Culture

Galit Alter, PhD, Group Leader at the Ragon Institute of MGH, MIT and Harvard and Professor of Medicine at Harvard Medical School, and Helen Chu, MD, Associate Professor of Medicine, Division of Allergy and Infectious Diseases, University of Washington School of Medicine, and UW Medicine physician, have recently published a paper which identifies five immune response markers which, collectively, were able to correctly classify both convalescent COVID-19 patients and those who did not survive the disease. The study was published in the journal Immunity.

Dr. Chu's team, responsible for the enrollment, collection, and management of the clinical work in this study, collected samples hospitalized COVID-19 patients. Overall, this study used samples from a cohort of 22 individuals, 12 of whom recovered, and 10 of whom died.

Dr. Alter's team used her systems serology technique, an approach that relies on 60+ assays to create a detailed profile of the immune response, to compare the immune responses of those who had survived to those who had not.

"Any given feature tells only a small part of the story. By looking at the overall profile of the immune response, we can begin to truly understand how the immune system responds to COVID-19 and then use that knowledge to prevent the worst outcomes of this disease," said Alter.

The virus that causes COVID-19, SARS-CoV-2, has two main proteins that the humoral immune system, which is responsible for antibody production, responds to. They are the spike (S) protein and the nucleocapsid (N) protein.

"Most vaccine candidates in development are designed to elicit antibodies against spike antigen, which is the response we observed with individuals who survived natural infection," Chu said. The N protein is produced at significantly higher levels in the virus than the S protein is, but previous studies have shown that an immune response to the N protein does not provide protection against coronaviruses related to SARS-CoV-2.

Using her systems serology technique, which creates a detailed profile of the humoral immune response, Dr. Alter's lab compared the immune responses from the recovered individuals to the deceased ones. They found that patients who had recovered had a humoral immune response that responded mostly to S protein, while deceased individuals had a shift in immunodominance such that that they had a stronger immune response to the N protein.

"The shift in immunodominance was only apparent after comparing robust, detailed profiles of the immune response from different groups of patients," Alter said.

This immunodominance shift could be detected by measuring five immune response markers: IgM and IgA1 responses to S protein and antibody-dependent complement deposit, IgM, and IgA2 response to N protein. Using these five markers, researchers were able to build a model that could correctly classify clinical samples as belonging to deceased or convalesced individuals. In order to verify this model, 40 clinical COVID-19 samples from Boston, 20 from convalesced individuals and 20 from deceased patients, were assayed. The results showed the same S protein to N protein shift in immunodominance in deceased individuals compared to convalesced ones. Furthermore, in the samples analyzed, this immunodominance shift was more predictive of recovery or death than using demographic factors such as age or sex.

"Finding these early antibody signatures may have implications for assessing COVID-19 vaccine candidates to ensure they produce an immune response similar to that of individuals who survive natural infection," Chu said.

How these predictive immune markers may be influenced by risk factors of COVID-19, time course of infection, or severity of disease is yet to be known. However, this study provides a potential way that at-risk patients can be identified based on individual immune responses and may drive help rational vaccine design.

TAMPA, Fla. (Aug. 7, 2020) -- Despite frequent news announcing "medical breakthroughs," advancements in biomedical and clinical science typically happen incrementally. Scientists refine our understanding of how the world works by harnessing new tools and data that can challenge conventional thinking - a continual process of revision that elicits new answers to old questions, and often poses different questions.

In an eNeuro paper published July 15, University of South Florida Health Morsani College of Medicine researchers describe a reporter mouse strain they created in pursuit of a new way to answer an old question: Is purinergic receptor gene P2X2 expressed in particular populations of sensory nerve cells?

"We needed a suitable mouse model to visualize where P2X2 is located so we might prove the gene is actually expressed in a very discrete group of sensory nerves. And because, moving forward, we want a reporter system that allows us to manipulate these vagal nodose nerves in precise, varied ways for therapeutic purposes," said senior author Thomas Taylor-Clark, PhD, a professor in the Department of Molecular Pharmacology and Physiology.

"This paper is an example of how reexamining questions with better techniques leads to clearer understanding, and in this day and age the clarity and reproducibility of data is a paramount issue in science."

The P2X2 receptor (P2X2 for short) belongs to a family of P2X ion channels that sit on the surface of cell membranes and are activated by the neurotransmitter adenosine triphosphate (ATP). P2X2 plays a key role in sensory processes, including taste, hearing, some aspects of blood pressure regulation, and sensing physical stimuli in visceral organs like the lungs and bladder.

Dr. Taylor-Clark studies airway sensory nerves affecting defensive behaviors, including cough, and what happens when they go wrong in disease and injury. To further their research, his team needed a more reliable approach to distinguish which subsets of cells express P2X2, especially in the brain and spinal cord (central nervous system) and the peripheral nervous system (nerves outside the brain and spinal cord). Existing pharmacological and biochemical techniques were not selective enough, yielding dramatically different gene expression patterns that hamper accurate estimates of P2X2-expressing cell types.

So, the USF Health researchers created a knockin mouse incorporating a powerful genetic approach that could be used in future experiments. They made a mouse that expresses the bacterial enzyme cre recombinase in cells expressing the P2X2 gene. The enzyme manipulates specific sites (lox sequences) in DNA. Then, they bred this P2X2-cre mouse with a second mouse having specific lox sequences that produce substantial levels of tdTomato - a bright red fluorescent protein - under the control of cre. In offspring of the P2X2-cre mice and the cre-sensitive mice, tdTomato is robustly expressed and specifically reported (visualized) in P2X2-expressing cells, even when levels of P2X2 expression are low.

"With this system, it's easier to see any cell type you want to investigate," Dr. Taylor-Clark said. "And, since many mouse strains have different cre-sensitive genetic expression patterns, you can manipulate virtually any gene or genetic process to test its role in tissue/organ function with a modular approach."

The researchers detailed where they found P2X2. As they suspected, the gene was expressed predominantly in the vagal sensory nerve system, where cell clusters relay sensory information about the state of the body's organs to the central nervous system. In particular, almost all nodose vagal neurons (more than 85%) expressed P2X2, compared to nearly none of the jugular neurons. (Nodose and jugular are the two groups of neurons in the vagal system.).

The researchers demonstrated some P2X2 expression in the tongue's taste buds, the carotid body, trachea (windpipe) and esophagus. They observed P2X2 in hair and support cells of the cochlea (inner ear bone important in hearing), but not, as some previous studies reported, in sensory nerves innervating the hair cells.

With a few exceptions, P2X2 expression was absent in central nervous system cell types. Earlier reporter mouse studies using established biochemical techniques indicated P2X2 expression in virtually every area of the brain, so the USF Health group was surprised to find P2X2 expressed in a very limited subset of neurons, Dr. Taylor-Clark said.

"But, actually, that was encouraging because if we manipulate (gene expression) we want the effects to be very narrow and targeted, not widespread," he added. "Selectivity is the hallmark of any therapeutic approach. Otherwise, you will not get the beneficial outcome you want, and you may get side effects you don't want."

Other studies have suggested that activating nodose sensory nerves diminishes cough, while activating jugular sensory nerves increases cough. Dr. Taylor-Clark hopes to test whether nodose neurons can protect against chronic cough by modifying the P2X2-cre system to selectively silence only the nodose neurons, without adversely blocking all other nerve impulses.

"Our next step is to manipulate this P2X2-cre system so that, instead of expressing tdTomato, we can express a protein that upon addition of a drug then either artificially activates or inhibits P2X2-expressing cells," he said. "Currently, little is understood about the physical interaction of the nodose nerve terminals (endings) in the trachea and other target organs, and how that changes with disease. Our goal is a detailed knowledge of all the different subtypes of sensory nerves and how they control organ function, so we can help drive targeted neuromodulaton therapies."

In severe cases of COVID-19, the infection can lead to obstruction of the blood vessels in the lung, heart and kidneys. Ludwig-Maximilians-Universitaet (LMU) in Munich researchers have now shown that activated immune cells and blood platelets play a major role in these pathologies.

The novel coronavirus SARS-CoV-2 infects the respiratory tract and in severe cases, the infection can result in lung failure, which necessitates the use of mechanical ventilation. In addition, these patients develop further complications, such as pulmonary embolisms or thromboses (clots) in their veins. Whether or not virus-associated respiratory failure is functionally related to the systemic increase in the incidence of intravascular clot formation has remained unclear. However, a new study led by LMU clinicians Leo Nicolai and Konstantin Stark, which appears in the journal Circulation, has identified a link between virus-induced changes in the blood vessels of the lung and the increased thrombotic risk. Upon post-mortem examination of the lungs of COVID-19 patients who had died of the disease, Nicolai and colleagues found many microclots within the finest branches of the pulmonary vasculature. Similar observations were made in the heart and the kidney.

These clots were primarily made up of platelets and activated immune cells, in particular neutrophils. Detailed analysis of the thrombi suggested that an activating interaction between platelets and neutrophils is responsible for promoting intravascular coagulation. Neutrophils belong to the innate immune system and their principal task is to fight invading pathogens. Their involvement in abnormal clotting has led to the designation of this process as immunothrombosis. In COVID-19 patients, the stimulation of clot formation eventually compromises the supply of blood to nearby tissues. This in turn ultimately leads to respiratory failure, while the tendency to trigger clotting becomes systemic.

Using multidimensional flow cytometry assays, the LMU researchers showed that in COVID-19 patients who had suffered lung failure and required mechanical ventilation, the numbers of activated neutrophils and platelets in the circulation were greatly enhanced. Since the two cell types reciprocally activate each other, these interactions lead to the formation of obstructive blood clots in the lung. In addition, activated neutrophils extrude mesh-like complexes made up of DNA and cytoplasmatic proteins, which are known as neutrophil extracellular traps (NETs). These normally serve to trap and destroy bacterial and viral pathogens, but they also play a significant role in immunothrombosis by stabilizing thrombi. While this process is initially localized in the lung exacerbating respiratory failure and result in a systemic thrombogenic state. "These findings contribute to a better understanding of the pathophysiology that underlie disease progression in COVID-19," says Konstantin Stark. "The study also identifies immunothrombosis as a promising target for the prevention and treatment of lung failure and thrombotic complications that arise in cases of COVID-19."

Chemical reactions driven by the geological conditions on the early Earth might have led to the prebiotic evolution of self-replicating molecules. Scientists at Ludwig-Maximilians Universitaet (LMU) in Munich now report on a hydrothermal mechanism that could have promoted the process.

Life is a product of evolution by natural selection. That's the take-home lesson from Charles Darwin's book "The Origin of Species", published over 150 years ago. But how did the history of life on our planet begin? What kind of process could have led to the formation of the earliest forms of the biomolecules we now know, which subsequently gave rise to the first cell? Scientists believe that, on the (relatively) young Earth, environments must have existed, which were conducive to prebiotic, molecular evolution. A dedicated group of researchers is engaged in attempts to define the conditions under which the first tentative steps in the evolution of complex polymeric molecules from simple chemical precursors could have been feasible. "To get the whole process started, prebiotic chemistry must be embedded in a setting in which an appropriate combination of physical parameters causes a non-equilibrium state to prevail," explains LMU biophysicist Dieter Braun. Together with colleagues based at the Salk Institute in San Diego, he and his team have now taken a big step toward the definition of such a state. Their latest experiments have shown the circulation of warm water (provided by a microscopic version of the Gulf Stream) through pores in volcanic rock can stimulate the replication of RNA strands. The new findings appear in the journal Physical Review Letters.

As the carriers of hereditary information in all known lifeforms, RNA and DNA are at the heart of research into the origins of life. Both are linear molecules made up of four types of subunits called bases, and both can be replicated - and therefore transmitted. The sequence of bases encodes the genetic information. However, the chemical properties of RNA strands differ subtly from those of DNA. While DNA strands pair to form the famous double helix, RNA molecules can fold into three-dimensional structures that are much more varied and functionally versatile. Indeed, specifically folded RNA molecules have been shown to catalyze chemical reactions both in the test-tube and in cells, just as proteins do. These RNAs therefore act like enzymes, and are referred to as 'ribozymes'. The ability to replicate and accelerate chemical transformations motivated the formulation of the 'RNA world' hypothesis. This idea postulates that, during early molecular evolution, RNA molecules served both as stores of information like DNA, and as chemical catalysts. The latter role is performed by proteins in today's organisms, where RNAs are synthesized by enzymes called RNA polymerases.

Ribozymes that can link short RNA strands together - and some that can replicate short RNA templates - have been created by mutation and Darwinian selection in the laboratory. One of these 'RNA polymerase' ribozymes was used in the new study.

Acquisition of the capacity for self-replication of RNA is viewed as the crucial process in prebiotic molecular evolution. In order to simulate conditions under which the process could have become established, Braun and his colleagues set up an experiment in which a 5-mm cylindrical chamber serves as the equivalent of a pore in a volcanic rock. On the early Earth, porous rocks would have been exposed to natural temperature gradients. Hot fluids percolating through rocks below the seafloor would have encountered cooler waters at the sea-bottom, for instance. This explains why submarine hydrothermal vents are the environmental setting for the origin of life most favored by many researchers. In tiny pores, temperature fluctuations can be very considerable, and give rise to heat transfer and convection currents. These conditions can be readily reproduced in the laboratory. In the new study, the LMU team verified that such gradients can greatly stimulate the replication of RNA sequences.

One major problem with ribozyme-driven scenario for replication of RNA is that the initial result of the process is a double-stranded RNA. To achieve cyclic replication, the strands must be separated ('melted'), and this requires higher temperatures, which are likely to unfold - and inactivate - the ribozyme. Braun and colleagues have now demonstrated how this can be avoided. "In our experiment, local heating of the reaction chamber creates a steep temperature gradient, which sets up a combination of convection, thermophoresis and Brownian motion", says Braun. Convection stirs the system, while thermophoresis transports molecules along the gradient in a size-dependent manner. The result is a microscopic version of an ocean current like the Gulf Stream. This is essential, as it transports short RNA molecules into warmer regions, while the larger, heat-sensitive ribozyme accumulates in the cooler regions, and is protected from melting. Indeed, the researchers were astonished to discover that the ribozyme molecules aggregated to form larger complexes, which further enhances their concentration in the colder region. In this way, the lifetimes of the labile ribozymes could be significantly extended, in spite of the relatively high temperatures. "That was a complete surprise," says Braun.

The lengths of the replicated strands obtained are still comparatively limited. The shortest RNA sequences are more efficiently duplicated than the longer, such that the dominant products of replication are reduced to a minimal length. Hence, true Darwinian evolution, which favors synthesis of progressively longer RNA strands, does not occur under these conditions. "However, based on our theoretical calculations, we are confident that further optimization of our temperature traps is feasible," says Braun. A system in which the ribozyme is assembled from shorter RNA strands, which it can replicate separately, is also a possible way forward.

Physical Review Letters, 2020

Astronomers using the Atacama Large Millimeter/submillimeter Array (ALMA) took a census of stellar eggs in the constellation Taurus and revealed their evolution state. This census helps researchers understand how and when a stellar embryo transforms to a baby star deep inside a gaseous egg. In addition, the team found a bipolar outflow, a pair of gas streams, that could be telltale evidence of a truly newborn star.

Stars are formed by gravitational contraction of gaseous clouds. The densest parts of the clouds, called molecular cloud cores, are the very sites of star formation and mainly located along the Milky Way. The Taurus Molecular Cloud is one of the active star-forming regions and many telescopes have been pointed at the cloud. Previous observations show that some cores are actually stellar eggs before the birth of stars, but others already have infant stars inside.

A research team led by Kazuki Tokuda, an astronomer at Osaka Prefecture University and the National Astronomical Observatory of Japan (NAOJ), utilized the power of ALMA to investigate the inner structure of the stellar eggs. They observed 32 starless cores and nine cores with baby protostars. They detected radio waves from all of the nine cores with stars, but only 12 out of 32 starless cores showed a signal. The team concluded that these 12 eggs have developed internal structures, which shows they are more evolved than the 20 quite cores.

"Generally speaking, radio interferometers using many antennas, like ALMA, are not good at observing featureless objects like stellar eggs," says Tokuda. "But in our observations, we purposely used only the 7-m antennas of ALMA. This compact array enables us to see objects with smooth structure, and we got information about the internal structure of the stellar eggs, just as we intended."

Increasing the spacing between the antennas improves the resolution of a radio interferometer, but makes it difficult to detect extended objects. On the other hand, a compact array has lower resolution but allows us to see extended objects. This is why the team used ALMA's compact array of 7-m antennas, as known as the Morita Array, not the extended array of 12-m antennas.

They found that there is a difference between the two groups in the gas density at the center of the dense cores. Once the density of the center of a dense core exceeds a certain threshold, about one million hydrogen molecules per cubic centimeter, self-gravity leads the egg to transform into a star.

A census is also useful for finding a rare object. The team noticed that there is a weak but clear bipolar gas stream in one stellar egg. The size of the stream is rather small, and no infrared source has been identified in the dense core. These characteristics match well with the theoretical predictions of a "first hydrostatic core," a short-lived object formed just before the birth of a baby star. "Several candidates for the first hydrostatic cores have been identified in other regions," explains Kakeru Fujishiro, a member of the research team. "This is the first identification in the Taurus region. It is a good target for future extensive observation."

Kengo Tachihara, an associate professor at Nagoya University mentions the role of Japanese researchers in this study. "Japanese astronomers have studied the baby stars and stellar eggs in Taurus using the Nagoya 4-m radio telescope and Nobeyama 45-m radio telescope since the 1990s. And, ALMA's 7-m array was also developed by Japan. The present result is part of the culmination of these efforts."

"We have succeeded in illustrating the growth history of stellar eggs up to their birth, and now we have established the method for the research," summarizes Tokuda. "This is an important step to obtain a comprehensive understanding of star formation."

In JST Strategic Basic Research Programs, a group of Zhongrui Duan (Researcher, Waseda University) and Motoki Tominaga (Associate professor, Waseda University) et al. succeeded in promoting plant growth and increasing seed yield by heterologous expression of protein from Arabidopsis (artificially modified high-speed motor protein(1) ) in Camelina sativa, which is expected as a useful plant for biodiesel.

Cytoplasmic streaming is seen in any plant cells from algae to higher plants as a phenomenon of active cytoplasmic movement with organelles, such as the endoplasmic reticulum and mitochondria. It is known that cytoplasmic streaming is generated by the sliding of motor protein myosin XI(2), which is binding to organelles, along the cytoskeleton constituting actin filaments. Previously, the research group has achieved the growth promotion and increasing size of the model plant Arabidopsis by the development of high-speed-type myosin. This technology has been expected to apply to other plant species than Arabidopsis.

In this study, the research group showed that the increase of seed yield and the growth promotion of stems and leaves in Camelina could be achieved by heterologous expression of high-speed-type myosin XI gene derived from Arabidopsis in Camelina.

Considering the increase of seed yield in Camelina enabled by the expression of high-speed-type myosin XI, it is expected to increase the productivity of biodiesel per area unit. In the future, it is aimed to increase the productivity and quality of camelina oil by co-expressing the genes related to fat synthesis and modification of fatty acid composition with high-speed-type myosin XI. Moreover, as the group showed that the promotion of plant growth by the high-speed-type myosin XI is also effective in other plant species than the model plant Arabidopsis, application development, such as the reduction of CO2 and biomass, is also expected by increasing the production of plant resources, such as corn, rice, sugar cane, and jatropha.

Researchers from Kumamoto University in Japan have used comprehensive genetic analysis to find that the enzyme NSD2, which is known to regulate the actions of many genes, also works to block cell aging. Their experiments revealed 1) inhibition of NSD2 function in normal cells leads to rapid senescence and 2) that there is a marked decrease in the amount of NSD2 in senescent cells. The researchers believe their findings will help clarify the mechanisms of aging, the development of control methods for maintaining NSD2 functionality, and age-related pathophysiology.

As the cells of the body continue to divide (cell reproduction), their function eventually declines and they stop growing. This cellular senescence is an important factor in health and longevity. Cell aging can also be stimulated when genomic DNA is damaged by physical stress, such as radiation or ultraviolet rays, or by chemical stress that occurs with certain drugs. However, the detailed mechanisms of aging are still unknown. Cell aging can be beneficial when a cell becomes cancerous; it prevents malignant changes by causing cellular senescence. On the other hand, it makes many diseases more likely with age. It is therefore important that cell aging is properly controlled.

Although senescent cells lose their proliferative ability, it has recently become clear that senescent cells secrete various proteins that act on surrounding cells to promote chronic inflammation and cancer development. Since senescent cells are more active than expected, cellular aging is thought to be responsible for whole body aging. This idea has been supported by reports of systemic aging suppression in aged mice after removal of accumulated senescent cells. In other words, if you can control cell aging, you may be able to control the progression of aging throughout the body.

When an oncogene is activated and begins to become cancerous, cellular senescence occurs to prevent it. Researchers at Kumamoto University previously reported that senescent cells markedly increased mitochondrial metabolic functions, and that the enzyme SETD8 methyltransferase prevents cellular senescence. Here, they discovered that NSD2 methyltransferase also plays a role in preventing senescence.

Previously, NSD2 was shown to regulate gene function. Furthermore, it was thought that methylation by NSD2 of the histone proteins wrapped around genomic DNA enhanced the function of genes in the vicinity. However, its association with cell aging was unknown. Using comprehensive genetic screening to suppress the action of the NSD2 gene in fibroblasts when knockdown (RNA interference method) was performed, cell senescence was induced and the typical characteristics of senescent cells appeared. In other words, the researchers had found that NSD2 plays a role in preventing cell senescence.

Next, they comprehensively analyzed all protein-coding gene expressions using mRNA sequencing to explore senescent cells with reduced NSD2. The expression of genes related to cell aging increased and, in particular, the function of genes of proteins that promote cell growth decreased. Histones located in these gene clusters are methylated by NSD2 in proliferating cells, but methylation was found to have decreased in senescent cells with reduced NSD2. Simply put, decreased NSD2 reduces the activities of genes involved in cell growth thus stopping growth.

Researchers then used serum response experiments to examine how NSD2 function is regulated. Normally, cells grow by the actions of proteins that promote growth (growth factors) in serum. Senescent cells, on the other hand, irreversibly stop proliferation and do not typically increase again. The experiment showed that the addition of serum rapidly increased the amount of NSD2, and that NSD2 is required for expression of growth-promoting genes and cell growth. Furthermore, it was found that senescent cells with reduced NSD2 completely lack the ability to grow in serum. Thus, NSD2 is thought to prevent cell senescence by maintaining both cell growth and serum response.

"NSD2 is the fourth protective factor of cellular senescence that our team has identified," said Professor Mitsuyoshi Nakao. "With the discovery that NSD2 protects against cellular senescence, this study clarifies a basic mechanism of aging. We expect this to be useful for elucidating aging mechanisms and developing control methods to regulate enzyme activity by chemicals or metabolites."

Taking advantage of a total lunar eclipse, astronomers using the NASA/ESA Hubble Space Telescope have detected ozone in Earth's atmosphere. This method serves as a proxy for how they will observe Earth-like planets around other stars in the search for life. This is the first time a total lunar eclipse was captured from a space telescope and the first time such an eclipse has been studied in ultraviolet wavelengths.

To prepare for exoplanet research with bigger telescopes that are currently in development, astronomers decided to conduct experiments much closer to home, on the only known inhabited terrestrial planet: Earth. Our planet's perfect alignment with the Sun and Moon during a total lunar eclipse mimics the geometry of a transiting terrestrial planet with its star. In a new study, Hubble did not look at Earth directly. Instead, astronomers used the Moon as a mirror that reflects the sunlight that has been filtered through Earth's atmosphere. Using a space telescope for eclipse observations is cleaner than ground-based studies because the data is not contaminated by looking through Earth's atmosphere.

These observations were particularly challenging because just before the eclipse the Moon is very bright, and its surface is not a perfect reflector since it's mottled with bright and dark areas. Furthermore, the Moon is so close to Earth that Hubble had to try and keep a steady eye on one select region, to precisely track the Moon's motion relative to the space observatory. It is for these reasons that Hubble is very rarely pointed at the Moon.

The measurements detected the strong spectral fingerprint of ozone, a key prerequisite for the presence - and possible evolution - of life as we know it in an exo-Earth. Although some ozone signatures had been detected in previous ground-based observations during lunar eclipses, Hubble's study represents the strongest detection of the molecule to date because it can look at the ultraviolet light, which is absorbed by our atmosphere and does not reach the ground. On Earth, photosynthesis over billions of years is responsible for our planet's high oxygen levels and thick ozone layer. Only 600 million years ago Earth's atmosphere had built up enough ozone to shield life from the Sun's lethal ultraviolet radiation. That made it safe for the first land-based life to migrate out of our oceans.

"Finding ozone in the spectrum of an exo-Earth would be significant because it is a photochemical byproduct of molecular oxygen, which is a byproduct of life," explained Allison Youngblood of the Laboratory for Atmospheric and Space Physics in Colorado, USA, lead researcher of Hubble's observations.

Hubble recorded ozone's ultraviolet spectral signature imprinted on sunlight that filtered through Earth's atmosphere during a lunar eclipse that occurred on 20-21 January, 2019. Several other telescopes also made spectroscopic observations at other wavelengths during the eclipse, searching for more of Earth's life-nurturing ingredients, such as oxygen, methane, water, and carbon monoxide.

"To fully characterize exoplanets, we will ideally use a variety of techniques and wavelengths," explained team member Antonio Garcia Munoz of the Technische Universität Berlin in Germany. "This investigation clearly highlights the benefits of the ultraviolet spectroscopy in the characterization of exoplanets. It also demonstrates the importance of testing innovative ideas and methodologies with the only habitable planet that we know of to date!"

The atmospheres of some exoplanets can be probed when the alien world passes across the face of its parent star, during a so-called transit. During a transit, starlight filters through the backlit exoplanet's atmosphere. If viewed close up, the planet's silhouette would look like it had a thin, glowing "halo" around it caused by the illuminated atmosphere, just as Earth does when seen from space.

Chemicals in the atmosphere leave their telltale signature by filtering out certain colors of starlight. The spectroscopy of transiting planets' atmospheres was pioneered by Hubble astronomers. This was especially innovative because extrasolar planets had not yet been discovered when Hubble was launched in 1990. Therefore, the space observatory was not initially designed for such experiments. So far, astronomers have used Hubble to observe the atmospheres of gas giant planets that transit their stars. But terrestrial planets are much smaller objects and their atmosphere thinner. Therefore, analyzing these signatures is much harder.

That's why researchers will need space telescopes much larger than Hubble to collect the feeble starlight passing through these small planets' atmospheres during a transit. These telescopes will need to observe planets for a longer period, many dozens of hours, to build up a strong signal. For Youngblood's study, Hubble spent five hours collecting data throughout the various phases of the lunar eclipse.

Finding ozone in the skies of a terrestrial extrasolar planet does not guarantee that life exists on the surface. "You would need other spectral signatures in addition to ozone to conclude that there was life on the planet, and these signatures cannot be seen in ultraviolet light," Youngblood said.

Astronomers must search for a combination of biosignatures, such as ozone and methane, when exploring the possibilities of life. A multiwavelength campaign is needed because many biosignatures--ozone, for example--are more easily detected at specific wavelengths. Astronomers searching for ozone also must consider that it builds up over time as a planet evolves. About 2 billion years ago on Earth, the ozone was a fraction of what it is now.

The upcoming NASA/ESA/CSA James Webb Space Telescope, an infrared observatory scheduled to launch in 2021, will be able to penetrate deep into a planet's atmosphere to detect methane and oxygen.

"We expect JWST to push the technique of transmission spectroscopy of exoplanet atmospheres to unprecedented limits," added Garcia Munoz. "In particular, it will have the capacity to detect methane and oxygen in the atmospheres of planets orbiting nearby, small-sized stars. This will open the field of atmospheric characterization to increasingly smaller exoplanets."

Legume plants fix atmospheric nitrogen with the help of symbiotic bacteria, called Rhizobia, which colonize their roots. Therefore, plants have to be able to precisely recognize their symbiont to avoid infection by pathogenic microbes. To this end, legumes use different LysM receptor proteins located on the outer cell surface of their roots. In the study published in Science, an international team of researchers led by Aarhus University show that pathogenic (chitin) or symbiotic signalling molecules (Nod factors) are recognized by small molecular motifs on the receptors that direct the signalling output towards either antimicrobial defence or symbiosis.

All land plants have LysM receptors that ensure detection of various microbial signals, but how a plant decides to mount a symbiotic or an immune response towards an incoming microbe is unknown. "We started by asking a basic and, maybe at start, naïve question: Can we identify the important elements by using very similar receptors, but with opposing function as background for a systematic analysis?" says Zoltán Bozsoki. "The first crystal structure of a Nod factor receptor was a breakthrough. It gave us a better understanding of these receptors and guided our efforts to engineer them in plants." Kira Gysel adds.

The study combines the structure-assisted dissection of defined regions in LysM receptors for biochemical experiments and in planta functional analysis. "To really understand these receptors, we needed to work closely together and combine structural biology and biochemistry with the systematic functional tests in plants," says Simon Boje Hansen. By using this approach, the researchers identified previously unknown motifs in the LysM1 domain of chitin and Nod factor receptors as determinants for immunity and symbiosis. "It turns out that there are only very few, but important, residues that separate an immune from a symbiotic receptor and we now identified these and demonstrate for the first time that it is possible to reprogram LysM receptors by changing these residues," says Kasper Røjkjær Andersen.

The long-term goal is to transfer the unique nitrogen-fixing ability that legume plants have into cereal plants to limit the need for polluting commercial nitrogen fertilizers and to benefit and empower the poorest people on Earth. Simona Radutoiu concludes, "We now provide the conceptual understanding required for a stepwise and rational engineering of LysM receptors, which is an essential first step towards this ambitious goal".

Geologists have developed a machine learning technique that highlights the potential for further deposits of the critical metal tungsten in SW England.

Tungsten is an essential component of high-performance steels but global production is strongly influenced by China and western countries are keen to develop alternative sources.

The work, published in the leading journal Geoscience Frontiers, has been led by Dr Chris Yeomans, from the Camborne School of Mines, and involved geoscientists from the University of Nottingham, Geological Survey of Finland (GTK) and the British Geological Survey.

The research applies machine learning to multiple existing datasets to examine the geological factors that have resulted in known tungsten deposits in SW England.

These findings are then applied across the wider region to predict areas where tungsten mineralisation is more likely and might have previously been overlooked. The same methodology could be applied to help in the exploration for other metals around the world.

Dr Yeomans, a Postdoctoral Research Fellow at the Camborne School of Mines, based at the University of Exeter's Penryn Campus in Cornwall said: "We're really pleased with the methodology developed and the results of this study.

"SW England is already the focus of UK mineral exploration for tungsten but we wanted to demonstrate that new machine learning approaches may provide additional insights and highlight areas that might otherwise be overlooked."

SW England hosts the fourth biggest tungsten deposit in the world (Hemerdon, near Plympton), that resulted in the UK being the sixth biggest global tungsten producer in 2017; the mine is currently being re-developed by Tungsten West Limited.

The Redmoor tin-tungsten project, being developed by Cornwall Resources Limited, has also been identified as being a potentially globally significant mineral deposit.

The new study suggests that there may be a wider potential for tungsten deposits and has attracted praise from those currently involved in the development of tungsten resources in SW England.

James McFarlane, from Tungsten West, said: "Tungsten has only been of economic interest in the last 100 years or so, during which exploration efforts for this critical metal have generally been short-lived.

"As such is very encouraging to see work that aims to holistically combine the available data to develop a tungsten prospectivity model in an area that has world-class potential".

Brett Grist, from Cornwall Resources added: "Our own work has shown that applying modern techniques can reveal world-class deposits in this historic and globally-significant mining district.

"Dr Yeomans' assertion, that the likelihood of new discoveries of tungsten mineralisation may be enhanced by a high-resolution gravity survey, is something in which we see great potential.

"Indeed, such a programme could stimulate the new discovery of economically significant deposits of a suite of critical metals, here in the southwest of the UK, for years to come."

Researchers from Nanyang Technical University, University of Washington, and University of British Columbia published a new paper in the Journal of Marketing that examines "unfair" negative reviews and demonstrates that they can have positive consequences for the reviewed firm.

The study, forthcoming in the Journal of Marketing, is titled "Negative Reviews, Positive Impact: Consumer Empathetic Responding to Unfair Word-of-Mouth" and is authored by Thomas Allard, Lea Dunn, and Katherine White.

Negative online reviews are abundant. Negative reviews generally provide diagnostic information about the inferior performance of the firm, which helps consumers make better decisions about their purchases. Those negative reviews usually lead to adverse consumer reactions such as decreased purchase or customer dislike for the brand. However, not all negative reviews are built from the same cloth. In some instances, the intensity of the negative reviews is not justified given the actions of the firm. These "unfair" negative reviews can have positive consequences for the reviewed firm.

Using six studies and four supplemental experiments (studying over 3,000 consumers), the research team provides converging evidence that unfairness in negative reviews evokes empathy for the firm from third-party consumers reading the reviews. This empathy is associated with increased purchase and patronage intentions. A study on the content of one thousand 1 - and 2- star hotel reviews from Trip Advisor finds that more than a quarter of these negative reviews contained elements that were perceived to be unfair, offering preliminary evidence about the prevalence of "unfair" negative reviews.

Allard explains that "Our findings suggest that unfair negative reviews consistently result in more favorable responses to the reviewed firm than fair negative reviews and, at times, even better than positive reviews. We highlight the role of empathy for the firm as a motivator for increased favorable firm intentions. We also identify how firms can leverage empathy from consumers reading reviews, even for those reviews that do not naturally evoke empathy." The first suggestion is to respond to all reviews in a manner that is more personable in visual appearance and tone (e.g., show your employees, use first names, respond from a person instead of a "brand"). The second suggestion is to spotlight the employees involved in the creation of the product or service (e.g., employee profiles, "meet your barista," naming the employee who helped make the product).

"Overall, our research highlights that unfair negative reviews are not necessarily bad for the brand and that firms can learn to capitalize on these reviews" says Dunn. By embracing the reviews, as some companies have done in the past (e.g., Ski Resorts, National Parks, Vienna Tourism all turned ridiculous 1-star reviews into something positive in their advertising campaigns), firms can strategically leverage consumer empathy and benefit from potential downstream consequences.

Compared to annual crops, perennial crops provide sustainable environmental benefits such as reduced soil and water erosion, reduced soil nitrate leaching, and increased carbon sequestration. Inclusion of sustainable cropping systems into mainstream agriculture has been a challenge given the lack of food-grade perennial grain cultivars.

In an article recently published in the Journal of Plant Registrations , a publication of the Crop Science Society of America, University of Minnesota researchers report the release of the first commercially available intermediate wheatgrass (IWG) cultivar. IWG is a cool-season perennial grain crop domesticated primarily for food use while maintaining the ecological benefits it offers.

The cultivar, named 'MN-Clearwater,' produces 696 kg ha-1 (621 lb ac-1) of grain on average with the first two years; it produces its highest grain yields under Minnesota conditions. It is relatively short at 113 cm and has minimal lodging with trace disease levels. MN-Clearwater is expected to perform well in US Upper Midwest, southern regions of Canada, and the US Northeast.

As the first IWG cultivar released for sale under the Kernza® trade name, we expect MN-Clearwater to be a cornerstone resource for the IWG research community as well as for interested growers, food processors, and commercial partners.

Adapted from Bajgain, P, Zhang, X, Jungers, JM, et al. 'MN-Clearwater', the first food-grade intermediate wheatgrass (Kernza perennial grain) cultivar. J. Plant Regist. 2020; 1- 10.

By visualizing coronavirus replication in an infected host cell, researchers may have answered a long-standing question about how newly synthesized coronavirus components are able to be incorporated into fully infectious viruses. Their work uncovers a coronavirus-specific structure in cells that may be a target for much-needed antiviral strategies against this family of viruses. Coronaviruses replicate their large genomes in the host cell's cytoplasm. They do this by transforming host cell membranes into peculiar double-membrane vesicles (DMVs). Newly made viral RNA needs to be exported from these DMVs to the cytosol to be packaged into complete, infectious forms of the virus. To date, however, no openings to the cytosol have been detected in the DMV replication compartments. Here, seeking to understand how viral RNA is exported from sealed DMVs, Georg Wolff and colleagues used electron tomography to visualize the middle stage of infection of a cell by mouse hepatitis coronavirus, used instead of SARS-CoV-2 due to biosafety constraints for in situ cryo-electron microscopy studies. They identified a coronavirus-specific crown-shaped structure - a molecular pore spanning the two DMV membranes - that likely plays a role during RNA release from the compartment. In further work using pre-fixed samples of SARS-CoV-2-infected cells, they showed that the structure is also present in SARS-CoV-2-induced DMVs. The authors "surmise" this structure may be a generic complex with a pivotal role in the coronavirus replication cycle, facilitating the export of newly synthesized viral RNA from the DMVs to the cytosol. "Although the exact mode of function of this molecular pore remains to be elucidated," Wolff et al. say, "it...may offer a general coronavirus-specific drug target."

ITHACA, N.Y. - How contagious is COVID-19, and how severe is the virus for those who've caught it?

Everyone wants firm numbers as schools make decisions about in-person versus remote learning, as local and state governments grapple with reopening, and as families care for sick loved ones.

But firm data is missing, said Francesca Molinari, the H.T. Warshow and Robert Irving Warshow Professor in the Department of Economics, in the College of Arts and Sciences. The best way to find out the share of the population that has been exposed to the virus is to either test everyone or to test a random sample of people. But currently not everyone gets tested, and testing is not random; moreover, tests are not perfect. These data challenges have led to wildly divergent predictions in recent months about how many people get infected and how many infected people die.

In research published in the Journal of Econometrics, Molinari and Charles F. Manski, the Board of Trustees Professor at Northwestern University, wrote that actual cumulative rates of COVID-19 infection are higher than reported rates of infection, and therefore actual infection fatality rates are lower than reported rates. The researchers reached these conclusions using a technique called "partial identification," which Molinari uses often in her econometrics research.

"You are interested in some quantity, but you cannot learn it exactly," she said. "In this particular instance, we are interested in the infection rate, and we recognize that because we don't have a random sample, we can't learn the exact infection rate from the data."

She and Manski made weak but logical assumptions about COVID-19 data from Illinois, New York and Italy from March 16 to April 24, thereby putting some limits around the incomplete data.

They assumed that the infection rate among those who are tested is higher than the rate among those who are not - a logical assumption because people showing symptoms are most likely to be tested. The researchers also allowed for the possibility that many negative test results were false - i.e., that the person tested was actually positive but not counted.

These two assumptions drive the actual cumulative infection rates up and push the actual fatality rates down, Molinari said. Cumulative infection rates in New York state as of April 24, according to the researchers, were between 1.7% and 61% of the state's 19.45 million residents (or between 330,650 and 12,020,100 people), with an upper infection fatality rate of 4.9%. That is substantially lower than the death rate among confirmed infected individuals, which on April 24 was 5.9%.

Infection rates for the same date in Illinois were between 0.04% and 52%; in Italy, they were between 0.06% and 47%.

"The bounds you get are wide," Molinari said, "but they are substantially tighter compared to the bounds you obtain if you assume nothing about the missing data."

Making key assumptions and narrowing the bounds helps policymakers and leaders better understand fatality rates as they try to limit spread of the virus and plan reactivations. Molinari hopes this research will contribute to serious analysis of policies.

Molinari and Manski are working on a follow-up analysis of a longer time period that adds data from California, Florida and Texas to the study.

Vast areas of the Martian night sky pulse in ultraviolet light, according to images from NASA's MAVEN spacecraft. The results are being used to illuminate complex circulation patterns in the Martian atmosphere.

The MAVEN team was surprised to find that the atmosphere pulsed exactly three times per night, and only during Mars' spring and fall. The new data also revealed unexpected waves and spirals over the winter poles, while also confirming the Mars Express spacecraft results that this nightglow was brightest over the winter polar regions.

"MAVEN's images offer our first global insights into atmospheric motions in Mars' middle atmosphere, a critical region where air currents carry gases between the lowest and highest layers," said Nick Schneider of the University of Colorado's Laboratory for Atmospheric and Space Physics (LASP), Boulder, Colorado. The brightenings occur where vertical winds carry gases down to regions of higher density, speeding up the chemical reactions that create nitric oxide and power the ultraviolet glow. Schneider is instrument lead for the MAVEN Imaging Ultraviolet Spectrograph (IUVS) instrument that made these observations, and lead author of a paper on this research appearing August 6 in the Journal of Geophysical Research, Space Physics. Ultraviolet light is invisible to the human eye but detectable by specialized instruments.

"The ultraviolet glow comes mostly from an altitude of about 70 kilometers (approximately 40 miles), with the brightest spot about a thousand kilometers (approximately 600 miles) across, and is as bright in the ultraviolet as Earth's northern lights," said Zac Milby, also of LASP. "Unfortunately, the composition of Mars' atmosphere means that these bright spots emit no light at visible wavelengths that would allow them to be seen by future Mars astronauts. Too bad: the bright patches would intensify overhead every night after sunset, and drift across the sky at 300 kilometers per hour (about 180 miles per hour)."

The pulsations reveal the importance of planet-encircling waves in the Mars atmosphere. The number of waves and their speed indicates that Mars' middle atmosphere is influenced by the daily pattern of solar heating and disturbances from the topography of Mars' huge volcanic mountains. These pulsating spots are the clearest evidence that the middle atmosphere waves match those known to dominate the layers above and below.

"MAVEN's main discoveries of atmosphere loss and climate change show the importance of these vast circulation patterns that transport atmospheric gases around the globe and from the surface to the edge of space." said Sonal Jain, also of LASP.

Next, the team plans to look at nightglow "sideways", instead of down from above, using data taken by IUVS looking just above the edge of the planet. This new perspective will be used to understand the vertical winds and seasonal changes even more accurately.

The Martian nightglow was first observed by the SPICAM instrument on the European Space Agency's Mars Express spacecraft. However, IUVS is a next-generation instrument better able to repeatedly map out the nightside glow, finding patterns and periodic behaviors. Many planets including Earth have nightglow, but MAVEN is the first mission to collect so many images of another planet's nightglow.