Astronomers Take A Closer Look At The Atmosphere Of Lava Planet K2-141b (Planetary Science)

Lava planets are a class of rocky exoplanets that orbit so close to their star that parts of their surface are molten. Indeed, dayside temperatures can be hot enough to maintain a rock vapour atmosphere detectable through transit and eclipse spectroscopy, as well as phase curves. Theoretical studies of lava planets and their relatively volatile sodium atmospheres have been published for CoRot-7b, Kepler-10b, 55 Cnc-e, KIC 12556548, and HD 219134b. These studies utilized a 1D model that solves for the flow of mass, momentum, and energy from the hot dayside to the cold nightside.

Lava planet formation ©gettyimages

Now, Giang Nguyen and colleagues, studied K2-141b, the highest signal-to-noise lava planet discovered to date, as its phase variations have been measured by K2, Spitzer and possibly in the future with the James Webb Space Telescope (JWST). They use essentially the same model as the above studies, but they employed more accurate surface temperature calculations. They consider three compositional end-members for the atmosphere: 1) pure sodium (Na), due to its high volatility, 2) silicon monoxide (SiO), or 3) pure silica (SiO2) due to their abundance in the crust of rocky planets. These three cases bracket the range of plausible atmospheric compositions.

They then compared how pure Na, SiO, or SiO2 atmospheres would impact future observations.

For that they used the model to determine the steady-state flow of a pure Na, SiO, and SiO2 atmosphere for lava planet K2-141b. Atmospheric pressure, wind velocity, and temperature for the three cases are shown in fig 2 below. Na is the most volatile molecule, making the Na atmosphere the thickest of the three with the maximum pressure at the subsolar point of 13.8 kPa. The Na atmosphere fully condenses out at 𝜃 = 102° where wind speed can reach up to 2.3 km/s. The atmospheric temperature of Na can drop to near zero before fully collapsing.

Figure 2. Top panel: atmospheric boundary-layer pressure for a pure sodium (Na), silicon monoxide (SiO), and silica (SiO2) atmosphere. Middle panel: wind velocity (left/black) and mach number (right/purple). Bottom panel: atmospheric and surface temperatures (solid purple line).

SiO is not as volatile as Na making the SiO atmosphere thinner with a maximum pressure of 5.25 kPa. The wind, however, accelerates much faster than the Na case with velocities reaching up to 2.2 km/s and the atmosphere condenses out at 𝜃 = 92°. The temperature also drops much faster. Running the model for SiO2 produces the thinnest atmosphere with a maximum pressure of 240 Pa and collapses at 𝜃 = 89°. The wind is slower with a maximum speed of 1.75 km/s but the SiO2 atmosphere is much warmer as the temperature remains above 1500 K.

Evaporation and condensation rates vary significantly between the Na, SiO, and SiO2 cases. Although Na and SiO have similar evaporation rates near the subsolar point, the SiO atmosphere starts to condense sooner than its Na counterpart. The evaporation rates for the three scenarios are shown in Fig. 3.

Figure 3. Left/black: evaporation rate per square metre (negative numbers denote condensation). Right/purple: velocity of magma ocean return flow. Negative values denote mass flow towards the subsolar point (in the negative 𝜃 direction). Solid purple lines denote calculations neglecting the transport of oxygen while dashed lines includes oxygen to maintain mass balance.

Besides this, they have shown that the significantly less volatile SiO2 atmosphere may be easier to observe due to the extreme geometry of this system. Transit spectroscopy of K2-141b is possible due to its proximity to its star which make dayside regions accessible at the start and end of transit, and leads to large acceleration throughout transit.

They also note that the extreme orbit of K2-141b leads to significant changes in radial velocity over the course of the transit.

Their calculated return flow of SiO2 through the magma ocean is slow (10-⁴ m/s), so mass balance can be easily achieved. This supports a steady-state silicate flow whereas the volatile Na atmosphere would be limited by the return flow through the magma ocean.

If we assume the composition of K2-141b to be similar to the Bulk Silicate Earth, then there is 100x more silicate material than Na, by mass. However, their results showed that the mass transport required for a steady-state flow of Na is much greater than the 10-⁴ m/s provided by the SiO2 magma ocean. This implies that a more realistic Na atmosphere is much thinner than what they predicted before because the steady-state flow cannot be sustained, leading to the “evolved” state. Also, any precipitation that falls beyond the magma ocean shore (𝜃 > 79°) must be brought back to maintain mass conservation. This may occur via solid state flow analogous to glaciers on Earth, or via isostatic adjustment. If mass is transported back too slowly, the resulting mass imbalance could lead to reorientation of the planetary spin.

According to researchers, although K2-141b is an especially good target for atmospheric observation, their results regarding atmospheric dynamics, replenishment via the magma ocean, and transit geometry may apply to other lava planets.

References: T. Giang Nguyen, Nicolas B. Cowan, Agnibha Banerjee, John E. Moores, “Modelling the atmosphere of lava planet K2-141b: implications for low and high resolution spectroscopy”, ArXiv, pp. 1-8 2020. https://arxiv.org/abs/2010.14101

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Study Identifies More Genes That Are Likely Behind Psoriasis And Eczema (Biology)

A new study identified 17 new genes that could be targeted for treatment of psoriasis and eczema, two common hereditary skin diseases with no cure.

Nail displaying the characteristic pitting of psoriasis. Photo: Seenms/CC BY-SA 3.0
Published Oct 27, 2020.

Pelin Sahlén, SciLifeLab researcher and senior lecturer at KTH Royal Institute of Technology, says that the combined KTH-Karolinska Institutet research team mapped 118 gene targets related to the skin conditions, psoriasis and atopic dermatitis, using a method the researcher developed 10 years ago to map the interactions between genetic information in different parts of the body.

The investigation focused on the role played by non-coding genetic variants, that is, DNA that provides no instructions for creating proteins. About 2 percent of DNA is comprised on protein-coding genes, and the remaining 98 percent is non-coding.

Most of the variants (97%) associated with complex diseases are non-coding, Sahlén says. “It is not a straightforward task to determine the gene they regulate.”

They looked in the three dimensional genome for interactions between gene-regulating sequences, known as promoters and enhancers, which determine what genes are active in various tissues.

These sequences can be found on a DNA strand either before or after the gene they regulate. “They are often far from the genes they regulate,” Sahlén says. “By using the Capture Hi-C (HiCap) method, we can connect the distal gene regulating sequences with genes by examining the three-dimensional structure of the skin genome.

“This means that we map the regulatory gene network to find new genes linked to diseases and biological processes.”

Sahlén first published the (HiCap) method in 2015. The method is aimed at understanding the contribution of the non-coding genome towards an organism’s well-being, survival and health, she says.

The work was funded by the Swedish Research Council, the Swedish Skin foundation and a Type 2 innovation grant from Sanofi Genzyme.

References: Chromatin Interactions in Differentiating Keratinocytes Reveal Novel Atopic Dermatitis and Psoriasis-Associated Genes, Journal of Allergy and Clinical Immunology, DOI: 10.1016/j.jaci.2020.09.035

Provided by KTH

How Do Some Frogs ‘Rebound’ After Disease While Others Perish? (Biology)

A new study shows how some species survive infectious disease epidemics, and how we can use this knowledge to assist and direct wildlife management.

Wildlife diseases are a major cause of wildlife decline around the world.

But despite their devastating effects, some wildlife species survive these disease epidemics and some populations even rebound, increasing their numbers.

Queensland’s Common Mistfrog populations have declined due to chytridiomycosis. Picture: Lee Skerratt/University of Melbourne.

Amphibians are some of the most threatened animals in the world, with over 30 per cent listed as vulnerable or endangered species on the International Union for Conservation of Nature (IUCN) list. And disease is a major cause of these declines.

But why do some species survive and others don’t?

To help answer this, Dr. Laura A Brannelly and her team decided to go through all of the relevant research literature to understand what makes a species thrive in natural conditions to improve species management outcomes, but also help avoid management mistakes.

They used amphibian declines as a case study for how best to understand the ways that species survive declines.

It turns out that for most species, they actually do not yet understand why they are persisting after disease caused declines.

This is partly because, as they show in their analysis, there is wide variation across species and life stages, which highlights the importance of community, where different species of frogs change disease impacts.

Even for species that have been heavily studied by different research teams, like the endangered common mist frog, Litoria rheocola, from the Australian tropics, they do not understand why some populations are surviving.

The fungal pathogen Batrachochytrium dendrobatidis causes the disease chytridiomycosis, which affects amphibian skin function. Picture: Shutterstock.

To help researchers better comprehend how species survive, they identified key criteria to guide future research that will help us understand the ways that populations rebound in the future.

They also show why we should use this information to improve management practices.

Frogs are declining globally due to the fungal pathogen Batrachochytrium dendrobatidis, known as Bd. The Bd fungus causes the disease chytridiomycosis, which affects amphibian skin function.

Amphibian skin is especially important for frogs because they use it to breath, absorb water and even maintain ions in their blood. This disease causes thickening of their skin, and disrupts the normal skin function in infected frogs, ultimately causing death due to cardiac arrest.

Chytridiomycosis occurs globally and has resulted in declines in over 500 species around the world in the last 50 years and has even caused 90 species extinctions including some species in Australia like the gastric brooding frog.

Many other species remain on the verge of extinction like the southern corroboree frog, which requires management to remain in the wild, including breeding programs, reintroductions and habitat management.

Despite these massive declines, there are some species who declined but then survived and remained, like the alpine tree frog, Litoria verreauxii alpina.

This species used to be widespread in the Australian Alps, but now remains at a handful of locations, although has remained stable at those locations for a couple of decades following the initial epidemic.

Even in some areas of pristine habitat, the alpine tree frog has gone extinct. Picture: Supplied.

In their latest study published in Ecology Letters, they highlight the conditions and traits that allow frogs to persist after an epidemic.

They found that frogs, like the alpine tree frog, can persist after their population has declined due to changes in the frog, such as through reproduction where infected animals actually increase their breeding behaviour or produce more offspring when infected.

Other frogs persist through increased resistance or tolerance to disease by evolving increased immunity or behaviour, such as avoiding disease or through regulating its body temperature by moving to warmer habitats or parts of habitats to help fight infection, a term called behavioural fever in ectotherms, commonly known as “cold-blooded” animals.

The habitat of the animals can also influence decline patterns because Bd thrives better in cooler, wetter habitats.

Frogs might also persist if virulence of the pathogen reduces over time which has not been observed but is possible.

And finally, an often overlooked way that animals can persist is through understanding how the disease is transmitted, and how the ecological community affects disease.

The alpine tree frogs are surviving because they are prioritising breeding and reproduction over increased immunity to the chytrid fungus. Picture: Laura Brannelly.

The ecological community includes the animals, plants and all other organisms in the frogs environment, and can include reservoir hosts that maintain disease in the system.

Reservoir hosts for the pathogen can be other species of frogs, but also include other organisms like crayfish that live with frogs. Reservoir hosts have a high tolerance to infection, meaning that they can carry high loads and not be impacted by the disease themselves.

In Australia a possible reservoir host is the southern brown frog, Litoria ewingii. And if a susceptible or threatened species, like the green and golden bell frog, Litoria aurea, live at sites with these reservoir hosts, then they might be more likely to decline.

Understanding the ways that species are persisting is important for management, because management actions will be more effective if we support how the animals are persisting naturally.

For example, the alpine tree frogs are surviving because they are prioritising breeding and reproduction over increased immunity. Since the arrival of chytridiomycosis, they are ensuring that they breed before succumbing to disease in a pond with permanent water, allowing the population to persist.

This means that management action should be focussed on supporting successful breeding and tadpole development and access to permanent water reserves.

If threatened species like the green and golden bell frog live at sites with fungus reservoir hosts, they might be more likely to decline. Picture: WikiCommons/Bernard Spragg

Through their research, they highlight that even with multiple decades of well-intentioned research devoted to understanding the impacts of chytridiomycosis on frogs, they know very little about how most species actually are persisting.

Without information to understand the ways that species persist after disease related declines, deciding on management actions is complicated. And even more importantly, it could lead to failure and exacerbate declines.

For example, for a species that is persisting at a low frog density which reduces transmission of Bd, adding captive-reared individuals to populations might increase the frog density and therefore increase transmission and disease within the population.

Without understanding how a species is persisting naturally, we could completely mismanage these threatened animals, and possibly lead to further declines.

They highlight that both researchers and managers need to work together, and research should be aimed at understanding the mechanisms of population persistence.

By using this knowledge we can plan management actions to support the ecology and biology of the species we are trying to save.

This work is a multi-institutional collaboration across the University of Melbourne, Griffith University, Southern Cross University, and international collaborations in the US and Spain.

Provided by University Of Melbourne

Super Asphalt Lasts Longer (Civil / Engineering)

Asphalt concrete is a great material for road surfacing purposes but it’s not always the most sustainable of options. Sandra Erkens, professor of Pavement Engineering Practice, is looking for ways of predicting and extending the lifespan of both existing and new pavement materials. Epoxy asphalt may well hold the key to more durable road surfaces. The beginning of November should see the start of the construction of a trial section on a Noord-Holland road to put the new super asphalt through its paces.

©tudelft

The Netherlands has some 140,000 kilometers of paved roads, most of which are covered with asphalt, a mixture of sand, small pebbles and other fillers held together by bitumen binder. Asphalt concrete differs from other materials commonly used in civil and pavement engineering in a number of ways Sandra Erkens says. ‘The main difference is the viscoelasticity of asphalt which enables it to adapt to the movement of the soft Dutch soil. This capacity to ‘flow’ means the material is less likely to break. This viscoelastic property – which is lacking in concrete, for example- means it has the ability to self-heal. Small cracks in the asphalt can disappear without any outside intervention. This happens especially if the material is left in peace for a while. And in our ever-busier country that is getting less likely with time.’

Asphalt behaviour issues

Much is still unclear about the behaviour of asphalt, particularly in the longer term, Erkens says. ‘Asphalt is exposed to a wide range of temperatures and weather conditions, and the nature and amount of traffic also varies. An additional complication when making predictions about the behaviour of asphalt is that the chemical composition of the material varies as well. This variation in properties means you never know what the behaviour of a particular stretch of asphalt is going to be. But that’s what makes it so interesting. There is still a lot left to study and find out when it comes to the properties, lifespan and overall sustainability of asphalt. And while all the asphalt in the Netherlands is already being recycled, for instance as new pavement foundation, or as part of new asphalt mixtures, much more can be done.’

Not very sustainable- as yet

The top layer of the asphalt structure has to be replaced on average every ten to twenty years. That is expensive and not very sustainable, Erkens says. ‘The production of asphalt is done at very high temperatures and that makes it very energy intensive and high in CO2 emissions. So even if we do re-use all our asphalt and most new asphalt is made using old asphalt, we still have a long way to go to make the process truly sustainable. Only then will we be able to meet the energy and CO2 goals, and achieve more circularity.’

To help green the polluting asphalt industry TU Delft has joined forces with construction company Dura Vermeer. Together they have been developing a sustainable super asphalt. The magic ingredient: epoxy. Erkens: ‘By mixing epoxy resin with bitumen and letting it harden, the asphalt becomes less sensitive to external factors, such as the weather. It also keeps its stiffness and hardness under higher temperatures. Considering the rise in temperature because of climate change that is definitely an important property. The great challenge we are facing is to preserve the advantages of regular asphalt, such as its capacity for self-healing and its recyclability.’

Relatively expensive

The use of epoxy asphalt is not completely new, Erkens says. ‘There are places in the United States which have had epoxy asphalt pavements for over forty years, particularly on bridge decks. Intense traffic and the expansion of the metal structure in high temperatures take a heavy toll on bridges, and the authorities want to keep the need for maintenance to a minimum to avoid long diversion routes for drivers. The reason it is not used more often is cost. It is relatively expensive and to make it commercially viable it would have to last three to four times longer than ordinary asphalt. It looks as if this material fits the bill but we’ll find out for certain when we test it in practice.’

Lifespan

Testing the durability of epoxy asphalt is still mainly laboratory-based. ‘We use fatigue testing to ascertain how often epoxy asphalt can sustain a certain load. This will give us an indication of its lifespan. The lab results seems to indicate that epoxy asphalt is less susceptible to fatigue and wear and tear than ordinary asphalt and will last longer. With Dura Vermeer we are also investigating how best to re-use epoxy asphalt. The first results show that it can be recycled using current methods.’

Epoxy asphalt trial area

In order to find out if the lab results stand up in practice the Noord-Holland authorities have commissioned Dura Vermeer to cover a stretch of the N249 in epoxy asphalt. Erkens: ‘Our TU Delft team will be monitoring the trial area for a number of years. We will be using sensors to monitor stiffness, and we will also be looking at wear and tear at the surface and the occurrence of cracks. This is not the first trial area but it the first to be monitored in such detail using equipment.’

Not sustainable everywhere

Despite the promising potential of epoxy asphalt Erkens does not expect the entire road network of the Netherlands to be covered in it by the next decade. ‘It can only have its longer lasting effect if it is left in peace for long periods of time. In and around urban areas there are road works at least every ten years to replace cables or pipes. Epoxy asphalt is far too expensive for that and its application in that case would not be sustainable.’

Other asphalt innovations

Epoxy asphalt is not the only sustainable solution, Erkens emphasises. ‘The provincial authorities, Rijkswaterstaat, research institutes and particularly construction companies are participating in various regional and national programmes, such as Asfalt-Impuls, to investigate more sustainable production methods for asphalt, by using lower temperatures to reduce energy use, for instance, and upping re-use and introducing asphalt rejuvenation techniques for maintenance. We are also looking at bio asphalt development and the application of epoxy in ZOAB, or porous asphalt. So although there is less traffic, things are definitely moving as far as the asphalt is concerned.’

Provided by Tudelft

Mega-droughts Are Tipped To Increase, Thanks To Climate Change (Earth Science)

Mega-droughts – droughts that last two decades or longer – are tipped to increase thanks to climate change, according to University of Queensland-led research.

©University Of Queensland

UQ’s Professor Hamish McGowan said the findings suggested climate change would lead to increased water scarcity, reduced winter snow cover, more frequent bushfires and wind erosion.   

The revelation came after an analysis of geological records from the Eemian Period – 129,000 to 116,000 years ago – which offered a proxy of what we could expect in a hotter, drier world.

“We found that, in the past, a similar amount of warming has been associated with mega-drought conditions all over south eastern Australia,” Professor McGowan said.

“These drier conditions prevailed for centuries, sometimes for more than 1000 years, with El Niño events most likely increasing their severity.”

The team engaged in paleoclimatology – the study of past climates – to see what the world will look like as a result of global warming over the next 20 to 50 years.

“The Eemian Period is the most recent in Earth’s history when global temperatures were similar, or possibly slightly warmer than present,” Professor McGowan said.

“The ‘warmth’ of that period was in response to orbital forcing, the effect on climate of slow changes in the tilt of the Earth’s axis and shape of the Earth’s orbit around the sun.

Professor Hamish McGowan gaining access to stalagmites around 120 metres below the surface in the Grotto Cave, NSW. © University Of Queensland

“In modern times, heating is being caused by high concentrations of greenhouse gases, though this period is still a good analogue for our current-to-near-future climate predictions.”

Researchers worked with the New South Wales Parks and Wildlife service to identify stalagmites in the Yarrangobilly Caves in the northern section of Kosciuszko National Park.

Small samples of the calcium carbonate powder contained within the stalagmites were collected, then analysed and dated at UQ.

That analysis allowed the team to identify periods of significantly reduced precipitation during the Eemian Period.

“They’re alarming findings, in a long list of alarming findings that climate scientists have released over the last few decades,” Professor McGowan said.

“We hope that this new research allows for new insights to our future climate and the risks it may bring, such as drought and associated bushfires.

“But, importantly, if humans continue to warm the planet, this is the future we may all be looking at.”

The research was part of a project supported by Snowy Hydro Ltd to develop understanding of likely climate variability in a warmer world and the impact on the hydroclimate of southeast Australia.

It was published in Nature Scientific Reports (DOI: 10.1038/s41598-020-75071-z).

Provided by University Of Queensland

Narcissists Are Drawn To Leadership Theories (Psychology)

The more narcissistic the leader, the higher their interest in leadership theories, according to University of Queensland research.

©University of Queensland

UQ School of Psychology researchers examined the extent to which a leader’s narcissism was associated with their endorsement of, and motivation to learn about, leadership theories.

Dr Nik Steffens said the findings build on previous research showing leadership was an activity that appeals to, and boosts, people’s inflated sense of self.

“The more narcissistic individuals are, the more they endorse various theories of leadership and the more they want to learn about them,” Dr Steffens said.

“This in turn suggests that what motivates some people to engage with leadership theory is more a personal concern for the self than a social concern for the greater good.

“Our findings chime with an emerging body of work which suggests that narcissists desire to be the centre of attention and that one way in which they are able to feed this ambition is by striving for positions of responsibility and power over others.

“It would appear that those who have self-serving tendencies not only have an elevated motivation to lead and exert their influence but are also those who are most keen to learn about contemporary theories of leadership.”

Professor Alex Haslam said while a lot had been written about the toxic effects of narcissistic leaders, there had been less reflection on the leadership theories that support and fuel their self-absorption.

“Theories of leadership tend to celebrate what makes individuals superior to others and propose that it is this superiority that allows organisations and societies to flourish,” Professor Haslam said.

“One consequence of this is that most prevailing leadership theories appeal directly to leaders’ narcissism.

“In a time where there are low levels of public trust in corporate and political leaders this is an arresting finding, as it suggests that rather than leadership and leadership theory being the solution to our current woes, they may actually be their cause.

“If the people who are drawn to the study of leadership are primarily interested in looking after themselves, we should not be surprised if they use their learning to do precisely this.”

The research is published in American Psychologist (doi.org/10.1037/amp0000738).

Provided by University Of Queensland

Glowing Mice “PKAchu” Shine Light On Night Vision (Biology)

Publishing in PNAS, biologists at Kyoto University report on a previously unknown mechanism in the retina that will perhaps lead to a better understanding of how our eyes see at night. The finding was made possible thanks to mice engineered to change fluorescence when a specific molecule — protein kinase A, or PKA — is activated.

Retinal cells from PKAchu. PKA is activated by darkness only in the stimulated area (Kyoto University/Matsuda Lab)

These ‘PKAchu’ mice were developed to provide researchers with a way of visualizing the activation of one of the body’s most essential and widely studied proteins.

“PKA is found in many cells and is involved in a wide variety of biological processes. It’s natural that researchers would find a way to observe its activities,” explains first author Shinya Sato of the Graduate School of Biostudies.

“PKAchu mice were developed in 2012 — ‘chu’ being Japanese for ‘squeak’— to allow us to closely monitor how PKA acts during specific biological processes. I decided to apply this to my work in retina biology.”

The team first developed a method for recording high resolution, microscopic images of living retinal tissue. They then observed how PKA reacts to light stimulation. Knowing the pathways involved, the team hypothesized that light would deactivate PKA.

But to their surprise, the exact opposite happened.

“We started with a six-second illumination of the tissue. Incredibly, this activated PKA in the selected area for nearly 15 minutes,” continues Sato. “We then did a ten-minute illumination, during which PKA was inactive. But when the lights were turned off, PKA kicked into gear. It was as if the darkness had activated it.”

Single-cell level analysis revealed that this lights-off PKA activation occurred only in rod cells, which are indispensable for our night vision.

Sato hypothesizes that this previously unknown mechanism of rod-specific PKA activation may be a key in boosting light sensitivity in our eyes, contributing to our night vision. Rod-type photoreceptor cells are thought to have evolved from color-sensing cone cells. PKA activation, it now appears, is rod-specific.

Michiyuki Matsuda, the study’s senior author, concludes: “We have not only uncovered many interesting aspects of retinal cells, but the further utility of PKAchu mice as well. We are excited to uncover the mechanisms and purpose behind these new findings, and perhaps illuminate our understanding of conditions such as night blindness.”

References: Shinya Sato, Takahiro Yamashita, and Michiyuki Matsuda (2020). Rhodopsin-mediated light-off-induced protein kinase A activation in mouse rod photoreceptor cells. Proceedings of the National Academy of Sciences of the United States of America. DOI】https://doi.org/10.1073/pnas.2009164117

Provided by Kyoto University

Priming The Immune System To Attack Cancer (Medicine)

An international team, co-led by the School of Dental Medicine’s George Hajishengallis, showed how immune ‘training’ transforms certain immune cells to target tumors.

So-called innate immune system training can inspire a more robust immune response against threats such as cancer. An international group led by Penn Dental Medicine researchers unpacked the mechanism by which the training plays out in the body. (Image: Courtesy of the Hajishengallis laboratory)

Immunotherapies, such as checkpoint inhibitor drugs, have made worlds of difference for the treatment of cancer. Most clinicians and scientists understand these drugs to act on what’s known as the adaptive immune system, the T cells and B cells that respond to specific threats to the body.

New research from an international team co-led by George Hajishengallis of the University of Pennsylvania School of Dental Medicine suggests that the innate immune system, which responds more generally to bodily invaders, may be an important yet overlooked component of immunotherapy’s success.

Their work, published in the journal Cell, found that “training” the innate immune system with β-glucan, a compound derived from fungus, inspired the production of innate immune cells, specifically neutrophils, that were primed to prevent or attack tumors in an animal model.

“The focus in immunotherapy is placed on adaptive immunity, like checkpoint inhibitors inhibit the interaction between cancer cells and T cells,” says Hajishengallis, a co-senior author on the work. “The innate immune cells, or myeloid cells, have not been considered so important. Yet our work suggests the myeloid cells can play a critical role in regulating tumor behavior.”

The current study builds on earlier work published in Cell by Hajishengallis and a multi-institutional team of collaborators, which showed that trained immunity, elicited through exposure to exposure to the fungus-derived compound β-glucan, could improve immune recovery after chemotherapy in a mouse model.

In that previous study, the researchers also showed that the “memory” of the innate immune system was held within the bone marrow, in hematopoetic stem cells that serve as precursors of myeloid cells, such as neutrophils, monocytes, and macrophages.

The team next wanted to get at the details of the mechanism by which this memory was encoded. “The fact that β-glucan helps you fight tumors doesn’t necessarily mean it was through trained immunity,” says Hajishengallis.

To confirm that link, the researchers isolated neutrophils from mice that had received the innate immune training via exposure to β-glucan and transferred them, along with cells that grow into melanoma tumors, to mice that had not received β-glucan. Tumor growth was significantly dampened in animals that received cells from mice that had been trained.

To further support this link between myeloid precurors and the protective quality of trained immunity, the scientists performed bone marrow transplants, transferring bone marrow cells from “trained” mice to untrained mice that had been irradiated, effectively eliminating their own bone marrow.

When challenged later, the mice that were recipients of bone marrow from trained mice fought tumors much better than those that received bone marrow from untrained mice. 

 “This is innate immune memory at work,” said Technical University Dresden’s Triantafyllos Chavakis, a long-term collaborator of Hajishengallis and co-senior author of the study.

The experiment relied on the memory of bone marrow precursors of neutrophils of the trained donor mice, which were transferred by transplantation to the recipient mice and gave rise to neutrophils with tumor-killing ability. 

The researchers found that the antitumor activity likely resulted from trained neutrophils producing higher levels of reactive oxygen species, or ROS, than did untrained neutrophils. ROS can cause harm in certain contexts but in cancer can be beneficial, as it acts to kill tumor cells.

Looking closely at the myeloid precursors in the bone marrow of trained animals, the team found significant changes in gene expression that biased the cells toward making neutrophils, specifically a type associated with anti-tumor activity, a classification known as tumor-associated neutrophils type I (TAN1).

Further investigation revealed that these changes elicited by innate immune training cause an epigenetic rewiring of bone marrow precursor cells, changes that acted to make certain genes more accessible to being transcribed and also pointed to the Type I interferon signaling pathway as a likely regulator of innate immune training. Indeed, mice lacking a receptor for Type I interferon  couldn’t generate trained neutrophils.

β-glucan is already in clinical trials for cancer immunotherapy, but the researchers say this finding suggests a novel mechanism of action with new treatment approaches.  

“This is a breakthrough concept that can be therapeutically exploited for cancer immunotherapy in humans,” Hajishengallis says, “specifically by transferring neutrophils from β-glucan-trained donors to cancer patients who would be recipients.”

Provided by Penn State

Designing New Mirror Materials For Better Gravitational-wave Detection (Physics)

Nicholas Demos, a first-generation college graduate and MathWorks Fellow in MIT’s Kavli Institute, is improving our ability to listen to the cosmos.

Nicholas Demos (left) shows a mirror-testing apparatus to Satoshi Tanioka, a visiting student from Sokendai University. Credits: Photo courtesy of the researchers.

Nicholas Demos, a physics graduate student, didn’t travel a conventional path to MIT. A first-generation college student, Demos didn’t have a clear trajectory in mind when he first attended California State University at Fullerton after high school. “It was kind of the path of least resistance,” Demos says.

When his father passed away in the middle of his undergraduate studies, Demos left school to run the family business, Novatech Lighting Systems, which makes handheld spotlights. He ran the company for five years, but business didn’t suit him, he says: “The pursuit of money wasn’t motivating at all to me.”

As soon as his brother graduated and could take over the business, Demos was ready to go back to school — this time with a clearer purpose. He chose to study physics, since he’d always excelled in math and science. Demos was the only student in his high school class to pass the AP calculus exam and even had what he calls a “side hustle” of building and selling computers out of his garage.

His renewed determination for academics paid off. After his first year back at CSU Fullerton, Demos’ physics professor, Geoffrey Lovelace, asked him to join his lab. The following summer, Demos began researching gravitational waves, just as a more sensitive version of the Laser-Interferometer Gravitational Wave Observatory (LIGO) became operational.

“The detector was reaching a sensitivity where everyone thought it should work,” says Demos, “Being on the cusp of a big discovery was exciting.”

On Sept. 14, 2015, a little more than a year after Demos began his research, LIGO detected a gravitational wave for the very first time. It thrilled everyone in the small but growing field, including Demos. The ability to observe gravitational waves provides “a totally different way to look at the universe,” says Demos. “It’s a big step forward for astrophysics; there’s potential for things we haven’t even thought of appearing. A lot of unknown unknowns.”

When Demos completed his undergraduate degree in 2017, he applied to MIT, hoping to continue working on LIGO. Matthew Evans, the MIT MathWorks Professor of Physics and Demos’ current advisor, says he was immediately impressed with Demos’ work. And according to Evans, Demos’ old advisor told him, “Nick was the best undergraduate he’d ever had.”

This mirror sample cracked during a process called annealing, where the sample is heated and allowed to slowly cool to reduce its thermal noise. While the mirror is transparent to visible light, it reflects 99.9995% of the infrared light that LIGO uses. Credits: Photo: Nicholas Demos.

Demos measures mirrors

Whereas telescopes look for cosmic phenomena, LIGO listens.

“LIGO is listening for the densest objects in the universe — neutron stars and black holes,” Demos says.

When these massive bodies near each other, they fall into a collapsing orbit, spinning faster and faster, closer and closer, until they collide.

“What LIGO detects is this chirp — this faster and faster, louder and louder signal — that is like the sound of spacetime vibrating,” Demos says.

These vibrations, or gravitational waves, travel vast distances through the universe, warping everything — stars, planets, people — in their path. What LIGO does is measure this stretching and squeezing of spacetime. “It’s basically a big, four-kilometer ruler,” Demos says.

To measure gravitational waves, a LIGO detector has dual four-kilometer vacuum chambers laid in an enormous “L” shape. Scientists split a beam of light and send it to the end of each chamber, where it bounces off of highly reflective mirrors and returns to the corner of the “L.”

When a gravitational wave ripples through the Earth, it will stretch one arm of LIGO while squashing the other. The light, which has a fixed speed and won’t warp with the rest of the world, then takes a different length of time to travel down each arm. The scientists can measure this difference to detect the wave.

The challenge is that the ripples caused by gravitational waves are minuscule since, despite appearances, gravity is a very weak force. In terms of the squashing and stretching, “we’re talking about these tiny, fractional changes,” says Demos, “roughly one-thousandth the size of a proton.”

This means that everything in the LIGO experiment must be extremely precise and very still. Otherwise, the gravitational wave signals will be lost in a sea of noise. Unfortunately, some sources of noise are harder to eliminate than others.

“The surface of the mirror is made up of atoms, and these atoms are jiggling about,” Demos says. “If you’re trying to measure something that’s smaller than a proton, that’s a problem, because your ruler is jiggling about on both ends.”

The noise from the movement of atoms, also called thermal noise, is nearly unavoidable — the motion only stops at the unreachable temperature of absolute zero. However, some materials have less of this thermal noise than others.

Demos’ job is to design and test new mirror materials to find those with the lowest thermal noise. In fact, he is one of the few people in the world able to test these samples. Matthew Evans and Research Scientist Slawomir Gras have developed the only apparatus able to quickly test full mirror samples, as opposed to just a single layer or a few layers of the materials used to coat the mirrors.

“Any coating that LIGO wants to use will first be characterized by our experiment,” Demos says.

The Evans lab is in the process of upgrading their setup to measure thermal noise across the surface of a sample, as opposed to only at a single point.

“This is a job which is really at the heart of progress in gravitational wave detection,” Evans adds. “Nick’s persistent determination to get things done has really made a big difference for us.”

Demos makes math work with MATLAB

In September, Demos was one of a select group of students in the School of Science to receive a $70,000 fellowship from MathWorks, a software company that produces mathematical computing programs like MATLAB and Simulink.

“The MathWorks Fellowship is a big honor,” says Demos, “It’s a huge relief financially because I don’t have to worry, my lab doesn’t have to worry, and I’ll be able to really pursue this.”

It’s particularly appropriate for Demos to win this fellowship, as he frequently uses MATLAB in his research. “He’s gone through all of our analysis software in MATLAB and really refactored that code from the ground up,” says Evans. He adds that Demos is very deserving of this award, but he’s not worried about the recognition going to Demos’ head.

“There’s a certain humility in his approach to things, which is not something you always find.”

Provided by MIT