Culture

The general picture of a shark is that of a fast and large ocean predator. Some species, however, question this image - for example angel sharks. They have adapted to a life on the bottom of the oceans, where they lie in wait for their prey. In order to be able to hide on or in the sediment, the body of angel sharks became flattened in the course of their evolution, making them very similar to rays, which are closely related to sharks.

Flattened body as indication for a successful lifestyle

The oldest known complete fossils of angel sharks are about 160 million years old and demonstrate that the flattened body was established early in their evolution. This also indicates that these extinct angel sharks already had a similar lifestyle as their extant relatives - and that this lifestyle obviously was very successful.

Angel sharks are found all over the world today, ranging from temperate to tropical seas, but most of these species are threatened. In order to understand the patterns and processes that led to their present low diversity and the possible consequences of their particular anatomy, the team has studied the body shapes of angel sharks since their origins using modern methods.

Today's species are very similar

For this purpose, the skulls of extinct species from the late Jurassic period (about 160 million years ago) and of present-day species were quantitatively analysed using X-ray and CT images and prepared skulls employing geometric-morphometric approaches. In doing so, the evolution of body shapes could be explained comparatively, independent of body size.

The results show that early angel sharks were different in their external shape, whereas modern species show a comparably lower variation in shape. "Many of the living species are difficult to identify on the basis of their skeletal anatomy and shape, which could be problematic for species recognition," explains Faviel A. López-Romero.

Angel sharks are well adapted, but react slowly to environmental changes

It has been shown that in living species the individual parts of the skull skeleton are more closely integrated than in their extinct relatives. This led to a reduced variability in appearance during the evolution of angel sharks. "The effect of integrating different parts of the skull into individual, highly interdependent modules can lead to a limited ability to evolve in different forms, but at the same time increases the ability to successfully adapt to specific environmental conditions," explains Jürgen Kriwet.

In the case of the angel sharks, increasing geographical isolation resulted in the development of different species with very similar adaptations. "But modular integration also means that such animals are no longer able to react quickly to environmental changes, which increases their risk of extinction," concludes Jürgen Kriwet.

Specific antibodies protect us against viral infections - or do they not? Researchers at the German Cancer Research Center (DKFZ) studied the immune response to papillomaviruses in mice and discovered a hitherto unknown mechanism by which the pathogens outwit the immune system: At the beginning of the infection cycle, they produce a longer version of a protein that surrounds the viral genome. The body produces antibodies against this protein, but they are not effective in fighting the pathogen.

The human immune system has a wide variety of defense strategies to protect the body against pathogens, one of which involves producing antibodies to fight viruses and bacteria. Over time, however, these pathogens have developed elaborate ways of escaping the immune system.

Scientists are already aware of some of these strategies. In human papillomaviruses (HPV), however, up until now they have only known about such strategies in innate, already present immunity and not in adaptive immunity, which does not develop until pathogens enter the body and is associated with the production of antibodies.

Frank Rösl and his co-workers from DKFZ under the supervision of Daniel Hasche have now discovered a new mechanism by which cutaneous papillomaviruses (specific to the skin) trick the immune system.

Certain cutaneous HPV, such as HPV5 and HPV8, occur as natural infections on the skin. They are not sexually transmitted, but are passed on from the mother to the newborn child. Thus, family members are usually colonized with the same HPV types. An infection normally goes unnoticed, because the body is able to overcome it. Depending on the individual status of a person's immune system, their genetic predisposition, age, and other external factors such as UV radiation, however, certain cutaneous HPV types are able to stimulate cell division in their host cells. This leads to skin changes and in rare cases to development of a squamous cell carcinoma, also known as fair-skin cancer.

The experiments were conducted in a particular mouse species, Mastomys coucha, which, like humans, can become infected with cutaneous papillomaviruses shortly after birth and produce specific antibodies against the virus. In combination with UV radiation, infected animals are more likely to develop squamous cell cancer.

The animals' immune system produces antibodies against the two viral proteins L1 and L2 that make up the virus particles, also called capsids. These antibodies can prevent the viruses from entering the host cells and thus neutralize the virus. However, the experiments carried out by the DKFZ scientists showed that besides the normal L1 protein, the viruses also produce a longer version. The latter is not able to actually take part in forming the viral capsid. Instead, it acts as a kind of bait against which the immune system directs its response and produces specific antibodies.

However, the scientists were able to demonstrate that these antibodies are not effective in fighting the papillomavirus. Instead of neutralizing the infectious pathogen through binding to L1, the antibodies merely bind the nonfunctional protein used as bait. While the immune system is busy producing these non-neutralizing antibodies, the virus can continue to replicate and spread throughout the body. It take several more months before neutralizing antibodies are produced that target the normal L1 protein and ultimately the infectious viruses themselves.

"In both rodents and humans, in almost all HPV types that can cause cancer, the L1 gene is designed such that a longer version of the protein can be produced. This is also true for high-risk HPV types such as HPV16 and HPV18, which can cause cervical cancer. It therefore appears to be a common mechanism that enables the viruses to replicate and spread efficiently during the early stage of infection", Daniel Hasche explained. "The fact that antibodies against papillomaviruses can be detected is therefore not necessarily associated with protection against infection. This will need to be taken into account in future when evaluating and interpreting epidemiological studies," Frank Rösl added.

RESEARCH TRIANGLE PARK, N.C. -- New rules of engagement on the battlefield will require a deep understanding of networks and how they operate according to new Army research. Researchers confirmed a theory that find that networks of no more than 150 are optimal for efficient information exchange.

"This is the beginning of a new way to address competition and conflict in today's complex world," said Dr. Bruce West, senior scientist, Army Research Office, an element of the U.S. Army Combat Capabilities Development Command's Army Research Laboratory. "To increase the utility of the Army's evolving network structures in terms of robustness, resilience, adaptability and efficiency, requires a deeper understanding of how networks actually function, both ours and those of our adversary."

Researchers at ARO and the University of North Texas tested a theory proposed by British anthropologist Robin Dunbar in the 1990s, which suggested that 150 was the largest group that humans can maintain stable social relations. In the vicinity of this size the social group becomes unstable and splinters into smaller groups.

"It takes a network to defeat a network," wrote retired Army Gen. Stanley McChrystal, in his book Team of Teams. He discusses understanding the implications of the theory, abstracting from battlefield experiences in Iraq battling the loosely networked but effective terrorist organization Al Qaeda.

Researchers published their findings in the peer-reviewed Proceedings of the National Academy of Sciences of the United States of America. In their study, they prove Dunbar's conjecture, demonstrating that certain sized network has better information transport properties than others, and that networks of no more than 150 are optimal for internally sharing information.

"A fundamental property of a network is the relation between its functionality and size, which is why understanding the source of the Dunbar Number is important," said West, a co-author of the paper.

The researchers propose that the number 150 arises as a consequence of internal dynamics of a complex network self-organizing within a social system.

Based on that theory, the researchers also indicated that a peaceful demonstration can be turned into a mob by just a few agitators, with the size of 150 being the most vulnerable to such disruption.

"The 150 optimum has been observed by Dunbar and others, but Dr. West and colleagues are the first to computationally capture the theorized process of information dynamics, which are fundamental to problem-solving, development of group factions, and formation of cohesive groups," said Dr. Lisa Troyer, who manages ARO's social and behavioral sciences research program. "This is an important leap forward by for social science theory and will likely lead to further research and insights on collective action."

Dunbar predicted that social groups have optimal sizes. He referred to these group sizes as nested layering and that they have a scaling ratio of approximately three. Consequently, he identified the sequence of sizes of cognitively efficient social groups 5, 15, 50, 150 and 500, explaining that these layers were not equal in terms of strength of relationships.

"The layering sequence is interesting because each number in the sequence is within a factor of two of the empirical magnitudes of entity sizes in the U.S. Army, ranging from a squad of roughly 15 to a platoon of approximately three times the squad size, next to a company consisting of three platoons and followed by a brigade the size of roughly three companies and so on," West said. "This is the intuition on which armies have been hierarchically constructed by military leaders since the Roman Empire."

According to West, understanding how information flows within, is analyzed by, and is accepted or rejected from groups of various sizes is crucial in the training of teams. He said that this is not only true in the development of a single team, but is just as important for the training of teams to work together, to form teams-of-teams.

"The size of a team may be the determining factor in the potential success of a complex mission that depends on adaptability and collective problem solving," West said. "The same understanding can be applied to the reverse process, that of insinuating disinformation within an adversarial group. The size of the group may at times be more important than the form the lie takes for its acceptance and immediate transmission, witness the recent riots."

New detailed observations with NSF’s NOIRLab facilities reveal a young exoplanet, orbiting a young star in the Hyades cluster, that is unusually dense for its size and age. Weighing in at 25 Earth-masses, and slightly smaller than Neptune, this exoplanet’s existence is at odds with the predictions of leading planet formation theories.

New observations of the exoplanet, known as K2-25b, made with the WIYN 0.9-meter Telescope at Kitt Peak National Observatory (KPNO), a Program of NSF’s NOIRLab, the Hobby-Eberly Telescope at McDonald Observatory and other facilities, raise new questions about current theories of planet formation [1]. The exoplanet has been found to be unusually dense for its size and age — raising the question of how it came to exist. Details of the findings appear in The Astronomical Journal.

Slightly smaller than Neptune, K2-25b orbits an M-dwarf star — the most common type of star in the galaxy — in 3.5 days. The planetary system is a member of the Hyades star cluster, a nearby cluster of young stars in the direction of the constellation Taurus. The system is approximately 600 million years old, and is located about 150 light-years from Earth.

Planets with sizes between those of Earth and Neptune are common companions to stars in the Milky Way, despite the fact that no such planets are found in our Solar System. Understanding how these “sub-Neptune” planets form and evolve is a frontier question in studies of exoplanets.

Astronomers predict that giant planets form by first assembling a modest rock-ice core of 5–10 times the mass of Earth and then enrobing themselves in a massive gaseous envelope hundreds of times the mass of Earth. The result is a gas giant like Jupiter. K2-25b breaks all the rules of this conventional picture: with a mass 25 times that of Earth and modest in size, K2-25b is nearly all core and very little gaseous envelope. These strange properties pose two puzzles for astronomers. First, how did K2-25b assemble such a large core, many times the 5–10 Earth-mass limit predicted by theory? [2] And second, with its high core mass — and consequent strong gravitational pull — how did it avoid accumulating a significant gaseous envelope?

The team studying K2-25b found the result surprising. “K2-25b is unusual,” said Gudmundur Stefansson, a postdoctoral fellow at Princeton University, who led the research team. According to Stefansson, the exoplanet is smaller in size than Neptune but about 1.5 times more massive. “The planet is dense for its size and age, in contrast to other young, sub-Neptune-sized planets that orbit close to their host star,” said Stefansson. “Usually these worlds are observed to have low densities — and some even have extended evaporating atmospheres. K2-25b, with the measurements in hand, seems to have a dense core, either rocky or water-rich, with a thin envelope.”

To explore the nature and origin of K2-25b, astronomers determined its mass and density. Although the exoplanet’s size was initially measured with NASA’s Kepler satellite, the size measurement was refined using high-precision measurements from the WIYN 0.9-meter Telescope at KPNO and the 3.5-meter telescope at Apache Point Observatory (APO) in New Mexico. The observations made with these two telescopes took advantage of a simple but effective technique that was developed as part of Stefansson’s doctoral thesis. The technique uses a clever optical component called an Engineered Diffuser, which can be obtained off the shelf for around $500. It spreads out the light from the star to cover more pixels on the camera, allowing the brightness of the star during the planet’s transit to be more accurately measured, and resulting in a higher-precision measurement of the size of the orbiting planet, among other parameters [3].

“The innovative diffuser allowed us to better define the shape of the transit and thereby further constrain the size, density and composition of the planet,” said Jayadev Rajagopal, an astronomer at NOIRLab who was also involved in the study.

For its low cost, the diffuser delivers an outsized scientific return. “Smaller aperture telescopes, when equipped with state-of-the-art, but inexpensive, equipment can be platforms for high impact science programs,” explains Rajagopal. “Very accurate photometry will be in demand for exploring host stars and planets in tandem with space missions and larger apertures from the ground, and this is an illustration of the role that a modest-sized 0.9-meter telescope can play in that effort.”

Thanks to the observations with the diffusers available on the WIYN 0.9-meter and APO 3.5-meter telescopes, astronomers are now able to predict with greater precision when K2-25b will transit its host star. Whereas before transits could only be predicted with a timing precision of 30–40 minutes, they are now known with a precision of 20 seconds. The improvement is critical to planning follow-up observations with facilities such as the international Gemini Observatory and the James Webb Space Telescope[4].

Many of the authors of this study are also involved in another exoplanet-hunting project at KPNO: the NEID spectrometer on the WIYN 3.5-meter Telescope. NEID enables astronomers to measure the motion of nearby stars with extreme precision — roughly three times better than the previous generation of state-of-the-art instruments — allowing them to detect, determine the mass of, and characterize exoplanets as small as Earth.

Notes

[1] The planet was originally detected by Kepler in 2016. Detailed observations for this study were made using the Habitable-zone Planet Finder on the 11-meter Hobby-Eberly Telescope at McDonald Observatory.

[2] The prediction from theory is that once planets have formed a core of 5–10 Earth-masses they begin to accrete gas instead: very little rocky material is added after that.

[3] Diffusers were first used for exoplanet observations in 2017.

[4] GHOST, on Gemini South, will be used to carry out transit spectroscopy of exoplanets found by Kepler and TESS. Their target list includes the star K2-25.

More information

This research was presented in a paper to appear in The Astronomical Journal.

The team is composed of Gudmundur Stefansson (The Pennsylvania State University and Princeton University), Suvrath Mahadevan (The Pennsylvania State University), Marissa Maney (The Pennsylvania State University), Joe P. Ninan (The Pennsylvania State University), Paul Robertson (University of California, Irvine), Jayadev Rajagopal (NSF’s NOIRLab), Flynn Haase (NSF’s NOIRLab), Lori Allen (NSF’s NOIRLab), Eric B. Ford (The Pennsylvania State University), Joshua Winn (Princeton), Angie Wolfgang (The Pennsylvania State University), Rebekah I. Dawson (The Pennsylvania State University), John Wisniewski (University of Oklahoma), Chad F. Bender (University of Arizona), Caleb Cañas (The Pennsylvania State University), William Cochran (The University of Texas at Austin), Scott A. Diddams (National Institute of Standards and Technology, and University of Colorado), Connor Fredrick (National Institute of Standards and Technology, and University of Colorado), Samuel Halverson (Jet Propulsion Laboratory), Fred Hearty (The Pennsylvania State University), Leslie Hebb (Hobart and William Smith Colleges), Shubham Kanodia (The Pennsylvania State University), Eric Levi (The Pennsylvania State University), Andrew J. Metcalf (Air Force Research Laboratory, National Institute of Standards and Technology, and University of Colorado), Andrew Monson (The Pennsylvania State University), Lawrence Ramsey (The Pennsylvania State University), Arpita Roy (California Institute of Technology), Christian Schwab (Macquarie University), Ryan Terrien (Carleton College), and Jason T. Wright (The Pennsylvania State University).

NSF’s National Optical-Infrared Astronomy Research Laboratory (NOIRLab), the US center for ground-based optical-infrared astronomy, operates the international Gemini Observatory (a facility of NSF, NRC–Canada, ANID–Chile, MCTIC–Brazil, MINCyT–Argentina, and KASI–Republic of Korea), Kitt Peak National Observatory (KPNO), Cerro Tololo Inter-American Observatory (CTIO), the Community Science and Data Center (CSDC), and the Vera C. Rubin Observatory. It is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with NSF and is headquartered in Tucson, Arizona. The astronomical community is honored to have the opportunity to conduct astronomical research on Iolkam Du’ag (Kitt Peak) in Arizona, on Maunakea in Hawaiʻi, and on Cerro Tololo and Cerro Pachón in Chile. We recognize and acknowledge the very significant cultural role and reverence that these sites have to the Tohono O’odham Nation, to the Native Hawaiian community, and to the local communities in Chile, respectively.

The WIYN 0.9-meter Telescope is founded on a partnership between the WIYN Consortium, led by the University of Wisconsin-Madison and Indiana University, and the NSF’s NOIRLab. Its operations include an international group of universities.

Links

Research paper
Penn State University release
McDonald Observatory release

Contacts:

Gudmundur StefanssonPrinceton UniversityTel: +1 814-777-8712Email: gstefansson@astro.princeton.edu

Jayadev RajagopalAstronomer at NOIRLabTel: 520 318 8292Cell: +1 520 528 3881Email: jrajagopal@noao.edu

Amanda KoczPress and Internal Communications OfficerNSF’s NOIRLabCell: +1 626 524 5884Email: akocz@aura-astronomy.org

An active immune system protects against diseases and infections. An overactive immune system is the body's worst enemy. One example of this is multiple sclerosis, which is a so-called autoimmune disease, while an overactive immune system also leads to some COVID-19 patients becoming seriously ill.

Now, a research group under the leadership of professor and virologist Søren Riis Paludan from the Department of Biomedicine at Aarhus University, Denmark, has identified a mechanism which is activated in the cells of the immune system when they are attacked by disease. The discovery involves the protein STING, which sends signals to the nucleus of the cell when an infection threatens.

"Until now we've known that the STING protein migrates from an inactive part of the cell to an active when the immune system is alerted, but with this study we can for the first time describe the mechanism that causes the 'migration'. At the same time, we've identified a new protein, STEEP ('STING ER exit protein'), which is responsible for this migration. These are both breakthroughs in terms of understanding the basic disease mechanisms," says Søren Riis Paludan about the study, which has just been published in Nature Immunology.

Previous research has shown that the cells in the immune system are activated through signalling systems organised in what are known as cascades. A system of step-by-step reactions which are e.g. initiated by infection, or when cancer cells are eaten by immune cells. One of these is the cGAS-STING signal cascade, which plays a key role in a number of diseases. The new study shows that STING's 'journey' within the cell trains the activity of the STING signal cascade.

"This part of the process is particularly important because of STING's essential function as part of an innate immune system. The new findings help us to better understand how infectious diseases affect the immune system," says Søren Riis Paludan.

For many years, it has been common knowledge that a well-functioning immune system is extremely important for our health. Even a commonplace infection becomes life-threatening if the immune system is not ready for the fight.

"The immune system is essential in the fight against infection, but if it isn't regulated precisely by the body's own fine-tuning system, it becomes over-activated and creates disease. For example, an overactive immune system has made some COVID-19 patients very ill and difficult to treat," says Søren Riis Paludan.

Identifying the mechanism behind STING's journey and the discovery of the new protein STEEP opens the way to a previously unknown branch in our understanding of the immune system.

"Fundamentally, we're trying to find answers to why in some cases the body's immune system reacts to infections and diseases by causing more illness instead of providing protection. With the STEEP protein, we have a potential source from which we can learn about new principles for how the immune system functions," says Søren Riis Paludan.

Using the supersharp radio "vision" of the National Science Foundation's continent-wide Very Long Baseline Array (VLBA), astronomers have discovered a Saturn-sized planet closely orbiting a small, cool star 35 light-years from Earth. This is the first discovery of an extrasolar planet with a radio telescope using a technique that requires extremely precise measurements of a star's position in the sky, and only the second planet discovery for that technique and for radio telescopes.

The technique has long been known, but has proven difficult to use. It involves tracking the star's actual motion in space, then detecting a minuscule "wobble" in that motion caused by the gravitational effect of the planet. The star and the planet orbit a location that represents the center of mass for both combined. The planet is revealed indirectly if that location, called the barycenter, is far enough from the star's center to cause a wobble detectable by a telescope.

This technique, called the astrometric technique, is expected to be particularly good for detecting Jupiter-like planets in orbits distant from the star. This is because when a massive planet orbits a star, the wobble produced in the star increases with a larger separation between the planet and the star, and at a given distance from the star, the more massive the planet, the larger the wobble produced.

Starting in June of 2018 and continuing for a year and a half, the astronomers tracked a star called TVLM 513-46546, a cool dwarf with less than a tenth the mass of our Sun. In addition, they used data from nine previous VLBA observations of the star between March 2010 and August 2011.

Extensive analysis of the data from those time periods revealed a telltale wobble in the star's motion indicating the presence of a planet comparable in mass to Saturn, orbiting the star once every 221 days. This planet is closer to the star than Mercury is to the Sun.

Small, cool stars like TVLM 513-46546 are the most numerous stellar type in our Milky Way Galaxy, and many of them have been found to have smaller planets, comparable to Earth and Mars.

"Giant planets, like Jupiter and Saturn, are expected to be rare around small stars like this one, and the astrometric technique is best at finding Jupiter-like planets in wide orbits, so we were surprised to find a lower mass, Saturn-like planet in a relatively compact orbit. We expected to find a more massive planet, similar to Jupiter, in a wider orbit," said Salvador Curiel, of the National Autonomous University of Mexico. "Detecting the orbital motions of this sub-Jupiter mass planetary companion in such a compact orbit was a great challenge," he added.

More than 4,200 planets have been discovered orbiting stars other than the Sun, but the planet around TVLM 513-46546 is only the second to be found using the astrometric technique. Another, very successful method, called the radial velocity technique, also relies on the gravitational effect of the planet upon the star. That technique detects the slight acceleration of the star, either toward or away from Earth, caused by the star's motion around the barycenter.

"Our method complements the radial velocity method which is more sensitive to planets orbiting in close orbits, while ours is more sensitive to massive planets in orbits further away from the star," said Gisela Ortiz-Leon of the Max Planck Institute for Radio Astronomy in Germany. "Indeed, these other techniques have found only a few planets with characteristics such as planet mass, orbital size, and host star mass, similar to the planet we found. We believe that the VLBA, and the astrometry technique in general, could reveal many more similar planets."

A third technique, called the transit method, also very successful, detects the slight dimming of the star's light when a planet passes in front of it, as seen from Earth.

The astrometric method has been successful for detecting nearby binary star systems, and was recognized as early as the 19th Century as a potential means of discovering extrasolar planets. Over the years, a number of such discoveries were announced, then failed to survive further scrutiny. The difficulty has been that the stellar wobble produced by a planet is so small when seen from Earth that it requires extraordinary precision in the positional measurements.

"The VLBA, with antennas separated by as much as 5,000 miles, provided us with the great resolving power and extremely high precision needed for this discovery," said Amy Mioduszewski, of the National Radio Astronomy Observatory. "In addition, improvements that have been made to the VLBA's sensitivity gave us the data quality that made it possible to do this work now," she added.

Researchers at Yale University School of Medicine have developed a new mouse model to study SARS-CoV-2 infection and disease and to accelerate testing of novel treatments and vaccines against the novel coronavirus. The study, published today in the Journal of Experimental Medicine (JEM), also suggests that, rather than protecting the lungs, key antiviral signaling proteins may actually cause much of the tissue damage associated with COVID-19.

Animal models that recapitulate SARS-CoV-2 infection and disease are urgently needed to help researchers understand the virus, develop therapies, and identify potential vaccine candidates. Mice are the most widely used laboratory animals, but they cannot be infected with SARS-CoV-2 because the virus is unable to employ the mouse version of ACE2, the cell surface receptor protein that the virus uses to enter human cells.

SARS-CoV-2 can infect mice genetically engineered to produce the human version of ACE2. However, the availability of these animals is low and limited to a single mouse strain, preventing researchers from investigating how the virus impacts mice that are immunocompromised or obese, conditions that significantly increase the fatality rate in humans.

In the new study, a team of researchers led by Akiko Iwasaki at Yale University School of Medicine developed an alternative mouse model of SARS-CoV-2 infection in which the animals are first infected with a different, harmless virus carrying the human ACE2 gene. Mice infected with this virus produce the human ACE2 protein and can then be infected with SARS-CoV-2. Iwasaki and colleagues found that SARS-CoV-2 can replicate in these mice and induce an inflammatory response similar to that observed in COVID-19 patients, where a wide variety of immune cells are activated and recruited to the lungs. "In addition, the infected mice also rapidly develop neutralizing antibodies against SARS-CoV-2," Iwasaki says.

The body's response to viral infection often depends on signaling molecules called type I interferons that can activate immune cells and induce the production of antiviral proteins and antibodies. But too much type I interferon, especially when the production is delayed, can lead to excessive inflammation and tissue damage. Indeed, while type I interferon signaling protects against the related coronavirus MERS-CoV, it causes lung damage in response to SARS-CoV-1, the virus responsible for a previous coronavirus outbreak in 2002-2003.

The role of type I interferons in COVID-19 is currently unclear. Iwasaki and colleagues found that, similar to COVID-19 patients, mice infected with SARS-CoV-2 activate a large number of genes associated with type I interferon signaling. The researchers then used their model system to infect mice lacking key components of the type I interferon pathway and found that they were no worse at controlling SARS-CoV-2 infection. However, these animals recruited fewer inflammatory immune cells into their lungs. "These results indicate that type I interferons do not restrict SARS-CoV-2 replication, but they may play a pathological role in COVID-19 respiratory inflammation," Iwasaki says. "This is especially concerning because type I interferons are currently being used as a treatment for COVID-19. The early timing of the IFN treatment will be important for it to provide protection and benefit."

Iwasaki adds, "The mouse model we developed offers a broadly available and highly adaptable animal model to understand critical aspects of SARS-CoV-2 viral infection, replication, pathogenesis, and protection using authentic patient-derived virus. The model provides a vital platform for testing prophylactic and therapeutic strategies to combat COVID-19."

Biomedical engineers at Duke University have shown that different strains of the same bacterial pathogen can be distinguished by a machine learning analysis of their growth dynamics alone, which can then also accurately predict other traits such as resistance to antibiotics. The demonstration could point to methods for identifying diseases and predicting their behaviors that are faster, simpler, less expensive and more accurate than current standard techniques.

The results appear online on August 3 in the Proceedings of the National Academy of Sciences.

For most of the history of microbiology, bacteria identification has relied on growing cultures and analyzing the physical traits and behaviors of the resulting bacterial colony. It wasn't until recently that scientists could simply run a genetic test.

Genetic sequencing, however, isn't universally available and can often take a long time. And even with the ability to sequence entire genomes, it can be difficult to tie specific genetic variations to different behaviors in the real world.

For example, even though researchers know the genetic mutations that help shield/protect bacteria from beta-lactam antibiotics--the most commonly used antibiotic in the world--sometimes the DNA isn't the whole story. While a single resistant bacteria usually can't survive a dose of antibiotics on its own, large populations often can.

Lingchong You, professor of biomedical engineering at Duke, and his graduate student, Carolyn Zhang, wondered if a new twist on older methods might work better. Maybe they could amplify one specific physical characteristic and use it to not only identify the pathogen, but to make an educated guess about other traits such as antibiotic resistance.

"We thought that the slight variance in the genes between strains of bacteria might have a subtle effect on their metabolism," You said. "But because bacterial growth is exponential, that subtle effect could be amplified enough for us to take advantage of it. To me, that notion is somewhat intuitive, but I was surprised at how well it actually worked."

How quickly a bacterial culture grows in a laboratory depends on the richness of the media it is growing in and its chemical environment. But as the population grows, the culture consumes nutrients and produces chemical byproducts. Even if different strains start with the exact same environmental conditions, subtle differences in how they grow and influence their surroundings accumulate over time.

In the study, You and Zhang took more than 200 strains of bacterial pathogens, most of which were variations of E. coli, put them into identical growth environments, and carefully measured their population density as it increased. Because of their slight genetic differences, the cultures grew in fits and starts, each possessing a unique temporal fluctuation pattern. The researchers then fed the growth dynamics data into a machine learning program, which taught itself to identify and match the growth profiles to the different strains.

To their surprise, it worked really well.

"Using growth data from only one initial condition, the model was able to identify a particular strain with more than 92 percent accuracy," You said. "And when we used four different starting environments instead of one, that accuracy rose to about 98 percent."

Taking this idea one step further, You and Zhang then looked to see if they could use growth dynamic profiles to predict another phenotype--antibiotic resistance.

The researchers once again loaded a machine learning program with the growth dynamic profiles from all but one of the various strains, along with data about their resilience to four different antibiotics. They then tested to see if the resulting model could predict the final strain's antibiotic resistances from its growth profile. To bulk up their dataset, they repeated this process for all of the other strains.

The results showed that the growth dynamic profile alone could successfully predict a strain's resistance to antibiotics 60 to 75 percent of the time.

"This is actually on par or better than some of the current techniques in the literature, including many that use genetic sequencing data," said You. "And this was just a proof of principle. We believe that with higher-resolution data of the growth dynamics, we could do an even better job in the long term."

The researchers also looked to see if the strains exhibiting similar growth curves also had similar genetic profiles. As it turns out, the two are completely uncorrelated, demonstrating once again how difficult it can be to map cellular traits and behaviors to specific stretches of DNA.

Moving forward, You plans to optimize the growth curve procedure to reduce the time it takes to identify a strain from 2 to 3 days to perhaps 12 hours. He's also planning on using high-definition cameras to see if mapping how bacterial colonies grow in space in a Petri dish can help make the process even more accurate.

From lowering your risk of obesity and cardiovascular disease to improving your concentration and overall daily performance, sleep has been proven to play a critical role in our health. In a new study, researchers at University of California San Diego School of Medicine report that sleep may also help people to learn continuously through their lifetime.

Writing in the August 4, 2020 online issue of eLife, researchers used computational models capable of simulating different brain states, such as sleep and awake, to examine how sleep consolidates newly encoded memories and prevents damage to old memories.

"The brain is very busy when we sleep, repeating what we have learned during the day. Sleep helps reorganize memories and presents them in the most efficient way. Our findings suggest that memories are dynamic, not static. In other words, memories, even old memories, are not final. Sleep constantly updates them," said Maksim Bazhenov, PhD, lead author of the study and professor of medicine at UC San Diego. "We predict that during the sleep cycle, both old and new memories are spontaneously replayed, which prevents forgetting and increases recall performance."

Bazhenov said that memory replay during sleep plays a protective role against forgetting by allowing the same populations of neurons to store multiple interfering memories. "We learn many new things on a daily basis and those memories compete with old memories. To accommodate all memories, we need sleep."

For example, imagine learning how to navigate to a parking lot by going left at one stop sign and right at one traffic light. The next day, you have to learn how to get to a different parking lot using different directions. Bazhenov said sleep consolidates those memories to allow recollection of both.

"When you play tennis, you have a certain muscle memory. If you then learn how to play golf, you have to learn how to move the same muscles in a different way. Sleep makes sure that learning golf does not erase how to play tennis and makes it possible for different memories to coexist in the brain," said Bazhenov.

The authors suggest that the restorative value of sleep may be what is lacking in current state-of-the-art computer systems that power self-driving cars and recognize images with performances that far exceed humans. However, these artificial intelligence systems lack the ability to learn continuously and will forget old knowledge when new information is learned. "We may need to add a sleep-like state to computer and robotic systems to prevent forgetting after new learning and to make them able to learn continuously," said Bazhenov.

Bazhenov said the study results could lead to developing new stimulation techniques during sleep to improve memory and learning. This may be particularly important in older adults or persons suffering from learning disabilities.

"While sleep is certainly involved in many important brain and body functions, it may be critical for making possible what we call human intelligence -- the ability to learn continuously from experience, to create new knowledge and to adapt as the world changes around us," said Bazhenov.

FAIRFAX, Va. -- A new study presented today at the Society of NeuroInterventional Surgery's (SNIS) 17th Annual Meeting serves as the first prospective validation of the Rapid Arterial Occlusion Evaluation (RACE) scale in accurately identifying a severe clot stroke called a Large Vessel Occlusion (LVO) by U.S.-based EMS personnel in a pre-hospital setting.

The study, Prospective, Multi-centered, EMS-administered, Pre-hospital Validation Study of the Rapid Arterial Occlusion Evaluation (RACE) Scale for Detecting Large Vessel Occlusion Stroke in the United States Compared to the Original RACE Validation Study from Spain: A Subanalysis of the PREDICT Study, evaluated 232 adult patients suspected of having a stroke by U.S.-based EMS who were transported to a participating comprehensive stroke center. All patients had the RACE scale administered prospectively and their results recorded in a secure web-based database.

The RACE scale was previously validated by EMS in Spain for accurately identifying this type of life-threatening condition and has been widely adopted in the United States. The health care infrastructure and EMS systems differ significantly between the two countries; the validity of the results from the Spanish study when applied to U.S. systems was untested prior to this study.

"Standardizing triage protocols is critical for improving stroke systems of care and improving outcomes for patients," said Dr. Robert F. James, senior author of the study and Professor and Vice Chair, Department of Neurosurgery, Indiana University School of Medicine. "The findings of this study advance the validity of the RACE scale, which will help EMS determine stroke severity in the field and ensure that patients receive proper care as soon as possible."

Rice is the most widely consumed staple food source for a large part of the world's population. It has now been confirmed that rice can contribute to prolonged low-level arsenic exposure leading to thousands of avoidable premature deaths per year.

Arsenic is well known acute poison, but it can also contribute to health problems, including cancers and cardiovascular diseases, if consumed at even relatively low concentrations over an extended period of time.

Compared to other staple foods, rice tends to concentrate inorganic arsenic. Across the globe, over three billion people consume rice as their major staple and the inorganic arsenic in that rice has been estimated by some to give rise to over 50,000 avoidable premature deaths per year.

A collaborating group of cross-Manchester researchers from The University of Manchester and The University of Salford have published new research exploring the relationship, in England and Wales, between the consumption of rice and cardiovascular diseases caused by arsenic exposure.

Their findings, published in the journal Science of the Total Environment, shows that - once corrected for the major factors known to contribute to cardiovascular disease (for example obesity, smoking, age, lack of income, lack of education) there is a significant association between elevated cardiovascular mortality, recorded at a local authority level, and the consumption of inorganic arsenic bearing rice.

Professor David Polya from The University of Manchester said: "The type of study undertaken, an ecological study, has many limitations, but is a relatively inexpensive way of determining if there is plausible link between increased consumption of inorganic arsenic bearing rice and increased risk of cardiovascular disease.

Professor Polya from The University of Manchester said "The study suggests that the highest 25 % of rice consumers in England and Wales may plausibly be at greater risks of cardiovascular mortality due to inorganic arsenic exposure compared to the lowest 25 % of rice consumers.

"The modelled increased risk is around 6 % (with a confidence interval for this figure of 2 % to 11 %). The increased risk modelled might also reflect in part a combination of the susceptibility, behaviours and treatment of those communities in England and Wales with relatively high rice diets."

While more robust types of study are required to confirm the result, given many of the beneficial effects otherwise of eating rice due to its high fibre content, the research team suggest that rather than avoid eating rice, people could consume rice varieties, such as basmati, and different types like polished rice (rather whole grain rice) which are known to typically have lower inorganic arsenic contents. Other positive behaviours would be to eat a balanced variety of staples, not just predominately rice.

Irvine, CA - August 4, 2020 - Researchers from the newly-established Center for Neural Circuit Mapping at the University of California, Irvine School of Medicine evaluate the properties of anterograde and retrograde viral tracers, comparing their strengths and limitations for use in neural circuit mapping. Results were published today as a primer in Neuron.

The article provides a comprehensive comparison of anterograde and retrograde viral and non-viral tracers for neural circuit analysis and describe neural circuit tracing history and background. It also examines the specific viruses used for neuroscience research, and provides essential information to guide other researchers on their choice of viral tracers.

Viral tracers are important tools for neuroanatomical mapping and genetic payload delivery. Genetically modified viruses allow for cell-type specific targeting, and overcome many limitations of non-viral tracers.

"A central goal of modern neuroscience research is to understand the cell-type specific connections between different regions of the brain and the detailed circuit organization within them," said lead author Xiangmin Xu, PhD, professor of anatomy and neurobiology, and director of the new Center for Neural Circuit Mapping. "Our primer evaluates currently applied anterograde and retrograde viral tracers and provides practical guidance on experimental uses, along with key technical and conceptual considerations for developing new safer and more effective anterograde trans-synaptic viral vectors for neural circuit analysis in multiple species."

Naturally occurring viruses have been used for neural circuit tracing for decades by exploiting the natural properties of viral propagation and transmission. Genetic modifications of such viruses have led to many improvements for neuroscience applications. In addition to anatomical mapping, genetically modified viral tracers have greatly facilitated functional studies of cell-type specific and circuit-specific neural networks in the brain.

Xu, along with other UCI School of Medicine investigators involved in the primer, including Rozanne Sandri-Goldin, PhD, chancellor's professor and chair of microbiology and molecular genetics, Todd Holmes, PhD, professor and vice chair of physiology and biophysics, and Bert Semler, PhD, distinguished professor of microbiology and molecular genetics and director for the UCI Center for Virus Research, recently launched the Center for Neural Circuit Mapping (CNCM) at the UCI School of Medicine. The CNCM focuses on neural circuit studies and new viral-genetic technology development. A critical component of the new center is the creation of a viral production facility to disseminate new molecular tools to the worldwide neuroscience community.

"Using new genetic-viral tools, our main goal with the CNCM is to advance the study of neural circuits using animal models to define mechanisms and pathways that underlie neurodevelopmental, neuropsychiatric and neurodegenerative disorders," said Xu. "Understanding the brain's neural circuitry is critical for successful translational progress in better treating these diseases."

Genes that are thought to play a role in how the SARS-CoV-2 virus infects our cells have been found to be active in embryos as early as during the second week of pregnancy, say scientists at the University of Cambridge and the California Institute of Technology (Caltech). The researchers say this could mean embryos are susceptible to COVID-19 if the mother gets sick, potentially affecting the chances of a successful pregnancy.

While initially recognised as causing respiratory disease, the SARS-CoV-2 virus, which causes COVID-19 disease, also affects many other organs. Advanced age and obesity are risk factors for complications but questions concerning the potential effects on fetal health and successful pregnancy for those infected with SARS-CoV-2 remain largely unanswered.

To examine the risks, a team of researchers used technology developed by Professor Magdalena Zernicka-Goetz at the University of Cambridge to culture human embryos through the stage they normally implant in the body of the mother to look at the activity - or 'expression' - of key genes in the embryo. Their findings are published today in the Royal Society's journal Open Biology.

On the surface of the SARS-CoV-2 virus are large 'spike' proteins. Spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell's machinery to allow the virus to replicate and spread.

The researchers found patterns of expression of the genes ACE2, which provide the genetic code for the SARS-CoV-2 receptor, and TMPRSS2, which provides the code for a molecule that cleaves both the viral spike protein and the ACE2 receptor, allowing infection to occur. These genes were expressed during key stages of the embryo's development, and in parts of the embryo that go on to develop into tissues that interact with the maternal blood supply for nutrient exchange. Gene expression requires that the DNA code is first copied into an RNA message, which then directs the synthesis of the encoded protein. The study reports the finding of the RNA messengers.

Professor Magdalena Zernicka-Goetz, who holds positions at both the University of Cambridge and Caltech, said: "Our work suggests that the human embryo could be susceptible to COVID-19 as early as the second week of pregnancy if the mother gets sick.

"To know whether this really could happen, it now becomes very important to know whether the ACE2 and TMPRSS2 proteins are made and become correctly positioned at cell surfaces. If these next steps are also taking place, it is possible that the virus could be transmitted from the mother and infect the embryo's cells."

Professor David Glover, also from Cambridge and Caltech, added: "Genes encoding proteins that make cells susceptible to infection by this novel coronavirus become expressed very early on in the embryo's development. This is an important stage when the embryo attaches to the mother's womb and undertakes a major remodelling of all of its tissues and for the first time starts to grow. COVID-19 could affect the ability of the embryo to properly implant into the womb or could have implications for future fetal health."

The team say that further research is required using stem cell models and in non-human primates to better understand the risk. However, they say their findings emphasise the importance for women planning for a family to try to reduce their risk of infection.

"We don't want women to be unduly worried by these findings, but they do reinforce the importance of doing everything they can to minimise their risk of infection," said Bailey Weatherbee, a PhD student at the University of Cambridge.

LA JOLLA--(August 4, 2020) A drug candidate developed by Salk researchers, and previously shown to slow aging in brain cells, successfully reversed memory loss in a mouse model of inherited Alzheimer's disease. The new research, published online in July 2020 in the journal Redox Biology, also revealed that the drug, CMS121, works by changing how brain cells metabolize fatty molecules known as lipids.

"This was a more rigorous test of how well this compound would work in a therapeutic setting than our previous studies on it," says Pamela Maher, a senior staff scientist in the lab of Salk Professor David Schubert and the senior author of the new paper. "Based on the success of this study, we're now beginning to pursue clinical trials."

Over the last few decades, Maher has studied how a chemical called fisetin, found in fruits and vegetables, can improve memory and even prevent Alzheimer's-like disease in mice. More recently, the team synthesized different variants of fisetin and found that one, called CMS121, was especially effective at, improving the animals' memory, and slowing the degeneration of brain cells.

In the new study, Maher and colleagues tested the effect of CMS121 on mice that develop the equivalent of Alzheimer's disease. Maher's team gave a subset of the mice daily doses of CMS121 beginning at 9 months old--the equivalent of middle age in people, and after the mice have already begun to show learning and memory problems. The timing of the lab's treatment is akin to how a patient who visits the doctor for cognitive problems might be treated, the researchers say.

After three months on CMS121, at 12 months old, the mice--both treated and untreated--were given a battery of memory and behavior tests. In both types of tests, mice with Alzheimer's-like disease that had received the drug performed equally well as healthy control animals, while untreated mice with the disease performed more poorly.

To better understand the impact of CMS121, the team compared the levels of different molecules within the brains of the three groups of mice. They discovered that when it came to levels of lipids--fatty molecules that play key roles in cells throughout the body--mice with the disease had several differences compared to both healthy mice and those treated with CMS121. In particular, the researchers pinpointed differences in something known as lipid peroxidation--the degradation of lipids that produces free radical molecules that can go on to cause cell damage. Mice with Alzheimer's-like disease had higher levels of lipid peroxidation than either healthy mice or those treated with CMS121.

"That not only confirmed that lipid peroxidation is altered in Alzheimer's, but that this drug is actually normalizing those changes," says Salk postdoctoral fellow Gamze Ates, first author of the new paper.

The researchers went on to show that CMS121 lowered levels of a lipid-producing molecule called fatty acid synthetase (FASN), which, in turn, lowered levels of lipid peroxidation. When the group analyzed levels of FASN in brain samples from human patients who had died of Alzheimer's, they found that the patients had higher amounts of the FASN protein than similarly aged controls who were cognitively healthy, which suggests FASN could be a drug target for treating Alzheimer's disease.

While the group is pursuing clinical trials, they hope other researchers will explore additional compounds that may treat Alzheimer's by targeting FASN and lipid peroxidation.

"There has been a big struggle in the field right now to find targets to go after," says Maher. "So, identifying a new target in an unbiased way like this is really exciting and opens lots of doors."

NASA's Aqua satellite took images of the Apple Fire as it continued to spread north across the head of the Mill Creek Canyon, and east into the San Gorgonio Wilderness near San Bernardino, Calif. on Aug. 03, 2020. The fire is now burning into more wilderness (where vegetation is sparse) than wooded area limiting the intensity of the fire due to a lack of fuel. Continued fire activity is due to the record low moisture content of the vegetation fuel, high temperatures and low humidity throughout the area. The fire has grown to 26,850 acres and is 15% contained. The smoke from the fire has traveled almost 400 miles south affecting air quality. The smoke from the Apple fire is also commingling with the smoke from the Cassadore Springs and the Blue River 2 fires in Arizona. The cause of the fire which had been under investigation is now listed as "human caused." Several areas around the fire have been evacuated. Contact local officials for more details or go to the Inciweb page for the fire.

NASA's Aqua satellite was able to provide two images of the fire. On the left side of the slider is the true color image of the Apple fire and the right side of the slider shows the corrected reflectance bands that help distinguish the areas of the ground that have been burned. This combination of bands is most useful for distinguishing burn scars from naturally low vegetation or bare soil and enhancing floods. It can also be used to distinguish snow and ice from clouds.

Weather concerns continue in the area. Warm and dry conditions are ongoing with winds gusting to 20 mph. Mid-week the conditions will persist with slightly cooler temperatures and a slight increase in relative humidity.