Culture

New research will help health-care practitioners to more accurately diagnose disease and illness in newborn babies from urine samples, according to a study by researchers at the University of Alberta and the Universidad Autónoma de Zacatecas.

The study examined the chemical composition of urine samples from 48 healthy, full-term newborn babies in the first hours after their birth, helping to establish a baseline for healthy chemical levels. Urine can be used to diagnose and monitor many conditions in infants, including metabolic disorders, genetic diseases, and birth-trauma effects.

"The challenge is that we do not have reference points for healthy ranges of these chemicals in urine for newborn babies," explained David Wishart, professor in the University of Alberta's Department of Biological Sciences, Department of Computing Science, and Department of Laboratory Medicine and Pathology. "As a result, it's hard for doctors or clinical chemists to determine if a newborn is really sick or their chemical concentrations in urine or blood are normal."

The research team, led by Wishart in partnership with Yamile Lopez-Herndandez from the Universidad Autónoma de Zacatecas in Zacatecas, Mexico, used mass spectrometry to measure the concentrations of nearly 140 different chemicals in the babies' urine. The results quantified 86 chemicals that had never been measured in newborn urine before and another 20 chemicals that had never even been measured in human urine before.

"This research is really intended to help doctors and clinical chemists make more informed diagnoses with newborns using urine analysis," explained Wishart. "It provides reference data that every doctor or neonatologist around the world can freely use in order to compare sick newborns with their healthy counterparts."

Researchers at Indiana University School of Medicine have discovered new information about how a dangerous parasite takes control of a patient's cells as it spreads throughout their body, an important finding that could help in the development of new drugs to treat this infection.

"The parasite essentially hijacks these cells, using them as vehicles to get to various organ systems, including the brain," said Leonardo Augusto, PhD, a postdoctoral fellow in the Department of Pharmacology and Toxicology and lead author on the National Institutes of Health-funded study, which was recently published in mBio. "It's like the parasite is taking the wheel of its host cell and using it to spread around the body."

Toxoplasma gondii infects up to one-third of the world's population. People typically become infected with it through exposure to cat feces, which is where it goes through its reproductive phases, or consumption of contaminated food and water. The parasite causes life-threatening issues in some patients because of its ability to disseminate to the brain. In the brain and other tissues, the parasite persists as a latent cyst, waiting to reactivate if immunity should wane, such as what happens in HIV/AIDS patients.

"One of the key problems in battling an infection like Toxoplasma is controlling its spread to other parts of the body," Augusto said. "Upon ingestion of the parasite, it makes its way into immune cells and causes them to move--a behavior called hypermigratory activity. How these parasites cause their infected cells to start migrating is largely unknown."

The team's new research is shedding light on this important clinical question, discovering that the parasite trips an alarm system in its host cell that leads to the activation of a protein called IRE1. IRE1 helps the cell cope with stress, which can involve getting it to move to a different location. In cells infected with Toxoplasma, IRE1 connects to the cytoskeleton, a network of structural proteins that gives the cell its shape and coordinates movement. By engaging this network through IRE1, Toxoplasma takes the wheel and causes hypermigration.

"When we infected host cells that were depleted of IRE1, they could no longer move," Augusto said. "These cells were greatly impaired at disseminating Toxoplasma to the brains of infected mice."

These findings reveal a new mechanism underlying host-pathogen interactions, demonstrating how host cells are co-opted to spread a persistent infection. A better understanding of this pathogen dissemination is helpful in the development of new drugs to curtail the spread of a Toxoplasma gondii infection throughout the body.

New study by researchers from the University of Konstanz, the co-located Max Planck Institute of Animal Behavior (both in Germany) and the University of Texas at Austin finds that groups led by subordinate males outperform those led by dominant and aggressive males

Being the strongest, biggest and most aggressive individual in a group might make you dominant, but it doesn't mean you make all the decisions.

A new study of fish behaviour published in the Proceedings of the National Academy of Sciences shows that dominant individuals can influence a group through force, but passive individuals are far better at bringing a group to consensus. The study, published by an international team from the Max Planck Institute of Animal Behavior, the University of Konstanz and the University of Texas at Austin, overturns assumptions that dominant individuals also have the greatest influence on their groups, and sheds light on the potential of domineering individuals to obstruct effective communication in organisations.

"The same traits that make you powerful in one context can actively reduce your influence in others, especially contexts in which individuals are free to choose who to follow," says senior author Alex Jordan, a group leader at the Max Planck Institute of Animal Behavior and at the University of Konstanz?s Cluster of Excellence "Centre for the Advanced Study of Collective Behaviour".

"Dominant individuals can force their will on the group by being pushy, but that also makes them socially aversive. When it comes to bringing peers to consensus during more sophisticated tasks, it is the least aggressive individuals that exert the greatest influence. Our results illustrate that although domineering individuals most often ascend to positions of power, they can in fact create the least effective influence structures at the same time."

Separating dominance and influence

To disentangle the effects of dominance and influence, the researchers studied groups of a social cichlid fish, Astatotilpia burtoni. "This species form groups with strict social hierarchies, in which dominant males control resources, territory, and space," says Mariana Rodriguez-Santiago, co-first author on the study and a doctoral student in the lab of co-corresponding author Hans Hofmann at UT Austin.

"We ask if the colourful dominant males, which are aggressive, central in their social networks, and control resources, are most influential? Or if drab subordinate males wield the greatest influence, despite being passive, non-territorial, and having little or no control over resources."

The researchers separated the effects of social dominance from social influence by examining how information flows between either dominant or subordinate males and their groups in two different contexts: routine social behaviour, or a more complex social learning task. In the more complex social learning task, dominant or subordinate male fish were trained that a certain coloured light on one side of the tank meant food would soon arrive at that location. These "informed" individuals were then placed into new groups of uninformed individuals and researchers asked which group - those with informed dominant or subordinate males - more quickly learned to associate a coloured light with food.

The cost of being domineering

The researchers observed the movement of the fish and found that in routine social interactions the dominant males exerted the greatest influential by chasing and pushing the group around. But in the more complex task, where influence was not forced on the group, but rather individuals had a choice about who to follow, it was subordinate males who wielded the greatest influence in their social groups. In groups with a subordinate male as demonstrator, fish quickly came to a consensus about which light to follow, moving together as a coherent unit to succeed in the task. With a dominant male as the informant, groups were far slower to reach consensus, if they did at all.

Breaking down behaviour with machine learning

By using additional machine-learning based animal tracking, employing cutting edge techniques developed in the computer sciences, researchers were able to break down the behavioural differences between dominant and subordinate males: dominant males were central in behavioural social networks (they frequently interacted with others) but they occupied peripheral locations in spatial networks (they were avoided by others). The technology provided insights never before available, revealing the mechanisms of influence as well as the outcome.

"By capturing behavioural data that are impossible to be measured with the naked eye, our automated tracking methods revealed that it was not the difference in social position between dominant and subordinate per se, but rather in the way they moved and interacted with others," says co-first author Paul Nührenberg, a doctoral student at the Cluster of Excellence "Centre for the Advanced Study of Collective Behaviour" at the University of Konstanz. "These behavioural differences lead directly to differences in social influence."

Rethinking leadership

This result touches on the evolution of animal societies as well as leadership structures in organisations. "In many societies, whether animal or human, individuals in positions of power all possess a similar suite of traits, which are aggression, intimidation and coercion," says Jordan. "But effective communication requires the presence of a diversity of voices, not just the loudest. Our results from a natural system show that allowing alternative pathways to positions of power may be useful in creating stronger advisory, governmental, and educational structures."

Facts:

A new study of fish behaviour conducted by researchers from the University of Konstanz, the co-located Max Planck Institute of Animal Behavior and the University of Texas at Austin shows that dominant individuals can influence a group through force, but passive individuals are far better at bringing a group to consensus.

Using the social cichlid, Astatotilpia burtoni, which forms strict social hierarchies of dominant and subordinate males, the study separated the effects of social dominance from social influence by examining groups in two different contexts: routine social behaviour, or a more complex social learning task.

The study used additional machine-learning based animal tracking, employing cutting edge techniques developed in the gaming and graphics industries, to break down the behavioural differences between dominant and subordinate males.

Original publication: Mariana Rodriguez-Santiago, Paul Nührenberg, James Derry, Oliver Deussen, Fritz A Francisco, Linda K Garrison , Sylvia F Garza, Hans A Hofmann, Alex Jordan, "Behavioral traits that define social dominance are the same that reduce social influence in a consensus task", Proceedings of the National Academy of Sciences. 16th July 2020 URL: https://www.pnas.org/content/early/2020/07/15/2000158117. DOI: 10.1073/pnas.2000158117

Researchers include scientists from the Cluster of Excellence "Centre for the Advanced Study of Collective Behaviour" at the University of Konstanz and the co-located Max Planck Institute of Animal Behavior in Germany, and the University of Texas at Austin.

Funded by the National Science Foundation BEACON, the DFG Cluster of Excellence 2117 "Centre for the Advanced Study of Collective Behaviour" (ID: 422037984).

Whether they travel only a few metres or tens of kilometres to a new host tree, female pine beetles use different strategies to find success--with major negative consequences for pine trees, according to new research by University of Alberta biologists.

The research, led by graduate student Kelsey Jones, examined the relationship between host colonization success by female mountain pine beetles and the distance travelled to find their new homes.

Since the early 1990s, an outbreak of mountain pine beetles has affected more than 18 million hectares of forest in the western provinces. Understanding the behaviour of these beetles is key in developing management strategies to prevent further damage to Alberta's boreal forest.

"It is hard to predict the continued invasion by the mountain pine beetle using information from this study alone," said Jones. "However, our work does indicate that beetles which fly for long distances can still call in many fellow beetles to mass attack trees. This indicates that, as beetles move further eastward and forest stands become thinner, they will likely still have the capacity to colonize hosts."

Some beetles fly distances more than 30 kilometres while others stay close to home, traveling no more than two metres away to find a new host tree. But this study shows that beetles may have different strategies for success that are based on the distance of an individual's dispersal flights.

"Both long and short-distance flight strategies are beneficial to mountain pine beetle host colonization in different ways," explained Jones, who completed her master's under the supervision of Maya Evenden, professor in theDepartment of Biological Sciences. "As short- and long-distance flyers successfully colonize host trees for reproduction, both strategies will remain in the population, maintaining genetic variability."

The study showed that female pine beetles who travel long distances tended to lose weight, but were able to produce the most pheromone, signalling their arrival to other beetles and therefore increasing their chances of attracting beetles from distant populations to facilitate mass attack of tree hosts. On the other hand, beetles who stuck close to home lost the least amount of weight, but also produced the smallest amount of pheromone, instead focusing their energy on host colonization.

Excessive pricing or 'price gouging' of essential hygiene and medical products during the current global pandemic could be prevented, claims a new paper from the University of Portsmouth.

The research paper, by law lecturer Dr Penny Giosa, informs academic and policy debate about excessive pricing due to Covid-19.

'Price gouging' is when businesses heavily inflate prices of products that are in high-demand. Some sellers have taken advantage of the global health crisis by increasing their prices in order to profit. This obviously has a hugely negative impact on the consumer.

Dr Giosa said: "Inflating the prices of essential items is unfair and exploitative during a global crisis. Some sellers have raised prices on items that are needed for safety, which is shocking."

Dr Giosa's work explores the provision of EU competition law, which the National Competition Authorities (NCAs) and the European Commission could enforce against excessive pricing.

The paper also investigates whether EU Member States should rely on price regulations in order to cap the wholesale and retail prices of some high-demand products due to the coronavirus pandemic.

Dr Giosa argues that imposing fines on companies that charge over the odds isn't an appropriate solution because there is no guarantee that prices won't rise again in future. Moreover, it would be very expensive for the NCAs to monitor the effectiveness of the fines resetting the prices to a 'non-excessive' level.

She argues that it would be more effective for NCAs and the European Commission to seek commitment from companies guilty of price-hiking, to discontinue their anti-competitive conduct and agree to set lower prices in future.

The article also makes a case for the application of price controls.

The free formation of prices does not always guarantee socially desirable outcomes, Dr Giosa said, "for instance in the exceptional case of emergency needs, companies may set excessive prices for necessary goods essential to consumers' continued health.

"In the case of Covid-19, facemasks are an explicit example. While in the long-run high prices should boost their supply, in the short-run there may be problems, like health workers in heavily affected countries being outbid by fearful private individuals in other countries who have a low risk of infection but high incomes."

This may result in a transfer of wealth from consumers to suppliers as well as in a reduction in total welfare to society, especially when excessive pricing regards goods necessary for public health and welfare, such as medical supplies and fuel.

With no cap on pricing, inflated prices are unlikely to disappear or reduce within a reasonable timeframe because new companies' ability to enter the market or expand production is affected.

Dr Giosa continued: "The severe economic turmoil that Covid-19 has caused means that the necessary finance for expansion of firms becomes harder to secure. Excessive prices are not self-correcting, because in the majority of cases excessive prices do not attract new entry of viable competitors, whether entry barriers into the market are high or low and whether potential entrants are informed about the incumbent firms' relative efficiency."

Astronomers studying galaxy evolution have long struggled to understand what causes star formation to shut down in massive galaxies. Although many theories have been proposed to explain this process, known as "quenching," there is still no consensus on a satisfactory model.

Now, an international team led by Sandra Faber, professor emerita of astronomy and astrophysics at UC Santa Cruz, has proposed a new model that successfully explains a wide range of observations about galaxy structure, supermassive black holes, and the quenching of star formation. The researchers presented their findings in a paper published July 1 in the Astrophysical Journal.

The model supports one of the leading ideas about quenching which attributes it to black hole "feedback," the energy released into a galaxy and its surroundings from a central supermassive black hole as matter falls into the black hole and feeds its growth. This energetic feedback heats, ejects, or otherwise disrupts the galaxy's gas supply, preventing the infall of gas from the galaxy's halo to feed star formation.

"The idea is that in star-forming galaxies, the central black hole is like a parasite that ultimately grows and kills the host," Faber explained. "That's been said before, but we haven't had clear rules to say when a black hole is big enough to shut down star formation in its host galaxy, and now we have quantitative rules that actually work to explain our observations."

The basic idea involves the relationship between the mass of the stars in a galaxy (stellar mass), how spread out those stars are (the galaxy's radius), and the mass of the central black hole. For star-forming galaxies with a given stellar mass, the density of stars in the center of the galaxy correlates with the radius of the galaxy so that galaxies with bigger radii have lower central stellar densities. Assuming that the mass of the central black hole scales with the central stellar density, star-forming galaxies with larger radii (at a given stellar mass) will have lower black-hole masses.

What that means, Faber explained, is that larger galaxies (those with larger radii for a given stellar mass) have to evolve further and build up a higher stellar mass before their central black holes can grow large enough to quench star formation. Thus, small-radius galaxies quench at lower masses than large-radius galaxies.

"That is the new insight, that if galaxies with large radii have smaller black holes at a given stellar mass, and if black hole feedback is important for quenching, then large-radius galaxies have to evolve further," she said. "If you put together all these assumptions, amazingly, you can reproduce a large number of observed trends in the structural properties of galaxies."

This explains, for example, why more massive quenched galaxies have higher central stellar densities, larger radii, and larger central black holes.

Based on this model, the researchers concluded that quenching begins when the total energy emitted from the black hole is approximately four times the gravitational binding energy of the gas in the galactic halo. The binding energy refers to the gravitational force that holds the gas within the halo of dark matter enveloping the galaxy. Quenching is complete when the total energy emitted from the black hole is twenty times the binding energy of the gas in the galactic halo.

Faber emphasized that the model does not yet explain in detail the physical mechanisms involved in the quenching of star formation. "The key physical processes that this simple theory evokes are not yet understood," she said. "The virtue of this, though, is that having simple rules for each step in the process challenges theorists to come up with physical mechanisms that explain each step."

Astronomers are accustomed to thinking in terms of diagrams that plot the relations between different properties of galaxies and show how they change over time. These diagrams reveal the dramatic differences in structure between star-forming and quenched galaxies and the sharp boundaries between them. Because star formation emits a lot of light at the blue end of the color spectrum, astronomers refer to "blue" star-forming galaxies, "red" quiescent galaxies, and the "green valley" as the transition between them. Which stage a galaxy is in is revealed by its star formation rate.

One of the study's conclusions is that the growth rate of black holes must change as galaxies evolve from one stage to the next. The observational evidence suggests that most of the black hole growth occurs in the green valley when galaxies are beginning to quench.

"The black hole seems to be unleashed just as star formation slows down," Faber said. "This was a revelation, because it explains why black hole masses in star-forming galaxies follow one scaling law, while black holes in quenched galaxies follow another scaling law. That makes sense if black hole mass grows rapidly while in the green valley."

Faber and her collaborators have been discussing these issues for many years. Since 2010, Faber has co-led a major Hubble Space Telescope galaxy survey program (CANDELS, the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey), which produced the data used in this study. In analyzing the CANDELS data, she has worked closely with a team led by Joel Primack, UCSC professor emeritus of physics, which developed the Bolshoi cosmological simulation of the evolution of the dark matter halos in which galaxies form. These halos provide the scaffolding on which the theory builds the early star-forming phase of galaxy evolution before quenching.

The central ideas in the paper emerged from analyses of CANDELS data and first struck Faber about four years ago. "It suddenly leaped out at me, and I realized if we put all these things together--if galaxies had a simple trajectory in radius versus mass, and if black hole energy needs to overcome halo binding energy--it can explain all these slanted boundaries in the structural diagrams of galaxies," she said.

At the time, Faber was making frequent trips to China, where she has been involved in research collaborations and other activities. She was a visiting professor at Shanghai Normal University, where she met first author Zhu Chen. Chen came to UC Santa Cruz in 2017 as a visiting researcher and began working with Faber to develop these ideas about galaxy quenching.

"She is mathematically very good, better than me, and she did all of the calculations for this paper," Faber said.

Faber also credited her longtime collaborator David Koo, UCSC professor emeritus of astronomy and astrophysics, for first focusing attention on the central densities of galaxies as a key to the growth of central black holes.

Among the puzzles explained by this new model is a striking difference between our Milky Way galaxy and its very similar neighbor Andromeda. "The Milky Way and Andromeda have almost the same stellar mass, but Andromeda's black hole is almost 50 times bigger than the Milky Way's," Faber said. "The idea that black holes grow a lot in the green valley goes a long way toward explaining this mystery. The Milky Way is just entering the green valley and its black hole is still small, whereas Andromeda is just exiting so its black hole has grown much bigger, and it is also more quenched than the Milky Way."

Recent studies indicate HIV infection heightens the risk of dental cavities - but a Rutgers researcher has found evidence that the risk of cavities comes not from HIV itself but from a weakened immune system, which could be caused by other diseases.

Modupe Coker, an epidemiologist and professor in Rutgers School of Dental Medicine's Department of Oral Biology, studies the link between dental cavities and HIV, including a high rate of children who were infected in the womb. Her research, published in Scientific Reports, sampled a total of nearly 300 children from three groups: children who have been HIV-positive since birth and whose mothers are HIV positive; HIV-negative children of HIV-positive mothers; and HIV-negative children of HIV-negative mothers.

Using blood samples, Coker measured levels of white blood cell, which indicate immunity strength. She found that for HIV-positive children whose immunity levels were normal, often due to successful antiviral treatment, the prevalence of cavities was lower. HIV-negative children with weakened immune systems, either due to malaria or other underlying conditions, were more likely to have cavities.

The findings were a surprise to Coker, given previous assumptions about HIV and dental disease. "It debunked our hypothesis but it's very exciting as it raises new ones,'' she said. "HIV infection alone might not be a significant risk factor, which was the assumption. Even though HIV kills immune cells, many children on therapy do well HIV infection alone isn't enough to suggest an increased risk for cavities. Immune status, function and competency play much bigger role.''

Coker also observed microbial differences in HIV-negative children with HIV-positive mothers. "These children looked more like the HIV-infected children early in life but later on, as they grow older, began to look like their unexposed counterparts with respect to the oral microbiota,'' she said.

Coker hopes to use her work involving dental cavities to explore genetics from a broader perspective. Her research is part of a study that examines other aspects of the microbiome in HIV-exposed or infected children, including its relationship to bacterial plaque and candida, a fungal infection that often appears in the mouth.

Korea Brain Research Institute (KBRI headed by Suh Pann-ghill) announced the discovery of the elevation of Ace2 as a SARS-CoV-2 entry receptor gene expression in elderly patients with Alzheimer's by Dr. Joo Jae-yeol and Dr. Lim Key-hwan.

The research results were published in the online version of the Journal of Infection dated June 30, and the title and authors of the paper are as follows.

*Title: Elevation of Ace2 as a SARS-CoV-2 entry receptor gene expression in Alzheimer's disease

*Author: Key-Hwan Lim(1st Author), Sumin Yang, Sung-Hyun Kim, Jae-Yeol Joo(Corresponding Author)

The novel coronavirus (SARS-CoV-2), which has put great strain on the world with the unprecedented scale of its spread, is reportedly hitting the elderly in their 70s and older the most dangerous. Especially, recent reports shown that older people who have chronic comorbidities such as chronic obstructive pulmonary has high mortality rate.

As such, KBRI's research team investigated the risk of SARS-CoV-2 infection in patients with Alzheimer's dementia through micro array data-set and total RNA sequencing (RNA-seq) in terms of perspective of brain disease.

The research team analyzed ACE2 gene expression through Big Data containing the brain tissue and blood genomic information of elderly patients with Alzheimer's disease and genome-wide association study and transcriptome analysis (RNA-seq). The research team discovered that the expression of the ACE2* gene, which is a SARS-CoV-2 binding protein for cell entry, is elevated in the elderly with Alzheimer's disease groups compared to the elderly not suffering from the disease, while also confirming the same change in the brain tissue of the Alzheimer's disease model mice.

*ACE2: Angiotensin-converting enzyme 2 used by the novel coronavirus as an entry receptor to penetrate the human cell

Based on the genome analysis of Alzheimer's disease patient groups with early-stage, mild, and severe, it was identified that ACE2 gene expression was gradually elevated along with the development of Alzheimer's disease. That means, as ACE2 helps SARS-CoV-2 penetrate the human cell, its greater elevation can lead to greater infection risk.

This study is significant in that it newly highlighted the interrelation between Alzheimer's disease and SARS-CoV-2 and proved the higher vulnerability of elderly Alzheimer's patients than the elderly without Alzheimer's. The results of this study are expected to be utilized as a new diagnosis method for the elderly with underlying degenerative brain diseases.

Dr. Joo Jae-yeol, who led this study, said, "We are happy to be able to provide new information on the prevention of the transmission of the novel coronavirus as the national government-run research institute specializing in brain research. We advise that elderly patients with Alzheimer's take extra care for infection prevention and control of the novel coronavirus and that our society pay special attention to such patients."

The research team has also discovered the Ube2h gene, which specifically elevates in Alzheimer's disease patient blood, early this year and has continually proposed diverse methods of Alzheimer's disease diagnosis and prevention of the transmission of the novel coronavirus based on follow-up studies.

This research was conducted as a KBRI in-house project supported by the Ministry of Science and ICT (MSIT), the Basic Research Program of the National Research Foundation of Korea (NRF).

It seems the universe has an odd sense of humor. While a crown-encrusted virus has run roughshod over the world, another entirely different corona about 100 million light years from Earth has mysteriously disappeared.

For the first time, astronomers at MIT and elsewhere have watched as a supermassive black hole's own corona, the ultrabright, billion-degree ring of high-energy particles that encircles a black hole's event horizon, was abruptly destroyed.

The cause of this dramatic transformation is unclear, though the researchers guess that the source of the calamity may have been a star caught in the black hole's gravitational pull. Like a pebble tossed into a gearbox, the star may have ricocheted through the black hole's disk of swirling material, causing everything in the vicinity, including the corona's high-energy particles, to suddenly plummet into the black hole.

The result, as the astronomers observed, was a precipitous and surprising drop in the black hole's brightness, by a factor of 10,000, in under just one year.

"We expect that luminosity changes this big should vary on timescales of many thousands to millions of years," says Erin Kara, assistant professor of physics at MIT. "But in this object, we saw it change by 10,000 over a year, and it even changed by a factor of 100 in eight hours, which is just totally unheard of and really mind-boggling."

Following the corona's disappearance, astronomers continued to watch as the black hole began to slowly pull together material from its outer edges to reform its swirling accretion disk, which in turn began to spin up high-energy X-rays close to the black hole's event horizon. In this way, in just a few months, the black hole was able to generate a new corona, almost back to its original luminosity.

"This seems to be the first time we've ever seen a corona first of all disappear, but then also rebuild itself, and we're watching this in real-time," Kara says. "This will be really important to understanding how a black hole's corona is heated and powered in the first place."

Kara and her co-authors, including lead author Claudio Ricci of Universidad Diego Portales in Santiago, Chile, have published their findings today in Astrophysical Journal Letters. Co-authors from MIT include Ron Remillard, and Dheeraj Pasham.

A nimble washing machine

In March 2018, an unexpected burst lit up the view of ASSASN, the All-Sky Automated Survey for Super-Novae, that surveys the entire night sky for supernova activity. The survey recorded a flash from 1ES 1927+654, an active galactic nucleus, or AGN, that is a type of supermassive black hole with higher-than-normal brightness at the center of a galaxy. ASSASN observed that the object's brightness jumped to about 40 times its normal luminosity.

"This was an AGN that we sort of knew about, but it wasn't very special," Kara says. "Then they noticed that this run-of-the-mill AGN became suddenly bright, which got our attention, and we started pointing lots of other telescopes in lots of other wavelengths to look at it."

The team used multiple telescopes to observe the black hole in the X-ray, optical, and ultraviolet wave bands. Most of these telescopes were pointed at the the black hole periodically, for example recording observations for an entire day, every six months. The team also watched the black hole daily with NASA's NICER, a much smaller X-ray telescope, that is installed aboard the International Space Station, with detectors developed and built by researchers at MIT.

"NICER is great because it's so nimble," Kara says. "It's this little washing machine bouncing around the ISS, and it can collect a ton of X-ray photons. Every day, NICER could take a quick little look at this AGN, then go off and do something else."

With frequent observations, the researchers were able to catch the black hole as it precipitously dropped in brightness, in virtually all the wave bands they measured, and especially in the high-energy X-ray band -- an observation that signaled that the black hole's corona had completely and suddenly vaporized.

"After ASSASN saw it go through this huge crazy outburst, we watched as the corona disappeared," Kara recalls. "It became undetectable, which we have never seen before."

A jolting flash

Physicists are unsure exactly what causes a corona to form, but they believe it has something to do with the configuration of magnetic field lines that run through a black hole's accretion disk. At the outer regions of a black hole's swirling disk of material, magnetic field lines are more or less in a straightforward configuration. Closer in, and especially near the event horizon, material circles with more energy, in a way that may cause magnetic field lines to twist and break, then reconnect. This tangle of magnetic energy could spin up particles swirling close to the black hole, to the level of high-energy X-rays, forming the crown-like corona that encircles the black hole.

Kara and her colleagues believe that if a wayward star was indeed the culprit in the corona's disappearance, it would have first been shredded apart by the black hole's gravitational pull, scattering stellar debris across the accretion disk. This may have caused the temporary flash in brightness that ASSASN captured. This "tidal disruption," as astronomers call such a jolting event, would have triggered much of the material in the disk to suddenly fall into the black hole. It also might have thrown the disk's magnetic field lines out of whack in a way that it could no longer generate and support a high-energy corona.

This last point is a potentially important one for understanding how coronas first form. Depending on the mass of a black hole, there is a certain radius within which a star will most certainly be pulled in by a black hole's gravity.

"What that tells us is that, if all the action is happening within that tidal disruption radius, that means the magnetic field configuration that's supporting the corona must be within that radius," Kara says. "Which means that, for any normal corona, the magnetic fields within that radius are what's responsible for creating a corona."

The researchers calculated that if a star indeed was the cause of the black hole's missing corona, and if a corona were to form in a supermassive black hole of similar size, it would do so within a radius of about 4 light minutes -- a distance that roughly translates to about 75 million kilometers from the black hole's center.

"With the caveat that this event happened from a stellar tidal disruption, this would be some of the strictest constraints we have on where the corona must exist," Kara says.

The corona has since reformed, lighting up in high-energy X-rays which the team was also able to observe. It's not as bright as it once was, but the researchers are continuing to monitor it, though less frequently, to see what more this system has in store.

"We want to keep an eye on it," Kara says. "It's still in this unusual high-flux state, and maybe it'll do something crazy again, so we don't want to miss that."

This research was funded, in part, by NASA.

COLUMBUS, Ohio -- A new proof-of-concept study reports evidence that a new testing method has the potential to rapidly identify radiation sickness based on biomarkers measured through a single drop of blood. Scientists at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) say the test could help save lives through early and real-time identification of the condition to enable timely clinical interventions.

Radiation sickness, or acute radiation syndrome (ARS), is a condition caused by irradiation of major volume or the entire body by a high dose of penetrating radiation in a very short time period - usually a matter of minutes. Historically, this has been most relevant through accidental exposures or mass casualty radiologic events, like the ones witnessed in Hiroshima and Nagasaki during World War II or even a reactor accident such as the one at Chernobyl in 1986.

The condition can rapidly weaken a person through its side effects and lead to death without intervention. The current diagnostic test ¬- a dicentric chromosome assay - requires three to four days to get results. ARS most often impacts the bone marrow and gastrointestinal systems early while the debilitating effects on pulmonary, cardiovascular and central nervous systems can be delayed. Death can occur in a matter of days for the most severe cases, but most patients die within several months of exposure. Rapid identification of exposure levels is critical for responding and triaging patient treatments.

"This new test uses a single drop of blood - collected from a simple finger prick - and results are ready in a few hours. It is rapid, scalable and can serve as a point-of-care-type diagnostic tool for real-time evaluation to screen a large number of individuals in a short time," says Naduparambil K. Jacob, PhD, an associate professor and scientist in the OSUCCC - James Translational Research Program.

For this test, researchers compare the relative expression of two small molecules called microRNAs in the blood. The first is microRNA-150 ¬- which Jacob's lab identified several years ago as a biomarker to measure the extent of bone marrow damage. This microRNA decreases as a function of radiation dose while the normalizer, called microRNA-23a, does not change. Comparing these two molecular measures allows scientists to quantify the actual radiation dose absorbed, and therefore the overall exposure risk.

"We measure ionizing radiation in grays. People who are exposed to two gray need to be identified and treated and it is predicted that if you are exposed to about four gray to the whole body, without timely treatment there is a 50 percent chance of survival," says Jacob.

He noted this tool would have critical relevance in responding to mass casualty disaster scenario like that Chernobyl, to identify at-risk military personnel and civilians who need immediate treatment. It also has relevance for cancer patients, especially bone marrow transplant patients and others who have intense radiation therapy, where overdosing as well as underdosing is of concern.

"Some patients develop major issues like thrombocytopenia and neutropenia as the result of radiation treatment. We can't look at a patient and determine how much radiation he or she has absorbed - but the impact can be cumulative. As a result, radiation sickness could occur weeks or months after the radiation therapy," explains Jacob. "With additional research, this new testing method could potentially help oncologists measure - in real time - absorbed radiation and intervene before radiation sickness occurs."

HOUSTON - (July 15, 2020) - Biomolecular engineers at Rice University have found a C-worthy technique that dramatically enhances the accuracy of gene editing.

The Rice lab of biomolecular engineer Xue Sherry Gao has introduced a set of tools that increase the accuracy of CRISPR-based edits in disease sequence models up to 6,000-fold compared with a current base editor, BE4max, that is considered state-of-the-art.

The work appears in the open-access journal Science Advances.

Cytosine base editors are able to convert cytosines (C) to thymines (T) in the human genome, which consists of three billion Cs, Ts, As (adenine) and Gs (guanine). The base pairs of C-G and A-T encode the genetic information in DNA. Even one incorrect base in the human genome -- a mutation -- can lead to genetic diseases.

"T-to-C mutations called single nucleotide polymorphisms account for somewhere around 38% of human pathogenic diseases," Gao said. "Cytosine base editors provide great promise to potentially treat these diseases by reversing the C mutation back to T.

"However, when there is a 'bystander' C located right upstream of the targeted C, the previous technology could not distinguish between the Cs, and both would be changed to Ts," she said. "We really only want to correct the disease-relevant C to a T and leave the bystander C unmodified.

"That provided the motivation for this project," Gao said. "We want to engineer a new cytosine base editor that can precisely modify the single targeted C while minimizing the unwanted C editing when consecutive 'CCs' are positioned in the editing window."

The Gao lab seeks to develop base editors through a series of protein-engineering efforts. The new cytosine base editors, called A3G-BEs, have dramatically increased precision by only editing the second of consecutive Cs.

To put their tests in "disease-relevant contexts," the Gao lab used their tools to modify human cells to create cystic fibrosis and several other disease model cell lines. All showed significant success at precisely creating the desired pathogenic C-to-T mutation, particularly the cystic fibrosis cells, which all three of the A3G-BE variants perfectly modified more than 50% of the time compared to 0.6% for BE4max.

The Gao lab also tested its new A3G-BEs' potential to correct mutations in disease treatment applications, including cystic fibrosis, holocarboxylase synthetase deficiency and pyropoikilocytosis, a type of anemia.

In experiments on cell models containing pathogenetic mutations, A3G-BEs significantly outperformed BE4max. In the case of holocarboxylase synthetase deficiency, the editor perfectly corrected only the target C nucleotides in more than 50% of the sequences, with a 6,496-fold higher correction than BE4max.

"We also identified 540 human pathogenic single nucleotide polymorphisms that could be precisely correctable by our A3G-BEs," Gao said. "A3G-BE also appears to decrease off-target edits (unwanted edits to other parts of the genome that could introduce mutations) at both the DNA and RNA levels." Decreasing off-targets has been a prime goal of CRISPR research.

"There are three billion base pairs in humans," she said. "I believe this technology's level of precision is going to be a significant contributor toward treating genetic disease."

When NASA's Aqua satellite passed over the Eastern Pacific Ocean, it gathered water vapor data on Tropical Depression 06E that showed it had opened up into a trough. A trough is an elongated area of low pressure.

On July 14 at 4:50 p.m. EDT (2050 UTC), NASA's Aqua satellite passed over the remnants of Tropical Depression 06E. The Moderate Resolution Imaging Spectroradiometer or MODIS instrument aboard Aqua gathered the water vapor content and temperature information. MODIS found minimal concentrations of water vapor and the circulation had opened up into a trough.

Water vapor analysis of tropical cyclones tells forecasters how much potential a storm has to develop. Water vapor releases latent heat as it condenses into liquid. That liquid becomes clouds and thunderstorms that make up a tropical cyclone. Temperature is important when trying to understand how strong storms can be. The higher the cloud tops, the colder and stronger the storms. TD6E showed very limited water vapor.

At 5 p.m. EDT on July 14, the National Hurricane Center (NHC) said a satellite overpass "indicated that the circulation of the tropical depression was no longer closed with light and variable winds evident on its south side. Therefore, the system no longer meets the criteria of a tropical cyclone."

At 5 p.m. EDT (2100 UTC) on July 14, NHC issued their final advisory on Tropical Depression 06E. At that time, the remnants of 06E were located near latitude 18.2 degrees north and longitude 118.0 degrees west, about 615 miles (990 km) west-southwest of the southern tip of Baja California, Mexico. The remnants were moving toward the west near 17 mph (28 kph). Maximum sustained winds were near 30 mph (45 kph) and waning. The estimated minimum central pressure is 1008 millibars.

The remnants were producing a very limited amount of shower activity. The NHC said that associated convection could pulse up and down for another day until the trough moves over cooler waters.

NASA's Aqua satellite is one in a fleet of NASA satellites that provide data for hurricane research.

Tropical cyclones/hurricanes are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

A brief reading and writing exercise designed to alleviate worries about sense of belonging helped students at a midwestern broad-access public university with a high Hispanic population stay in school, raising continuous enrollment over 2 years by 9% among socially disadvantaged students, according to a new study. The findings suggest that social belonging interventions may decrease dropout rates at broad-access institutions, which accept more than 75% of applicants and serve many first-generation college students and racial and ethnic minority students. Although broad-access institutions provide valuable educational opportunities for disadvantaged groups, they are also plagued by low graduation rates. To investigate whether concerns about belonging (combined with financial constraints and lower levels of academic preparedness) may undermine student success at these institutions, Mary Murphy and colleagues tested the impact of a customized reading and writing exercise administered to 1,063 first-year students. While similar exercises have been tested at more selective universities with high admission standards, past assessments have tended not to focus on broad-access institutions. In addition to keeping students in school, the researchers determined that that the exercise helped disadvantaged students' GPAs to increase by 0.19 points in the semester following their participation in the exercise. Murphy et al. note that more information is needed about the specific educational contexts in which similar interventions would be conducted in order to better assess their effectiveness.

In another study, researchers demonstrated that data from 30 community and technical colleges across Washington state illustrate the same "shape" of educational inequality despite each cohort's individual differences - each institution shared the same exponential distribution of students who earn a given number of college credits. Based on these findings, Christopher Quarles and colleagues conclude that "student capital," which includes factors that a student attains from their parents, mentors, and friends to help build their capacity to succeed in school, is a finite resource within a given population - unlike intelligence, which can be built up over time. As a result, poorer and less educated populations have fewer of the resources necessary for aspiring college students to gather the social and academic skills as well as the economic resources they need to succeed. The findings suggest future student success intervention designs may work best when they build up the resources and skills that students need to succeed in college. "Social psychological interventions, done well, can provide one form of student capital to students, by giving them the mindsets that will help them succeed," Quarles added.

The so-called "love hormone" or "cuddle hormone" oxytocin is not only involved in strengthening the mother-child relationship and regulating social bonding. It also plays an important role in different mental health disorders like autism, Asperger's syndrome, social anxiety or addiction vulnerability. Furthermore, oxytocin starts labor, the birth process, and features in many aspects of sexual reproduction - as well as corresponding disorders. The hormone exerts all these effects by binding to the oxytocin receptor. Substances that target the oxytocin receptor thus have great therapeutic potential for a variety of diseases.

New drugs are difficult to develop

Since its discovery nearly 30 years ago, researchers have tried to develop drugs that bind specifically to the oxytocin receptor. However, conducting such experiments proved to be very difficult. Except for the hormone oxytocin itself, hardly any drug targeting the oxytocin receptor has been approved for clinical use. A team led by Andreas Plückthun, professor at the Department of Biochemistry of the University of Zurich (UZH), has now determined the detailed three-dimensional structure of the oxytocin receptor bound to the drug candidate retosiban, which was developed for the suppression of preterm labor.

"The elucidation of the oxytocin receptor's structure was an extremely challenging undertaking, which only succeeded thanks to a combination of directed evolution and protein engineering methods we developed over the last few years," says Plückthun. "Understanding the exact three-dimensional interaction of retosiban and the oxytocin receptor at the atomic level serves as the blueprint for developing new therapeutics that regulate the receptor's functioning."

Improved understanding of receptor mechanism

The scientists also made an additional discovery. "To allow efficient propagation of oxytocin-induced signaling, the oxytocin receptor has to interact with two additional substances - cholesterol and magnesium," says PhD candidate Yann Waltenspühl. Determining the exact receptor shape enabled the researchers to identify interaction regions for both of these substances. "The identification of these previously unknown regions fundamentally improves the understanding of the receptor mechanism," adds the first author of the study.

Boosting the development of new therapeutics for other diseases

The new findings might also be directly applicable to the very closely related vasopressin receptors. The hormone vasopressin controls the water content of body fluids and the blood pressure, and its receptors are therefore drug targets for the treatment of many diseases - from kidney disease to heart failure. Just like the oxytocin receptor, the vasopressin receptors have also been implicated in autism spectrum disorders. "Our work could thus boost the development of new drugs for a very broad range of widespread and severe human diseases," concludes Andreas Plückthun.

A new finger-stick test can use a single drop of blood to quickly estimate how much harmful radiation mice have been exposed to, according to a study. The test, which could sniff out radiation doses from hours to 1 week after exposure, could potentially address the need for a rapid and workable test to estimate radiation exposure in people after high-risk radiological events. Acute radiation syndrome is a dangerous condition that occurs when someone has been exposed to large amounts of radiation in a short period of time, usually in situations involving a nuclear reactor breakdown or the detonation of a nuclear device. Patients with acute radiation syndrome must be quickly diagnosed and treated to achieve the best clinical outcomes, as radiation exposure rapidly damages sensitive organs such as the gut and lungs. However, there are currently no FDA-approved tests that can feasibly estimate radiation doses by looking at biomarkers in blood or tissues. Marshleen Yadav and colleagues devised a new test that takes a single drop of blood and measures changes in the quantity of two microRNAs, one of which is secreted by radiation-sensitive circulating immune cells. First, the authors studied serum samples from patients with leukemia who had been exposed to radiation, and confirmed that concentrations of one of the microRNAs consistently dropped after radiation exposure. Yadav et al. then exposed mice to various doses of radiation and observed that their test could estimate doses of both gamma rays and neutrons (simulating exposure to an improvised nuclear device) from 6 hours to 7 days after exposure. The test also distinguished mice exposed to 2 Grays of radiation - considered the minimum dose that requires triage in radiological events - suggesting the approach may be especially useful for patients who have not yet begun to show symptoms.