Culture

A specific region of messenger RNAs, the 3' untranslated region (3'UTR), plays an important role for cells to function properly. During embryonic development, 3'UTRs in hundreds of RNAs lengthen exclusively in neurons, which is crucial for the cells of the brain to function properly. The lab of Valérie Hilgers at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg was now able to show that in Drosophila, an elegant and robust mechanism secures this process of 3'UTR extension. In their newest study they describe for the first time a hierarchical mechanism of take-over of function starting from the protein ELAV as a Master Regulator of neuronal transcript signatures, with a second-in-command protein FNE that is only activated if the Master is absent.

Neurons, also known as nerve cells, send and receive signals in our brain. They are particularly complex and unique in many aspects: Neurons do not divide or regenerate like many other cell types, and they can be excitatory, inhibitory or modulatory in their effect and motor, sensory or secretory in their function.

RNA molecules play an important role in making sure that neurons function properly. Nearly every known neurological or neurodegenerative disease in humans is associated with the malfunction of RNA regulation. During gene expression, messenger RNA molecules (mRNAs) are transcribed from the DNA and are later translated into a protein. But RNA is not simply the intermediate between DNA and protein.
RNA has important regulatory roles

Several regions of the mRNA molecule are not translated into a protein, for example the 3' untranslated region (3'UTR) that immediately follows the protein-coding region of the mRNA after the stop codon. Interestingly, the 3'UTR has a lot of regulatory roles on its own. For example, it can determine when and where a gene is active, dictates where in the cell a protein finds its place, and plays a particular role in synapse formation and maintenance of memory.

A unique RNA mechanism, which was discovered only a decade ago, distinguishes the nerve cells from all other cells: the addition of a long stretch of non-coding sequence to many mRNAs. This phenomenon, termed "3'UTR extension", is of crucial importance for neurons to maintain their unique identity, and to function properly.

The lab of Valérie Hilgers at the MPI of Immunobiology and Epigenetics in Freiburg focuses on this distinctive RNA processing mechanism. In previous work from the lab, it was found that in Drosophila, the protein ELAV is important for promoting 3'UTR extension in neurons. In this study, the team set out to learn more about ELAV.

ELAV as Master regulator of neuron biology

It turned out that ELAV is a so-called "Master regulator". In Biology, Master regulators are proteins that are deemed responsible for the control of a whole regulatory program of the cell. Thus, they are in charge of important, transformative events, on their own. Without them, the transformative event cannot take place. Relying on one single effector for such important tasks puts the cell at risk; this is why usually, several proteins share the work in biological systems.

But the scientists found an unusual system of robustness that ensures the formation and maintenance of neuronal transcript signatures in Drosophila. "Under normal conditions, ELAV acts as a Master regulator and single-handedly mediates 3'UTR extension. Interestingly, it also represses the expression of the exon of another gene of the same family called FNE. But if we put the system under stress by mutating ELAV, we could show that a new, activated form of FNE is expressed, which translocates into the nucleus to perform the function of ELAV in its absence," says Judit Carrasco, first author of the study.
EXAR mechanism manages succession

The team termed this hitherto unknown mechanism EXAR (EXon-Activated Rescue). "Considering the importance of "3'UTR extension" for the proper functioning of neurons, it makes sense to use such a robust mechanism, where succession is clearly defined", says Valérie Hilgers, who is also member of CIBSS - Centre for Integrative Biological Signalling Studies, Cluster of Excellence at the University of Freiburg.

This new insight into ELAV and the EXAR mechanism is a promising avenue for future research. ELAV is one of the best-conserved proteins in animals; it is found in every nerve cell of every animal. In humans, for instance, ELAV proteins are involved in numerous neurological diseases. The concrete mechanisms of how ELAV influences the health of neurons are not quite clear yet. The Hilgers lab in Freiburg wants to understand how ELAV proteins act on RNA to keep a neuron healthy.

The sign of a healthy personal relationship is one that is equally mutual - where you get out just as much as you put in. Nature has its own version of a healthy relationship. Known as mutualisms, they are interactions between species that are mutually beneficial for each species. One example is the interaction between plants and pollinators, where your apple trees are pollinated and the honeybee gets nectar as a food reward. But what makes these mutualisms persist in nature? If rewards like nectar are offered freely, does this make mutualisms more susceptible to other organisms that take those rewards without providing a service in return?

A team of researchers from the College of Arts and Sciences at Syracuse University, including co-principal investigators Kari Segraves, professor of biology, and David Althoff, associate professor of biology, along with postdoctoral researcher Mayra Vidal, former research assistant professor David Rivers, and Sheng Wang '20 Ph.D., recently researched that question and the results have been published in this month's edition of the prestigious journal Science.

They investigated the abilities of simple versus diverse communities of mutualists, comparing how each deal with cheaters. Cheaters are species that steal the benefits of the mutualism without providing anything in return. An example of one of nature's cheaters are nectar robbers. Nectar-robbing bees chew through the side of flowers to feed on nectar without coming into contact with the flower parts that would result in pollination.

The research team wanted to test if having multiple mutualists with similar roles allows the community as a whole to persist when cheaters take away the mutualists' resources. The idea was to examine whether having more species involved in a mutualism, such as many pollinator species interacting with many different plant species, made the mutualism less susceptible to the negative effects of cheaters. They also wanted to analyze whether increasing the number of mutualist species allowed all the mutualists to persist or if competition would whittle down the number of mutualists species over time. In essence, the team wanted to understand the forces governing large networks of mutualists that occur in nature.

A&S researchers tested their ideas by producing mutualisms in the lab using yeast strains that function as mutualistic species. These strains were genetically engineered to trade essential food resources. Each strain produced a food resource to exchange with a mutualist partner. They engineered four species of each type of mutualist as well as two cheater strains that were unable to make food resources.

The researchers assembled communities of yeast that differed both in the number of species and the presence of cheaters. They found that communities with higher numbers of mutualist species were better able to withstand the negative effects of cheaters because there were multiple species of mutualists performing the same task. If one species was lost from the community due to competing with a cheater, there were other species around to perform the task, showing that the presence of more species in a community can lessen the negative effects of cheaters.

"It's similar to thinking about a plant that has many pollinator species," says Segraves. "If one pollinator species is lost, there are other pollinator species around to pollinate. If a plant only has one species of pollinator that goes extinct, the mutualism breaks down and might cause extinction of the plant."

Their results highlight the importance of having multiple mutualist species that provide similar resources or services, essentially creating a backup in case one species goes extinct. Segraves compares this phenomenon to the relationship between retailers and consumers. Communities typically have multiple banks, grocery stores, restaurants and hospitals to ensure that there are always goods and services available should something happen to one company or facility, or, as with COVID today, grocery stores now have multiple suppliers to fend off shortages.

Segraves says future research will explore the possibility of a mutualist species becoming a cheater. The group is testing if mutualists that perform the same function might set up an environment that allows one of those mutualist species to become a cheater since there are other mutualists around that can fill that role. They predict that the mutualist species that is experiencing the most competition from the other mutualists will be the species that switches to cheating. They also hope to determine how the mutualists and cheaters evolved over time to provide a deeper understanding of the actual changes that led to differing outcomes in the communities.

INFORMS Journal Marketing Science New Study Key Takeaways:

"Word-of-mouth" is not always a substitute for advertising.

When consumers learn about products from other consumers, businesses should increase advertising spending to prove their product is high-quality.

When all consumers share their experiences, a high-quality business may be better served by reducing its advertising spending.

As more negative experiences are shared, it can be optimal for a high-quality business to spend more on advertising.

CATONSVILLE, MD, October 19, 2020 - Most people have seen or heard from a friend, neighbor or family member about a product or service they've used and how their experience was. It's called observational learning or word-of-mouth. These communications don't provide an unbiased assessment of true quality. Given this, businesses are faced with the difficult decision of determining when and how to spend their ad dollars. New research in the INFORMS journal Marketing Science finds when consumers learn about products/services from other consumers, a business may actually want to spend more money to credibly signal its quality.

The study, "When Consumers Learn, Money Burns: Signaling Quality Via Advertising with Observational Learning and Word of Mouth," details that word of mouth and advertising are not the same. Word of mouth is believed to be "free" advertising; but this may not always be the case. In fact, the opposite may be true when the role of advertising is to credibly signal product quality to consumers.

Word-of-mouth interactions may involve underreporting (not everyone shares experiences), positive reporting (when positive experiences are communicated more widely than negative ones) or negative reporting (when negative experiences are communicated more widely than positive ones).

"While both word of mouth and advertising can provide information regarding quality to consumers, one would suspect a high-quality business should have to spend less on advertising as it would benefit from word of mouth," said Yogesh Joshi, a professor at the University of Maryland. "However, this research shows that word of mouth, rather than softening the need for spending on advertising, may require a high-quality business to allocate more resources to these quality signaling efforts."

Joshi and his co-author Andres Musalem of the University of Chile and Instituto Sistemas Complejos de Ingeniería (ISCI) say the benefits for a low-quality business force a high-quality one to spend more on advertising, to prove their worth and that their quality is better than the low-quality business that's getting traction from word of mouth.

"When all consumers share their experiences, a high-quality business may be better served by reducing its investment in advertising, and in certain cases by a lot," said Joshi. "Further, as more negative experiences are shared, it can be optimal for a high-quality business to spend more on advertising because as the sharing of negative experiences increases, some late consumers who would have otherwise been exposed to no experiences are now exposed to complaints."

When quality differences across types are not too strong, and consumers share more complaints, the researchers say a high-quality business may need to allocate more resources to its quality-signaling advertising efforts.

Just like humans, microbes have equipped themselves with tools to recognize and defend themselves against viral invaders. In a continual evolutionary battle between virus and host, CRISPR-Cas act as a major driving force of strain diversity in host-virus systems.

A new study led by Professor of Life Sciences Shai Pilosof (Ben-Gurion University of the Negev, Beer-Sheva, Israel), Professor of Microbiology Rachel Whitaker (University of Illinois Urbana-Champaign), and Professor of Ecology and Evolution Mercedes Pascual (University of Chicago) highlights the role of diversified immunity in mediating host-pathogen interactions and its eco-evolutionary dynamics. The study also included Professor of Bioengineering and Bliss Faculty Scholar Sergei Maslov (University of Illinois Urbana-Champaign), Sergio A. Alcal´a-Corona (University of Chicago), and PhD graduate students Ted Kim and Tong Wang (University of Illinois Urbana-Champaign).

Their findings were reported in the journal Nature Ecology & Evolution.

"The motivation for this study was to figure out how the structure of immunity in microbial populations impacts the dynamics of virus-host interactions," said Whitaker.

Now famous for its application in genetic engineering (Nobel Prize in Chemistry, 2020), the CRISPR-Cas system originated as an adaptive immune system for microbes. In this system, "protospacers" -- segments of DNA from the infecting virus -- are incorporated into the microbial host genome, termed "spacers." The host molecular machinery uses these spacers to recognize, target and destroy viruses, analogous to the human adaptive immune system.

Researchers used computational models to explore the influence of microbial immune diversity on population dynamics of host-virus interactions. Their simulations revealed two alternating major regimes: the virus diversification regime (VDR) where viruses proliferate and diversify, and the host-controlled regime (HCR) where hosts constrain virus diversification, leading to their extinction.

As the viruses diversified in VDR regimes, so too did the hosts. The viruses that were able to escape host control harbored mutations in their protospacers, thereby leading to higher encounter rates with hosts. From these increased encounters, hosts were able to acquire new spacers, increasing CRISPR diversity. In turn, the immunity network exhibited weighted-nestedness, which enabled host control.

"Weighted-nestedness means that some microbial strains have redundant immunity to many viruses while others have limited immunity to a few," said Whitaker. "It is this structure that leads to the dynamics of host stability punctuated by viral epidemics."

To test the weighted-nestedness immunity structure predicted by their theory, researchers compared the data to empirical datasets from natural systems. Their findings revealed the presence of virus control via distributed and redundant immunity in these static empirical datasets.

"We next want to test this model in dynamic natural systems," said Whitaker. "We are focused on collecting high-resolution temporal data on hot springs and wastewater treatment because they are relatively simple with few viruses and microbial species."

By understanding the dynamics of host-virus populations in natural systems, researchers can better control microbes in industrial settings.

"Some industrial applications like wastewater treatment, yogurt, and solvent production depend on stable microbial populations," said Whitaker. "Often, these applications fail because of viral epidemics that kill these microbes. We believe that understanding CRISPRs diversity and structure can support the design of stable microbial populations that are immune to virus infection."

LIVERMORE, Calif. -- The development of a new method to make non-volatile computer memory may have unlocked a problem that has been holding back machine learning and has the potential to revolutionize technologies like voice recognition, image processing and autonomous driving.

A team from Sandia National Laboratories, working with collaborators from the University of Michigan, published a paper in the peer-reviewed journal Advanced Materials that details a new method that will imbue computer chips that power machine-learning applications with more processing power by using a common material found in house paint in an analog memory device that enables highly energy-efficient machine inference operations.

"Titanium oxide is one of the most commonly made materials. Every paint you buy has titanium oxide in it. It's cheap and nontoxic," explains Sandia materials scientist Alec Talin. "It's an oxide, there's already oxygen there. But if you take a few out, you create what are called oxygen vacancies. It turns out that when you create oxygen vacancies, you make this material electrically conductive."

Those oxygen vacancies can now store electrical data, giving almost any device more computing power. Talin and his team create the oxygen vacancies by heating a computer chip with a titanium oxide coating above 302 degrees Fahrenheit (150 degree Celsius), separate some of the oxygen molecules from the material using electrochemistry and create vacancies.

"When it cools off, it stores any information you program it with," Talin said.

Energy efficiency a boost to machine learning

Right now, computers generally work by storing data in one place and processing that data in another place. That means computers have to constantly transfer data from one place to the next, wasting energy and computing power.

The paper's lead author, Yiyang Li, is a former Truman Fellow at Sandia and now an assistant professor of materials science at the University of Michigan. He explained how their process has the potential to completely change how computers work.

"What we've done is make the processing and the storage at the same place," Li said. "What's new is that we've been able to do it in a predictable and repeatable manner."

Both he and Talin see the use of oxygen vacancies as a way to help machine learning overcome a big obstacle holding it back right now -- power consumption.

"If we are trying to do machine learning, that takes a lot of energy because you are moving it back and forth and one of the barriers to realizing machine learning is power consumption," Li said. "If you have autonomous vehicles, making decisions about driving consumes a large amount of energy to process all the inputs. If we can create an alternative material for computer chips, they will be able to process information more efficiently, saving energy and processing a lot more data."

Research has everyday impact

Talin sees the potential in the performance of everyday devices.

"Think about your cell phone," he said. "If you want to give it a voice command, you need to be connected to a network that transfers the command to a central hub of computers that listen to your voice and then send a signal back telling your phone what to do. Through this process, voice recognition and other functions happen right in your phone."

Talin said the team is working on refining several processes and testing the method on a larger scale. The project is funded through Sandia's Laboratory Directed Research and Development program.

For recreational fishing enthusiasts, the thrill of snagging their next catch comes with discovering what's hooked on the end of the line. In many freshwater streams and rivers -- across the central and eastern parts of the U.S. -- anglers are often catching a popular freshwater game fish: the smallmouth bass. Now, scientists have discovered a new level of biodiversity within that species.

Previously, scientists identified two subspecies of smallmouth bass: the widespread Northern smallmouth bass and a much smaller subgroup called the Neosho smallmouth bass. The Neosho are native to an ecologically isolated region of the lower Midwest known as the Central Interior Highlands, which weave through southwestern Missouri, northern Arkansas and northeastern Oklahoma.

To help the conservation departments manage the present diversity of this smaller subspecies of smallmouth bass, two University of Missouri researchers -- Joe Gunn and Lori Eggert -- worked with the Missouri Department of Conservation, Oklahoma State University's Department of Natural Resource Ecology and Management and the Oklahoma Cooperative Fish and Wildlife Research Unit of the U.S. Geological Survey at Oklahoma State University to collect over 800 fin samples from smallmouth bass at 43 different sites in the Central Interior Highlands. The MU researchers helped analyze the samples for genetic diversity.

"Management is necessary because this is a gamefish," said Eggert, a conservation biologist and professor emeritus in the Division of Biological Sciences in MU's College of Arts and Science. "Human actions have already strongly affected the species and will continue to do so. This management generally takes the form of 'stocking' to enhance opportunities for recreational anglers. If the source and subspecies of fish used in stocking particular streams is not considered, stocking events could lead to 'genetic swamping' of the local fish. In some cases, this could lead to one subspecies dominating the other in streams outside its native range. Letting 'nature take its course' is not an option."

For years, Eggert has studied the ecology and evolution of animal populations, including most notably African forest elephants. She originally wanted to become a veterinarian, but her passion for conservation biology developed while in college and grew as she served as an intern in the genetics program at the Zoological Society of San Diego. There, she was able to learn about conservation efforts on behalf of species such as the Przewalski's horse of Mongolia and the giant panda in China.

Eggert knows a proper understanding of the genetic diversity of animal populations is important when managing these populations.

"With the Neosho being a native fish to the Central Interior Highlands, this study highlights the importance of thinking about management actions when moving fish between streams," Eggert said. "In the past, it's just been 'a fish is a fish,' and hatcheries were providing fish without anyone first considering where these fish are originally coming from. It's not just 'a fish is a fish.' A fish being added to a Neosho stream should really come from a Neosho stream. We also need to look at which Neosho stream is involved, because each may be home to a genetically different population, and we don't quite know yet how important the mixing of these different genetic populations is to their overall health within an ecosystem."

Gunn, a graduate student in MU's College of Arts and Science, is currently working toward a doctorate in the Division of Biological Sciences, with an emphasis in conservation biology. Since he was little, he's always loved nature, and enjoys thinking about complex concepts in ecology and evolution. He wants to use his knowledge and understanding of animal species to make a positive impact on the management and preservation of threatened species and their environments.

Gunn said this study shows there is considerable diversity within the smallmouth bass family.

"Our methods have been used before to identify previously unknown lineages of animal populations," Gunn said. "This can be applied to species within any group, whether it's mammals, fish, reptiles or birds. There are also very interesting dynamics between different groups, and these same methods can also be used to identify genetic structures and morphological differentiation within a specific species. Here, we've found considerable diversity between the two known subspecies of smallmouth bass, the Neosho and the Northern smallmouth bass, the latter of which can be found in a larger area of the U.S."

Nearly every organism hosts a collection of symbiotic microbes--a microbiome. It is now recognized that microbiomes are major drivers of health in all animals, including humans, and that these symbiotic systems often exhibit strong daily rhythms.

New research led by University of Hawai'i at Manoa scientists revealed that, in the mutually beneficial relationship between with the Hawaiian bobtail squid, Euprymna scolopes, and the luminescent bacterium, Vibrio fischeri, an immune protein called "macrophage migration inhibitory factor" or "MIF," is the maestro of daily rhythms. This finding, published in the Proceedings of the National Academy of Sciences, could provide important clues on factors affecting human microbiome rhythms, as the MIF protein is also found in abundance in mammalian symbiotic tissues.

To survive, the nocturnal Hawaiian bobtail squid depends on V. fischeri, which gives it the ability to mimic moonlight on the surface of the ocean and deceive monk seals and other predators, as it forages for food. The symbiotic bacteria also require nutrition, especially at night when they are more numerous and their light is required for the squid's camouflage.

The research team, led by Eric Koch, who was a graduate researcher at the Pacific Biosciences Research Center (PBRC) in the UH Manoa School of Ocean and Earth Science and Technology (SOEST) at the time of the study, determined the squid regulates production of MIF as a way to control the movement of specialized immune cells, called hemocytes, which provide chitin for bacteria to feed on.

At night, when the team found MIF was low in the squid's light organ, hemocytes were allowed into the regions where the bacteria reside and chitin was delivered. During the day, MIF was very high, which inhibits the hemocytes from coming into the symbiotic tissues and dumping their chitin at the wrong time.

This cycling of nutrients has cascading effects on all of the other rhythms associated with the symbiotic system--perhaps affecting overall health, development or reproduction.

For nearly three decades, professors Margaret McFall-Ngai and Edward Ruby at PBRC have used the squid-bacterial symbiosis system to characterize animal microbiomes.

"We had recognized daily rhythms in the squid-vibrio symbiosis since 1996, but how the rhythm is controlled was not known," said McFall-Ngai. "This study brought the whole thing into sharp focus, allowing us to understand how the rhythm works and how it matures in the animal."

Such discoveries can pave the way for understanding how microbiomes function--what they do and how they do it--in other organisms and environments.

"A recent study of the mammalian, and human, gut microbiome has shown that MIF is present at high levels and controls the interactions of the microbes with the host cell," said McFall-Ngai. "As has happened with other phenomena, such a developmental inducers, the simplicity of the squid-vibrio system has provided a window into the mechanisms of symbiosis. Because these mechanisms appear to be highly conserved among all animals, including humans, understanding how they function promises to give us the tools to foster healthy people and resilient ecosystems."

More research is needed before a less invasive form of ventilation is used near the end of life for patients who have cancer and dementia, recommends the authors of a scientific paper published in JAMA Internal Medicine.

While analyzing data from nearly 2.5 million Medicare-funded hospitalizations within the last 30 days of a patient's life, the researchers found overall use of non-invasive ventilation increased substantially. That increase was nearly nine-fold, going from 0.8% of patients in 2000 to 7.1% of patients 2017. This change came without much data measuring the therapy's effectiveness for certain patient groups such as those with cancer and dementia, the authors noted.

Non-invasive ventilation delivers air through a face mask to help hospitalized patients breathe, similar to how breathing machines help people with sleep apnea at night. It also avoids some of the drawbacks of mechanical ventilation, such as needing to sedate a patient and insert a tube into the windpipe, both of which increase various health risks and make patient communication difficult.

Studies have shown non-invasive ventilation can help hospitalized patients with congestive heart failure and chronic lung disease. However, there is very little data supporting non-invasive ventilation use for hospitalized patients who are near the end of life and have breathing problems from other diseases such as cancer and dementia. Some small studies suggest this therapy also may provide cancer patients with more quality time with their loved ones toward the end of life.

"But just because non-invasive ventilation can work well for some patients, that doesn't automatically mean it will work well for others," said Donald Sullivan, M.D., M.A., M.C.R., the paper's lead author.
"More hospitalized patients are using non-invasive ventilation toward the end of their lives, even though there isn't a lot of evidence that clearly lays out the therapy's pros and cons.

"To help our patients and their families make informed decisions, we need to know more about when non-invasive ventilation may be helpful, and when it might be harmful," added Sullivan, who is also an associate professor of medicine (pulmonary and critical care medicine) in the OHSU School of Medicine.

Wearing a mask can make patients with altered cognition anxious and distressed. People dying of dementia may need to be sedated to receive this therapy. Ultimately, this therapy could prolong suffering for patients near the end of life, Sullivan said.

Sullivan and his co-authors recommend pursuing randomized clinical trials to evaluate the safety and effectiveness of non-invasive ventilation in different patient groups.

Sex, age, and severity of disease may be useful in identifying COVID-19 survivors who are likely to have high levels of antibodies that can protect against the disease, according to a new study co-led by researchers at Johns Hopkins Bloomberg School of Public Health.

The findings suggest that older males who have recovered from COVID-19 after having been hospitalized are strong candidates for donating plasma for treating COVID-19 patients. Doctors have been using infusions of plasma--the part of blood that contains antibodies--from recovered COVID-19 patients to treat COVID-19 patients and also as a possible prophylaxis to prevent COVID-19.

Doctors have used convalescent plasma to treat patients or immunize persons at high risk of virus exposure during outbreaks of measles, mumps, polio, Ebola, and even the 1918 pandemic flu.

Clinical trials of convalescent plasma treatment against COVID-19 are ongoing, and doctors until now haven't had guidance for selecting COVID-19 survivors who are likeliest to have strong antibody responses.

"We propose that sex, age, and severity of disease should be used to guide the selection of donors for convalescent plasma transfer studies because we found that these were significant patient characteristics that not only predicted the amount of antibody but the quality of that antibody," says study lead author Sabra Klein, PhD, professor in the Bloomberg School's Department of Molecular Microbiology and Immunology.

The study, published October 19 in the Journal of Clinical Investigation, was a collaboration with several other research groups including that of Arturo Casadevall, MD, PhD, Bloomberg Distinguished Professor and chair of the Department of Molecular Microbiology and Immunology, and co-corresponding author Aaron Tobian, MD, PhD, professor in the Department of Pathology and director of the Transfusion Medicine Division at the Johns Hopkins School of Medicine.

For their study, the researchers tested the blood of 126 COVID-19 survivors and found high variability in their antibody levels and their antibodies' ability to neutralize the COVID-19-causing coronavirus, SARS-CoV-2. Three factors were associated with stronger antibody responses: having been sick enough with COVID-19 to be hospitalized, being older, and being male.

Initial studies of recovered COVID-19 patients have revealed a significant variability in their antibody responses to the virus--some survivors having very weak responses that would almost certainly be ineffective in helping new patients. The researchers in the new study looked for factors that might help explain some of that variability and guide clinicians to the patients most likely to have high levels of SARS-CoV-2 neutralizing antibodies.

The researchers examined samples of plasma from the 126 recovered patients using several tests. These included tests of the plasma's ability in cell cultures to neutralize cell-to-cell infection with SARS-CoV-2, as well as commercial tests for levels of antibodies to the coronavirus's spike protein--the protein that studs the surface of coronavirus particles and allows the virus to attach to and infiltrate human cells.

Consistent with several prior studies, the researchers found considerable variability among the subjects in their spike-protein antibody levels and plasma coronavirus-neutralization potency. But on average, the plasma of survivors who had been hospitalized with COVID-19 had markedly more anti-spike protein antibodies and neutralized the virus more effectively--suggesting that disease severity prompts a stronger immune response.

"We know that the magnitude of antibody responses correlates with disease severity in other infectious diseases, such as active tuberculosis," Klein says.

Older age and male sex, which prior studies in both China and Europe have shown are associated with more severe COVID-19, were also associated with stronger antibody responses, though these links were weaker than for hospitalization status.

As part of their study, the researchers also tested study participants with commercial test kits and found that recovered COVID-19 patients who have strong neutralizing antibody responses also are very likely to have high levels of coronavirus anti-spike antibodies. This suggests that this type of test kit, which is relatively inexpensive, might be a good tool for identifying suitable plasma donors for clinical trials and treatments.

COLLEGE PARK, Md. - Anxiety, the most common family of mental illnesses in the U.S., has been pushed to epic new heights by the COVID-19 pandemic, with the Centers for Disease Control and Prevention estimating that nearly 1 in 3 U.S. adults and a staggering 41% of people ages 18-29 experienced clinically significant anxiety symptoms in late August. Now, the findings of a recent UMD-led study indicate that some long-accepted thinking about the basic neuroscience of anxiety is wrong.

The report by an international team of researchers led by Alexander Shackman, an associate professor of psychology at UMD, and Juyoen Hur, an assistant professor of psychology at Yonsei University in Seoul, South Korea, provides new evidence that fear and anxiety reflect overlapping brain circuits. The findings run counter to popular scientific accounts, highlighting the need for a major theoretical reckoning. The study was published last week in the Journal of Neuroscience.

"The conceptual distinction between 'fear' and 'anxiety' dates back to the time of Freud, if not the Greek philosophers of antiquity," said Shackman, a core faculty member of UMD's Neuroscience and Cognitive Science Program, and 2018 recipient of a seed grant award from UMD's Brain and Behavior Initiative, "In recent years, brain imagers and clinicians have extended this distinction, arguing that fear and anxiety are orchestrated by distinct neural networks.

However, Shackman says their new study adds to a rapidly growing body of new evidence suggesting that this old mode is wrong. "If anything, fear and anxiety seem to be constructed in the brain using a massively overlapping set of neural building blocks," he said.

Prevailing scientific theory holds that fear and anxiety are distinct, with different triggers and strictly segregated brain circuits. Fear--a fleeting reaction to certain danger--is thought to be controlled by the amygdala, a small almond-shaped region buried beneath the wrinkled convolutions of the cerebral cortex. By contrast, anxiety--a persistent state of heightened apprehension and arousal elicited when threat is uncertain--is thought to be orchestrated by the neighboring bed nucleus of the stria terminalis (BNST). But new evidence from Shackman and his colleagues suggests that both of these brain regions are equally sensitive to certain and uncertain kinds of threats.

Leveraging cutting-edge neuroimaging techniques available at the Maryland Neuroimaging Center, their research team used fMRI to quantify neural activity while participants anticipated receiving a painful shock paired with an unpleasant image and sound--a new task that the researchers dubbed the "Maryland Threat Countdown".

The timing of this "threat" was signaled either by a conventional countdown timer--i.e. "3, 2, 1..."--or by a random string of numbers--e.g. "16, 21, 8." In both conditions, threat anticipation recruited a remarkably similar network of brain regions, including the amygdala and the BNST. Across a range of head-to-head comparisons, the two showed statistically indistinguishable responses.

The team examined the neural circuits engaged while waiting for certain and uncertain threat (i.e. "fear" and "anxiety"). Results demonstrated that both kinds of threat anticipation recruited a common network of core brain regions, including the amygdala and BNST.

These observations raise important questions about the Research Domain Criteria (RDoC) framework that currently guides the U.S. National Institute of Mental Health's quest to discover the brain circuitry underlying anxiety disorders, depression, and other common mental illnesses. "As it is currently written, RDoC embodies the idea that certain and uncertain threat are processed by circuits centered on the amygdala and BNST, respectively. It's very black-and-white thinking," Shackman noted, emphasizing that RDoC's "strict-segregation" model is based on data collected at the turn of the century.

"It's time to update the RDoC so that it reflects the actual state of the science. It's not just our study; in fact, a whole slew of mechanistic studies in rodents and monkeys, and new meta-analyses of the published human imaging literature are all coalescing around the same fundamental scientific lesson: certain and uncertain threat are processed by a shared network of brain regions, a common core," he said.

As the crown jewel of NIMH's strategic plan for psychiatric research in the U.S., the RDoC framework influences a wide range of biomedical stakeholders, from researchers and drug companies to private philanthropic foundations and foreign funding agencies. Shackman noted that the RDoC has an outsized impact on how fear and anxiety research is designed, interpreted, peer reviewed, and funded here in the U.S. and abroad.

"Anxiety disorders impose a substantial and growing burden on global public health and the economy," Shackman said, "While we have made tremendous scientific progress, existing treatments are far from curative for many patients. Our hope is that research like this study can help set the stage for better models of emotion and, ultimately, hasten the development of more effective intervention strategies for the many millions of children and adults around the world who struggle with debilitating anxiety and depression."

PITTSBURGH, Oct. 19, 2020 - Older people who report greater levels of social engagement have more robust gray matter in regions of the brain relevant in dementia, according to new research led by scientists at the University of Pittsburgh Graduate School of Public Health. It is the first to use a particularly sensitive type of brain imaging to conduct such an evaluation.

The findings, reported today in the Journal of Gerontology: Psychological Sciences, suggest that "prescribing" socialization could benefit older adults in warding off dementia, much the way prescribing physical activity can help to prevent diabetes or heart disease.

"Our data were collected before the COVID-19 pandemic, but I believe our findings are particularly important right now, since a one-size-fits-all social isolation of all older adults may place them at risk for conditions such as dementia," said lead author Cynthia Felix, M.D., M.P.H., a geriatrician and a post-doctoral associate in Pitt Public Health's Department of Epidemiology. "Older adults should know it is important for their brain health that they still seek out social engagement in safe and balanced ways during the pandemic."

Felix and her colleagues used information about social engagement from 293 community-dwelling participants from the Health, Aging and Body Composition (Health ABC) study. These participants, who averaged 83 years old, also received a sensitive brain scan called Diffusion Tensor Imaging MRI that measured the cellular integrity of brain cells used for social engagement.

These participants provided detailed information about their social engagement and were scored using a tool Felix developed. High scores were awarded to people who did things like play board games; go to movies; travel long distance; attend classes, lectures or adult education events; participate in church or other community activities; get together with children, friends, relatives or neighbors at least once a week; volunteer or work; be married and live with others.

Felix and colleagues found that greater social engagement is related to better microstructural integrity of brain gray matter in these older adults. Maintaining brain health is of critical importance. Once brain cells die, dementia typically follows.

Social engagement with at least one other relative or friend activates specific brain regions needed to recognize familiar faces and emotions, make decisions and feel rewarded. The good news is that even moderate "doses" seem to be beneficial.

"We need to do more research on the details, but that's the beauty of this--social engagement costs hardly anything, and we do not have to worry about side-effects," Felix said. "There is no cure for dementia, which has tremendous costs in terms of treatment and caregiving. Preventing dementia, therefore, has to be the focus. It's the 'use it or lose it' philosophy when it comes to the brain."

Felix notes that cause-and-effect still need to be disentangled: Does greater social engagement keep these brain regions healthy? Or is it that having a healthy brain results in better social engagement?

Similar to how large public health studies assess the best programs to encourage physical activity to prevent chronic disease in older people, Felix believes her team's findings, coupled with previous research, provides justification for randomized control trials to assess the impact of specific types and amounts of social activities on brain health.

Enriched by her prior public health training at Johns Hopkins University, Felix recognizes the critical role of public health in applying this finding on a large scale.

"It would be good if we develop programs across the U.S. through which structured social activities can be prescribed for community-dwelling older adults, aimed at reducing rates of dementia and the resulting health care costs," Felix said. "Existing platforms providing group physical activities can be a good starting point."

CHAMPAIGN, Ill. -- Researchers studied the effects of a 12-week exercise regimen on 148 active-duty Air Force airmen, half of whom also received a twice-daily nutrient beverage that included protein; the omega-3 fatty acid, DHA; lutein; phospholipids; vitamin D; B vitamins and other micronutrients; along with a muscle-promoting compound known as HMB. Both groups improved in physical and cognitive function, with added gains among those who regularly consumed the nutritional beverage, the team reports.

The findings appear in the journal Scientific Reports.

Participants were randomly assigned to the two groups. The exercise regimen combined strength training and high-intensity interval aerobic fitness challenges. One group received the nutritional beverage and the other consumed a placebo beverage that lacked the added nutrients. Neither the researchers nor the participants knew who received the nutrient-enriched beverage or placebo.

"The exercise intervention alone improved strength and endurance, mobility and stability, and participants also saw increases in several measures of cognitive function. They had better episodic memory and processed information more efficiently at the end of the 12 weeks. And they did better on tests that required them to solve problems they had never encountered before, an aptitude called fluid intelligence," said Aron Barbey, a professor of psychology at the University of Illinois at Urbana-Champaign who led the study with postdoctoral researcher Christopher Zwilling.

"Those who also consumed the nutritional supplement saw all of these improvements and more. For example, they were better able to retain new information in their working memory and had quicker responses on tests of fluid intelligence than those taking the placebo," Barbey said.

Physical power increased in both groups as a result of the physical training, Zwilling said.

"Power is a measure of physical fitness that is based on several factors, such as how fast a participant can pull a heavy sled over a set distance, how far they can toss a weighted ball, and how many pushups, pullups or situps they can perform in a set time period," he said.

The physical training reduced participants' body fat percentage and increased their oxygen-uptake efficiency, or VO2 max. The airmen also performed better than they had initially on several measures of cognitive function. The most notable of these was an increase in the accuracy of their responses to problems designed to measure fluid intelligence.

"But we also wanted to know whether taking the supplement conferred an advantage above and beyond the effect of exercise," Zwilling said. "We saw that it did, for example in relationship to resting heart rate, which went down more in those who took the supplement than in those who didn't."

Participants who consumed the nutritional beverage also saw greater improvements in their ability to retain and process information. And their reaction time on tests of fluid intelligence improved more than their peers who took the placebo, the researchers found.

"Our work motivates the design of novel multimodal interventions that incorporate both aerobic fitness training and nutritional supplementation, and illustrates that their benefits extend beyond improvements in physical fitness to enhance multiple measures of cognitive function," Barbey said.

The U. of I. team conducted the intervention with study co-author Adam Strang, a scientist in the Applied Neuroscience Branch of Wright-Patterson Air Force Base near Dayton, Ohio, along with his colleagues in the Air Force Research Laboratory. The U. of I. team also worked with research fellow and study co-author Tapas Das and his colleagues at Abbott Nutrition, who led the design of the nutritional beverage, which is a mixture of nutrients targeting both muscle and brain. The specially designed beverage provided ingredients that previous studies have shown are associated with improved physical cognitive function.

Transportation is the top source of greenhouse gas emissions in the United States, accounting for almost 30 percent of total emissions. In the national and global effort to reduce emissions and mitigate climate change, electric vehicles (EVs) provide an attractive option. But despite dropping prices and rising popularity, EVs continue to make up a small percentage of the automotive industry's market share.

Are Americans resistant to purchasing these vehicles? And what are some of the biggest barriers--or perceived barriers--to widespread adoption? A new report out from researchers at Stanford University, Resources for the Future, and ReconMR has some answers.

Interviews with 502 American adults from May 28 to August 10, 2020 reveal American perceptions of EVs and illustrate whether those perceptions may lead to purchasing reluctance. The report also identifies sources of hesitation among three subgroups: sex, education, and prior exposure to EVs.

Topline Findings

57% of future car buyers are willing to consider buying an EV.

The most important driver of openness to purchasing an EV is belief that global warming will be a serious problem for the US in the future

The perception that batteries may catch on fire, that maintenance costs are higher, and that EVs have weaker acceleration than gas-powered cars are sources of hesitation among potential buyers.

Perceived difficulty of replacing batteries and lack of mechanics as compared to gas-powered vehicles are also predictors of purchasing reluctance.

65% of respondents have not driven nor know anyone who has driven an EV.

"Purchasing a vehicle is a big decision that consumers don't make lightly, and making a change from familiar gas-powered vehicles to electric vehicles involves venturing into the unknown to some degree. The decision to do so is likely shaped by perceptions of the features of EVs, so understanding those perceptions is a useful way to identify sources of hesitation inhibiting the adoption of this comparatively new technology," report co-author Jon Krosnick said. "Highlighting ways in which public perceptions don't line up with reality can pave pathways for educating people and alleviating concerns, which could lead to increased interest in EVs."

Any Red Sea diver will have encountered colorful triggerfish along coral reefs, and some divers will have experienced the painful bite of their huge teeth if they get too close to their nesting grounds. Now, Ph.D. student Matthew Tietbohl and colleagues at KAUST report a peculiar feeding strategy by a titan triggerfish that highlights their innate ability to learn and adapt.

Tietbohl and his colleagues were on Mar Mar island in the south central Red Sea looking for signs of turtle nesting when they saw a titan triggerfish come up on to the shoreline and attack, and eventually grab, a Red Sea ghost crab. Most interesting was that the triggerfish partially beached itself in shallow water for the first attack, a hunting behavior that has not been previously reported in any fish belonging to the order Tetraodontiformes, which comprises 350 coral reef species, including triggerfish. Several subsequent attacks ensued in very shallow water, without beaching, with the fish slowly approaching the crab and then rushing at it horizontally. The fish finally grabbed the crab in several centimeters of water and dragged it into deeper water, where it was eaten.

"Triggerfish seem to be particularly adept at taking advantage of a wide variety of prey," says Tietbohl. "They will jet water from their mouths to uncover invertebrate food buried in the sand, and flip rocks and break coral to get at prey. Given this diverse range of feeding behaviors, it is not too surprising that they have found a way to take advantage of semiterrestrial prey too."

Tietbohl believes that their discovery highlights the importance of observational studies as a means for investigating marine life. He and his colleagues suggest that triggerfish could serve as model systems for studying learning and cognition in coral reef fish.

All modern life uses energy to reproduce itself. During this process, organisms build and break down larger molecules such as fats and sugars using a remarkably common set of reactive intermediate energy carrier molecules. These intermediate energy carriers (for example ATP) are often not building blocks in and of themselves, but they allow the energy coupling between separate reactions needed to push forward cellular reproduction. One class of these compounds are thioesters, chemical compounds that contain a high-energy carbon-sulfur bond. It has been speculated for some time that thioesters might be among the most ancient versions of such metabolic reactive intermediates, partly because modern organisms still use thioesters to help break down sugars and make proteins from amino acids. Just how reactive intermediate compounds like thioesters could have been formed before life evolved, or as early life was taking its first baby steps, remains shrouded in mystery. New work from researchers at the Earth-Life Science Institute (ELSI) at Tokyo Institute of Technology, shows that a simple compound that can be found in some modern volcanic gases - a thioacid (a compound formed from an organic acid and hydrogen sulfide, which is the compound largely responsible for the "rotten egg" smell of many hot springs) - readily reacts with simple sulfur containing thiol compounds similar to those fundamental to modern metabolism to form reactive thioesters similar to those found in modern biology. This reaction happens readily in water and may have served as a starting point for the evolution of more complex biochemistry. During the research, they found that when they included iron (which is the most abundant element on Earth and comprises about 5% of Earth's surface layer, known as the crust), in their reactions, the reaction product yields increased.

The team suggests this may mean energy coupling between multiple reactions, in which one reaction drives another forward, may have its origins in non-living environmental chemistry. Remarkably, they also found a side product of the reaction they discovered can be used to make a second type of versatile energy-coupling compound required by all living things: FeS (short for iron-sulfur) clusters. These are small aggregates of only a few atoms each of iron and sulfur, which help organisms metabolize as they move electrons from one molecule to another. One important example of such a FeS-cluster-using-pathway is photosynthesis, which transfers electrons from water to CO2 to make sugars and oxygen. This work thus provides a new understanding of how high energy molecules and electron transfer reactions may have been naturally produced as early metabolism was evolving.

Although scientists have been trying to understand the origins of life's building blocks, things like amino acids, nucleotides, peptides, and so on, for some time, little effort has been given to understanding how energy transfer originated in prebiotic chemistry. Understanding this energy exchange could be as important as understanding the origin of building blocks, so the ELSI team decided to search for reactions which could be coupled together energetically. As lead author, Sebastian Sanden notes "We were already studying FeS minerals, and we knew how easy their formation was, so we wanted to see if we could couple this excess wasted energy to another reaction." The thioacid they began their study with contains sulfur, which they knew then only had to be reacted with iron to make the FeS clusters they were already studying.

The experiments and analyses the ELSI researchers performed had to be done in rapid succession to track the progress of the reaction. They developed techniques for doing this, and thus they were able to determine how fast these reactions happened. Their preliminary thioester-making experiments did not proceed as fast as they initially hoped, but by adding a catalyst and increasing the temperature, they found that maximum thioester yields were obtained in less than an hour, as opposed to a few days before making these changes.

The team thinks it is especially fascinating that these kinds of reactions may create "cascade reactions" which make more and more complex molecules: pyruvate decomposes, helping form a thioester, which then allows peptides (smaller cousins of proteins) to form via the newly discovered thioester route. The team hopes to test this experimentally next and to create a system that can increase the number of components it contains and their complexity by itself, perhaps all the way to self-reproduction. Some modern microbes in fact use pyruvate decomposition and thioester formation assisted by FeS clusters in their metabolism, and it is possible that the reactions the team discovered recapitulate how early prebiological or biological evolution discovered them. As the lead investigator on this work, ELSI Associate Professor Shawn McGlynn says, "This work provides new connections between multiple prebiotic reaction components that may have been critical to establishing early energy metabolism on Earth."

While this work may shine new light on how naturally occurring energy exchange reactions may have helped "jump-start" metabolism, it may also be important for the field of "green chemistry," which is concerned with finding the most energetically effective and environmentally friendly methods to make chemical compounds. While toxic heavy metals like cadmium and mercury and solvents like chloroform are often used in industrial organic chemistry, the reactions discovered by this research group are very efficient and work in water using non-toxic iron as a catalyst.