Culture

Researchers have revealed a new molecular mechanism by which bacteria adhere to cellulose fibers in the human gut. Thanks to two different binding modes, they can withstand the shear forces in the body. Scientists of the University of Basel and ETH Zurich published their results in the journal "Nature Communications".

Cellulose is a major building block of plant cell walls, consisting of molecules linked together into solid fibers. For humans, cellulose is indigestible, and the majority of gut bacteria lack the enzymes required to break down cellulose.

However, recently genetic material from the cellulose-degrading bacterium R. champanellensis was detected in human gut samples. Bacterial colonization of the intestine is essential for human physiology, and understanding how gut bacteria adhere to cellulose broadens our knowledge of the microbiome and its relationship to human health.

The bacterium under investigation uses an intricate network of scaffold proteins and enzymes on the outer cell wall, referred to as a cellulosome network, to attach to and degrade cellulose fibers. These cellulosome networks are held together by families of interacting proteins.

Of particular interest is the cohesin-dockerin interaction responsible for anchoring the cellulosome network to the cell wall. This interaction needs to withstand shear forces in the body to adhere to fiber. This vital feature motivated the researchers to investigate in more detail how the anchoring complex responds to mechanical forces.

By using a combination of single-molecule atomic force microscopy, single-molecule fluorescence and molecular dynamics simulations, Professor Michael Nash from the University of Basel and ETH Zurich along with collaborators from LMU Munich and Auburn University studied how the complex resists external force.

Two binding modes allow bacteria to stick to surfaces under flow

They were able to show that the complex exhibits a rare behavior called dual binding mode, where the proteins form a complex in two distinct ways. The researchers found that the two binding modes have very different mechanical properties, with one breaking at low forces of around 200 piconewtons and the other exhibiting a much higher stability breaking only at 600 piconewtons of force.

Further analysis showed that the protein complex displays a behavior called a "catch bond," meaning that the protein interaction becomes stronger as force is ramped up. The dynamics of this interaction are believed to allow the bacteria to adhere to cellulose under shear stress and release the complex in response to new substrates or to explore new environments.

"We clearly observe the dual binding modes, but can only speculate on their biological significance. We think the bacteria might control the binding mode preference by modifying the proteins. This would allow switching from a low to high adhesion state depending on the environment," Professor Nash explains.

By shedding light on this natural adhesion mechanism, these findings set the stage for the development of artificial molecular mechanisms that exhibit similar behavior but bind to disease targets. Such materials could have applications in bio-based medical superglues or shear-enhanced binding of therapeutic nanoparticles inside the body. "For now, we are excited to return to the laboratory and see what sticks," says Nash.

Generally speaking, "ridge subduction" involves subduction of spreading oceanic ridges, aseismic ridges or oceanic plateaus and inactive arc ridges, and this common and important geological process has become one of the hot topics in current geological research globally. However, many issues concerning ridge subductions need to be further studied.

A research entitled "Ridge subduction, magmatism and metallogenesis", with Wang Qiang as the first author, Tang Gongjian, Hao Lulu, Wyman Derek, Ma Lin, Dan Wei, Zhang Xiuzheng, Liu Jinheng, Huang Tongyu and Xu Chuanbing as co-authors, is published in Science China Earth Sciences. The researchers aim to provide a systematic review on recent progress in the study of ridge subduction and discuss some developing research frontiers in the fields related to ridge subduction.

Spreading oceanic ridges, aseismic ridges or oceanic plateaus and inactive arc ridges together account for more than 20-30% of the total area of the world's ocean floor (Figure 2). Ridge subduction closely related to "the generation of arc magmatism, material recycling, growth and evolution of continental crust, deformation and modification of overlying plates and metallogenesis", is a significant geological process in modern oceanic plate tectonics.

The perpendicular or highangle subduction of mid-oceanic spreading ridges is commonly characterized by the occurrence of a slab window, and the formation of adakite-high-Mg andesite-Nb-enriched basalt-oceanic island basalt (OIB) or mid-oceanic ridge basalt (MORB)-type rock suite, and is closely associated with Au mineralization.

On the eastern side of the Pacific Ocean, aseismic ridges or oceanic plateaus are being subducted flatly or at low angles beneath South and Central American Continents, which may cause slab rollback or tearing and the formation of an adakite-high-Mg andesite-adakitic andesite-Nb-enriched basalt suite, and is closely associated with Cu-Au mineralization.

However, on the western side of the Pacific Ocean, aseismic ridges and oceanic plateaus are associated with steep subduction (with angles>30°), which generate large scale eruptions of basalts, basaltic andesites and andesite.

The subduction of inactive arc ridges in Southwest Japan generated basalts, high-Mg andesites and adakites, and Au mineralization.

In addition to arc magmatism and metal mineralization, ridge subduction may also trigger subduction erosion in the overlying plate.

"Many issues concerning ridge subductions remain controversial", said the researchers. "Future frontiers of research will include characterizing the spatial and temporal patterns of ridge subduction events, clarifying the associated geodynamic mechanisms, quantifying subduction zone material recycling, establishing the associated deep crustal and mantle events that generate or influence magmatism and Cu-Au mineralization, establishing criteria to recognize pre-Cenozoic ridge subduction, the onset of modern-style plate tectonics and the growth mechanisms for Archean continental crust."

New Orleans, LA - A study of a gateway receptor for SARS-CoV-2 led by Walter J. Lukiw, PhD, Professor of Neuroscience, Neurology and Ophthalmology at LSU Health New Orleans' Neuroscience Center of Excellence and School of Medicine, may help explain the wide variety of symptoms and organs involved with SARS-CoV-2 infection and COVID-19. The results suggest that a multi-organ infection with SARS-CoV-2 may be via the angiotensin-converting enzyme 2 (ACE2) receptor, which is found almost everywhere throughout the body. The findings are published in the journal Cellular and Molecular Neurobiology, available here.

To better understand the mechanism and pathways of SARS-CoV-2 infection and susceptibility to specific cell and tissue types as well as organ systems, the research team analyzed 85 human tissues for the presence of ACE2 receptors. ACE2 is a protein that is found on the surface of many immune and nonimmune cell types. An enzyme, it is part of the system that regulates blood pressure and fluid and electrolyte balance. It may also help regulate cardiovascular, neurovascular and renal function, as well as fertility. ACE2 receptors act like locks on cells, and the SARS-CoV-2 spike proteins act like keys that open the locks letting the virus enter cells to rapidly multiply. As well as controls, tissues tested included lung, digestive, renal-excretory, reproductive, eye tissues, and 21 different regions of the brain.

"Besides strong ACE2 expression in respiratory, digestive, renal-excretory and reproductive cells, high ACE2 expression was also found in the amygdala, cerebral cortex and brainstem," reports Dr. Lukiw. "This may help explain cognitive deficits associated with SARS-CoV-2 infection. Some of the highest ACE2 expression levels were found in the pons and medulla oblongata in the human brainstem, an anatomical region of the brain containing the medullary respiratory centers, and this may in part explain the susceptibility of many CoV-19 patients to severe respiratory distress."

The team further noted that ACE2 receptor activity was also easily detected in the eye, suggesting that the visual system may provide an additional entry point for SARS-CoV-2 invasion and that under certain conditions, eyeglasses or face shields may be as important as face masks in reducing SARS-CoV-2 transmission and infection.

"Several important research gaps remain," Lukiw concludes. "A real danger of SARS-CoV-2 infection is not only its highly transmissible and contagious nature and lethality, but also its simultaneous and multipronged attack on many human cell and tissue types involving vital and critical respiratory, immunological, vascular, renal-excretory and neural systems as well as an unprecedented coordinated disruption of the complex neurophysiology, neurochemistry, neurobiology and neurology of the cells of the brain and central nervous system (CNS) that normally regulate these multiple physiological systems."

The COVID-19 pandemic has deeply affected our daily lives and put individuals, institutions, and societies to the test in several regards. The new policies adopted by governments to contain the pandemic, and the economic and psychological impact it has had on people, have caused significant changes in higher education systems.

The international travel restrictions, growing fear and anxiety, increasing prejudices, and burden of economic slowdowns, among other factors, could become obstacles for international students willing to attend university abroad. However, the present situation is highly dynamic, and predicting the lasting impacts of the COVID-19 crisis on international university education is difficult.

In the latest issue of the East China Normal University (ECNU) Review of Education, four education researchers provide their unique perspectives on how the pandemic will affect international student mobility (ISM) and identity.

In the first article, Dr Jiao Guo from ECNU, China, focuses on how Chinese students and their families are reacting to the pandemic. She recognizes that many Chinese families are understandably stressed not only because of the health risk that COVID-19 poses, but also by the anti-Chinese sentiment that has sadly become more noticeable in many Western countries.

Dr Guo argues, however, that the effect of the current crisis on Chinese student applications to universities abroad will vary. Based on an emotion-moderated sunk cost theory, a concept borrowed from the fields of economics and business decision-making, she speculates that some Chinese families will remain on course towards a university education overseas, perhaps with a destination change or a delay of a year or two. She says, "These are families with children who have nearly finished their K-12 education in international Chinese schools, who feel that they have already invested too much time, money, and effort into their children's education to change plans. On the other hand, working class families with children in public schools should be more inclined to opt for local education in one of China's universities."

In the second article, Dr Hantian Wu from Zhejiang University, China, analyzes the prospects for ISM from a historical perspective. He argues that internationalized higher education systems will have to re-predict their development trends and that studying how previous global crises affected the education sector is a plausible strategy for doing so. He goes over several medieval and premodern crises, including the Black Death and the Spanish flu outbreak of 1918, to prove that higher education systems are remarkably resilient. For instance, Chinese student inflow into western countries increased considerably in the immediate aftermath of the Spanish flu. Modern history also seems to be consistent with this trend, as observed, for example, post the 2001 terrorist attacks on the United States.

Nonetheless, Dr Wu cautions against taking historical events as conclusive evidence: "Discussions about recurring issues in modern history may be convincing, but they also should not be regarded as persuasive evidence for proving that history repeats itself. Still, it seems appropriate to conclude that a single sudden crisis can hardly bring fundamental changes to the overall trend of student mobility."

In the third article, Dr Jie Zheng from ECNU holds forth that the current pandemic might change how students and policy makers view neoliberal globalization. Dr Zheng argues that the optimism surrounding globalization has been a driving factor for the explosive growth of ISM in the past few years. "In the past two decades, we have been proud of our 'global village' and global vision. We have enjoyed a deterritorialization of social life and free mobility worldwide. Indeed, imagination has been transformed by the media and those narratives of possible lives and fantasies might have stimulated people's desire for movement," she states.

The ongoing pandemic challenges this neoliberal logic of "free trade, free market, free mobility." The focus, she concludes, has inevitably shifted to developing online education systems that could, in the future, open doors to possibilities for a more inclusive and environmentally sustainable society.

But such a society will also depend on the global citizen that emerges from the pandemic. In the fourth article, Dr Tao Wang from ECNU argues that the breakdown of neoliberal globalization and the dual stigmatization of the Chinese student, both by Chinese nationalists and by nationalists of several other countries, had made the cosmopolitan identity complex.

Yet, he remains optimistic. He says, "I predict that a new generation of 'glocal' citizens will emerge who can navigate smoothly between their local and global identities, understanding global challenges, respecting cultural diversity, and participating in cross-cultural communication. These citizens will bring about the beginning of a shared positive global future."

The COVID-19 pandemic is certainly changing the education landscape for good. But what the new landscape will look like when the dust settles, remains to be seen. Perhaps these new perspectives will prove useful to individuals and organizations who must take action and, willingly or unwillingly, shape the future.

Linguistic researchers use an extensive body of research on English and other Western languages to make broad assumptions about trends in human language, including an apparent universal preference for suffixes (e.g., less, able, ment) over prefixes (e.g., fore, anti, trans). Since psychological scientists recognize the powerful link between language and cognition, a tendency for suffixes to dominate human language may reflect a universal trait of how we think and process the world around us.

However, new research published in the journal Psychological Science reveals that even though many populations favor suffixes in the same way English speakers do, others do not, including speakers of the African Bantu language Kîîtharaka. This unexpected discovery challenges the idea that Western languages are sufficient when studying language and its connection to psychological science.

"The original hypothesis that humans generally prefer suffixes makes a lot of intuitive sense, at least to us English speakers," said Alexander Martin, a language researcher at the University of Edinburgh and lead author on the paper. "We were surprised, therefore, to see just how starkly the two populations [English speakers and Kîîtharaka speakers] differed in this regard."

For their research, Martin and his colleagues studied specific word characteristics among the two populations--one whose language relies more frequently on suffixes (51 English speakers) and one whose language relies more on prefixes (72 Kîîtharaka speakers). Participants were presented with a sequence of either shapes or syllables followed by two additional sequences. They were then asked to identify the sequence most similar to the original sequence. Based on their results, the researchers were able to identify which parts of sequences the speakers considered most important and therefore less likely to be modified.

English speakers considered the beginnings of words as more important, a language characteristic that reflects English's use of suffixes. Kîîtharaka speakers, however, were inclined to treat endings as more important, opting to select sequences that altered the beginnings of words.

"This finding really challenged a previous claim about human language," said Martin. "It showed that the abundance of suffixes across the world's languages might not simply be a reflection of general human perception."

A preference for prefixes over suffixes by some language speakers has larger implications than diverse human cognition. It might be a sign that language research has not been exhaustive in the past.

"The important take-home here is that if we want to understand how language is shaped by universal features of human cognition or perception, we need to look at a diverse sample of humans," said Martin.

The WEIRD Preference for Suffixes

Prior research has established that English speakers favor the beginnings of words. This is reflected in the structure of English: when modifying a word to change its meaning, English tends to add suffixes. For example, common suffixes in the English language include "-wise," which you might add onto the end of "clock," or "like," or "-al," which often tails behind "accident" or "fiction."

These past language studies, however, have focused predominantly on Western, educated, industrialized, rich, and democratic (WEIRD) populations. Such studies have concluded that suffixes are generally preferred over prefixes. Martin and his colleagues observed that such research excludes populations that do not fall into "WEIRD" categories, and conclusions drawn from them could therefore be unrepresentative of universal human cognition.

The Nexus of Language and Cognition

"How the human brain perceives and processes the world around it impacts language, but not every feature of language is a direct reflection of this," said Martin. "For example, how we use language, like for communication, can also affect language patterns." The study's conclusions further illuminate the relationship between human cognition and language systems and patterns. However, Martin cautioned against assuming that different languages must mean drastically different perceptions of the world.

"When we look at speakers of other languages, especially those who speak languages that haven't been studied extensively, we are able to understand that we've been seeing the world through a biased lens. That's something we think psychologists should care about," he said.

UNIVERSITY PARK, Pa. -- Consumers are expected to spend more than $100 billion at online pharmacies in the next few years, but not all of these businesses are legitimate. Without proper quality control, these illicit online pharmacies are more than just a commercial threat, they can create serious health threats.

In a study, a team of Penn State researchers report that an algorithm they developed may be able to spot illicit online pharmacies that could be providing customers with substandard medications without their knowledge, among other potential problems.

"There are several problems with illicit online pharmacies," said Soundar Kumara, the Allen E. Pearce and Allen M. Pearce Professor of Industrial Engineering. "One is they might put bad content into a pill, and the other problem is they might reduce the content of a medicine, so, for example, instead of taking 200 milligrams of a medication, the customers are only taking 100 milligrams -- and they probably never realize it."

Besides often selling sub-standard and counterfeit drugs, illicit pharmacies may provide potentially dangerous and addictive drugs, such as opioids, without a prescription, according to the researchers, who report their findings in the Journal of Medical Internet Research, a top-tier peer-reviewed open-access journal in health/medical informatics. The paper, "Managing Illicit Online Pharmacies: Web Analytics and Predictive Models Study," can be accessed here.

The researchers designed the computer model to approach the problem of weeding out good online pharmacies from bad in much the same way that people make comparisons, said Kumara, who is also an associate of Penn State's Institute for Computational and Data Sciences.

"The essential question in this study is, how do you know what is good or bad -- you create a baseline of what is good and then you compare that baseline with anything else you encounter, which normally tells you whether something is not good," said Kumara. "This is how we recognize things that might be out of the norm. The same thing applies here. You look at a good online pharmacy and find out what the features are of that site and then you collect the features of other online pharmacies and do a comparison."

Hui Zhao, associate professor of supply chain and information systems and the Charles and Lilian Binder Faculty Fellow in the Smeal College of Business, said that sorting legitimate online pharmacies from illicit ones can be a daunting task.

"It's very challenging to develop these tools for two reasons," said Zhao. "First is just the huge scale of the problem. There are at least 32,000 to 35,000 online pharmacies. Second, the nature of online channels because these online pharmacies are so dynamic. They come and go quickly -- around 20 a day."

According to Sowmyasri Muthupandi, a former research assistant in industrial engineering and currently a data engineer at Facebook, the team looked at several attributes of online pharmacies but identified the relationships between the pharmacies and other sites as a critical attribute in determining whether the business was legitimate, or not.

"One novelty of the algorithm is that we focused mostly on websites that link to these particular pharmacies," said Muthupandi. "And among all the attributes we found that it's these referral websites that paint a clearer picture when it comes to classifying online pharmacies."

She added that if a pharmacy is mainly reached from referral websites that mostly link to or refer illicit pharmacies, then this pharmacy is more likely to be illicit.

Zhao said that the algorithm the team developed could help consumers identify illicit online pharmacies, which are estimated to represent up to 75% of all online drug merchants. As an added danger, most consumers lack the awareness of the prevalence and the danger of these illicit pharmacies and consequently use the site without knowing the potential risks, she said.

The researchers said a warning system could be developed that alerts the consumer before a purchase that the site may be an illicit pharmacy. Search engines, social media, online markets, such as Amazon, and payment or credit card companies could also use the algorithm to filter out illicit online pharmacies, or take the status of the online pharmacies into consideration when ranking search results, deciding advertising allocations, making payments, or disqualifying vendors.

Policy makers, government agencies, patient advocacy groups and drug manufacturers could use such a system to identify, monitor, curb illicit online pharmacies and educate consumers.

Infants from households reporting very low "food security," a measure of access to adequate and healthy meals, tend to weigh more than those from households with relatively high food security, suggests a new study led by a researcher at Johns Hopkins Bloomberg School of Public Health.

The study tracked nearly 700 infants in North Carolina over their first year of life, with regular interviews of the infants' mothers. The researchers found that when mothers reported very low food security per a standard government questionnaire, the infants were more likely to have above-average body mass indices (BMIs), higher fat levels, and other measures indicating greater obesity risk.

The reasons for the association between food insecurity and higher obesity risk are not yet understood but may be related to poor nutrition and overfeeding. The results suggest that household food insecurity may be especially hazardous for infants, given that diet and weight gain in infancy are thought to have a potentially large impact on the future risks of obesity and related health conditions.

The study was published August 28 in Pediatrics.

Study lead author Sara Benjamin-Neelon, PhD, JD, the Helaine and Sidney Lerner Associate Professor in the Bloomberg School's Department of Health, Behavior and Society, began the study in 2013 when she was a faculty member at Duke University's School of Medicine, and completed data collection in 2017 at the Bloomberg School. The 666 infants tracked in the study were from lower-income households in Durham, NC. Most of the infants (68.6 percent) were African American, 14.9 percent were white, and 55.4 percent of the households reported annual incomes below $20,000. Benjamin-Neelon and her colleagues visited the homes of the infants when they were 3, 6, 9, and 12 months old, and interviewed the mothers by phone an additional eight times over the year.

"The findings are especially relevant today when there is such widespread food insecurity in the U.S. due to the COVID-19 crisis," says Benjamin-Neelon, PhD, JD, who also directs the Lerner Center for Public Health Promotion at the Bloomberg School.

For their analysis, the researchers compared the weight and length of infants in the study to a global population of healthy infants from eight counties to determine "at risk of overweight." They found that infants from households categorized as low and very low food security tended to move into this overweight risk category over the 3-month visit to the 12-month visit period (53.2 percent to 66.9 percent), whereas infants from households with high and marginal food security--those with moderate access to adequate, healthy food--tended to move out of this category (46.8 to 33.1 percent) during the period.

Infants in households with low and very low food security also were generally more likely (1.72 and 1.55 times more likely) to be at risk of overweight. Additionally, infants from very low food security households were significantly heavier by comparison with infants from food-secure households, and had more fat accumulation by standard caliper-based measures.

"One possible explanation for this link is that food insecurity is associated with lower quality diets that promote obesity, although infants, especially in the first six months of life, should be consuming limited foods-mainly just human breastmilk or infant formula," Benjamin-Neelon says. "Another possibility may be related to infant feeding practices. Mothers wanting to make sure their infants are fed enough could be overfeeding or feeding in a way that overrides infant fullness cues like propping a bottle or encouraging infants to finish the bottle."

Benjamin-Neelon and colleagues found, to their surprise, that mothers' participation in either of two federal food assistance programs, WIC and SNAP, did not modify the apparent links between food insecurity and being overweight.

"As a former WIC nutritionist, I thought it was important to assess whether such programs modified the association between food insecurity and obesity," Benjamin-Neelon says. "However, just because it didn't make a difference in this study does not mean that women with infants and young children should not participate in these valuable programs."

She and her colleagues believe that larger and longer-term studies are needed to resolve the many questions about food insecurity and obesity, including whether the association in infancy continues into later childhood.

SAN FRANCISCO, CA--August 28, 2020-- TK Adenosine triphosphate, or ATP, is the cellular energy currency that is as valuable to the human body as the dollar is to the US economy. Too high or too low levels of ATP in some cell types have been linked to a variety of diseases. However, scientists have lacked an understanding of how cells regulate ATP levels on a broad scale and how cells' energy levels can be protected or restored in the setting of disease.

Now, researchers at Gladstone Institutes have performed a massive and detailed cellular energy audit; they analyzed every gene in the human genome to identify those that drive energy production or energy consumption. The result is a collection of data they call the "ATPome," which not only provides new directions for the field of metabolism research, but also identifies genes and proteins that can be targeted to manipulate cellular energy and treat disease.

"Essentially all cellular functions require energy but, before our study, we had very little knowledge about how to restore energy to cells when levels have gone awry," said Gladstone Associate Investigator Ken Nakamura, MD, PhD, the senior author of the study published online in the journal Nature Communications. "Our findings have implications for treating a broad array of disorders, including neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, mitochondrial disorders, heart disease, diabetes, and cancer."

When cells need energy, they turn the energy you consume in food into ATP molecules. Then, the cell breaks apart the ATP molecule to release the energy, which is used to fuel chemical reactions. When cells don't have enough ATP, disease can result. Dysregulated energy production may also play a central role in some cancers. But a lack of understanding of how cells regulate energy has made it difficult to target these energy imbalances therapeutically.

In the new study, Nakamura and his colleagues leveraged a screening approach they had previously developed that uses a chemical sensor to quantify how much ATP is present in individual cells. In addition, they turned to CRISPR gene-editing technology to selectively turn down--or turn up--the expression of nearly every gene in the human genome, one at a time. This way, the team could measure the effect of altering each gene on ATP levels. They repeated the experiments under three different metabolic conditions, forcing the cells to rely on different pathways to produce ATP.

The set of experiments revealed new genes and pathways that help boost cellular energy by either promoting energy production or slowing energy consumption. It also showed that the cell's fuel source is a critical factor in determining which genes are needed to maintain ATP levels.

"Before this study, we knew a lot more about how energy is produced than about how it is consumed," said Neal Bennett, PhD, a Gladstone postdoctoral scholar and first author of the study. "A better understanding of how energy is consumed could lead to truly novel ways of regulating ATP levels in diseases of energy dysregulation. For instance, in diseases such as stroke or heart attack where cells experience an acute deficiency of energy supply, our study may point to ways to temporarily preserve energy levels by reducing the amount of energy they consume."

The team was also surprised to observe a new role for a critical molecular pathway called HIF1. The pathway has long been linked to the production of ATP when cells are in low-oxygen conditions. But Nakamura's group found that the HIF1 pathway strongly suppresses ATP production even under normal oxygen conditions. This means that putting the brakes on HIF1 could be one way to increase energy production by mitochondria.

Nakamura believes that the new ATPome database his group generated will likely have far-reaching utility for scientists studying the role of cellular energy in disease. Being able to manipulate cellular energy could help biologists limit the amount of energy available to cancer cells, or increase ATP in brain cells affected by neurodegeneration, among other therapeutic applications.

"What we've done is put together a basic blueprint for how genes play a role in energy production, consumption, and possibly energy dysfunction," said Nakamura, who is also an associate professor of neurology at UC San Francisco (UCSF). "From here, we have to extend the results into other cell types and gain an understanding of how this basic blueprint is altered by different diseases, in order to develop novel therapeutic approaches to manipulate energy metabolism."

Nakamura's lab is collaborating with other researchers at Gladstone and UCSF to study how energy usage might differ in brains affected by Parkinson's or Alzheimer's disease; in the heart--an organ that requires high amounts of energy and is prone to energy failure; and in cancer, which may be fueled by excessive energy.

UNIVERSITY PARK, Pa. -- Small-scale poultry farmers in Vietnam tend to respond to viral outbreaks of highly pathogenic avian influenza (HPAI) by rapidly selling their birds as a way to avoid financial loss, according to a new study by an international team of researchers. As these birds are commingled with other birds in markets and trading networks, this practice may increase the likelihood of widespread disease transmission. The findings could have implications for government policymaking in the many regions of the world where small-scale poultry farming and avian influenza risk co-occur.

"Avian influenza is deadly to humans, with a case fatality rate between 25% and 50%," said Maciej Boni, associate professor of biology, Penn State. Fortunately, reports of human-to-human transmission over the past 15 years have been either absent or anecdotal. COVID-19 took us by surprise, but with HPAI we have a known threat with the potential to become pandemic. If we ignore the active role that poultry farmers play in the control and dissemination of avian influenza, we may miss another opportunity to curtail an emerging disease outbreak at a stage when it is still controllable."

Lead author Alexis Delabouglise, an animal health economist at CIRAD-Agricultural Research for Development in France who was a postdoctoral scholar at Penn State when the research was performed, explained that small-scale poultry farming is practiced by millions of Vietnamese households and by millions more throughout southeast Asia, mostly on a scale of fewer than 100 birds per farm. These farmers make decisions on a daily basis -- often in response to economic incentives -- about when and where to sell their flocks. And their decisions can influence disease spread.

"If the price of poultry goes up, farmers might expand their farming activities, which could create more outbreak risk," said Delabouglise. "If there is an outbreak on a neighboring farm, they might choose to sell their poultry early to avoid their own birds from being infected and to avoid lower prices. And if there is an outbreak on their own farm, the evidence in our study shows that they would be likely to sell their birds early to avoid both monetary loss and epidemiological risk."

Boni and colleagues, including researchers at the Oxford University Clinical Research Unit (OUCRU) in Ho Chi Minh City, conducted a longitudinal study of small-scale poultry farms in the Mekong river delta region of southern Vietnam with a goal of characterizing the effects of disease outbreaks on poultry harvest rates, as well as on two prevention practices -- vaccination and farm disinfection. The team followed 53 farmers and their management of more than 1,000 poultry flocks for a period of two years -- from 2015 to 2017.

"Working with partners in endemic countries day-in and day-out on study details and public health priorities is key to establishing collaborations that allow these long-term follow-up studies to succeed," said Boni, who led a research group at OUCRU for eight years.

Delabouglise, the statistical lead on the project, used mixed-effects general additive models to investigate farmers' probabilities of harvesting -- either selling or slaughtering -- flocks, of performing avian influenza vaccination on flocks that were not previously vaccinated and of disinfecting farm facilities when faced with an outbreak. Their findings appeared in eLife on August 25.

"We found that farmers did send their chickens to market early when there were outbreaks occurring on their farms," said Delabouglise. "Specifically, small-scale farmers increased their harvest of broiler chickens by 56% during outbreaks with no sudden deaths and by 214% during outbreaks with sudden deaths. This has the potential to exacerbate the outbreak and spread the virus even further."

The team noted that sudden deaths -- the deaths of chickens less than one day after the onset of clinical symptoms -- are considered to be indicative of HPAI infection. Interestingly, the team found that the probability of disinfection was not affected by the occurrence of outbreaks.

Finally, the team found that the likelihood of vaccination against avian influenza strongly increased with flock size. The probability of vaccination was almost zero for flocks of 16 birds or fewer and nearly 100% for flocks of more than 200 birds. According to Delabouglise, one reason that millions of small-scale poultry farmers may not be vaccinating their birds could be their desire to avoid transaction costs associated with declaring flocks to governmental veterinary services before vaccination. Another reason could be that due to their small size, their vaccination status is not controlled and, therefore, vaccination is less worthwhile from the farmers' perspective.

"Crucially, it is these smaller flocks that are more likely to be sold into trading networks during outbreaks," he said. "The rapid sale of sick birds can contaminate other birds at traders' storage places and those at live bird markets. It also exposes consumers and traders, slaughterers and retailers to an increased risk of infection."

Delabouglise noted that, on the flip side, a massive arrival of underage birds in a live bird market, or a price decrease due to the temporary oversupply of poultry, may be a sign that an outbreak is occurring.

"This is an interesting area for surveillance of livestock diseases," he said.

Delabouglise said that the team's results could help governmental agencies create policies that aim to avoid the spread of HPAI.

"Small-scale farmers could play an active role in the control of emerging infectious diseases if they are given the opportunity to depopulate their farm upon disease detection without disseminating pathogens in trade circuits," he said. "Policymakers could encourage the establishment of formal trade agreements that encourage such 'virtuous' management of disease outbreaks in poultry."

One such "virtuous" management strategy could be for farmers to sell their sick chickens as feed for pythons and crocodiles raised on neighboring farms. Another could be to set up agreements with neighboring large commercial farmers who can give them financial indemnities to destroy the birds as a way of protecting their own flocks.

"It would be impossible to have reliable public-health control over the millions of small-scale poultry flocks in a place like Vietnam," said Delabouglise, "but providing economic incentives to responsibly manage birds during disease outbreaks is feasible."

Other authors on the paper include Nguyen Thi Le Thanh, Wellcome Trust Major Overseas Programme; Huynh Thi Ai Xuyen, Ca Mau Sub-Department of Livestock Production and Animal Health; Benjamin Nguyen-VanYen, Wellcome Trust Major Overseas Programme and Ecole Normale Superieure; Phung Ngoc Tuyet, Ca Mau Sub-Department of Livestock Production and Animal Health; and Ha Minh Lam, Wellcome Trust Major Overseas Programme and University of Oxford.

The Defense Threats Reduction Agency, the Wellcome Trust and the Pennsylvania State University supported this research.

Researchers from the University of Minnesota, with support from Medtronic, have developed a groundbreaking process for multi-material 3D printing of lifelike models of the heart's aortic valve and the surrounding structures that mimic the exact look and feel of a real patient.

These patient-specific organ models, which include 3D-printed soft sensor arrays integrated into the structure, are fabricated using specialized inks and a customized 3D printing process. Such models can be used in preparation for minimally invasive procedures to improve outcomes in thousands of patients worldwide.

The research is published in Science Advances, a peer-reviewed scientific journal published by the American Association for the Advancement of Science (AAAS).

The researchers 3D printed what is called the aortic root, the section of the aorta closest to and attached to the heart. The aortic root consists of the aortic valve and the openings for the coronary arteries. The aortic valve has three flaps, called leaflets, surrounded by a fibrous ring. The model also included part of the left ventricle muscle and the ascending aorta.

"Our goal with these 3D-printed models is to reduce medical risks and complications by providing patient-specific tools to help doctors understand the exact anatomical structure and mechanical properties of the specific patient's heart," said Michael McAlpine, a University of Minnesota mechanical engineering professor and senior researcher on the study. "Physicians can test and try the valve implants before the actual procedure. The models can also help patients better understand their own anatomy and the procedure itself."

This organ model was specifically designed to help doctors prepare for a procedure called a Transcatheter Aortic Valve Replacement (TAVR) in which a new valve is placed inside the patient's native aortic valve. The procedure is used to treat a condition called aortic stenosis that occurs when the heart's aortic valve narrows and prevents the valve from opening fully, which reduces or blocks blood flow from the heart into the main artery. Aortic stenosis is one of the most common cardiovascular conditions in the elderly and affects about 2.7 million adults over the age of 75 in North America. The TAVR procedure is less invasive than open heart surgery to repair the damaged valve.

The aortic root models are made by using CT scans of the patient to match the exact shape. They are then 3D printed using specialized silicone-based inks that mechanically match the feel of real heart tissue the researchers obtained from the University of Minnesota's Visible Heart Laboratories. Commercial printers currently on the market can 3D print the shape, but use inks that are often too rigid to match the softness of real heart tissue.

On the flip side, the specialized 3D printers at the University of Minnesota were able to mimic both the soft tissue components of the model, as well as the hard calcification on the valve flaps by printing an ink similar to spackling paste used in construction to repair drywall and plaster.

Physicians can use the models to determine the size and placement of the valve device during the procedure. Integrated sensors that are 3D printed within the model give physicians the electronic pressure feedback that can be used to guide and optimize the selection and positioning of the valve within the patient's anatomy.

But McAlpine doesn't see this as the end of the road for these 3D-printed models.

"As our 3D-printing techniques continue to improve and we discover new ways to integrate electronics to mimic organ function, the models themselves may be used as artificial replacement organs," said McAlpine, who holds the Kuhrmeyer Family Chair Professorship in the University of Minnesota Department of Mechanical Engineering. "Someday maybe these 'bionic' organs can be as good as or better than their biological counterparts."

Overcoming the nation's opioid epidemic will require clinicians to look beyond opioids, new research from Oregon Health & Science University suggests.

The study reveals that among patients who participated in an in-hospital addiction medicine intervention at OHSU, three-quarters came into the hospital using more than one substance. Overall, participants used fewer substances in the months after working with the hospital-based addictions team than before.

The study published in the Journal of Substance Abuse Treatment.

"We found that polysubstance use is the norm," said lead author Caroline King, M.P.H., a health systems researcher and current M.D./Ph.D. student in the OHSU School of Medicine's biomedical engineering program. "This is important because we may need to offer additional support to patients using multiple drugs. If someone with opioid use disorder also uses alcohol or methamphetamines, we miss caring for the whole person by focusing only on their opioid use."

About 40% of participants reported they had abstained from using at least one substance at least a month after discharge - a measure of success that isn't typically tracked in health system record-keeping.

Researchers enrolled 486 people seen by an addiction medicine consult service while hospitalized at OHSU Hospital between 2015 and 2018, surveying them early during their stay in the hospital and then again 30 to 90 days after discharge.

Treatment of opioid use disorder can involve medication such as buprenorphine, or Suboxone, which normalizes brain function by acting on the same target in the brain as prescription opioids or heroin.

However, focusing only on the opioid addiction may not adequately address the complexity of each patient.

"Methamphetamine use in many parts of the U.S., including Oregon, is prominent right now," said senior author Honora Englander, M.D., associate professor of medicine (hospital medicine) in the OHSU School of Medicine. "If people are using stimulants and opioids - and we only talk about their opioid use - there are independent harms from stimulant use combined with opioids. People may be using methamphetamines for different reasons than they use opioids."

Englander leads the in-hospital addiction service, known as Project IMPACT, or Improving Addiction Care Team.

The initiative brings together physicians, social workers, peer-recovery mentors and community addiction providers to address addiction when patients are admitted to the hospital. Since its inception in 2015, the program has served more than 1,950 people hospitalized at OHSU.

The national opioid epidemic spiraled out of control following widespread prescribing of powerful pain medications beginning in the 1990s. Since then, it has often been viewed as a public health crisis afflicting rural, suburban and affluent communities that are largely white.

Englander said the new study suggests that a singular focus on opioids may cause clinicians to overlook complexity of issues facing many populations, including people of color, who may also use other substances.

"Centering on opioids centers on whiteness," Englander said. "Understanding the complexity of people's substance use patterns is really important to honoring their experience and developing systems that support their needs."

Researchers say the finding further reinforces earlier research showing that hospitalization is an important time to offer treatment to people with substance use disorder, even if they are not seeking treatment for addiction when they come to the hospital.

Researchers from Sechenov University together with Russian and Iranian colleagues described currently known approaches to the treatment of SARS-CoV-2 infection. In the paper published in Journal of Molecular Medicine, they wrote about how different groups of drugs worked and how promising each approach was.

SARS-CoV-2 - a coronavirus that caused the pandemic in early 2020 - is a close relative of two other viruses (SARS-CoV and MERS-CoV) that triggered epidemics in 2003 and 2013-2015. Most often, the disease is accompanied by fever, dry cough, increased fatigue, and loss of taste and smell. Most symptoms are associated with an overreaction of the patient's immune system, which, in severe cases, causes damage to lung tissue and systemic inflammation.

The first approach considered in the article is immunotherapy. It is known that antibodies contained in the serum of people who have had a viral disease can speed up the recovery of other patients. Despite the simplicity of this method, it has several limitations: the number of potential donors is still small, the activity of antibodies decreases over time (which is why the serum from the patients who had the disease long ago is less valuable), and the antibodies themselves can help the virus spread in the body - a phenomenon known as antibody-dependent enhancement of infection.

Similarly, we can use T-lymphocytes - cells that can destroy damaged or infected cells of the body. Scientists have noticed that the number of T-cells of the CD8+ subpopulation is significantly reduced in patients with COVID-19, and the more severe the disease the lower this number. T-cells directed against a specific virus can be produced in vitro and offered to patients as therapy.

Another area of research is related to the suppression of certain enzymes, in particular AAK1 and GAK, which are needed for the virus to enter a cell. Some of the drugs that act as inhibitors of these enzymes have already been tested and used, although for another purpose, such as, for example, the treatment of rheumatoid arthritis (this approach is called 'drug repurposing').

'Analysis of clinical trials registered in ClinicalTrials.gov has shown a wide variety of therapeutic agents offered for the treatment of COVID-19. And, of course, most of them are associated with the use of previously known drugs used in the treatment of other diseases,' commented Anastasia Shpichka, one of the authors of the study, a leading researcher at the Institute for Regenerative Medicine, Sechenov University.

There are other ways to prevent the virus from entering cells. Since the receptor that is built into the cell membrane and lets the virus inside is known (this is the ACE2 protein), it is possible to create an analogue that will bind to viral particles and 'distract' them from the patient's cells. Such analogues of the ACE2 receptor have already been developed, tested and shown to slow down the spread of the virus in the body, but not stop it, which indicates the presence of other entry points into human cells.

The use of antiviral drugs gives contradictory results. Remdesivir, which showed good efficacy against SARS-CoV-2 in some studies, did not bring noticeable benefits in others. Chloroquine, used to treat malaria, was considered a promising drug, but its side effects do not allow it to be recommended for the treatment of COVID-19. Attempts to use HIV medications against SARS-CoV-2 also yield mixed results.

One more direction in the fight against COVID-19 is suppression of excessive immune system reaction, which especially affects the lung tissue. One treatment option may be mesenchymal stem cells, used in the treatment of inflammatory and autoimmune diseases. Studies of the effectiveness of this method in the treatment of COVID-19 are already underway. Another class of drugs that limit inflammatory response is corticosteroids. They can reduce mortality among patients with severe disease.

Despite the efforts of scientists from all over the world, aimed at finding an effective COVID-19 treatment, the optimal algorithm has not yet been found. The key to creating a drug can be either a discovery as part of one of these approaches or a new solution, for example, found at the intersection of scientific disciplines or borrowed from the experience of treating other diseases.

DARIEN, IL – A new study of sleep, religious affiliation, and perceptions of heaven found that atheists and agnostics are significantly more likely to be better sleepers than Catholics and Baptists.

Preliminary results show that 73% of atheists and agnostics reported getting seven or more hours of nightly sleep, which is recommended by the American Academy of Sleep Medicine to promote optimal health. In contrast, 63% of Catholics and only 55% of Baptists reported sleeping at least seven hours per night. Atheists and agnostics also reported experiencing less difficulty falling asleep.

“Mental health is increasingly discussed in church settings — as it should be — but sleep health is not discussed,” said lead author Kyla Fergason, a student at Baylor University in Waco, Texas. “Yet we know that sleep loss undercuts many human abilities that are considered to be core values of the church: being a positive member of a social community, expressing love and compassion rather than anger or judgment, and displaying integrity in moral reasoning and behavior. Could getting better sleep help some people grow in their faith or become better Christians? We don’t know the answer to that question yet, but we do know that mental, physical and cognitive health are intertwined with sleep health in the general population.”

The study involved a population-based sample of 1,501 participants in the Baylor Religion Survey, which includes questions on religious affiliation, behaviors, and perceptions. Participants also rated their difficulty falling asleep and their average total sleep time.

Results also show that those participants who reported sleeping seven or more hours per night were significantly more likely to believe that they would get into heaven. However, these perceptions of heaven were unrelated to difficulty falling asleep at night. According to the authors, this pattern indicates that better sleep leads to a more optimistic outlook, which in this case is manifesting as positive expectations of getting into heaven.

The research abstract was published recently in an online supplement of the journal Sleep and will be presented as a poster Aug. 28-30 during Virtual SLEEP 2020. SLEEP is the annual meeting of the Associated Professional Sleep Societies, a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society.

DARIEN, IL – An experimental study suggests that sleep restriction may hinder information disclosure during criminal interviews, contradicting widespread assumptions about the effectiveness of sleep deprivation as an interrogation tool.

Preliminary results show that even mildly sleep-restricted participants provided around 7% less information during their initial disclosure. Sleep-restricted individuals also reported less overall motivation to recall information.

“Historically, sleep has been used as a tool to compel disclosure or confessions, while sleep loss remains common among interview subjects such as victims or witnesses,” said lead author Zlatan Krizan, who has a doctorate in personality and social psychology and is a professor of psychology at Iowa State University in Ames, Iowa. “However, there was little direct, scientific evidence on whether sleep enhances or inhibits intelligence disclosures during investigative interviews prior to this study. These findings carry direct implications for science and practice of investigative interviewing and contradict longstanding assumptions about the role of sleep in gathering human intelligence.”

The study involved 120 healthy participants who were recruited from the university community. They were assigned to maintain or restrict their sleep for two days, with objective estimates of sleep duration gathered using actigraphy. Sleep-restricted participants slept 4.5 hours less on average, losing about one night of sleep over two days. Following the sleep manipulation, participants were interviewed about past illegal acts they admitted to.

According to the authors, the results suggest that even moderate sleep loss can inhibit criminal disclosure during interviews.

We are conscious beings, yet most of the activity in our brains remains nonconscious. Can we harness this hidden pool of information? Notably, one important challenge is the astronomical vastness and complexity of such nonconscious information. How can the human brain 'know' what aspects of such complex activity may be relevant, given that it is by definition nonconscious and thereby 'unknown'? There is no magic formula to solve this problem, and research in artificial intelligence suggests that even the best of our current algorithms struggle to handle this vastness of dimensionality in everyday, real-life problems.

The international team used a state-of-the-art method to read nonconscious brain states in real-time. This technique used brain scanning to monitor and detect the occurrence of specific complex patterns of activity, that were then used to determine the optimal answer to a simple action selection. In the learning sessions, participants received a small monetary reward if they selected the correct option, which was determined based on their nonconscious brain activity. This experiment allowed researchers to show how participants can learn to use the nonconscious contents of their mind to make profitable decisions. Interestingly, although based on their self-reports, participants were not aware of the learning, when they were confident in their choices, they were also more likely to be correct and receive a reward. This suggests an unexpected form of nonconscious metacognition; the participants were not aware of learning per se, but somehow, some brain mechanisms must 'know'. These striking results illustrate the incredible power of the nonconscious mind and how important our feeling of confidence may be in our everyday life.

Dr. Aurelio Cortese, Senior Researcher at the Advanced Telecommunications Research Institute International, Kyoto, led the research:

"Strikingly, participants were taught to make rational choices on their own nonconscious brain activity through a very simple trial-and-error learning procedure. The extent of this learning was predicted by participants' ability to self-introspect in their decisions. Such approaches may be used in the future to improve 'dormant' skills".

Dr. Hakwan Lau, Professor in the UCLA Psychology Department, a co-author on the study and a leading expert in confidence and metacognition:

"This study is unique in its kind in that it shows, for the first time, the depth of the human brain's ability to reconfigure and learn in conditions we would have thought as impossible until recently. The fact that confidence seemed to support participant's ability to learn the task nonconsciously opens new questions on its function and role in guiding behaviour".

Dr. Mitsuo Kawato, Director of the Computational Neuroscience Laboratories at ATR, Kyoto, was the senior author on the study, and has pioneered the state-of-the-art technology that led to the inception of this study. He explained:

"One of the most challenging questions in modern neuroscience and artificial intelligence is how can the brain solve the 'curse of dimensionality'. There are billions of neurons in the brain, and most of its activity is complex and nonconscious. How to efficiently make the best decisions when time and experience are generally so limited? Here we provide a first indication by showing that our feeling of confidence may be part of the answer".

The sample size was relatively small (18 people), but carried over 3 sessions, making the total (54 neuroimaging sessions) in line with basic science investigations of similar kinds.