Culture

Targeted therapies developed to reduce lung fibrosis

image: A new treatment option for lung fibrosis is being developed by Philip Low, a Purdue University scientist, and his team.

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Philip Low/Purdue University

WEST LAFAYETTE, Ind. - A new treatment option for lung fibrosis is being developed by Purdue University scientists. Lung fibrosis has been a concern for COVID-19 patients.

People with idiopathic pulmonary fibrosis (IPF) have a life expectancy of less than five years. Fibrotic diseases cause organ failure that lead to about 45% of all deaths in the United States. Existing therapies do little to slow progression.

Now, Philip S. Low, the Purdue Ralph C. Corley Distinguished Professor of Chemistry and Presidential Scholar for Drug Discovery, has led a team to develop two targeted therapies for people with IPF. The two different therapeutic approaches are published in Science Translational Medicine and EMBO Molecular Medicine.

"This is a horrible disease that claimed the lives of my next-door neighbor and a good friend's wife," Low said. "We developed two targeted therapies that allow us to use powerful drugs with high toxicities because we specifically deliver them to diseased cells without harming healthy ones."

The first of the Purdue team's novel targeted molecules is designed to slow fibrosis and extend life. The second IPF therapy suppresses fibrosis-inducing cytokine production.

The two therapies will be moving into human clinical trials within the next several months. The developments come as a number of people with COVID-19 or who have recovered from COVID-19 experience lung fibrosis or other related conditions.

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Purdue University

The mental state of flow might protect against harmful effects of quarantine

A survey of over 5,000 people in Chinese cities affected by COVID-19 in early 2020 suggests that people who quarantined for a longer period of time generally experienced poorer well-being--but that experiencing the mental state of flow reduced or eliminated that link. Kate Sweeny and colleagues at the University of California, Riverside, U.S., Central China Normal University, China and Nanjing University, China and colleagues present these findings in the open-access journal PLOS ONE on November 11, 2020.

A person experiences flow when they become so absorbed in an enjoyable activity that they lose track of their external surroundings. Previous studies have found that flow is associated with greater well-being in a variety of stressful settings.

Sweeny and colleagues hypothesized that flow could be associated with greater well-being for people who experienced the stressful uncertainty of the rise of COVID-19 in China in early 2020. They also hypothesized that greater well-being might be associated with mindfulness, in which a person is also absorbed in the present moment, but in contrast to flow, they maintain awareness of their external surroundings.

In February 2020, the researchers tested these hypotheses by conducting an online survey of 5,115 people in Wuhan and other large cities in China that were affected by COVID-19. The survey evaluated self-reported levels of flow, mindfulness, and well-being.

Statistical analysis of the survey data showed that both flow and mindfulness were linked to better well-being of several types, such as less loneliness and more positive emotion. Additionally, people who experienced a longer period of quarantine reported poorer well-being of several types. However, the link between longer quarantine and poorer well-being was significantly weaker or disappeared entirely for people who experienced high levels of flow--but not mindfulness.

The study could not test the causal relationship between flow and well-being, though future research could investigate whether engaging in activities that induce flow directly helps to ease the negative impact of quarantining. Research could also explore which flow-inducing activities are most effective for which people.

The authors add: "In a sample collected via social media in February 2020 in China, experiencing flow and mindfulness was associated with better well-being. More interestingly, whether people were in quarantine was irrelevant for well-being among people who experienced a lot of flow in the previous week, but the same was not true for mindfulness."

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PLOS

Born to be young?

image: Flycatcher egg being illuminated in order to inject thyroid hormones specifically into the egg yolk.

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Tom Sarraude

The environment provided by the mother during embryo development has major consequences on later-life health and lifespan. This can arise through effects on cellular ageing which is often estimated with the length of telomeres. Telomeres are the protective end caps of chromosomes and their length is a marker of 'biological age'.

While telomeres normally shorten with age, short telomeres at a given age predict higher disease and mortality risks. Prenatal exposure to maternal stress hormones as well as instability during embryo development have previously been found to result in short telomeres, i.e. accelerated cellular ageing.

A new study funded by the Academy of Finland and the Turku Collegium for Science and Medicine manipulated prenatal exposure to maternal thyroid hormones using egg injection in an avian model.

"The telomere biology of humans is closer to the telomere biology of birds than those of traditional laboratory models. In both human and birds, telomere length is measured in a minimally-invasive way from small blood samples," says Collegium Researcher Antoine Stier from the University of Turku (Finland), the main author of the research article.

While authors of the study had reasons to expect shorter telomeres in chicks born from eggs injected with thyroid hormones, they were quite surprised to find that those chicks actually exhibited longer telomeres right after birth.

"Based on the natural decline of telomere length observed with age in the same collared flycatcher population, we estimated that chicks hatching from thyroid hormones injected eggs were approximately 4 years 'younger at birth' than chicks hatched from control eggs," adds Collegium Researcher Suvi Ruuskanen.

Although the molecular mechanisms underlying such effects remain to be discovered, the new findings suggest that prenatal thyroid hormones might have a role in setting the 'biological age' at birth.

"Considering the interest and controversies surrounding gene therapy trials in humans to elongate telomeres as an anti-ageing therapy, this discovery opens potential avenues to better understand the influence of telomere elongation in animal models," Stier says.

The study was conducted on a long-term monitored population of wild collared flycatcher breeding in Gotland island, and relied on extensive collaborations with the University of Uppsala (Sweden), Lyon, Glasgow and Aberdeen.

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University of Turku

Golden ticket: Researchers examine what consumers desire in chocolate products

image: Participants in a study on what premium chocolate consumers desire in chocolate products tasted five different chocolate bars: mainstream (Hershey's Milk Chocolate Bar), premium (a Lindt Cocoa Dark Chocolate Bar, a Green and Black's Organic Dark Chocolate Bar, and an Endangered Species Dark Chocolate with Sea Salt and Almonds); and craft (Dandelion Chocolate 70% Ambanja, Madagascar).

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Allison Brown, Penn State

UNIVERSITY PARK, Pa. -- Gold foil, ornate labels and an intriguing backstory are product characteristics highly desired by premium chocolate consumers, according to research conducted by food scientists in Penn State's College of Agricultural Sciences.

The study is one of the first to thoroughly research what American premium chocolate consumers find to be desirable attributes in their chocolate bars. An additional focus was on these consumers' perceptions of craft chocolate, which is made from scratch -- bean to bar -- by small companies using fine flavor cocoa beans.

Much like craft beer and specialty coffee, craft chocolate is gaining popularity among consumers who are seeking a unique experience, noted lead researcher Allison Brown, food science doctoral candidate in the college's International Agriculture and Development dual-title degree program.

She added that study outcomes, which were published in the journal PLOS ONE, will aid craft chocolate companies when making decisions about product development and marketing.

"The U.S. craft chocolate market is estimated to be worth $100 million and growing," Brown said. "However, many companies are small startups with few employees. They do not have marketing teams to guide their brand strategies. Our findings will help them make decisions that could have a large impact on their businesses."

Brown -- joined by Helene Hopfer, assistant professor of food science, and Alyssa Bakke, sensory scientist in the Sensory Evaluation Center at Penn State -- conducted the mixed-method study, which involved a "projective mapping" activity and focus groups.

Projective mapping, Brown explained, is a technique in which consumers group products on a sheet of paper based upon similarities and differences in the products. They also may add words to explain their groupings.

For this study, participants mapped 47 different chocolate product stickers on a piece of paper and brought these maps to the focus groups, where they discussed their reasons for putting the chocolates into categories they named "artisan," "Halloween candy" or "special occasion," among others.

In the second half of the focus groups, participants tasted five chocolate bars in three categories: mainstream (Hershey's Milk Chocolate Bar), premium (a Lindt Cocoa Dark Chocolate Bar, a Green and Black's Organic Dark Chocolate Bar, and an Endangered Species Dark Chocolate with Sea Salt and Almonds); and craft (Dandelion Chocolate 70% Ambanja, Madagascar).

They gave their opinions on flavor, packaging, sustainability labels and other aspects that they found to be appealing and unappealing. These discussions were coded to determine themes, which fell into three main categories of attributes: search, reflected by segmentation, price, availability and packaging; credence, or the degree to which the consumer trusted the product; and experience, such as feeling joy when consuming the chocolate or the use of chocolate as a gift.

Overall, participants responded favorably to every sample because, as Brown pointed out, "It's hard to make chocolate undesirable." However, they focused more on extrinsic cues, such as packaging, rather than intrinsic cues, such as flavor, to judge product quality.

For example, almost all consumers found the craft chocolate sample to be novel and exciting, likening it to coffee and wine in terms of flavor and packaging elements. They were wowed by the product's intricate label design and thick gold foil, with one consumer saying it was "like getting a golden ticket from Willy Wonka."

Consumers also associated high-quality chocolate with the presence of the percentage of cocoa on the label and additional ingredients such as sea salt, almonds or fruit.

Products with higher price tags -- and those available only at specialty stores or online -- also were deemed to be top notch. "These are more sophisticated, so my brain just thinks they must taste better, so they must be high quality," said a participant. "Also, they're more expensive."

Sustainability labels, such as "Organic" and "Fair Trade," piqued some participants' interest, while others distrusted their presence on the chocolate bar. These attitudes were reflected in participants' willingness to pay for products with certifications -- some participants indicated they would spend more for these products, while others would not pay more for chocolate with sustainability labels.

Meaning was another selling point, with the consumers placing a higher value on chocolate bars made by companies that had an interesting backstory, supported a cause or featured a person's name. For example, the Endangered Species bar was a hit because its label indicates that proceeds support wildlife conservation. "Participants viewed it as a guilt-free indulgence," Brown said.

Consumers cited positive childhood experiences as the origin of many of the attributes they look for in chocolate products. Chocolate flavors or packaging reminiscent of holidays, campfires or gift giving were highly sought after.

The findings clearly outline how craft chocolates are perceived differently from premium and mainstream chocolates, noted Hopfer.

"Consumers picked up on the exclusive and specialty nature of these products," she said. "The findings highlight the importance of a story behind the product and show that consumers derive a purpose and joy from chocolate. We also determined the importance of availability, price and packaging as proxies for perceived chocolate quality."

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Penn State

Conservatives and liberals motivated by different psychological factors, new study shows

Liberalism and conservatism are associated with qualitatively different psychological concerns, notably those linked to morality, shows a new study that explores how political ideology and moral values are connected to motivated social cognition. The findings, which appear in the journal PLOS ONE, offer deeper psychological insights into the nature of political division in the United States.

"Psychological research on the different motives underlying support for liberal versus conservative leaders and agendas, such as those separating Biden and Trump supporters, can help to explain why, for instance, one group is much more focused on promoting equality and social justice than the other," explains John Jost, a professor of psychology, politics, and data science at New York University and the study's senior author.

The work centered on the concept of "moral foundations" and its connection to political ideology. In this, and similar research, social scientists have sought to determine how important matters such as "whether or not someone conformed to the traditions of society" or "whether or not someone cared for someone weak or vulnerable" are to morality.

Previously, some have argued that liberals have an impoverished sense of morality, emphasizing only issues of fairness and harm avoidance, which they see as individualistic, whereas conservatives have a broader "moral palette" that values ingroup loyalty, obedience to authority, and the enforcement of purity sanctions, which they view as "binding foundations."

In the PLOS ONE article, however, the researchers found something important that previous studies have failed to consider.

Specifically, the studies by Jost and his colleagues, including Michael Strupp-Levitsky, who conducted the work as an NYU undergraduate and is now a doctoral candidate at Long Island University-Brooklyn, showed that those moral foundations known to be more appealing to liberals than conservatives--specifically, fairness and harm avoidance--are linked to empathic motivation, whereas the moral foundations that are more appealing to conservatives than to liberals --such as ingroup loyalty and deference to authority--are not.

In fact, the "binding foundations" cited by previous studies as evidence of a broad "moral palette" are associated with authoritarianism, social dominance, and economic system justification--matters quite apart from morality. Moreover, they are also associated with psychological motives to reduce uncertainty and threat, consistent with a theory of political ideology as motivated social cognition that Jost and other collaborators proposed in 2003.

"All of this may help to explain why the endorsement of 'binding foundations' is associated with prejudice, outgroup hostility, and other antisocial outcomes, whereas the endorsement of 'individualizing foundations' is negatively associated with prejudice, outgroup hostility, and other antisocial outcomes," explains Jost.

To explore these matters in the PLOS ONE work, the researchers conducted two studies.

They asked American participants a series of questions that sought to capture different motivations (e.g., "I have an intense fear of death" and "I only think as hard as I have to"), empathies (e.g., "After being with a friend who is sad about something, I usually feel sad"), and moral intuitions (e.g., "Respect for authority is something all children need to learn") as well as beliefs about system justification (i.e., the legitimacy of the existing social, economic, and political order) and political orientation (e.g., conservative, liberal) on social and economic issues. Here, the researchers sought to illuminate the relationship between political ideology and motivated social cognition.

Their results showed that liberalism and conservatism were indeed associated with qualitatively different psychological concerns, as suggested in previous research.

The motivational basis of conservative preferences for "binding" intuitions has for years been assumed to be independent of needs to reduce uncertainty and threat and to represent a broad, prosocial sense of morality. However, the new findings in PLOS ONE indicate that the endorsement of "binding foundations" is linked to the very same motives associated with many other conservative preferences, including authoritarianism, social dominance, system justification, and underlying psychological needs to reduce uncertainty and threat.

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New York University

Review of plants' role in antibacterial activity clears new paths for drug discovery

Scientists have compiled the first comprehensive review of plant natural products that play a role in antibacterial activity, to serve as a guide in the search for new drugs to combat antibiotic-resistant pathogens.

Chemical Reviews published the work by researchers at Emory University, which includes 459 plant natural products that met rigorous criteria for demonstrating antibacterial activity. The review is also deposited on the Shared Platform for Antibiotic Research and Knowledge (SPARK), sponsored by Pew Charitable Trusts.

"We hope that chemists and pharmacology researchers will use our review as a guide to dig deeper into the promising potential of many plant compounds," says Cassandra Quave, senior author of the review and associate professor in Emory's Center for the Study of Human Health and Emory School of Medicine's Department of Dermatology. Quave is also a member of the Emory Antibiotic Resistance Center.

In the United States, at least 2.8 million people get antibiotic-resistant infections each year and more than 35,000 people die from them, according to the Centers for Disease Control and Prevention.

"If ever there was a time to cultivate our knowledge and tap into the chemical power of plants, this is it," Quave says. "We're seeing a rise in antimicrobial resistance across the globe. And, at the same time, we're also losing vast amounts of plant biodiversity."

Two in five plants are currently estimated to be threatened with extinction, according to the State of the World's Plants and Fungi Report, published in 2020 by the Royal Botanic Gardens, Kew.

Quave is a leader in the field of medical ethnobotany, studying how Indigenous people incorporate plants in healing practices to uncover promising candidates for new drugs. The Quave lab has identified compounds from plants such as the Brazilian peppertree, the American beautyberry and the European chestnut that inhibit dangerous antibiotic-resistant bacteria.

Her lab found, for instance, that triterpenoid acids from the Brazilian peppertree "disarm" methicillin-resistant Staphylococcus aureus, known as MRSA, by blocking its ability to produce toxins.

The first antibiotic, penicillin, was derived from microbes in mold that kill bacteria. Since then, scientists have found other microorganisms that live in soil that are easy to grow in a laboratory setting and can kill pathogens resistant to some drugs. The ability of bacteria to continue to evolve resistance, however, is outpacing the ability to generate effective drugs from these sources.

"One obstacle to plant natural products making it into the new drug pipeline is the complexity of the discovery process," Quave says. "You have to identify a promising plant candidate, tease through the hundreds of chemicals contained within a particular plant to identify the active compound, and then isolate enough of this compound to do experiments on it. It's not nearly as easy as sequencing a soil microbe and growing up a big vat of it to conduct experiments."

Tapping the knowledge of traditional people who have used plants for centuries to treat infections offers valuable clues for where to focus research, she adds.

"In recent decades, interest has grown in investigating plants as potential drug candidates," Quave says. "Technologies have improved to more easily access and study bioactive molecules within plants. And more papers are being published that follow standardized procedures for evaluation of antimicrobial activities among plant compounds."

For the current review, the Quave lab looked at nearly 200 papers published between 2012 and 2019 that met strict standardization criteria for authenticating plant-derived compounds that significantly inhibited antibacterial activity. The co-authors spanned undergraduates who conducted the initial literature reviews to graduate students and scientists specialized in biology, chemistry, pharmacology and/or botany.

The 459 compounds included in the review encompass a diverse range of species -- including those from commonly known plant families such as citrus, daisies, beans and mint. The compounds fall into three major classes of chemicals: About half are phenolic derivatives, around 25 percent are terpenoids, nearly 6 percent are alkaloids and the remainder are classified as other metabolites.

The review authors selected 183 of the compounds and provided further discussion of their antibacterial activity, biosynthesis, chemical structure, mechanism of action and their potential as antibiotics.

"These are all compounds as they appear in nature, not synthesized or derivatized by chemists," Quave explains. "We wanted to provide a systematic overview that brings promising drug candidates to the forefront, opening up new chemical space for discovery. Our review can serve as a starting point for chemists to consider whether they could possibly optimize any of these compounds to become scaffolds for antibiotics treatments."

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Emory Health Sciences

Cloth face masks that can be disinfected by the sun

image: When activated by daylight, a new type of cotton face mask releases reactive oxygen species (ROS) that kill viruses and bacteria.

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Adapted from <i>ACS Applied Materials & Interfaces</i> <b>2020</b>, DOI: 10.1021/acsami.0c15540

During the COVID-19 pandemic, many people have become accustomed to wearing cotton face masks in public places. However, viruses and bacteria that stick to the mask could be transferred elsewhere when the wearer removes or touches it. Now, researchers reporting in ACS Applied Materials & Interfaces have developed a special type of cotton face mask that kills up to 99.9999% of bacteria and viruses within 60 minutes of daylight exposure.

Face masks made of various cloth materials can filter nanoscale aerosol particles -- such as those released by a cough or sneeze -- potentially helping to reduce the spread of diseases, including COVID-19. But live bacteria and viruses on the surface of the mask could still be contagious. Peixin Tang, Gang Sun, Nitin Nitin and colleagues wanted to develop a new cotton fabric that would release reactive oxygen species (ROS) when exposed to daylight, killing microbes attached to the fabric's surfaces while being washable, reusable and safe for the wearer. Then, a person could disinfect their cloth mask during their lunch hour outside in the sun, or by spending a longer period of time under office or building lights, which are much less intense than sunlight.

The researchers made their antimicrobial fabrics by attaching positively charged chains of 2-diethylaminoethyl chloride (DEAE-Cl) to ordinary cotton. Then, they dyed the modified cotton in a solution of a negatively charged photosensitizer (a compound that releases ROS upon exposure to light), which attached to the DEAE chains by strong electrostatic interactions. The team found that a fabric made with a dye called rose Bengal as the photosensitizer killed 99.9999% of bacteria added to the fabric within 60 minutes of daylight exposure and inactivated 99.9999% of T7 bacteriophage -- a virus thought to be more resistant to ROS than some coronaviruses -- within 30 minutes. Further testing showed that the material could be handwashed at least 10 times and constantly exposed to daylight for at least 7 days without losing its antimicrobial activity. The fabric shows promise for making reusable, antibacterial/antiviral cloth face masks and protective suits, the researchers say.

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American Chemical Society

Climate-adapted plant breeding

image: At various locations in Europe with different climatic conditions, the researchers in Prof. Chris-Carolin Sch&ouml;n's team have cultivated old maize varieties to investigate their genetic potential.

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Photo: Tom Freudenberg/pict-images

The famous seed vault in Spitsbergen and national gene banks retain hundreds of thousands of seed samples to preserve old varieties of crop plants and the genetic diversity associated with them. Are these seed banks gold mines or seed cemeteries?

Researchers around the globe are investigating whether retained samples contain genes that have been lost through breeding which could be beneficial in counteracting climate change. A research team led by Chris-Carolin Schön, Professor of Plant Breeding at the TUM, is now presenting a solution to harness the genetic potential of old varieties, so-called landraces.

Have good plant characteristics been lost through breeding?

Since the 1960s, maize has been grown in Europe's fields mainly in the form of hybrid varieties. Hybrid varieties are developed through a specific breeding scheme and, for example are "trimmed" for high yield per hectare or low susceptibility to pests. In order to breed the best variety, a kit of characteristics is needed that could be relevant both today and in the future. Thus, genetic diversity is the basic prerequisite for breeding improved crop plants.

Hybrid varieties, however, carry only a small selection of traits compared to old varieties, the landraces. The question then is whether in addition to undesirable traits, beneficial traits have been lost in the course of many breeding generations. Therefore, the call for landraces has recently been revived, as they are characterized by high biodiversity and are considered a natural source of new genetic variation for breeding. Genetic variation reflects different variants of a gene and can be recognized by differences in the plant's appearance.

Cold-tolerant varieties: Are they the winners in times of climate change?

The early development of young plants is of particular importance in times of climate change. Drought and heat are the conditions most damaging to crops, such as maize, when they occur during flowering. When a plant can be cultivated early in the year because it can cope with cold, it has already left its flowering period behind when temperatures are particularly high in summer. This means that it is less damaged and yield losses can be avoided.

Professor Schön and her colleagues have been examining landrace varieties for cold tolerance characteristics. For this purpose, they have developed a genome-based method of identifying and making targeted use of beneficial gene resources. After a preliminary study, in which the researchers identified the genetic differences of individual varieties, the researchers selected three landraces for cultivation in different locations with varying climatic conditions within Europe.

Landraces provide advantageous genes for crop improvement

The research team focused on traits related to early plant development and also took into account the stability of the plant (How well does it withstand wind?) and the growth form (straight or bushy?). Using molecular methods that scan the entire genome, they were able to link the data from the field trials to genes relevant to the specific traits.

"We have shown how to find new genetic variation for important traits in agricultural production. The variation in these traits is determined by many genes and is not sufficiently available in current breeding material," says Manfred Mayer, lead author of the study. "This opens the door to the development of improved climate-adapted hybrid varieties."

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Technical University of Munich (TUM)

Tree rings may hold clues to impacts of distant supernovas on Earth

Massive explosions of energy happening thousands of light-years from Earth may have left traces in our planet's biology and geology, according to new research by University of Colorado Boulder geoscientist Robert Brakenridge.

The study, published this month in the International Journal of Astrobiology, probes the impacts of supernovas, some of the most violent events in the known universe. In the span of just a few months, a single one of these eruptions can release as much energy as the sun will during its entire lifetime. They're also bright--really bright.

"We see supernovas in other galaxies all the time," said Brakenridge, a senior research associate at the Institute of Arctic and Alpine Research (INSTAAR) at CU Boulder. "Through a telescope, a galaxy is a little misty spot. Then, all of a sudden, a star appears and may be as bright as the rest of the galaxy."

A very nearby supernova could be capable of wiping human civilization off the face of the Earth. But even from farther away, these explosions may still take a toll, Brakenridge said, bathing our planet in dangerous radiation and damaging its protective ozone layer.

To study those possible impacts, Brakenridge searched through the planet's tree ring records for the fingerprints of these distant, cosmic explosions. His findings suggest that relatively close supernovas could theoretically have triggered at least four disruptions to Earth's climate over the last 40,000 years.

The results are far from conclusive, but they offer tantalizing hints that, when it comes to the stability of life on Earth, what happens in space doesn't always stay in space.

"These are extreme events, and their potential effects seem to match tree ring records," Brakenridge said.

Radiocarbon spikes

His research hinges on the case of a curious atom. Brakenridge explained that carbon-14, also known as radiocarbon, is a carbon isotope that occurs only in tiny amounts on Earth. It's not from around here, either. Radiocarbon is formed when cosmic rays from space bombard our planet's atmosphere on an almost constant basis.

"There's generally a steady amount year after year," Brakenridge said. "Trees pick up carbon dioxide and some of that carbon will be radiocarbon."

Sometimes, however, the amount of radiocarbon that trees pick up isn't steady. Scientists have discovered a handful of cases in which the concentration of this isotope inside tree rings spikes--suddenly and for no apparent earthly reason. Many scientists have hypothesized that these several-year-long spikes could be due to solar flares or huge ejections of energy from the surface of the sun.

Brakenridge and a handful of other researchers have had their eye on events much farther from home.

"We're seeing terrestrial events that are begging for an explanation," Brakenridge said. "There are really only two possibilities: A solar flare or a supernova. I think the supernova hypothesis has been dismissed too quickly."

Beware Betelgeuse

He noted that scientists have recorded supernovas in other galaxies that have produced a stupendous amount of gamma radiation--the same kind of radiation that can trigger the formation of radiocarbon atoms on Earth. While these isotopes aren't dangerous on their own, a spike in their levels could indicate that energy from a distant supernova has traveled hundreds to thousands of light-years to our planet.

To test the hypothesis, Brakenridge turned to the past. He assembled a list of supernovas that occurred relatively close to Earth over the last 40,000 years. Scientists can study these events by observing the nebulas they left behind. He then compared the estimated ages of those galactic fireworks to the tree ring record on the ground.

He found that of the eight closest supernovas studied, all seemed to be associated with unexplained spikes in the radiocarbon record on Earth. He considers four of these to be especially promising candidates. Take the case of a former star in the Vela constellation. This celestial body, which once sat about 815 lightyears from Earth, went supernova roughly 13,000 years ago. Not long after that, radiocarbon levels jumped up by nearly 3% on Earth--a staggering increase.

The findings aren't anywhere close to a smoking gun, or star, in this case. Scientists still have trouble dating past supernovas, making the timing of the Vela explosion uncertain with a possible error of as much as 1,500 years. It's also not clear what the impacts of such a disruption might have been for plants and animals on Earth at the time. But Brakenridge believes that the question is worth a lot more research.

"What keeps me going is when I look at the terrestrial record and I say, 'My God, the predicted and modeled effects do appear to be there.'"

He hopes that humanity won't have to see those effects for itself anytime soon. Some astronomers think they've picked up signs that Betelgeuse, a red giant star in the constellation Orion, might be on the verge of collapsing and going supernova. And it's only 642.5 light-years from Earth, much closer than Vela.

"We can hope that's not what's about to happen because Betelgeuse is really close," he said said.

Credit: 
University of Colorado at Boulder

Detecting Alzheimer's disease before symptoms arise

image: Dr. Andrew Kiselica is an assistant professor in the MU School of Health Professions.

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MU School of Health Professions

COLUMBIA, Mo. -- Both of Andrew Kiselica's grandfathers developed dementia when he was in graduate school. As Kiselica was going through neuropsychology training in graduate school, he saw his mother's father become unable to walk or speak due to severe dementia. The University of Missouri researcher said that personal experience has motivated his work to identify and prevent neurodegenerative diseases like Alzheimer's.

Now an assistant professor of health psychology, Kiselica recently finished a study that has resulted in procedures for defining the preclinical stages of Alzheimer's disease. Since there are no current treatments to reverse the course of Alzheimer's, this finding can help drug developers identify who could potentially benefit from a future Alzheimer's treatment before symptoms of cognitive decline start to arise.

"Most families have had this experience of watching someone who is vibrant and full of life essentially turn into someone they can barely recognize," said Kiselica, an assistant professor in the School of Health Professions. "I don't want people to have to go through that as their last phase of life. The experience with my grandparents has been the driving force behind my desire to study this disease."

Defined by cognitive changes that impact one's ability to complete basic activities in daily life, dementia is most commonly caused by Alzheimer's disease, a brain disorder where a buildup of amyloid plaque in the brain leads to memory loss and other cognitive issues.

By looking at datasets from the National Alzheimer's Coordinating Center, Kiselica examined more than 400 individuals who had been declared "cognitively normal," and particularly focused on 101 of these individuals who had a buildup of amyloid plaque in the brain that is associated with Alzheimer's disease.

After analyzing test results that provided data on their memory and attention, caregiver observations of signs of cognitive decline, and neurobehavioral symptoms like anxiety and depression, Kiselica found that those with the amyloid plaque in their brain were more likely to show Alzheimer's-related symptoms compared to those without the amyloid plaque, as expected. More significantly, Kiselica found that 42% of those with the amyloid plaque showed no signs of cognitive decline at all.

"We have developed clear procedures for classifying individuals who are asymptomatic or symptomatic in the preclinical stages of Alzheimer's disease," Kiselica said. "This is important because if a drug to treat Alzheimer's is approved by the FDA down the road, the drug will likely be most effective on those with Alzheimer's-related changes in the brain but no outward signs of cognitive decline yet."

Kiselica added that if those with Alzheimer's-related brain pathology and outward signs of cognitive decline take a proposed Alzheimer's drug in the future, it is possible it will be ineffective because the disease will not be able to reverse course once symptoms start to show up. Therefore, his research can help the developers of future drugs designed to treat Alzheimer's disease or dementia know what type of people to include in their clinical trials.

"This is one of the first studies to demonstrate procedures for defining people in preclinical stages of Alzheimer's disease who do and do not show signs of cognitive and behavioral changes," Kiselica said. "I hope in some small way, my research can lead to improving quality of life for people suffering with neurodegenerative diseases like Alzheimer's."

"An initial empirical operationalization of the earliest stages of the Alzheimer's continuum" was recently published in

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University of Missouri-Columbia

Balance dysfunction after traumatic brain injury linked to diminished sensory acuity

image: Dr. Pilkar is a research scientist in the Center for Mobility and Rehabilitation Engineering Research, and director of the Balance and Assessment Laboratory at Kessler Foundation.

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Kessler Foundation

East Hanover, NJ. November 11, 2020. Kessler Foundation researchers have linked balance dysfunction in individuals with traumatic brain injury with diminished sensory acuity. This study used a psychophysical approach to develop a new metric called the perturbation perception threshold (PPT) for objectively quantifying impaired sensory acuity after traumatic brain injury. The article, "Evaluating sensory acuity as a marker of balance dysfunction after a traumatic brain injury: A psychophysical approach" (doi: 10.3389/fnins.2020.00836), was published August 11, 2020 in Frontiers in Neuroscience. It is available open access at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431558

The authors are Rakesh Pilkar, PhD, Kiran Karunakaran, PhD, Akhila Veerubhotla, PhD, Naphtaly Ehrenberg, MS, Oluwaseun Ibironke, and Karen Nolan, PhD, from the Center for Mobility and Rehabilitation Engineering Research at Kessler Foundation.

Balance problems limit independence, and increase the risk of falls and/or injury after traumatic brain injury. To improve rehabilitation interventions, more knowledge is needed about the integration of the visual, vestibular and somatosensory factors that contribute to balance, and how brain injury can adversely affect this complex system of balance control.

Despite the importance of accurately perceiving external perturbations to maintaining balance, limited research has been done on the contributions of sensory acuity to balance dysfunction after traumatic brain injury, according to lead author Dr. Pilkar, the research scientist who directs the Center's Balance Assessment and Training Laboratory.

Study investigators sought to quantify the threshold for perceiving perturbation in individuals with and without traumatic brain injury, and determine the influence on static and dynamic balance. They provoked body sway during standing and measured response thresholds. Lower thresholds for perceiving these perturbations indicate better body awareness to maintain balance in dynamic settings.

Participants included ten individuals with traumatic brain injury (TBI group) and 11 healthy controls (control group), all of whom underwent comprehensive baseline balance assessment (Berg Balance Scale, Timed-Up and Go, 5-min Walk Test, and 10-meter Walk Test). Using a responsive platform called the Neurocom Smart Equitest Clinical Research System, researchers delivered measured stimuli in three frequencies that briefly moved the platform in an anterior-posterior direction. Participants were asked to respond to 21 trials randomized for movement (perturbation) or no movement (nonperturbation). Each individual's responses to these trials were recorded while standing on the platform, to establish their PPT.

Results revealed significant differences in PPT between the TBI and control groups. Compared with the control group, the TBI group had higher PPT and lower functional scores on static and dynamic balance. While further research is needed, these findings have important implications for the rehabilitation of individuals with TBI. "As a means of detecting and quantifying sensory acuity PPT may serve as a novel marker for the sensory integration deficits that underlie balance impairments in individuals recovering from traumatic brain injury," said Dr. Pilkar. "This line of research will provide the information we need to develop new rehabilitative treatments that restore balance and reduce the risk for falls, and improve long-term outcomes after traumatic brain injury."

Credit: 
Kessler Foundation

Job interest not a big predictor of job satisfaction

image: Kevin Hoff, assistant professor of industrial-organizational psychology at University of Houston, reviewed data from 65 years of research conducted between 1949 and 2016 on the link between interest fit and job satisfaction.

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University of Houston

Most people closing in on a high school or college degree, and even those casting their career fates without a diploma, at some point take an interest assessment to help determine how their interests relate to different jobs. According to the U.S. Department of Labor, The Occupational Information Network's (O*NET) My Next Move website, which hosts the Interest Profiler, averages over 1 million site visits per month.

And now it can be told - a report by a University of Houston researcher reveals that your interest in an occupation does not matter as much as you might think when it comes to job satisfaction.

"Our main finding was that interest fit significantly predicts satisfaction, but it's not as strong of a relation as people expect," reports Kevin Hoff, assistant professor of industrial-organizational psychology, in the Journal of Vocational Behavior. "Other things that lead to satisfaction include the organization you work for, your supervisor, colleagues and pay."

For those forging a career, the takeaway seems hopeful.

"To be satisfied with a job, you don't have to worry too much about finding a perfect fit for your interests because we know other things matter, too. As long as it's something you don't hate doing, you may find yourself very satisfied if you have a good supervisor, like your coworkers, and are treated fairly by your organization," said Hoff.

To reach these conclusions, Hoff and team systematically reviewed data from 65 years of research conducted between 1949 and 2016 on the link between interest fit and job satisfaction. They examined 105 studies with 39,602 participants.

The research also indicates that the relationship between interest fit and job performance is more critical than the link to satisfaction.

"Being interested in your work seems more important for job performance and the downstream consequences of performing well, like raises or promotions," said Hoff.

The use of vocational interests to predict job satisfaction dates to the 1940's when interest assessments were first described as a tool to help people discover satisfying work.

"In popular career guidance literature, it is widely assumed that interest fit is important for job satisfaction. Our results show that people who are more interested in their jobs tend to be slightly more satisfied, but interest assessments are more useful for guiding people towards jobs in which they will perform better and make more money" reports Hoff.

Credit: 
University of Houston

Folding proteins feel the heat, and cold

image: An illustration shows the dynamics of protein folding in a solution as previously understood and as revealed by new models developed at Rice University, Tulane University and the Johns Hopkins University School of Medicine.

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Illustration by Dilip Asthagiri

HOUSTON - (Nov. 11, 2020) - It's a long-standing assumption that the presence of water influences how proteins fold. A new study is challenging the details.

A paper in the American Chemical Society's Journal of Physical Chemistry Letters shows proteins that presumably evolved to avoid water as they fold may actually behave in ways scientists did not anticipate.

That discovery could change how scientists think about hydrophobic (water-avoiding) and hydrophilic (water-attracting) interactions in solutions, according to a Rice University engineer.

Collaborators from Rice and Tulane universities and the Johns Hopkins University School of Medicine created atom-level models of polypeptides that showed folding is also influenced by thermal expansion of the solvents they occupy, but not in ways that match previous assumptions.

The long-held view is that hydrophobic amino acids, which avoid water by coming together as efficiently as possible, are a dominant force in protein folding, said Dilip Asthagiri, an associate research professor of chemical and biomolecular engineering at Rice's Brown School of Engineering.

The new study shows temperature, a factor not always included in protein folding models, also influences the phenomenon. That should prompt a reassessment of how proteins folding in a solution are stabilized, according to the researchers.

"There are many proteins that are intrinsically disordered that don't fold at all," Asthagiri said. "One way the non-folding has been rationalized has been to look at the balance of hydrophobic groups and charged groups and, assuming the latter dominate, conclude the polypeptide does not fold.

"We showed in 2017 that in a model of an intrinsically disordered peptide that has no side chains, hydrophilic effects can in fact overwhelm the collapse driven by the still-substantial hydrophobic effects and drive the unfolding, even in the absence of charged residues," he said. "That study and the one published earlier in 2016 highlighted the role of hydrophilic effects. But we didn't look at temperature effects."

So the team led by Asthagiri set out to model precisely how polypeptides, a classification that includes proteins in biological systems, fold and unfold as they connect with water at various temperatures.

When the researchers calculated the free energy of a hydrated deca-alanine peptide sequence, along with its side-chains, they found that forces of attraction between the solvent and peptide play a role as well, particularly when more than one peptide is involved.

They found that in the temperature ranges they modeled, the matrix of solvent around the polypeptides expands when heated, decreasing the population of solvent molecules that are around and contacting the peptides. This can make binding interactions between the solvent and peptides less favorable.

They noted the effect is minor for small molecules in a solvent, but amplified for larger peptides and proteins. They also said the theory suggests hydrophilic effects can contribute to the denaturation, or unfolding, of proteins in cold solutions.

"The solution environment is an important contributor to the structure of proteins," said Tulane chemical engineer and co-corresponding author Lawrence Pratt, a longtime mentor to Asthagiri. "Everything the solution does, including the water, has to do with how these proteins put themselves together and the functions they perform."

He said hydrophobic effects in protein folding have been recognized since the 1940s. "It's a rather tricky thing, though, because it has unusual temperature dependencies," Pratt said. "You know, things live or die if you change the temperatures.

"Some hydrophobic effects get stronger when you raise the temperature, so things get to be more stable," he said. "But Dilip shows this increase in strength with increasing temperature can come from other places, including effects that all chemists would say are hydrophilic.

"Both hydrophobic and hydrophilic effects come into play," he said. "And they're competing, and they're collaborating. And so being able to distinguish them individually in a very convincing way is a big step in sorting all this behavior out."

Credit: 
Rice University

The young resumed risky behaviors earlier than the elderly as COVID-19 pandemic dragged on

Early in the COVID-19 pandemic, old and young individuals did not differ in taking precautions, but over time, older people quickly adopted preventive behaviors and they engaged in more preventive behaviors. Older people engaged in fewer risky behaviors relative to younger people on month after the beginning of the pandemic and this age difference persisted over time; both young and older people started engaging in more potentially risky behaviors. These findings come from a new study by Jung Ki Kim at the University of Southern California, Los Angeles, published November 10 in the open-access journal PLOS ONE.

The risk of dying from COVID-19 dramatically increases with age, because the elderly are more likely to have underlying health conditions and a weaker immune system. To see if older individuals were more likely to take precautions against COVID-19, such as handwashing, quarantining and social distancing, Kim and her USC colleague, Eileen Crimmins, examined data on COVID-19-related behaviors from a nationally representative sample of American households participating in the Understanding America Study.

They discovered that early on, old and young people were equally likely to take precautions, but a month into the pandemic, young people were more likely to engage in some risky behaviors, like visiting friends. As the pandemic progressed, however, both old and younger people resumed some potentially risky activities. The researchers also found that people who are female, of higher socioeconomic status, a member of a racial or ethnic minority group, or left-of-center politically, or who live in a place with high numbers of COVID-19 cases, were more likely to try to limit their risk of infection.

Overall, the new study shows that people of different ages responded differently to the threat posed by COVID-19, and that these responses changed with the course of the pandemic. Given the more severe consequences for older people who are infected - and the lack of a cure - the authors encourage older individuals to continue taking precautions and to avoid risky behaviors until a vaccine can be developed and distributed.

The authors add: "It is encouraging to observe older people taking more preventive personal behaviors as the pandemic progressed. This may have alleviated their risk of infection. However, at the same time, it is concerning that people increased risky social behaviors over time, particularly older people, who could have more adverse consequences from meeting with family and friends."

Credit: 
PLOS

Internal clocks drive beta cell regeneration

image: Image of pancreatic islets showing proliferation markers (in red staining) in the nuclei (in blue) of insulin-producing-cells (in green).

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© UNIGE/Dibner

Certain parts of our body, such as the skin or liver, can repair themselves after a damage. Known as cell regeneration, this phenomenon describes how cells that are still functional start to proliferate to compensate for the loss. For the past 30 years, scientists have been investigating the regenerative potential of beta cells, pancreatic cells in charge of the production of insulin. Beta-cell population is indeed partially destroyed when diabetes occurs, and regenerating these cells represents an outstanding clinical challenge. By studying diabetic mice, scientists from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG, observed that this regeneration mechanism was under the influence of circadian rhythms - the molecular clocks regulating metabolic functions according to a 24-hour cycle of alternating day-night. In addition, the scientists identified the essential role of the core clock component BMAL1 in this process. These results, to be read in the journal Gene and Development, allow new perspectives to be envisaged to promote beta cell regeneration.

Compensatory proliferation, in which cells begin to actively divide to replace those that have been damaged, is a biological mechanism that is both well-known and poorly understood. &laquoAnd this is particularly true for pancreatic beta cells, whose regenerative mechanism stays largely unexplored despite decades of research,» explains Dr Charna Dibner, head of the Circadian Endocrinology Laboratory at UNIGE Faculty of Medicine's the Departments of Medicine and Cell Physiology and Metabolism, as well as at the Diabetes Centre, and at the HUG. &laquoHowever, deciphering this phenomenon and above all finding out how to promote it could be a game changer for controlling diabetes.»

Day-night rotation is essential

To explore the connection between internal biological clocks and beta cell regeneration, Charna Dibner's team first observed two groups of mice with only 20% beta cells remaining after targeted massive ablation. Mice in a first group were arrhythmic, whereas the control group had perfectly functional clocks. &laquoThe result was very clear: the mice bearing dysfunctional clocks were unable to regenerate their beta cells, and suffered from severe diabetes, while the control group animals had their beta cells regenerated; in just a few weeks, their diabetes was under control,» says Volodymyr Petrenko, a researcher in Dr. Dibner's laboratory and the leading scientist in this study. By measuring the number of dividing beta cells across 24 hours, the scientists also noted that regeneration is significantly greater at night, when the mice are active.

The BMAL1 gene, metronome of cell activity

The arrhythmic mice were lacking the BMAL1 gene, which codes for the protein of the same name, a transcription factor known for its key action in the functioning of circadian clock. &laquoOur analyses show that the BMAL1 gene is essential for the regeneration of beta cells,» adds Volodymyr Petrenko. In addition, large-scale transcriptomic analyses over a 24-hour period, conducted in collaboration with Prof. Bart Vandereycken at the Mathematics Department of the UNIGE, revealed that the genes responsible for regulating cell cycle and proliferation were not only upregulated, but also acquired circadian rhythmicity. "BMAL1 seems to be indeed central for our investigation," stresses Charna Dibner. "However, whether the regeneration requires functional circadian clocks themselves, or only BMAL1, whose range of functions goes beyond clocks remains unclear. That is what we would like to find out at present." The scientists also want to explore the function of alpha cells, which produce glucagon, the hormone that antagonises insulin, in this model. The arrhythmic mice indeed showed very high levels of glucagon in the blood. "A detailed understanding of these mechanisms must now be pursued, in an attempt to explore the possibility of triggering beta cell regeneration in humans in the future" conclude the authors.

Credit: 
Université de Genève