Culture

New COVID-19 vaccine may offer broad protection from coronaviruses

image: Steven L. Zeichner, MD, PhD, of UVA Children's, says the vaccine could be produced very quickly, at very low cost, in existing factories around the world. The vaccine was developed using a platform Zeichner invented to speed vaccine development.

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Dan Addison | UVA Communications

A COVID-19 vaccine that could provide protection against existing and future strains of the COVID-19 coronavirus, and other coronaviruses, and cost about $1 a dose has shown promising results in early animal testing.

Vaccines created by UVA Health's Steven L. Zeichner, MD, PhD, and Virginia Tech's Xiang-Jin Meng, MD, PhD, prevented pigs from being becoming ill with a pig model coronavirus, porcine epidemic diarrhea virus (PEDV). The vaccine was developed using an innovative approach that Zeichner says might one day open the door to a universal vaccine for coronaviruses, including coronaviruses that previously threatened pandemics or perhaps even coronaviruses that cause some cases of the common cold.

Their coronavirus vaccine offers several advantages that could overcome major obstacles to global vaccination efforts. It would be easy to store and transport, even in remote areas of the world, and could be produced in mass quantities using existing vaccine-manufacturing factories.

The UVA and Virginia Tech scientists created the vaccine using a new platform Zeichner invented to rapidly develop new vaccines. So the testing success bodes well for both the COVID-19 vaccine and Zeichner's vaccine-development approach.

"Our new platform offers a new route to rapidly produce vaccines at very low cost that can be manufactured in existing facilities around the world, which should be particularly helpful for pandemic response," Zeichner said.

New Vaccine Approach

Zeichner's new vaccine-production platform involves synthesizing DNA that directs the production of a piece of the virus that can instruct the immune system how to mount a protective immune response against the virus.

That DNA is inserted into another small circle of DNA called a plasmid that can reproduce within bacteria. The plasmid is then introduced into bacteria, instructing the bacteria to place pieces of proteins on their surfaces. The technique uses the common bacteria E. coli.

One major innovation is that the E. coli have had a large number of its genes deleted. Removing many of the bacteria's genes, including genes that make up part of its exterior surface or outer membrane, appears to substantially increase the ability of the immune system to recognize and respond to the vaccine antigen placed on the surface of the bacteria.

To produce the vaccine, the bacteria expressing the vaccine antigen are simply grown in a fermenter, much like the fermenters used in common microbial industrial processes like brewing, and then killed with a low concentration of formalin.

"Killed whole-cell vaccines are currently in widespread use to protect against deadly diseases like cholera and pertussis. Factories in many low-to-middle-income countries around the world are making hundreds of millions of doses of those vaccines per year now, for a $1 per dose or less," Zeichner said. "It may be possible to adapt those factories to make this new vaccine. Since the technology is very similar, the cost should be similar too."

The entire process, from identifying a potential vaccine target to producing the gene-deleted bacteria that have the vaccine antigens on their surfaces, can take place very quickly, in only two to three weeks, making the platform ideal for responding to a pandemic.

Targeting Coronavirus

Zeichner and Meng's vaccine takes an unusual approach in that it targets a part of the spike protein of the virus, the "viral fusion peptide," that is essentially universal among coronaviruses. The fusion peptide has not been observed to differ at all in the many genetic sequences of SARS-CoV-2, the virus that causes COVID-19, that have been obtained from thousands of patients around the world during the pandemic.

Meng and Zeichner made two vaccines, one designed to protect against COVID-19, and another designed to protect against PEDV. PEDV and the virus that causes COVID-19 are both coronaviruses, but they are distant relatives. PEDV and SARS-CoV-2, like all coronaviruses, share several of the amino acids that constitute the fusion peptide. PEDV infects pigs, causing diarrhea, vomiting and high fever, and has been a large burden on pig farmers around the world. When PEDV first appeared in pig herds in the US, it killed almost 10% of US pigs - a pig pandemic.

One advantage of studying PEDV in pigs is that Meng and Zeichner could study the ability of the vaccines to offer protection against a coronavirus infection in its native host - in this case, pigs. The other models that have been used to test COVID-19 vaccines study SARS-CoV-2 in non-native hosts, such as monkeys or hamsters, or in mice that have been genetically engineered to enable them to be infected with SARS-CoV-2. Pigs are also very similar in physiology and immunology to people - they may be the closest animal models to people other than primates.

In some unexpected results, Meng and Zeichner observed that both the vaccine against PEDV and the vaccine against SARS-CoV-2 protected the pigs against illness caused by PEDV. The vaccines did not prevent infection, but they protected the pigs from developing severe symptoms, much like the observations made when primates were tested with candidate COVID-19 vaccines. The vaccines also primed the immune system of the pigs to mount a much more vigorous immune response to the infection. If both the PEDV and the COVID-19 vaccines protected the pigs against disease caused by PEDV and primed the immune system to fight the disease, it is reasonable to think that the COVID-19 vaccine would also protect people against severe COVID-19 disease, the scientists say.

Next Steps

Additional testing - including human trials - would be required before the COVID-19 vaccine could be approved by the federal Food and Drug Administration or other regulatory agencies around the world for use in people, but the collaborators are pleased by the early successes of the vaccine-development platform.

Zeichner added that he was encouraged that a collaboration between UVA and Virginia Tech, schools with a well-known sports rivalry, has produced such promising results.

"XJ is just an amazing collaborator and a wonderful scientist. And he is incredibly generous with his time and the resources he has available," Zeichner said. "If UVA and Virginia Tech scientists can work together to try to do something positive to address the pandemic, then maybe there is some hope for collaboration and cooperation in the country at large."

Credit: 
University of Virginia Health System

Incongruent messaging key to getting people to register as organ donors

A new study from the UBC Sauder School of Business finds a subtle shift in organ donor messaging can lead to a big boost in registration.

Organ donation saves countless lives every year, and most people think it's the right thing to do -- but when it comes to people actually registering to donate, the numbers around the world are surprisingly low. This is particularly so in countries that rely on informed consent and require people to learn about organ donation before they opt-in to register as a donor.

In fact, in Canada, just 32 per cent of people have registered to become organ donors.

Transplant agencies have tried a range of strategies to increase donation levels, including the introduction of in-hospital organ donation coordinators, greater public education and marketing campaigns.

Some campaigns emphasize how low organ donation rates are and plead with people to sign up, hoping the meagre numbers will motivate people to help. In marketing, this is known as a low descriptive norm. Others take the opposite tack, and emphasize how positive people feel about organ donation, which encourages people to conform to the expectations of others, a high injunctive norm. For example, one UK government advertisement stated, "96 per cent believe donating organs is the right thing to do."

But what happens when you combine the two approaches? According to the new study, titled Everybody Thinks We Should But Nobody Does: How Combined Injunctive and Descriptive Norms Motivate Organ Donation Registration, highlighting the incongruence between what people believe and what they do -- or don't do -- can spur their willingness to register.

According to UBC Sauder PhD candidate Rishad Habib (she/her), who co-authored the study with UBC Sauder colleagues Dr. Katherine White and Dr. JoAndrea Hoegg, by focusing on how low registration numbers are, some agencies may be unknowingly alienating potential donors.

"If you tell people that nobody is doing something, does that really motivate them to register?" says Habib. "By communicating that the numbers are low, they might be inadvertently communicating that it's not very important, or not worthwhile."

On the flipside, if marketers focus on how many people support organ donation, they risk making people feel like they don't need to act.

For the study, the researchers tested all three approaches -- focusing on the low rates, the high support, and a combination of the two -- in online surveys, lab surveys and in a public field study.

In one study, research assistants set up a table at the UBC student centre and regularly rotated banners encouraging passersby to register. They also asked people if they were already registered, and if they weren't, they would show them an iPad displaying the different messaging on the banners.

For example, one read, "Only 20 per cent of Canadians are registered as organ donors" while another said, "90 per cent of Canadians believe people should register as organ donors." The people were then offered the chance to sign up.

Roughly 20 per cent of people who were given only the individual messages signed up; but when people were given the combined message, registrations jumped to 33 per cent, which represents an almost 70 per cent increase -- a leap that could help save lives.

"It motivates responsibility," explains Habib. "When the two messages are combined, people think, 'No one's doing it, but it's important. So I need to step up and register."

Habib hopes the findings, which were published in the Journal of Consumer Psychology, will help transplant organizations create more effective communication strategies; in fact, the study has already influenced at least one organ donation registry's online and TV campaigns.

"You could apply this to other situations where there's a positive behaviour, but there aren't a lot of people doing it -- like mask wearing at the start of the pandemic," she says. "If the behaviour levels are low, but the support for the behaviour is high, then it makes sense to communicate both."

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University of British Columbia

New model describes the (scaling) laws of the jungle

image: New research finds hidden order in sessile organisms, from arid grassland to canopied rainforest.

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Illustration: Mesa Schumacher for the Santa Fe Institute

A forest looks like a hotbed of randomness, with trees and plants scattered in wild and capricious diversity. But appearances can be deceiving, say a trio of complexity researchers at the Santa Fe Institute (SFI). Underneath that apparent messiness lurk extraordinary regularities, governed by the biological mechanisms that drive universal forces of growth, death, and competition.

In a paper published April 9 in the journal PNAS, the SFI group, led by Program Postdoctoral Fellow and now Complexity Science Hub Vienna Postdoctoral Scientist Eddie Lee, describes a new framework that can reproduce those spatial and temporal patterns that emerge in places and spaces where plants grow together. The framework uses computational and statistical tools to connect metabolic principles, which control how an individual organism lives and thrives, to the diverse arrangements of trees, shrubs, and other vegetation readily observed in landscapes, forests and beyond.

"This paper goes a long way in showing how things that look arbitrary and capricious can in fact be understood within a mathematical framework," says SFI Distinguished Shannan Professor and former President Geoffrey West, who collaborated with Lee and Chris Kempes, SFI Professor, on the model.

Scientists have long sought mathematical laws that connect the similar patterns that emerge at large and small scales of existence. "If you look at the microscopic structure of multicellular life, you see a lot of the same patterns playing out," says Lee. The metabolic rate of an organism follows a power scaling law with its mass, for example. Previous attempts at establishing such mathematical laws for the assemblage of plants in a forest have been a source of vociferous debate.

In previous work, West and others have developed models that start with the metabolic constraints on a single, optimized tree to make predictions about patterns that might emerge in a community of such trees. The model accurately showed how features like growth rate or canopy size might change with plant size -- and how those features might affect competition with other organisms or change the structure of the entire forest.

Kempes says that this idealized model paved the way for connecting biological principles like metabolism to mathematical, macro-level patterns, but over time researchers began to focus on how real-world situations differ in detail from that model. Not every tree or population follows the optimal rules, though, leading researchers like Lee to investigate new ways to generalize the core tenets.

"What happens when that law for scaling deviates for individual species, or for different contexts? How does that work?" says Kempes. "How do all those fit together?"

The new model extends essential ideas from earlier works for how to set up a model informed by the biological principles of growth, death, and resource competition, but it also allows a user to generalize those ideas to a wide range of species and situations, says Kempes. A user might relax certain assumptions about tree allometries -- relationships between size and shape -- or incorporate ideas about how trees interact with other organisms, like termites.

By turning these "knobs" on the simulation, Lee says, researchers can more closely reproduce the diverse ways that forests diverge from the idealized model. They can also clearly connect biological principles at the level of the organism to how forest structure plays out on larger scales.

West says the new approach will not only reveal scaling laws that have been previously gone unnoticed but also shine a light on new areas of investigation. "One of the great things about having an analytical model of this kind is that it points to where data is missing, or where data is poor," he says, "and the kinds of things people should be measuring."

The model also shows how a physics-inspired approach -- which often focuses on idealized situations -- can contribute to advances in understanding biological complexity. "There is this marvelous interplay between the fields," West says.

Credit: 
Santa Fe Institute

Mirror, mirror...viewing your own face, even subconsciously, is rewarding

image: Subliminal presentation of face (upper) and brain regions showing self-face related activation (bottom).

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Osaka University

Osaka, Japan - As humans, we each have a powerful ability to easily recognize our own face. But now, researchers from Japan have uncovered new information about how our cognitive systems enable us to distinguish our own face from those of others, even when the information is presented subliminally.

In a study published this month in Cerebral Cortex, researchers from Osaka University have revealed that a central element of the dopamine reward pathway in the brain was activated when participants were subliminally shown images of their face. This provides new clues regarding the underlying processes of the brain involved in self-facial recognition.

When we are exposed to a subliminal image of our face—meaning we are not fully aware of it—many brain regions are activated in addition to those that process face information. Furthermore, our brain responds differently to supraliminal (conscious) and subliminal (subconscious) images of our face compared to faces of others. However, whether we use the same or different neural networks to process subliminal versus supraliminal faces has not been established, something the researchers at Osaka University aimed to address with this research.

"We are better at recognizing our own face compared to faces of others, even when the information is delivered subliminally," says lead author of the study Chisa Ota. "However, little is known about whether this advantage involves the same brain or different areas that are activated by supraliminal presentation of our face."

To address this, the researchers used functional magnetic resonance imaging (fMRI) to examine the differences between brain activity elicited by subliminally presented images of the faces of participants and faces of others. They also examined brain activation produced by subliminally presented images of faces with modified features.

"The results provided us with new insights regarding the neural mechanisms of the self-face advantage," explains Tamami Nakano, senior author. "We found that activation in the ventral tegmental area, which is a central component of the dopamine reward pathway, was stronger for subliminal presentations of the participant's face compared with faces of others."

Instead, subliminal presentation of the faces of others induced activation in the amygdala of the brain, which is known to respond to unfamiliar information. This difference in brain responses to the face of the participant or those of others was consistent even when the faces were modified, as long as the shapes of the facial features were retained.

"Our findings indicate that the dopamine reward pathway is involved in enhanced processing of one's own face even when the information is subliminal", says Tamami Nakano. "Furthermore, discrimination of one's own face from those of others appear to rely on the information of facial parts."

These findings advance the understanding of the neural mechanisms of subliminal self-facial processing. Given that the dopamine reward pathway is automatically involved in unconscious self-facial processing, this research may have applications in efforts to unconsciously manipulate motivation.

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Osaka University

Where are the women on the Spanish-language Wikipedia site?

With its more than 40 million articles in 301 different languages, Wikipedia is one of the largest human collaboration efforts in history. One of the main pillars on which this wish to bring together the sum of all knowledge is based is the achievement of a neutral space. However, several studies suggest that the site suffers from a persistent gender bias as regards both content and the composition of its community. An analysis of the gender gap in the Spanish-language version of Wikipedia by an interdisciplinary team at the UOC has revealed that only 11.6% of its registered editors are women.

According to the new study, which has been published in the journal PLOS ONE, the difference could be partially due to female editors being less persistent. "Women edit less and give up sooner. This is part of the reason the gap is not narrowing," note the authors. In spite of this, the results reveal a small group of veteran female editors, some of whom have edited more than men, a fact that could help design measures to highlight and increase women's participation in this space.

The paper is signed by UOC researchers Julià Minguillón of the Learning Analytics for Innovation and Knowledge Application in Higher Education group (LAIKA), of the Faculty of Computer Science, Multimedia and Telecommunications, Julio Meneses and Sergi Fàbregues of the Gender and IT group (GenTIC), of the Internet Interdisciplinary Institute (IN3) and of the Faculty of Psychology and Education Sciences, and by Professor Eduard Aibar of the Philosophy for Contemporary Challenges group (MUSSOL) of the Faculty of Arts and Humanities. Núria Ferran, a researcher at the Faculty of Audiovisual Media of the University of Barcelona, also took part.

A new method for identifying gender

With over 1.58 million pages, the Spanish version of Wikipedia is the ninth largest, as well as the fourth largest by number of registered editors (around 17,000). One of the challenges facing the new study has been identifying these people's gender, as many of them have chosen not to reveal it in their Wikipedia personal profiles. To ascertain this, in addition to collecting the information published by the users themselves, the researchers also created a systematic method to establish their gender based on their names and the use of grammatical gender in the descriptions appearing in their profiles. This procedure made it possible to identify the gender of 49% of editors, as compared with only 38.8% who had specified it on their personal page.

According to the results of this innovative process, the number of active female editors in the Spanish-language version of Wikipedia accounts for 7.4% of all existing profiles, a figure that rises to 11.6% if you take into account only those profiles whose genders we know for certain. "These differences mean that the Spanish-language Wikipedia site is a male-dominated territory that may plausibly be considered a misogynistic place by female editors. Additionally, the high percentage of unknown profiles hinders efforts to reduce this perception, as women perceive anonymous editors as more critical of their contributions," the researchers highlight.

Lower retention rates among female editors

In general, the study also found differences in editing practices, as women have lower retention rates. According to the authors, this can be explained "partly by female editors being less persistent and tending to leave Wikipedia much more quickly, particularly in the first few weeks." However, an analysis of the most active people on the site revealed the disappearance or even reversal of gender differences between men and women in some cases: "There is a small group of veteran female editors who have edited more than male editors in terms of editing practices and involvement in different parts of Wikipedia," they highlight.

The types of contributions made are another differentiating factor between men and women. According to the study, female editors edit a higher percentage of non-article pages; in other words, in places whose specific purpose is to interact with other participants, particularly discussion pages, where articles' flaws and possible improvements are discussed. These findings seem to corroborate those of previous studies suggesting that men tend to be contributors while women tend to behave more as collaborators. However, the researchers highlight that "when taking into account only the most active editors, although women have a higher average number of edits in all namespaces, the differences between women and the most active men are not statistically significant."

Greater interest in gender-related matters

The researchers also found differences between the two groups' interests based on an analysis of the categories used by Wikipedia to group articles by subject area. Although the authors describe these categories as "too general," the study suggests that women are "slightly less" interested in editing science and nature pages.

As for content pages, men always outperform women by three to one. In fact, women often do not contribute at all or contribute significantly less, although with one exception: gender gap-related pages and WikiProjects. "We found only two groups of pages in which women seem more active than men: the 'Women' and 'Feminism' WikiProjects and another group of pages relating to gender issues. It therefore appears that women are more interested in making contributions in this field," they stress.

Highlighting the work of the most active female editors

In view of this bias, the researchers suggest a variety of measures to encourage participation by women. Firstly, they propose changes to the way the website works, such as facilitating editing -- particularly regarding the management of references -- to "avoid incomplete or erroneous edits that are almost certain to be subsequently deleted." They also recommend improving the identification of "abusive behaviours," particularly by veteran editors who may be "less than fully impartial in relation to gender issues, a problem that is not exclusive to women and may also affect other minority groups," they note.

They additionally emphasize the importance of supporting female editors for longer after taking part in Wikipedia welcome activities such as WikiProjects or Wikimarathons, where they get together in one place to edit and improve a subject matter or group of articles. Highlighting the involvement of the group of most active female editors is another recommendation made by the researchers, who assert that "raising awareness of women's successful experiences could provide a good starting point to encourage other women to continue editing and thus promote their long-term commitment to Wikipedia." Finally, the conclusions of the paper also stress the need to research why women stop editing Wikipedia and take a closer look at the role of Wikimarathons to encourage more women to take up and maintain the editing habit over time.

Credit: 
Universitat Oberta de Catalunya (UOC)

SMART breakthrough to enhance travel behavior research with artificial neural networks

image: A comparison summary of deep neural networks (DNNs) and discrete choice models (DCMs) characteristics

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Singapore-MIT Alliance for Research and Technology (SMART)

Singapore, 19 April, 2021 - Researchers at the Future Urban Mobility (FM) Interdisciplinary Research Group (IRG) at Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore, have created a synthetic framework known as theory-based residual neural network (TB-ResNet), which combines discrete choice models (DCMs) and deep neural networks (DNNs), also known as deep learning, to improve individual decision-making analysis used in travel behaviour research.

In this research paper, Theory-based residual neural networks: A synergy of discrete choice models and deep neural networks, recently published in established transportation science journal Transportation Research: Part B, SMART researchers explain their developed TB-ResNet framework and demonstrate the strength of combining the DCMs and DNNs methods, proving that they are highly complementary.

As machine learning is increasingly used in the field of transportation, the two disparate research concepts, DCMs and DNNs, have long been viewed as conflicting methods of research.

By synergising these two important research paradigms, TB-ResNet takes advantage of DCMs' simplicity and DNNs' expressive power to generate richer findings and more accurate predictions for individual decision-making analysis, which is important for improved travel behaviour research. The developed TB-ResNet framework is more predictive, interpretable, and robust as compared to DCMs and DNNs, with findings consistent over a wide range of data sets.

Accurate and efficient analysis of individual decision-making in the everyday context is critical for mobility companies, governments and policy makers seeking to optimise transport networks and tackle transport challenges, especially in urban cities. TB-ResNet will eliminate existing difficulties faced in DCMs and DNNs, and allow stakeholders to take a holistic, unified view towards transport planning.

Postdoctoral Associate at MIT Urban Mobility Lab and lead author of the paper, Shenhao Wang, said, "Improved insights to how travellers make decisions about travel mode, destination, departure time, and planning of activities are crucial to urban transport planning for governments and transport companies worldwide. I look forward to further developing TB-ResNet and its applications for transport planning now that it has been acknowledged by the transport research community."

SMART FM Lead Principal Investigator and Associate Professor at MIT Department of Urban Studies and Planning, Jinhua Zhao, said, "Our Future Urban Mobility research team focuses on developing new paradigms and innovating future urban mobility systems in and beyond Singapore. This new TB-ResNet framework is an important milestone that could enrich our investigations for impacts of decision-making models for urban development."

The TB-ResNet can also be widely applied to understand individual decision-making cases as illustrated in this research, whether it is about travels, consumption, voting, among many others.

The TB-ResNet framework was tested in three instances in this study. Firstly, researchers used it to predict travel mode decisions between transit, driving, autonomous vehicles, walking, and cycling, which are major travel modes in an urban setting. Secondly, they evaluated risk alternatives and preferences when monetary payoffs with uncertainty are involved. Examples of such situations include insurance, financial investment, and voting decisions.

Lastly, they examined temporal alternatives, measuring the trade-off between current and future money payoffs. A typical example of when such decisions are made would be in transport development where shareholders analyse infrastructure investment with large down payment and long-term benefits.

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Singapore-MIT Alliance for Research and Technology (SMART)

Bad to the bone: Hebrew University reveals impact of junk food on kids' skeletal development

A team of researchers from the Hebrew University of Jerusalem has proven the linkages between ultra-processed foods and reduced bone quality, unveiling the damage of these foods particularly for younger children in their developing years. The study, led by Professor Efrat Monsonego-Ornan and Dr. Janna Zaretsky from the Department of Biochemistry, Food Science and Nutrition at the University's Faculty of Agriculture, was published in the journal Bone Research and serves as the first comprehensive study of the effect of widely-available food products on skeleton development.

Ultra-processed foods--aka, junk food--are food items products that undergo several stages of processing and contain non-dietary ingredients. They're popular with consumers because they are easily accessible, relatively inexpensive and ready to eat straight out of the package. The increasing prevalence of these products around the world has directly contributed to increased obesity and other mental and metabolic impacts on consumers of all ages.

Children tend to like junk food. As much as 70% percent of their caloric consumption are estimated to come from ultra-processed foods. While numerous studies have reflected on the overall negative impact of junk food, few have focused on its direct developmental effects on children, particularly young children.

The Hebrew University study provides the first comprehensive analysis for how these foods impact skeletal development. The study surveyed lab rodents whose skeletons were in the post embryonic stages of growth. The rodents that were subjected to ultra-processed foods suffered from growth retardation and their bone strength was adversely affected. Under histological examination, the researchers detected high levels of cartilage buildup in the rodents' growth plates, the "engine" of bone growth. When subjected to additional tests of the rodent cells, the researchers found that the RNA genetic profiles of cartilage cells that had been subjected to junk food were showing characteristics of impaired bone development.

The team then sought to analyze how specific eating habits might impact bone development and replicated this kind of food intake for the rodents. "We divided the rodents' weekly nutritional intake--30% came from a 'controlled' diet, 70% from ultra-processed foods", shared Monsonego-Ornan. They found that the rodents experienced moderate damage to their bone density albeit there were fewer indications of cartilage buildup in their growth plates. "Our conclusion was that even in reduced amounts, the ultra-processed foods can have a definite negative impact on skeletal growth."

These findings are critical because children and adolescents consume these foods on a regular basis to the extent that 50 percent of American kids eat junk food each and every day. Monsonego-Ornan added. "when Carlos Monteiro, one of the world's leading experts on nutrition, said that there is no such thing as a healthy ultra-processed food, he was clearly right. Even if we reduce fats, carbs nitrates and other known harmful substances, these foods still possess their damaging attributes. Every part of the body is prone to this damage and certainly those systems that remain in the critical stages of development."

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The Hebrew University of Jerusalem

SARS-CoV-2 variants from mink evade inhibition by antibodies

image: Introduction of SARS-CoV-2 into farmed mink leads to the emergence of viral variants that partially evade antibody-mediated neutralization. A) SARS-CoV-2-infected workers introduced the virus into farmed mink populations, causing an epidemic spread of the virus in the animals. As a result, the virus mutated in mink and gave rise to a novel SARS-CoV-2 variant. This novel variant was subsequently transmitted back to workers, sparking transmission chains in the local community. B) SARS-CoV-2 from mink harbor one or more mutations in the viral spike protein, which is used by the virus to enter cells and constitutes the main target for neutralizing antibodies. These mutations enable the virus to partially evade from neutralization by antibodies from convalescent individuals and synthetic antibodies used for COVID-19 therapy.

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Markus Hoffmann

It has been known for about a year that minks can become infected with SARS-CoV-2. The virus had been transmitted from humans to farmed mink and mutated in infected animals. Mutations were acquired in the spike protein, which is crucial for the entry of the virus into host cells and represents the central point of attack for antibodies. These SARS-CoV-2 variants from mink were transmitted back to humans, raising concerns that minks could be a continuing source of infection of humans with SARS-CoV-2 variants with altered biological properties. Researchers at the German Primate Center (DPZ) - Leibniz Institute for Primate Research in Göttingen, Germany, have now shown that an antibody used for COVID-19 therapy is unable to effectively inhibit SARS-CoV-2 harboring a spike mutation acquired in minks. In addition, the mutation reduced the inhibition of the virus by antibodies produced in SARS-CoV-2 infected humans. These results show that SARS-CoV-2 can acquire mutations in minks that may reduce control of the virus by the human immune system (Cell Reports).

More than three million people have died worldwide from the pandemic spread of SARS coronavirus-2 and its associated disease COVID-19, according to the World Health Organization (WHO). Animal-to-human transmission of the virus is believed to be the origin of the pandemic, which began in Wuhan, China, in December 2019. In April 2020, mink in Dutch mink farms developed a respiratory disease due to infection with SARS-CoV-2, which was transmitted from infected farm workers to the animals. The virus mutated in mink and different virus variants emerged, which were transmitted back to farm workers and then also transmitted from human to human. This observation was also made in Denmark and millions of minks were killed to prevent the transmission of new viral variants to humans.

The spike protein in the envelope of SARS-CoV-2 is responsible for the entry of the virus into cells in which it replicates. Researchers led by Markus Hoffmann and Stefan Pöhlmann of the German Primate Center have studied mutations detected in the spike protein of SARS-CoV-2 from mink, including mutation Y453F. The researchers wanted to find out whether this mutation affects inhibition of the virus by antibodies that are used for COVID-19 therapy or are produced in COVID-19 patients.

"Our results show that one of two antibodies from an antibody cocktail used for COVID-19 therapy no longer efficiently inhibits the viral variant with the Y453F mutation. Furthermore, our study demonstrates that the Y453F mutation reduces inhibition of the virus by antibodies produced by COVID-19 patients. This means that people who were infected with SARS-CoV-2 may have reduced protection against mink variants of the virus", says Markus Hoffmann, first author of the study. In sum, SARS-CoV-2 can mutate in minks in a way that reduces immune control by antibodies. Whether this is also possible in other animals to which the virus can be transmitted by infected individuals is currently unclear. "In the meantime, the Y453F mutation has also occurred in humans, but not through infection with a mink variant. When the virus replicates for a long time in people who are immunocompromised, resistant variants can emerge. In this case, the resistance-mediating mutation was identical to the one observed in mink," says Stefan Pöhlmann.

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Deutsches Primatenzentrum (DPZ)/German Primate Center

Traumatic brain injuries can increase risk of stroke for up to five years, finds study

Stroke risk for patients with traumatic brain injuries is at its highest in the four months following injury and remains significant for up to five years post-injury, finds a new systematic review led by a team at the University of Birmingham.

Traumatic brain injury (TBI) is a global health problem affecting over 60 million people a year worldwide. Incidences of TBI are rising due to a range of factors including increased falls in the elderly, military conflict, sports injuries and road traffic accidents. However, advances in critical care and imaging have led to a reduction in TBI-related mortality.

Previous studies have associated TBI with a long-term risk of neurological diseases including dementia, Parkinson's and epilepsy, and TBI has been proposed as an independent risk factor for stroke.

This latest review, which brings together 18 studies from four countries and publishes today (April 9) in the International Journal of Stroke, is the first of its kind to investigate post-injury stroke risk.

Funded by the National Institute for Health Research's Surgical Reconstruction and Microbiology Research Centre based at University Hospitals Birmingham NHS Foundation Trust, the review showed that TBI patients have an 86% increased risk of stroke compared to patients who have not experienced a TBI. Stroke risk may be at its highest in the first four months post-injury, but remains significant for up to five years, found the review.

Significantly, the findings suggest that TBI is a risk factor for stroke regardless of the severity or subtype of the injury. This is particularly noteworthy because 70% to 90% of TBI's are mild and suggests that TBI's should be considered a chronic condition even if it is mild and patients recover well.

Researchers also found that the use of anti-coagulants, such as VKA's and statins, could help to reduce stroke risk post-TBI, while the use of some classes of anti-depressants are associated with increased stroke risk post-TBI.

Lead author Dr Grace Turner, of the University of Birmingham's Institute of Applied Health Research, said: "Stroke is the second leading cause of death and third leading cause of disability worldwide, however, urgent treatment can prevent stroke related death and long-term disability.

"Our review found some evidence to suggest an association between reduced stroke risk post-TBI and the stroke prevention drugs VKAs and statins but, as previous studies have found, stroke prevention drugs are often stopped when an individual experiences a TBI.

She said more research is required to investigate the effectiveness of stroke prevention drugs post-TBI to help inform clinicians' prescribing and facilitate shared decision making.

Dr Turner added: "As our review has shown, TBI patients should be informed of the potential for increased stroke risk and with the risk of stroke at its highest in the first four months post-injury, this is a critical time period to educate patients and their care givers on stroke risk and symptoms.

"This initial four-month period should also be used by clinicians to administer stroke prevention medication and lifestyle advice to mitigate the excess risk of stroke associated with TBI."

Credit: 
University of Birmingham

Defects in a specific cell type may cause ulcerative colitis

There are many variants of "goblet cells" in the intestines and they seem to have different functions, according to a new study from the University of Gothenburg. The study indicates that defects in goblet cells of a particular type may be a factor contributing to ulcerative colitis, an inflammatory bowel disease.

The entire inside of our intestines is covered by a thin layer of mucus that protects the fragile mucous membrane (mucosa) from bacteria and other microorganisms. If the microorganisms repeatedly come into contact with the intestinal mucosa, inflammation and even cell changes may result. These increase the risk of intestinal cancer. In a healthy colon, the mucus layer is up to a millimeter thick. This layer, which undergoes complete renewal hourly, is formed from cells of a special type, known as goblet cells.

Many different goblet cells

In the present study, now published in the journal Science, the scientists separated goblet cells from other cells and investigated which proteins each individual goblet cell expresses. There proved to be many different subtypes of these cells, and goblet cells' functions turned out to vary more than researchers have previously realized.

"We believe this is important knowledge that may enable us to influence the protective function of the gut in the future. The system that maintains the protective intestinal mucus layer seems to be able to change its functions, and we could utilize this capacity by reprogramming the layer with various signals, for example by using new drugs", says Malin Johansson, Associate Professor at Sahlgrenska Academy, University of Gothenburg, who led the research behind the present study.

Connected with ulcerative colitis

The most impermeable part of the mucus layer is formed by glands in the gut. In particular, the research team studied one of the specific types of goblet cells, found on the outermost surface of the mucosa. These goblet cells provide another type of mucus, which contributes to the protection of the gut but allows certain nutrients to pass through.

"If the function of these specific cells is impaired, we see that unprotected cell surfaces arise. These lead to inflammation, both in studies on mice and in samples from patients with ulcerative colitis," Johansson says.

Appear to cause damage to mucosal protection

In the study, these specific goblet cells seemed to be repelled by the mucosa earlier than normal in patients with ulcerative colitis. Accordingly, the cells became fewer.

"To our surprise, we were able to observe this both in patients with active ulcerative colitis and in those who were temporarily asymptomatic. This indicates that premature rejection of the particular goblet cells we've been studying damages the mucus protection and that this is a contributing cause of inflammatory bowel disease. It could also be a partial explanation for these patients' elevated cancer risk," Johansson says.

There are some 30,000 people in Sweden with ulcerative colitis, which is a chronic but intermittent inflammatory bowel disease.

Credit: 
University of Gothenburg

Intellectual disability is rarely inherited -- risk for younger siblings is low

The prevalence of intellectual disabilities, which means difficulties with learning and understanding new things, is roughly 1-2% in the population. People with a severe intellectual disability need help from others in daily activities throughout their lives.

Such disabilities can be caused by genetic changes or external factors. According to estimates, roughly 2,500 genes underlie intellectual disability, of which approximately half remain unidentified.

In recent years, the diagnostics for intellectual disabilities have improved thanks to advancements in techniques that make it possible to sequence the entire genome. These techniques can also help to identify causes of intellectual disability not found in other medical examinations and tests. Exome sequencing, that is, the sequencing of the protein-coding regions of genes in the genome, enables the identification of new pathogenic gene variants as well. Identifying genes is a prerequisite for identifying disease mechanisms and developing treatments.

The study conducted at the University of Helsinki utilised exome sequencing to determine the potential genetic background of intellectual disability. The study participants included Finnish families with family members with delayed cognitive development for which no clear cause had been identified. The results were recently published in the Human Genetics journal.

It was found that in 64% of the study participants the cause of their developmental disorder was a known intellectual disability gene. The majority of these variants, 75%, was the result of random mutations taking place during foetal development (de novo), and variants not found in the parents' genome. An inherited mutation was identified in no more than a quarter of the pathogenic genes studied. More large-scale structural variants, which are usually not inherited, were found in only 8% of the families.

"Based on our findings, the risk of recurrence of intellectual disability in the next child of individual families is usually low," says Docent Irma Järvelä. According to Järvelä, this is a significant and relieving piece of information for many families.

She believes the use of exome sequencing as a primary method of examination in the diagnostics for intellectual disabilities is well justified. The technique makes it possible to investigate the cause of disability faster than before, which alleviates the uncertainty and concern felt by families, as well as generates savings in healthcare.

"The more familiar we are with the factors underlying intellectual disabilities and their hereditary nature, the better we are able to help families that encounter these serious disorders," Järvelä adds.

Human settlement history does not increase the prevalence of inherited diseases

The Finnish population has become known for its recessively inherited severe diseases caused by single gene defects known as founder variants, with some 40 of such diseases known so far.

The recently published study demonstrated that de novo variants created in early foetal development are the most common cause for intellectual disabilities also in the Finnish population. Known variants associated with recessive diseases were identified in only 5% of the families included in the study, a result in line with other European populations.

"In spite of the isolated nature of our population, Finns are not different from other European populations in terms of the inheritance of intellectual disabilities," Järvelä says.

A distant family connection going back 7 to 10 generations reduces the risk of establishing an recessively inherited disease even in small populations.

"In the light of contemporary gene research, the Finnish disease heritage appears an increasingly rare find. Related research in Finland is of a high medical standard," Järvelä emphasises.

In the recently published study, nine new candidate genes were identified, of which a handful were found to be recessive. In further research, one of these genes could turn out to be a previously unknown gene enriched in the Finnish population.

The study was conducted in cooperation with Finnish doctors involved in the treatment of people with intellectual disabilities and the Department of Medical Genetics at the University of Helsinki as well as Columbia University and the Baylor College of Medicine in the United States.

Credit: 
University of Helsinki

What does the study of domesticated birds tell us about the evolution of human language?

image: Researchers analysed the genomic, neurobiological and singing-type differences between the domesticated Bengalese finch (see image above) and its closest wild relative.

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UNIVERSITY OF BARCELONA

Language is one of the most remarkable abilities humans have. It allows us to express complex meanings and transmit knowledge from generation to generation. An important question in human biology is how this ability evolved, and researchers from the universities of Barcelona, Cologne and Tokyo have tackled this issue in a recent article, published in the journal Trends in Cognitive Sciences.

The article has among its authors experts from the Institute of Complex Systems of the UB (UBICS) Thomas O’Rourke and Pedro Tiago Martins, led by ICREA research professor Cedric Boeckx. According to this new study, the evolution of language would be related to another noteworthy feature of Homo sapiens: tolerance and cooperation towards each other.

The study draws on evidence from such diverse fields as archaeology, evolutionary genomics, neurobiology, animal behaviour and clinical research on neuropsychiatric disorders. The authors hypothesize that a reduction of reactive aggression, resulting from the evolution and process of self-domestication of our species, could have led to an increase in our language complexity. According to the authors, this development would be caused by a reduced impact on brain networks of stress hormones, neurotransmitters that activate in aggressive situations, and which would be crucial for how we learn to speak. To show this interaction, the researchers analysed the genomic, neurobiological and singing-type differences between the domesticated Bengalese finch and its closest wild relative.

Looking for keys of the human language evolution in birdsong

A central aspect of the authors’ approach in the study is that the aspects that make language special can be elucidated by comparing them to the communication systems of other animals. “For instance, take how children learn to speak and how birds learn to sing: unlike most animal communication systems, juvenile birdsong and the child speech only develop properly in presence of adult tutors. Without the vocal support from adults, the great range of sounds available to humans and songbirds does not develop properly”, the researchers note.

Moreover, although speech and birdsong evolved independently, the authors suggest both communication systems are associated with similar patterns in brain connectivity and are negatively affected by stress: “Birds that are regularly under stress during their development sing a more stereotypical song as adults, while children with chronic stress problems are more susceptible to developing repetitive tics, including vocalizations in the case of Tourette syndrome”.

In this context, Kazuo Okanoya, one of the authors of the study, has been studying the Bengalese finch for years. This domesticated songbird sings a more varied and complex song than its wild ancestor. The study points out that the same happens with other domesticated species. The Bengalese finch has a weakened stress response and is less aggressive than its wild counterpart. In fact, according to the authors, there is more and more “evidence of multiple domesticated species having altered vocal repertoires compared to their wild counterparts”.

The impact of domestication in stress and aggressiveness

For the researchers, these differences between domestic and wild animals are “a central piece in the puzzle of the evolution of human language”, since our species and domesticated species share particular physical changes related to their closest wild species. Modern humans have a flattened face, a rounded skull and reduced tooth size compared to our extinct archaic relatives, the Neanderthals. Domesticates have comparable changes to facial and cranial bone structures, often accompanied by the development of other traits such as skin depigmentation, floppy ears and curly tails. Finally, modern humans have marked reductions in measures of stress response and reactive aggression compared to other living apes. These similarities do not stop at physical traits since, according to researchers, the genomes of modern humans and multiple domesticated species show changes targeting the same genes.

In particular, a disproportionate number of these genes downregulate the activity of the glutamate neurotransmitter system, which drives the brain response to stressful experiences. Authors note that “glutamate, the brain’s main excitatory neurotransmitter, interacts with dopamine, in birdsong learning, aggressive behaviour, and the repetitive vocal tics of Tourette syndrome”.

Alterations in stress hormone balance in the striatum

In the study, authors show how the activity of glutamate tends to promote the release of dopamine in the striatum, an evolutionary old brain structure important for reward-based learning and motor output. “In adult songbirds, the increase in dopamine release in this striatal area is correlated with the learning of a more restricted song, which replaces experimental vocalizations typical of young birds”. “Regarding human beings and other mammals” —the authors add—, “dopamine release in the dorsal striatum promotes restrictive and repetitive motor outputs, such as vocalizations, while other more experimental and exploratory behaviours are supported by the dopaminergic activity of the ventral striatum”.

According to the study, many of the glutamatergic signaling genes that have changed in recent human evolution code for receptors that reduce the excitation of the dorsal striatum. Meanwhile, these receptors tend not to reduce activity, and even promote the dopamine release, in ventral striatal regions.

The authors say these alterations in the balance of stress hormones in the striatum were an important advance in the evolution of vocal learning in the lineage of modern humans. “These results suggest the glutamate system and its interactions with dopamine are involved in the process in which humans acquired their varied and flexible ability to speak. Selection against reactive aggression in our species would have altered the interaction of these neurotransmitters promoting the communicative skills of our species. These findings shed light on new ways for comparative biological research on the human language faculty” conclude researchers.

Credit: 
University of Barcelona

Sustainable chemical synthesis with platinum

image: The source of phenols in these experiments was lignin, which is involved in the tough structural components of rigid plant bodies such as trees. So woody biomass like this is the ideal raw material as it can be more sustainably sourced than petroleum.

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CC0 - Pixabay/ybernardi

Researchers used platinum and aluminum compounds to create a catalyst which enables certain chemical reactions to occur more efficiently than ever before. The catalyst could significantly reduce energy usage in various industrial and pharmaceutical processes. It also allows for a wider range of sustainable sources to feed the processes, which could reduce the demand for fossil fuels required by them.

There are many chemicals used in a wide range of industries, including pharmaceuticals, that you probably don't notice in everyday life; for example, benzene, toluene, xylene and ethylbenzene, to name a few. These are created at chemical production plants that use petroleum to feed the processes in question. But there is now a way to produce those chemicals in a more sustainable way.

Assistant Professor Xiongjie Jin and Professor Kyoko Nozaki from the Department of Chemistry and Biotechnology at the University of Tokyo and their team have created a new catalyst, a material that enables or speeds up a specific chemical reaction, that allows for more sustainable production of so-called aromatic hydrocarbons. At present the process typically requires temperatures of 200 degrees Celsius or more and pressures of 2 or more atmospheres. But with the team's new catalyst, the temperature can be brought down to between 100 degrees and 150 degrees Celsius, and the pressure to just 1 atmosphere, or ambient pressure. This could hugely reduce the energy cost of production.

"Our 'Pt catalyst' makes use of platinum nanoparticles and an aluminum metaphosphate substrate, which is rarely ever used in catalysts," said Jin. "Source molecules interacting with this catalyst at the right temperature and pressure break down into useful aromatic hydrocarbon compounds. This process is called hydrogenolysis. But the most exciting part for us is not just that the catalyst improves reaction efficiency, but that it opens up new options for the kinds of source materials that can now be used in these processes."

Currently, nonrenewable petroleum-based substances are used to create aromatic hydrocarbons, and this is not a sustainable scenario in the long run. The Pt catalyst allows the use of renewable woody biomass as source material, in particular a family of compounds known as lignins, which contain phenols, the basis of the reactions in question. Another benefit of the Pt catalyst is that it can be recycled and reused several times over. All these factors combined could lead to a vastly more sustainable way to produce aromatic hydrocarbons on an industrial scale.

"We hope our study contributes to the (United Nations) Sustainable Development Goals by making industrially important chemicals from renewable resources instead of petroleum, and at a lower energy cost," said Jin. "Our next steps will be to further increase the lifetime of the Pt catalyst and also to make the catalyst work directly on lignins, mitigating the need to break it down into phenols before the reactions can take place."

Credit: 
University of Tokyo

New properties of strontium titanate are significant for electronics research

image: EPR spectra of the (001)-oriented single-crystal samples having the shape of a bar and a plate of STO:Fe3+ at T = 300 K (a) and of a plate of STO:Mn4+ at T = 150 K (b). The orientations of the samples with respect to the magnetic field B are marked in the figure. Black lines are the measured spectra, the red ones are the fits and the blue lines show the simulated spectra of the non-perturbed cubic-symmetry centers (see text). Orientation dependence of the resonance fields for the Fe3+ centers in the STO:Fe (001)-plate (c) with the magnetic field rotated in the (001) and (100) crystallographic planes (rhombs and circles, respectively); its fit using the Hamiltonian (1) is shown by solid lines. Temperature dependences of the parameter corresponding to the axial component of the crystal field for a plate (squares) and a bar (circles) shaped samples (d); dotted lines are the guides for the eye.

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Kazan Federal University

While studying strontium titanate with electron paramagnetic resonance, a team from KFU's Center for Quantum Technology has found that the shape of a specimen of strontium titanate influences its internal symmetry. The research was co-conducted by the Ioffe Institute of Physics and Technology (Russia) and the Institute of Physics of the Czech Academy of Sciences.

At room temperature, SrTiO3 is a crystal with high cubic symmetry, that is, the lattice of strontium titanate, like bricks, is composed of unit cells, each of which is a regular cube. However, the researchers showed the picture is a bit more nuanced. In thin plates and columns measuring microns in width, the symmetry decreases to tetragonal (uniaxial), with a structure was not previously observed in SrTiO3. That is, each elementary cell turns into a parallelepiped.

"The results are of great scientific and practical importance. In many cases, the scale of breaking is not as important as its very presence. A decrease in symmetry opens up the possibility of phenomena that are forbidden in a cubic structure," said Roman Yusupov, Lead Research Associate of the Center for Quantum Technology.

He noted that strontium titanate is actively used in thin-film technologies, where the functional properties of materials are determined by layers that sometimes have a thickness of several atoms. They are crucial for electronic devices, such as processors, monitors, mobile screens, high-capacity batteries, and storage devices.

"Thin films are based on substrates -- typically thin (less than one millimeter in thickness) slabs of materials other than the film material. The properties of thin films are largely determined by the structure of the substrate. One of the widely used substrate materials is strontium titanate," explains Yusupov.

By changing the distortion magnitude of substrates, it's possible to change the characteristics of thin films deposited on them, and thus contribute to creating new devices, sensors, and detectors.

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Kazan Federal University

Study shows education is not enough to overcome inequality

A recent study finds that social inequality persists, regardless of educational achievement - particularly for men.

"Education is not the equalizer that many people think it is," says Anna Manzoni, author of the study and an associate professor of sociology at North Carolina State University.

The study aimed to determine the extent to which a parent's social status gives an advantage to their children. The research used the educational achievements of parents as a proxy for social status, and looked at the earnings of adult children as a proxy for professional success.

To address the research question, Manzoni examined data from people who were interviewed as part of the National Survey of College Graduates between 2010 and 2017. Specifically, Manzoni focused on United States citizens between 35 and 67 years old who reported on their wages and parental education. The final sample size was 56,819 individuals: 32,337 men and 24,482 women.

The analysis found that if a son gets a degree similar to the degree that a parent had, the son will earn more money than if his parent did not achieve the same level of education.

For example, imagine that Son A becomes a doctor, and he had a parent who was also a doctor. Meanwhile, Son B also becomes a doctor, but his parents only had bachelor's degrees. The study found that, in general, Son A will earn more money than Son B, even though they have the same degree.

This effect also exists for daughters, but it is much weaker.

"The effect we see here essentially preserves social stratification for sons - less so for daughters," Manzoni says. "We like to think that if someone makes it to college, becomes a lawyer, becomes a doctor, they have 'made it.' But what we see is that even earning an advanced degree is unlikely to put you on the same professional footing as someone who earned the same degree but started higher on the social ladder.

"One take-away is that expanding access to education is valuable, but education alone is not enough to resolve our society's challenges in regard to inequality," Manzoni says.

"This work shows that social origin matters, but it's not clear what drives this structural inequality," Manzoni adds. "Is it social capital? Access to networks? Differing financial resources? Is parental background becoming more important as a larger percentage of the population is getting a college degree? Is the advantage at the beginning of a child's career? There is still a lot of room for additional research on this subject."

Credit: 
North Carolina State University