help of VR visualization of protein interactions, it will be possible in the future to better recognize correlations and identify those genetic aberrations that are responsible for rare diseases.

The larger and more complex networks are, the more difficult their visualization on the screen becomes. Conventional computer programs quickly reach their limits. This challenge was addressed by network scientist Jörg Menche and his research group at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences. They developed a VR platform for exploring huge amounts of data and their complex interplay in a uniquely intuitive fashion.

The body as a network

The representation of complex data can be particularly important in the search for the cause of rare diseases, because the human body, with its approximately 20,000 proteins that are encoded in the human genome and interact with each other, represents a huge complex network. Whether movement or digestion - at the molecular level, all biological processes are based on the interaction between proteins. If the protein interactions are illustrated in a network, a barely representable picture of about 18,000 dots - proteins - and about 300,000 lines between these dots will be created. Menche and his research group used the virtual reality (VR) platform they developed to make this image "readable" and, in collaboration with St. Anna Children's Cancer Research, succeeded in making the entirety of protein interactions visible for the first time. This makes it possible to interactively explore the vast and complex network.

Approaching the cause of rare immune diseases

For their study, published in Nature Communications, first author Sebastian Pirch and Menche's research group identified connection patterns between different protein complexes in the human body and linked them to their biological functions. In addition, the scientists used global databases to identify specific protein complexes associated with a particular disease. "While conventional forms of representation would look like a proverbial 'hairball', the 3-dimensional representation enables the precise analysis and observation of the different protein complexes and their interactions," says study author Pirch. This can be particularly important in the identification of rare genetic defects and crucial for therapeutic measures. "On the one hand, our study represents an important proof of concept of our VR platform; on the other hand, it directly demonstrates the enormous potential of visualizing molecular networks," says project leader Menche. "Especially in rare diseases, severe immune diseases, protein complexes associated with specific clinical symptoms can be analyzed in more detail to develop hypotheses about their respective pathobiological mechanisms. This facilitates the approach to disease causes and subsequently the search for targeted therapeutic measures."

About the VR platform

The platform developed by Menche's research group is designed for maximum flexibility and extensibility. Key features include the import of user-defined code for data analysis, easy integration of external databases, and a high degree of design freedom for arbitrary elements of user interfaces. The researchers were able to draw on technology normally used in the development of 3D computer games, such as the globally popular game Fortnite. By publishing the source code, the researchers hope to convince other developers of the potential of virtual reality for analyzing scientific data.

How can I prepare myself for something I do not yet know? Scientists from the Fritz Haber Institute in Berlin and from the Technical University of Munich have addressed this almost philosophical question in the context of machine learning. Learning is no more than drawing on prior experience. In order to deal with a new situation, one needs to have dealt with roughly similar situations before. In machine learning, this correspondingly means that a learning algorithm needs to have been exposed to roughly similar data. But what can we do if there is a nearly infinite amount of possibilities so that it is simply impossible to generate data that covers all situations?

This problem comes up a lot when dealing with an endless number of possible candidate molecules. Organic semiconductors enable important future technologies such as portable solar cells or rollable displays. For such applications, improved organic molecules - which make up these materials - need to be discovered. Tasks of this nature are increasingly using methods of machine learning, while training on data from computer simulations or experiments. The number of potentially possible small organic molecules is, however, estimated to be on the order of 1033. This overwhelming number of possibilities makes it practically impossible to generate enough data to reflect such a large material diversity. In addition, many of those molecules are not even suitable for organic semiconductors. One is essentially looking for the proverbial needle in a haystack.

In their work published recently in Nature Communications the team around Prof. Karsten Reuter, Director of the Theory Department at the Fritz-Haber-Institute, addressed this problem using so-called active learning. Instead of learning from existing data, the machine learning algorithm iteratively decides for itself which data it actually needs to learn about the problem. The scientists first carry out simulations on a few smaller molecules, and obtain data related to the molecules' electrical conductivity - a measure of their usefulness when looking at possible solar cell materials. Based on this data, the algorithm decides if small modifications to these molecules could already lead to useful properties or whether it is uncertain due to a lack of similar data. In both cases, it automatically requests new simulations, improves itself through the newly generated data, considers new molecules, and goes on to repeat this procedure. In their work, the scientists show how new and promising molecules can efficiently be identified this way, while the algorithm continues its exploration into the vast molecular space, even now, at this very moment. Every week new molecules are being proposed that could usher in the next generation of solar cells and the algorithm just keeps getting better and better.

In the brain, more than a hundred molecular substances act as transmitters that control communication pathways between nerve cells via thousands of different receptor types. In a review article, an international research team discusses how the activation of certain nerve cell receptors affects neuronal networks in the brain. The authors from Ruhr-Universität Bochum (RUB), Pompeu Fabra University in Barcelona and Oxford University present concepts to quantify receptor-specific modulations of brain states. They have also developed a computer model that can predict the impact of individual receptor types on brain activity.

In addition, the researchers show how the predictions obtained in the computer can be verified and refined by experimental methods. They hope this will lead to new ways of diagnosing and treating mental disorders. They report on their work and the current state of research in a State-of-the-Art Review in the FEBS Journal, published by the Federation of European Biochemical Societies in April 2021.

Simulating dynamics of brain states in a computer model

Much is already known about the molecular structure of neuronal receptors. But researchers know little about how individual receptor types modify holistic dynamics in the brain's networks. To simulate this in a computer model, the research team compiled data from three different imaging techniques: information on the anatomical connectivity in the brain, recorded with diffusion-weighted magnetic resonance imaging; information about resting-state activity of participants, obtained from measurements using functional magnetic resonance imaging, fMRI for short; and the distributions of receptor types, recorded with positron emission tomography. Using this input, the researchers were able to create an individual receptome for each subject reflecting the overall distribution of receptor types in the brain.

This enabled the researchers to simulate interactions between neurons dependent on activations of individual receptor types in the computer model. For example, they virtually activated the serotonin receptor 5-HT2A and observed the following changes in the in-silico model brain. "Activity patterns were surprisingly similar to those observed in the scanner after human subjects had been administered psilocybin or LSD - both psychedelic substances that specifically bind to the 5-HT2A receptor," explains Associate Professor Dr. Dirk Jancke, Head of the Bochum Optical Imaging Lab, lead author of the review article. The computer model was thus able to predict changes in the overall dynamics of the brain after activation of a single receptor type.

Testing predictions in experiments

Pharmacological substances are usually not specific to only one type of receptor; another drawback is that they can't be used to activate neurons locally in a targeted manner. This means that more complex predictions and tests on human subjects are only possible to a limited extent.

The authors therefore propose to refine their hypotheses by using optogenetic methods and to test them in animal experiments. The research group led by co-author Professor Stefan Herlitze from the Department of General Zoology and Neurobiology at RUB is one of the pioneers of this technique. Viral vectors are used to instruct cells to produce certain proteins. With this technique, gene-modified mice can, for example, be made to produce light-activated receptors and proteins that fluoresce when nerve cells are active.

In previous studies, the authors used the method for the first time to show how serotonin affects visual information processing. "Our results suggest that the 5-HT2A receptor suppresses current visual inputs," explains Dirk Jancke. "External stimuli thus become less important for the brain and, at the same time, internally occurring processes are relatively amplified. Hallucinations could have their cause in the fact that this imbalance has become too strong."

Prognosis, diagnosis and therapeutic potential

Mental illnesses are often based on dysfunctions of transmitter systems and, consequently, on changes in the activation of various receptors in the receptome. This is associated with specific modulations of brain states, which can manifest themselves in subtle changes in the dynamics of wide-spread and entangled neuronal networks in the brain. Through their research, the scientists hope to initiate new concepts using biomarkers to better diagnose and more specifically treat mental disorders. "Conceivable are specific pharmacological therapies and stimulation techniques in combination with concomitant psychiatric treatments, which help to learn new contexts to rebalance pathological brain states," says Jancke.

How primates get from A to B gives vital information about their cognitive evolution, say researchers in a new study looking at the travel paths of animals in the wild. Using data from 164 wild primate populations, the global survey examines the mental abilities that primates, including ourselves, use to know where and when to travel in the most efficient way.

A birds eye view

Co-author Miguel de Guinea, expert in Evolutionary Anthropology at Oxford Brookes University commented: "Imagine looking down on a huge outdoor market from high in the sky, perhaps from a drone hovering quietly above. The people below move in different ways. Some wander haphazardly among the stalls: they are learning what's available but are clearly not busy. Others take bee-line routes across the market to a destination they obviously wanted to reach, then, after buying what they need, head back in much the same way.

"If you could distinguish individuals, and watch them on many occasions, these patterns are likely to change, sometimes dependent on fruit and vegetables in season. We would also begin to learn about social aspects, as networks of repeated contacts show who is friendly with whom. We can get a good idea of people's knowledge, their needs, their ability to think ahead and how they learn over time - just from watching their travel paths. The same observations have been made by the research team using data from GPS devices and in-field studies of wild primates, giving us fascinating information about their development."

Travel decision-making adds to picture

The original data was gathered from small GPS devices, used routinely in primate fieldwork: sometimes these are attached to the animals themselves, but in many studies a researcher follows the animals, usually noting a rich variety of background information on what they are doing and for how long.

The international team developed a conceptual framework to highlight ways in which these data can be analysed. Currently, primate cognition is studied by comparing measures such as brain size, or conducting experiments with artificial problems to primates in captivity. The evidence from travel decision-making amongst wild populations will enhance these approaches and give a fuller picture of the cognitive development of these species.

An urgent vision for primate research

Lead-author Karline Janmaat from the University of Amsterdam said: "Our ultimate dream is to set up a consortium to support data sharing and collaboration among primatologists. Hopefully this attracts MSc and PhD students from around the world to share and compare their collected data to these existing datasets."

The researchers say that further research is urgent, because so many species are now threatened with extinction in the wild. Since 1970, two-thirds of all vertebrate populations have been lost, and large, day-living animals like primates have been significantly impacted.

Miguel de Guinea stressed: "Time is fast running out - if we don't act now we may never be able to understand the drivers of cognitive evolution. By applying our research methodology and findings we can make use of previously collected valuable data from wild populations and apply that to our understanding of the cognitive evolution of primate species."

The research Using natural travel paths to infer and compare primate cognition in the wild is published in iScience.

An evolutionary biologist from the University of Bonn brought a new octopus species to light from depths of more than 4,000 meters in the North Pacific Ocean. The sensational discovery made waves in the media a few years ago. Researchers in Bonn have now published the species description and named the animal "Emperor dumbo" (Grimpoteuthis imperator). Just as unusual as the organism is the researchers' approach: in order to describe the new species, they did not dissect the rare creature, but instead used non-destructive imaging techniques. The results have now been published in the prestigious journal BMC Biology.

In the summer of 2016, Dr. Alexander Ziegler from the Institute of Evolutionary Biology and Ecology at the University of Bonn spent several months in the North Pacific aboard the research vessel SONNE. The crew lowered the steel basket to the seabed around 150 times in order to retrieve rocks, sediments, and living creatures. One organism in particular caused a media stir: a dumbo octopus. The animal, about 30 centimeters in size, was found in waters more than 4,000 meters deep. However, the octopus could not be recovered alive: "The deep-sea organism is not adapted to the environmental conditions of the ocean surface," Ziegler explains.

Dumbo octopuses are a group of deep-sea-dwelling octopuses that includes 45 species. The name is based on the flying elephant from the Walt Disney movie of the same name, who is made fun of because of his unusually large ears - the fins of the dumbo octopuses, which are on the sides of the head resemble these elephant ears. However, the dumbo on the research vessel SONNE differed significantly from the known octopus species. "It was clear to me straight away that we had caught something very special," the biologist reports. So Ziegler immediately photographed the unusual animal, took a small tissue sample for DNA analysis, and then preserved the octopus in formalin.

Together with his former master's student Christina Sagorny, Ziegler has now published a description of the previously unknown species. Just as unusual as the octopus was the methodology used. The animals are usually dissected by zoologists, as the internal organs are also important for the description of a new species. "However, as this octopus is very valuable, we were looking for a non-destructive method," explains the researcher.

High-field MRI instead of scalpel

The eight-armed cephalopod therefore did not end up under the scalpel, but in the high-field magnetic resonance imaging system of the German Center for Neurodegenerative Diseases (DZNE) in Bonn. This device is routinely used to image test persons' brains. Thankfully, Dr. Eberhard D. Pracht from the DZNE agreed to conduct a high-resolution scan of the dumbo octopus in 3D. As part of her master's thesis, Christina Sagorny then investigated whether high-field MRI can be used to study internal organs and other soft tissues just as well as through conventional dissection. "The quality is actually even better," Ziegler says.

One of the few exceptions: the beak and rasping tongue (radula) of the cephalopod are made of hard chitin that does not image well using MRI. The biologists therefore also consulted the micro-computed tomography system of the paleontologists at the University of Bonn. This technique showed the beak and radula razor-sharp and in 3D. "These hard part structures are an integral part of the species description of octopuses," Ziegler explains. The researchers also decoded the animal's genetic material to reconstruct the family relationships. Ziegler: "The DNA showed beyond a doubt that we were looking at a species of the genus Grimpoteuthis."

Examination of the reproductive organs revealed the dumbo octopus to be an adult male. Compared to other species of this genus, it displays several special characteristics. For example, an average of 71 suckers were detected on each arm, which the animal needs to catch prey and which reflect body size. The length of the cirri, which are small appendages on the arms that the deep-sea animals presumably use to sense their prey, also differs from species already known.

The web that stretches between the arms, with which the dumbo slowly floats down in the water column, catching worms and crustaceans as if in a bell, also only reaches just over halfway from the mouth down the arms. "The web is much longer in dumbo octopus species that mainly float freely in the water column," Ziegler says. This would indicate that the new species lives close to the seafloor, because otherwise the web would be a hindrance to movements on the bottom.

As the species-describing researchers, Sagorny and Ziegler had the privilege of naming the new species: they decided on Grimpoteuthis imperator - in English "Emperor dumbo". Background: the animal was discovered not far from Japan in an underwater mountain range whose peaks are named after Japanese emperors.

Digital copy of the organism

The combination of non-destructive methods produced a crisp digital copy of the animal. Anybody interested can download it from the online database "MorphoBank" for further research and learning purposes. The preserved octopus itself is kept in the archives of the Museum für Naturkunde in Berlin, Germany. "There, it can then still be analyzed 100 years from now, for example when more modern investigation methods or new questions arise," Ziegler explains. "Our non-destructive approach could set a precedent, especially for rare and valuable animals," said the Bonn-based evolutionary biologist.

There are many different types of cancer, but they all have one thing in common: errors in the signals that control normal cell behaviour can cause uncontrolled cell growth and cell division, leading to a tumour. An enzyme called SHP2 plays a key role in this regard. SHP2 is a signalling molecule that in its activated state stimulates cell proliferation. In a normal healthy body, the rates of cell proliferation and cell death are balanced and tumours do not develop. However, if SHP2 becomes too active, the number of cells being created outweighs the number that die, which can lead to the formation of dangerous tumours. Enhanced SHP2 activity resulting from genetic mutations has been shown to play a central role in a number of types of leukaemia.

'It would be of immense value if we could effectively inhibit the SHP2 protein. But if you want to inhibit something, you first have to find out how it is activated,' says Jochen Hub, explaining the issue at the core of this long-standing scientific puzzle. Hub, Professor of Theoretical Physics at Saarland University, specializes in molecular dynamics simulations and his group develops computer models of biological processes. Hub and his research colleague Dr. Massimiliano Anselmi, who is the lead author of the research paper, have been able to simulate the SHP2 activation mechanism.

The two researchers made a surprising discovery: 'Over the last twenty years, there has been a consensus amongst experts that SHP2 is activated when a closed binding pocket on the SHP2 protein opens when a peptide docks onto this binding site.' A simple comparison would be opening a closed door (the 'binding pocket' or 'binding cleft' as it is also known) with a key (the peptide). However, no one has managed to produce clear experimental evidence that confirms this theoretical conjecture.

'We've now been able to show that the model simply isn't right', explains Jochen Hub. 'It turns out that the binding pocket is not actually closed, and so cannot be opened by the peptide.' The sophisticated simulations carried out by the Saarbrücken research team show that it is in fact other structures in the SHP2 molecule that open in the presence of the peptide. These flexible structures, known as beta sheets, play the role that scientists had for so long erroneously attributed to the binding pocket. When the peptide 'key' is 'inserted', the beta sheets open, changing the shape of the SHP2 molecule and thus causing it to become activated.

'This finding is of considerable significance. Because we now know that the binding pocket is not the crucial site for SHP2 activation, it may be possible to develop much more targeted agents that can prevent the activation of SHP2,' says Jochen Hub when describing the consequences of decoding the activation mechanism. As a result of this research work, Hub and particularly Massimiliano Anselmi have now opened the door for novel therapeutic approaches to treating certain forms of cancer. The Saarbrücken simulation specialists are hoping to collaborate with experimental teams to corroborate their findings.

Researchers at the University of Cincinnati say a regulatory protein found in skeletal muscle fiber may play an important role in the body's fight or flight response when encountering stressful situations.

The protein, fast skeletal myosin binding protein-C (fMyBP-C), plays a foundational role in the proper regulation of contractile structure and function in the body's fast twitch muscles -- these muscles produce sudden bursts of power to sprint into action, jump or lift heavy objects. Fast skeletal myosin binding protein-C modulates the speed and force of fast skeletal muscle contraction.

"This response is very critical for the higher animal and human survival. Just imagine, you are walking through a forest and suddenly you see a tiger in front of you," says Sakthivel Sadayappan, PhD, a professor in the UC Division of Cardiovascular Health and Disease. "You will immediately act, either to fight or run away from the animal. For that action, fast muscle is essential, and fast myosin binding protein-C is the key molecule to regulate the speed of action."

Myosin-binding protein-C is a thick filament regulatory protein found in striated muscle in both the heart and skeletal system. The protein performs different functions in the two organs, regulating contractility in the heart and playing a role in the development of fast and slow muscle fibers in skeletal muscle tissue.

Sadayappan along with researchers at UC College of Medicine, Florida State University, the University of Massachusetts Medical School and the Illinois Institute of Technology published research in the scholarly journal PNAS to further the understanding of the protein in skeletal function and regulation. Their findings are available online.

The study's lead author is Taejeong Song, PhD, a postdoctoral fellow in the Sadayappan Lab at the UC College of Medicine.

Song says that research examined the role of the protein in fast-twitch muscles by generating a knockout mouse--an animal in which researchers have either inactivated, replaced or disrupted the existing fast myosin binding protein-C gene to study its impact.

"We found that knockout mice demonstrated a reduced ability to exercise, showed less maximal muscle force and a diminished ability for muscle to recover from injury," explains Sadayappan. "Our study concludes that fast myosin binding protein-C is essential in regulating the force generation and speed of contraction of fast muscles."

Song says advancing the knowledge of fast myosin binding protein-C may someday assist in addressing skeletal muscular disorders.

"Individuals lose their ability of muscle force generation for various reasons," says Song. "They may be extremely inactive or hospitalized for long periods of time. Aging may also be the cause for some. We also think if we can manipulate the workings of fast myosin binding protein-C in skeletal muscle that we can prevent or at least slow down the loss of muscle function in genetic muscle disease such as distal arthrogryposis. Our research is trying to figure out this problem in human health."

People with type 2 diabetes tend to have poorer muscle function than others. Now a research team at Lund University in Sweden has discovered that in type 2 diabetes, a specific gene is of great importance for the ability of muscle stem cells to create new mature muscle cells. The findings are published in Nature Communications.

"In people with type 2 diabetes, the VPS39 gene is significantly less active in the muscle cells than it is in other people, and the stem cells with less activity of the gene do not form new muscle cells to the same degree. The gene is important when muscle cells absorb sugar from blood and build new muscle. Our study is the first ever to link this gene to type 2 diabetes", says Charlotte Ling, professor of epigenetics at Lund University who led the study.

In type 2 diabetes, the ability to produce insulin is impaired, and patients have chronically elevated blood sugar. Muscles are generally worse at absorbing sugar from food, and muscle function and strength are impaired in patients with type 2 diabetes.

A muscle consists of a mixture of fiber types with different properties. Throughout life, muscle tissue has the ability to form new muscle fibers. There are also immature muscle stem cells that are activated in connection with, for example, injury or exercise. In the current study, the researchers wanted to investigate whether epigenetic patterns in muscle stem cells can provide answers to why impaired muscle function occurs in type 2 diabetes.

Two groups were included in the study: 14 participants with type 2 diabetes and 14 healthy people in a control group. The participants in the groups were matched by age, gender and BMI (body mass index). The researchers studied epigenetic changes in the muscle stem cells in both groups, and under exactly the same conditions, they also extracted mature muscle cells and compared them. In total, they identified 20 genes , including VPS39, whose gene expression differed between the groups in both immature muscle stem cells and mature muscle cells. The researchers also compared the epigenetic patterns of muscle cells before and after cell differentiation in both groups.

"Despite the fact that both groups' muscle stem cells were grown under identical conditions, we saw more than twice as many epigenetic changes in the type 2 diabetes group during the differentiation from muscle stem cell to mature muscle cells. Muscle-specific genes were not regulated normally, and epigenetics did not function in the same way in cells from people with type 2 diabetes", says Charlotte Ling.

"The study clearly showed that muscle stem cells that lack the function of the gene VPS39, which is lower in type 2 diabetes, also lack the ability to form new mature muscle cells. This is because muscle stem cells that lack VPS39 due to altered epigenetic mechanisms cannot change their metabolism in the same way as muscle stem cells from controls - the cells therefore remain immature or break down and die", says Johanna Säll Sernevi, postdoc researcher at Lund University.

To confirm the findings, the researchers also used animal models with mice that had a reduced amount of the VPS39 gene, to mimic the disease. The mice subsequently had altered gene expression and reduced uptake of sugar from blood into the muscle tissue, just like the individuals with type 2 diabetes.

The comprehensive study is a collaboration between Swedish, Danish and German researchers, who believe that the findings open up new avenues for treating type 2 diabetes.

"The genome, our DNA, cannot be changed, although epigenetics in effect does. With this new knowledge, it is possible to change the dysfunctional epigenetics that occur in type 2 diabetes. For example, by regulating proteins, stimulating or increasing the amount of the VPS39 gene, it would be possible to affect the muscles' ability to regenerate and absorb sugar", concludes Charlotte Ling.

The giant star featured in this latest Hubble Space Telescope anniversary image is waging a tug-of-war between gravity and radiation to avoid self-destruction. The star, called AG Carinae, is surrounded by an expanding shell of gas and dust -- a nebula -- that is shaped by the powerful winds of the star. The nebula is about five light-years wide, which equals the distance from here to our nearest star, Alpha Centauri.

The huge structure was created from one or more giant eruptions several thousand years ago. The star's outer layers were blown into space, the expelled material amounting to roughly 10 times the mass of our Sun. These outbursts are typical in the life of a rare breed of star called a Luminous Blue Variable (LBV), a brief unstable phase in the short life of an ultra-bright, glamorous star that lives fast and dies young. These stars are among the most massive and brightest stars known. They live for only a few million years, compared to the roughly 10-billion-year lifetime of our own Sun. AG Carinae is a few million years old and resides 20 000 light-years away inside our Milky Way galaxy. The star's expected lifetime is between 5 million and 6 million years.

LBVs have a dual personality. They appear to spend years in semi-quiescent bliss and then they erupt in a petulant outburst, during which their luminosity increases -- sometimes by several orders of magnitude. These behemoths are stars in the extreme, far different from normal stars like our Sun. In fact AG Carinae is estimated to be up to 70 times more massive than our Sun and shines with the blinding brilliance of 1 million suns.

Major outbursts such as the one that produced the nebula featured in this image occur a few times during a LBV's lifetime. A LBV star only casts off material when it is in danger of self-destruction. Because of their massive forms and super-hot temperatures, luminous blue variable stars like AG Carinae are in a constant battle to maintain stability. It's an arm-wrestling contest between radiation pressure from within the star pushing outward and gravity pressing inward. This arm-wrestling match results in the star's expanding and contracting. The outward pressure occasionally wins the battle, and the star expands to such an immense size that it blows off its outer layers, like a volcano erupting. But this outburst only happens when the star is on the verge of coming apart. After the star ejects the material, it contracts to its normal (large) size, settles back down, and becomes stable again.

LBV stars are rare: fewer than 50 are known among the galaxies in our local group of neighbouring galaxies. These stars spend tens of thousands of years in this phase, a blink of an eye in cosmic time. Some are expected to end their lives in titanic supernova blasts, which enrich the Universe with the heavier elements beyond iron.

Like many other LBVs, AG Carinae remains unstable. It has experienced lesser outbursts that have not been as powerful as the one that created the present nebula. Although AG Carinae is semi-quiescient now, its searing radiation and powerful stellar wind (streams of charged particles) have been shaping the ancient nebula, sculpting intricate structures as outflowing gas slams into the slower-moving outer nebula. The wind is travelling at up to 1 million kilometres per hour, about 10 times faster than the expanding nebula. Over time, the hot wind catches up with the cooler expelled material, ploughs into it, and pushes it farther away from the star. This "snowplough" effect has cleared a cavity around the star.

The red material is glowing hydrogen gas laced with nitrogen gas. The diffuse red material at upper left pinpoints where the wind has broken through a tenuous region of material and swept it into space. The most prominent features, highlighted in blue, are filamentary structures shaped like tadpoles and lopsided bubbles. These structures are dust clumps illuminated by the star's light. The tadpole-shaped features, most prominent at left and bottom, are denser dust clumps that have been sculpted by the stellar wind. Hubble's sharp vision reveals these delicate-looking structures in great detail.

The image was taken in visible and ultraviolet light. Hubble is ideally suited for observations in ultraviolet light because this wavelength range can only be viewed from space.

How do the billions of cells communicate in order to perform tasks? The cells exert force on their environment through movement - and in doing so, they communicate. They work as a group in order to infiltrate their environment, perform wound healing and the like. They sense the stiffness or softness of their surroundings and this helps them connect and organize their collective effort. But when the connection between cells is distrubeddisturbed, a situation just like when cancer is initiated, can appear.

Assistant Professor Amin Doostmohammadi at the Niels Bohr Institute, University of Copenhagen has investigated the mechanics of cell movement and connection in an interdisciplinary project, collaborating with biophysicists in France, Australia, and Singapore, using both computer modelling and biological experiments. The result is now published in Nature Materials.

Amin Doostmohammadi explains: "We need to understand how cells translate this "knowledge from sensing" at the individual cell level and transform it into action on the collective level. This is still kind of a black box in biology - how do cell talk to their neighbors and act as a collective?"

The force of surrounding tissue dictates cell behavior

Individual cells have a contractile mode of motion: they pull on the surface they are located on to move themselves forward. However, cells lining up cavities and surfaces in our body, like the tubes of blood vessels or the cells at the surface of organs, are able to generate extensile forces. They do the opposite, they stretch instead of contract - and they form strong connections with their neighbors. Contractile cells are able to switch to becoming extensile cells, when coming into contact with their neighbors. If, for instance, when contractile cells sense a void or an empty space, like when a wound appears, they can loosen their cell - cell connection, become more individual, and when healing the wound, they form strong connections with their neighbors again, becoming extensile, closing the gap, so to speak.

Weakening cell connection can be the hallmark of cancer initiation

The cells connect to their neighbors by adherens junctions. They connect their internal cytoskeleton to one another and become able to transmit forces through the strong contacts. "So we asked ourselves what would happen if we prohibited the cells from making this strong connection - and it turned out that extensile, strongly connected cells turned into contractile cells with weaker connections. This is significant, because the loss of this contact is the hallmark of cancer initiation. The cells losing contact start behaving more as individuals and become able to infiltrate their surroundings. This process also happens when an embryo develops, but the key difference here is that when the healthy cells have achieved their goal, like forming an organ, they go back to their original form. Cancer cells do not. They are on a one way street", Amin Doostmohammadi says.

The basic action and reaction of cells are determined by surroundings and communication

How cells "decide" when to go from one form to another is a complicated mix of reacting to their environment, changes in the chemical composition of it, the mechanical stiffness or softness of the tissue - and many proteins in the cells are involved in the process. The key finding of this study is that this reaction to surroundings is constantly shifting: There is a constant cross-talk between cell - surroundings and cell - cell, and this is what determines the actions and reactions of the cells.

Are treatments for cancer within the scope of this new understanding in cell mechanics?

"We must always be careful, when talking about a serious and very complex disease like cancer", Amin Doostmohammadi says. "But what we can say is that this study brings us one step closer to understanding the basic mechanics of cell behavior, when the cells go from the normal behavior to the aggressive, cancer type cell behavior. So, one of the big questions this study raises is if we might be able to target the mechanics of the cells by some form of therapy or treatment, instead of targeting the DNA or chemical composition of the cells themselves? Could we target the environment instead of the cells? This is basic research, connecting physics and biology, into the mechanics of cell behavior, based on their sensing and responding to the surroundings and coordinating their effort - our improved understanding of this may well lead to new therapies, and there are trials going on at the moment at a preliminary stage".

New research provides evidence that people have transmitted SARS-CoV-2, the virus that causes COVID-19, to cats during the pandemic in the UK. The study, which is published in Veterinary Record, detected the virus last year in cats that developed mild or severe respiratory disease.

Investigators used a range of laboratory techniques to show that two domestic cats from households with suspected cases of COVID-19 were infected with SARS-CoV-2.

"These findings indicate that human-to-cat transmission of SARS-CoV-2 occurred during the COVID-19 pandemic in the UK, with the infected cats displaying mild or severe respiratory disease. Given the ability of the coronavirus to infect companion animals, it will be important to monitor for human-to-cat, cat-to-cat and cat-to-human transmission," said lead author Margaret Hosie, PhD, of the MRC-University of Glasgow Centre for Virus Research.

New research led by Curtin University has revealed how radar satellites can improve the ability to detect, monitor, prepare for and withstand natural disasters in Australia including bushfires, floods and earthquakes.

The research used Synthetic Aperture Radar data obtained by the European Space Agency Sentinel-1 satellite, amongst others, to evaluate Australia-specific case studies.

Lead researcher Dr Amy Parker, an ARC Research Fellow from Curtin's School of Earth and Planetary Sciences, said the Sentinel-1 satellite mission provided the first complete global Synthetic Aperture Radar (SAR) dataset and the first opportunity to use this type of data to assess hazards in new locations, including Australia.

"What makes SAR so valuable is that it provides all-weather and night-and-day capability to remotely monitor the Earth's surface, unlike traditional optical Earth Observation (EO) imagery which is at the mercy of cloud, fog, rainfall and smoke," Dr Parker said.

"SAR data can be used to precisely map topography, track movements of the ground surface, characterize land-use change, and map damage to infrastructure, all of which can significantly improve how we track and respond to natural disasters.

"But despite SAR satellites being well-documented as a hazard monitoring tool, the uptake of such data varies, and in Australia the use of SAR data has been limited."

The research applied SAR data to nine case studies covering critical issues such as bushfires, floods and earthquakes to assess the power of SAR as a disaster mitigation and prevention tool.

"For example we looked at the 2016 Wildman Coastal Plains Floods in the Northern Territory and found that SAR has added benefits in mapping flood patterns and floodplain dynamics."

Dr Parker said these benefits can also be applied to maintaining mine site safety and better understanding seismic hazards and activity.

"Globally, Australia is one of the largest users of Earth observation data derived from satellites, which contributes to national hazard monitoring and response and more than 100 state and federal government programs. Our research shows SAR data can effectively complement this." Dr Parker said.

"Previously SAR data has been considered too expensive to use as a tool for hazard mitigation, but our findings show, through Sentinel-1 we now have economically viable wall-to-wall, consistent sensor imaging of Australia.

"The uptake of SAR data for hazard applications globally will continue to benefit from validated case studies such as ours, the development of tools that support operational use, and the continued provision of open-access imagery by large-scale satellite missions."

Researchers from Nanjing University, National Sun Yat-sen University, and Northwestern University published a new paper in the Journal of Marketing that shows that the spatial distance between products and consumers can affect perceived value and willingness to pay.

The study, forthcoming in the Journal of Marketing, is titled "Values Created from Far and Near: Influence of Spatial Distance on Brand Evaluation" and is authored by Xing-Yu (Marcos) Chu, Chun-Tuan Chang, and Angela Y. Lee.

No one ever questions why some retail products are on display in cabinets behind the sales counter, where shoppers can only view them from a distance, while other displays take center stage to greet shoppers as they walk inside the store. Consumers likely reason that the former practice is to protect high-value products from potential damage or theft and that the latter practice is to entice shoppers to purchase these items. However, there are additional hidden advantages to these practices. This research team finds that keeping a distance between consumers and products enhances the perceived value and prestige of luxury items while proximity increases the perceived sincerity and closeness of popular products.

The researchers propose that the spatial distance between the product and the consumer, whether in real life or in ads or websites, may enhance or devalue consumers' perceptions of the product depending on whether the brand image reflects status or broad appeal. Specifically, distance signals prestige when status and luxury are relevant to the brand image, in which case a far distance should help enhance the brand image. On the other hand, distance signals social closeness when popularity and broad appeal are relevant to the brand image, in which case a close distance should help to enhance that brand image.

Across seven studies, they show that the distance between the product and the consumer, whether in real life or in ads, can have a profound influence on how consumers evaluate the product and make purchase decisions. The researchers observe the relationship between spatial distance and consumer perception and price judgments in a variety of contexts that include store display, window display, print ads, and websites. In the first study, participants designing a mock ad positioned the image of a product further away from the image of the model when the ad was for a prestigious brand than for a popular brand. In the next set of studies, participants estimated the same distance between the model and an expensive handbag to be further apart than for an inexpensive handbag; but they estimated the distance between the model and a popular brand to be closer than for an unpopular brand.

In the next two studies, participants evaluated an expensive leather backpack more favorably when they were standing five feet (versus three feet) away, but an everyday-use canvas backpack more favorably when they were standing three ft (versus five feet) away. Participants in the sixth study evaluated a coffeemaker with the tagline "Aromatic coffee, distinguished taste. Luxurious life, prestigious choice" more positively when it was positioned further away from the model in an ad, but the coffeemaker with the tagline "Aromatic coffee, trendy taste. Cozy life, popular choice" more positively when it was positioned closer to the model in the ad. Finally, in the last study, consumers receiving a text sent to their mobile phone were more likely to click on the ad with a "Luxurious lifestyle, Prestigious choice" tagline and visit the website to redeem a discount coupon when the product image is further away from the model in the ad. But they were more likely to click on the ad with a "Cozy lifestyle, Popular choice" tagline when the product image is closer to the model in the ad.

These findings offer useful insights to marketers about how to leverage visual cues in window and store displays and in advertising. By strategically matching the distance between the product and the consumer, marketers can effectively enhance value and increase consumers' willingness to pay a price premium for luxury brands by enhancing perceived prestige. Alternatively, they can enhance value and increase consumers' willingness to pay a price premium for brands with broad appeal by enhancing perceived social closeness. For luxury brands or products with an exclusive brand image, a distal distance signals prestige and exclusivity. In contrast, for popular brands or products that appeal to a wide customer base, a proximal distance signals connectedness and sincerity.

Images are powerful communication tools. Today's time-starved consumers are bombarded by information. Chu explains that "Vivid images can capture attention and convey meaning without words and lengthy messages. Marketers can easily incorporate the insights from our research into their communication strategy--whether it be window displays, store layouts, website designs, billboards, print ads, etc. Far distance can enhance perceived status for brands with a prestigious brand image whereas proximal distance can enhance social connectedness for brands with a popular brand image." Marketers should also be aware of the corresponding downsides--keeping a distance can dampen the perceived connectedness of popular products, while proximity can lower the perceived prestige of luxury products.

What The Study Did: This study assesses the association between COVID-19 and maternal and neonatal outcomes in pregnant women with COVID-19 diagnosis compared with pregnant women without COVID-19 diagnosis.

Authors: Aris T.Papageorghiou, M.D., of the University of Oxford in the United Kingdom, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2021.1050)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #
Media advisory: The full study and editorial are linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamapediatrics/fullarticle/10.1001/jamapediatrics.2021.1050?guestAccessKey=fed2ea98-6893-42aa-87e4-9664222f3842&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=042221

What The Study Did: This cohort study examines viral dynamics and transmission of infection for NBA players, staff and vendors who had clinically recovered from SARS-CoV-2 infection but continued to have positive test results following discontinuation of isolation precautions.

Authors: Christina Mack, Ph.D., M.S.P.H., of IQVIA, Real World Solutions, in Durham, North Carolina, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2021.2114)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #
Media advisory: The full study and editor's note are linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2021.2114?guestAccessKey=9fb714a9-50a9-46b1-a7cc-6c1a91b034c1&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=042221