Culture

Douglas Wilbur '14, a visiting Ph.D. scholar in the Department of Communication at UTSA, has published a study that shows how researchers can craft message campaigns to protect individuals from adopting extremist views.

According to his research, when people are explicitly told that they are free to accept or reject propagandistic claims, the likelihood of choosing a moderate view increases. This was a result of a survey of attitudes that tested counter-propaganda strategies, which stressed a person's autonomy, and then measured sentiments after exposure.

The study was recently published in Social Influence with collaborators at the University of Missouri.

"It's ironic, if you think about it. Empowering individuals to make choices when they encounter extremist messaging appears to help people resist such claims," Wilbur said. "What this research showed is consistent with other findings. You tend to see a trend where people will make the right choice."

The Pew Research Center found that two out of every three Americans say social media has a negative impact on what occurs within the U.S. The primary reasons listed in that same survey were misinformation and hate speech.

To combat propaganda in the past, strategists have relied on attitude inoculation theory. Analogous to how physical vaccines inoculate people against a virus, communication messages use psychological inoculation through exposure to both negative messages but also techniques to resist such attacks. As a result, people train and build their psychological immunity to resist future persuasion attempts. The shortcoming of this approach, however, is that it's difficult to apply to large groups.

With that limitation in mind, Wilbur tested two counter-propaganda strategies for boosting peoples' resistance to extremist propaganda. One is based on self-determination theory, or DPT, which argues that people are curious, active, and health-seeking as long as their psychological needs are met. Primarily, in this approach, the individual needs to have agency and control over their actions. Similarly, the other strategy tested relies on psychological reactance theory, or PRT, which assumes that people have strong negative reactions when they feel their freedom is threatened.

Wilbur recruited close to 400 participants online and told them they would read extremist messages. Respondents were randomly assigned to either a neutral control condition, a DPT approach ('it is your choice to agree or not'), or the PRT condition ('don't let them manipulate you'). They then read and rated their agreement of two anti-immigrant extremist messages. After exposure, both campaigns produced lower agreement to the extremist messages when compared to the control condition--regardless of political affiliation.

Wilbur elaborated that the benefits of these agency-based campaigns is that they can be built beforehand and are not message-specific. These proactive strategies and the resulting advantages are a departure from previous approaches that Wilbur himself used during his military tour in Afghanistan. There, he served as a communications officer and was tasked with blocking Al-Qaeda recruiting efforts, yet the existing communications methods at his disposal were slow and reactive.

"Al-Qaeda would put out a video to recruit. Then we would have to discredit it, but this would take time to get a counter-product (opposing argument via pamphlets or videos) out there," Wilbur recalled.

His approach aims to disrupt the radicalization process among vulnerable population groups.

"If we could prime people to think they have autonomy, then yes, they would be more likely to resist propagandist messages," Wilbur said. "We can even build messages about the COVID-19 vaccine--campaigns that tell people that they can chose whether to take the vaccine or not. You want to stress freedom."

NEW YORK, NY (April 16, 2021)--SARS-CoV-2, the virus that causes COVID-19, likely does not directly infect the brain but can still inflict significant neurological damage, according to a new study from neuropathologists, neurologists, and neuroradiologists at Columbia University Vagelos College of Physicians and Surgeons.

"There's been considerable debate about whether this virus infects the brain, but we were unable to find any signs of virus inside brain cells of more than 40 COVID-19 patients," says James E. Goldman, MD, PhD, professor of pathology & cell biology (in psychiatry), who led the study with Peter D. Canoll, MD, PhD, professor of pathology & cell biology, and Kiran T. Thakur, MD, the Winifred Mercer Pitkin Assistant Professor of Neurology.

"At the same time, we observed many pathological changes in these brains, which could explain why severely ill patients experience confusion and delirium and other serious neurological effects--and why those with mild cases may experience 'brain fog' for weeks and months."

The study, published in the journal Brain, is the largest and most detailed COVID-19 brain autopsy report published to date, suggests that the neurological changes often seen in these patients may result from inflammation triggered by the virus in other parts of the body or in the brain's blood vessels.

No Virus in Brain Cells

The study examined the brains of 41 patients with COVID-19 who succumbed to the disease during their hospitalization. The patients ranged in age from 38 to 97; about half had been intubated and all had lung damage caused by the virus. Many of the patients were of Hispanic ethnicity. There was a wide range of hospital length with some patients dying soon after arrival to the emergency room while others remained in the hospital for months. All of the patients had extensive clinical and laboratory investigations, and some had brain MRI and CT scans.

To detect any virus in the neurons and glia cells of the brain, the researchers used multiple methods including RNA in situ hybridization, which can detect viral RNA within intact cells; antibodies that can detect viral proteins within cells; and RT-PCR, a sensitive technique for detecting viral RNA.

Despite their intensive search, the researchers found no evidence of the virus in the patients' brain cells. Though they did detect very low levels of viral RNA by RT-PCR, this was likely due to virus in blood vessels or leptomeninges covering the brain.

"We've looked at more brains than other studies, and we've used more techniques to search for the virus. The bottom line is that we find no evidence of viral RNA or protein in brain cells," Goldman says. "Though there are some papers that claim to have found virus in neurons or glia, we think that those result from contamination, and any virus in the brain is contained within the brain's blood vessels."
"If there's any virus present in the brain tissue, it has to be in very small amounts and does not correlate with the distribution or abundance of neuropathological findings," Canoll says.

The tests were conducted on more than two dozen brain regions, including the olfactory bulb, which was searched because some reports have speculated that the coronavirus can travel from the nasal cavity into the brain via the olfactory nerve. "Even there, we didn't find any viral protein or RNA," Goldman says, "though we found viral RNA and protein in the patients' nasal mucosa and in the olfactory mucosa high in the nasal cavity." (The latter finding appears in an unpublished study, currently on BioRxiv, led by Jonathan Overdevest, MD, PhD, assistant professor of otolaryngology, and Stavros Lomvardas, PhD, professor of biochemistry & molecular biophysics and neuroscience.)

Hypoxic Damage and Signs of Neuronal Death

Despite the absence of virus in the brain, in every patient the researchers found significant brain pathology, which mostly fell into two categories.

"The first thing we noticed was a lot of areas with damage from a lack of oxygen," Goldman says. "They all had severe lung disease, so it's not surprising that there's hypoxic damage in the brain."

Some of these were large areas caused by strokes, but most were very small and only detectable with a microscope. Based on other features, the researchers believe these small areas of hypoxic damage were caused by blood clots, common in patients with severe COVID-19, that temporarily stopped the supply of oxygen to that area.

A more surprising finding, Goldman says, was the large number of activated microglia they found in the brains of most patients. Microglia are immune cells that reside in the brain and can be activated by pathogens.

"We found clusters of microglia attacking neurons, a process called 'neuronophagia,'" says Canoll. Since no virus was found in the brain, it's possible the microglia may have been activated by inflammatory cytokines, such as Interleukin-6, associated with SARS-CoV-2 infection.

"At the same time, hypoxia can induce the expression of 'eat me' signals on the surface of neurons, making hypoxic neurons more vulnerable to activated microglia," Canoll says, "so even without directly infecting brain cells, COVID-19 can cause damage to the brain."

The group found this pattern of pathology in one of their first autopsies, described by Osama Al-Dalahmah, MD, PhD, instructor in pathology & cell biology, in a case report published last March in Acta Neuropathologica Communications. Over the next few months, as the neuropathologists did many more COVID brain autopsies, they saw similar findings over and over again and realized that this is a prominent and common neuropathological finding in patients who die of COVID.

The activated microglia were found predominantly in the lower brain stem, which regulates heart and breathing rhythms, as well as levels of consciousness, and in the hippocampus, which is involved in memory and mood.

"We know the microglia activity will lead to loss of neurons, and that loss is permanent," Goldman says. "Is there enough loss of neurons in the hippocampus to cause memory problems? Or in other parts of the brain that help direct our attention? It's possible, but we really don't know at this point."

Persistent Neurological Problems in Survivors

Goldman says that more research is needed to understand the reasons why some post-COVID-19 patients continue to experience symptoms.

The researchers are now examining autopsies on patients who died several months after recovering from COVID-19 to learn more.

They are also examining the brains from patients who were critically ill with acute respiratory distress syndrome (ARDS) before the COVID-19 pandemic to see how much of COVID-19 brain pathology is a result of the severe lung disease.

"It is machination, it is deception," said the Director General of the Berlin Royal Museums in his defence when criticized for buying a fake. Wilhelm Bode did not budge an inch: the sculpture he acquired in 1909 was an as yet unknown production of the great Renaissance master, Leonardo da Vinci. After one hundred years and numerous controversies, a group of scientists led by a CNRS researcher* has just proven him wrong once and for all. The Flora wax bust, conserved at the Bode Museum in Berlin, recently underwent radiocarbon (14C) dating, which provided both a precise date and an incontrovertible result: it was made in the nineteenth century, nearly 300 years after da Vinci's death. As the sculpture was made primarily from spermaceti, a kind of wax extracted from whales, the researchers had to develop a new calibration method to accurately date the work of art. Their results, which were published on 15 April 2021 in Scientific Reports, show how 14C dating can be applied to unusual materials.

*- The researchers involved work at the Chemistry Research Institute of Paris (CNRS/Chimie ParisTech), the Centre for Research and Restoration of Museums of France (Ministry of Culture), and the Carbon-14 Measurement Laboratory (CEA/CNRS/IRD/IRSN/Ministry of Culture), a national platform managed by the Laboratory for Sciences of Climate and Environment (CNRS/CEA/Université de Versailles Saint-Quentin-en-Yvelines).

In a new publication from Opto-Electronic Advances; DOI https://doi.org/10.29026/oea.2021.200031, Researchers led by Professor Baohua Jia at Swinburne University of Technology, Victoria, Australia, Professor Cheng-Wei Qiu at National University of Singapore, Singapore and Professor Tian Lan at Beijing Institute of Technology, Beijing, China considered the generation of super-resolved optical needle and multifocal array using graphene oxide metalenses.

Ultrathin and lightweight, metalenses are becoming increasingly significant for their use in photonic chips, biosensors and micro imaging systems such as smart phone cameras.

Compared to conventional lenses, metalenses can improve the image quality of current cameras, by enhancing resolution and removing spherical and chromatic aberrations. A single ultrathin (less than the thickness of 1/100 of a human hair) metalens element can be used instead of the multiple element imaging systems required by conventional lenses. Due to the unique light-matter interaction in a confined 2D plane, 2D materials are ideal for use with metalenses, further reducing the required thickness of the lens. 2D Graphene family materials, for example graphene oxides, are air-stable, have many applications and are low-cost and easy to fabricate in large scale. They remain stable in extreme environments, for example lower earth orbit in aerospace, so have potential use in satellites replacing the current bulky lenses and improving imaging quality and lowering launch costs.

The authors of this article developed 200 nm thick graphene oxide metalenses to generate specialized focal intensity distributions. The graphene oxide metalenses have the capability of controlling light amplitude (i.e., transparency of the lens) and phase (refractive index and thickness of the lens) simultaneously. This differs from other metalenses, which introduce the modulations through multi-step nanofabrication or multilevel of nano-elements, the modulations of graphene oxide lenses are locally introduced by the laser photo-reduction process, which converts graphene oxide to graphene material. During the reduction process, the material becomes thinner and has a higher refractive index and absorption. Based on the simultaneous phase and amplitude modulations, the authors demonstrate precise control of the focal intensity distributions by creating a super-resolved ultra-long optical needle and an axial multifocal array, which are extremely challenging for other metalenses.

Graphene oxide metalenses will find broad applications in integrated photonics and compact photonic systems, including microscopic imaging, optical manipulation and photonic chips, and can be integrated on microfluidic chips to form lab-on-a-chip biophotonic devices. This research forms a basis for the development of graphene-based ultrathin integratable photonic devices and paves the way for broader applications, such as replacing current cell phone camera lens potentially allowing a reduction in the thickness of current cell phones.

If you are exposed to silica (quartz) dust at work - e.g. from working with concrete and granite - you have a greater risk of certain types of rheumatic disease. This is shown by results from Aarhus University and Aarhus University Hospital, which have just been published in the International Journal of Epidemiology.

Exposure to silica dust at work, which is the case especially at workplaces within construction and industry, may lead to autoimmune rheumatic diseases. Photo: Unsplash.

Exposure to silica dust at work, which is the case especially at workplaces within construction and industry, may lead to autoimmune rheumatic diseases. Photo: Unsplash.

As the research results from Aarhus University show, exposure to silica dust comes at a cost.

"Exposure to silica dust at work, which is the case especially at workplaces within construction and industry, may lead to autoimmune rheumatic diseases - even at low levels of exposure," says one of the researchers behind the largest study of its kind, Medical Doctor and PhD Signe Hjuler Boudigaard from Aarhus University and Aarhus University Hospital.

Silica dust is formed when flint, sandstone, granite and concrete are grinded or processed in other ways. Some of the dust consists of small particles which - when you inhale them - are carried right down into the smallest parts of the lungs. This so-called respirable dust accumulates in the lungs, where it causes an inflammatory reaction and activates the immune system.

The risk of rheumatic diseases increases

The researchers examined the association between exposure to silica dust and the rheumatic diseases systemic sclerosis, rheumatoid arthritis, lupus erythematosus and small vessel vasculitis, which is a chronic inflammation of the small blood vessels.

They found that the risk of autoimmune rheumatic diseases increased with increasing exposure levels of silica dust. The risk for persons with the highest exposure was one-and-a-half times greater compared to non-exposed people.

The survey comprised 1,541,505 men and 1,470,769 women from the Danish labour force from 1979 to 2015. A total of 17,000 were diagnosed with one of these autoimmune diseases,

and of these, 1,490 had been exposed to silica dust at work. The study shows a clear association between level of exposure to silica dust at work and autoimmune rheumatic disorders, most clearly for systemic sclerosis and rheumatoid arthritis.

"The most important competing factor is tobacco smoking. We accounted for smoking and there was still an association between silica exposure and autoimmune rheumatic diseases. We know that smoking is not randomly distributed in the population, so it was important to take this into account," says Henrik Kolstad, professor at Aarhus University and Aarhus University Hospital and continues:

"In Denmark and Europe, the occupational exposure limit for silica dust is twice the limit in the USA. It's therefore clearly relevant to include our findings when reviewing the current Danish occupational exposure limit"

The next step is to examine whether exposure to silica dust leads to increased levels of antibodies specific for autoimmune rheumatic diseases. According to Henrik Kolstad, the purpose of these studies is to substantiate the causal relationship and gain insight into the possible causal mechanisms.

The leading newspapers in two nuclear waste management forerunner countries, Finland and France, fulfil their "watchdog" roles in highly distinct ways. The Finnish Helsingin Sanomat (HS) tends to reproduce government and industry framings, whereas Le Monde cherishes its role as an independent critic of the powers that be. These differences reflect distinct cultural, political and media traditions in the two countries.

"The critical watchdog model works in a liberal democracy such as the French, based on mistrust towards the governing elites. But would it backfire in Finland by undermining the very institutional trust that the Nordic democracies have been built upon throughout history?" asks the first author of the article, Research Fellow Markku Lehtonen from the Department of Humanities at the Pompeu Fabra University in Barcelona. Lehtonen continues: "Or perhaps the near-absence of criticism reflects weaknesses in the Finnish democracy?"

During the analysis period, from 2005 to 2018, both countries' deep geological disposal projects were advancing towards implementation.

The study, published in the journal Risk, Hazards, & Crisis in Public Policy, examined nuclear waste reporting - in particular related to risks and safety - in Helsingin Sanomat and Le Monde. During the analysis period, from 2005 to 2018, both countries' deep geological disposal projects were advancing towards implementation.

In its reporting on the final disposal of nuclear waste, Helsingin Sanomat focused on "performance?relevant information", exhibiting strong confidence in the safety and viability of the repository and trust in the actors behind the project. Le Monde, in turn, prioritised "morality-relevant information", highlighting the challenges of trust and mistrust between the involved parties, and, to a lesser extent, scepticism in relation to the viability and safety of the project.

Where Helsingin Sanomat underlined the consistent advancement towards a reliably operating repository, Le Monde evoked the numerous uncertainties and obstacles still facing the repository project, including the multiple conflicts and controversies among the involved actors.

"Le Monde constantly reminded of the ambiguous legacy of the French nuclear sector, as a symbol of modernisation, technological prowess, and economic prosperity on the one hand, and as an incarnation of failed promises on the other. Helsingin Sanomat, in turn, underlined continuity, predictability, and certainty. It described the Finnish repository project as a success story essential for the national interest," Lehtonen points out.

In addressing intergenerational equity, Helsingin Sanomat echoed the government and industry argument that a deep geological repository spares future generations from having to tackle the waste problem. By contrast, Le Monde pointed out a major dilemma: burying waste in a repository would deprive future generations of the freedom to decide what to do with the waste, including the possibility that thanks to technological development the waste could be turned into a resource.

"The findings help to understand why the nuclear waste disposal project has advanced in such an unproblematic manner in Finland," notes Research Fellow Matti Kojo from Tampere University, a co-author of the article.

A comprehensive analysis of leading newspapers over fourteen years

The now published study examined nuclear waste reporting - in particular related to risks and safety - in Helsingin Sanomat and Le Monde. The authors underline that the final set of material included only those articles in which the country's own repository project was a central topic (135 articles in HS and 210 in Le Monde).

Finland expects to become the first country in the world to have solved its problem of high-level radioactive waste, with its ONKALO repository expected to become operational by the mid-2020s. France's "Cigéo" facility is to start operating in the early 2030s.

The authors underline that the final set of material included only those articles in which the country's own repository project was a central topic.

The research group has previously compared, among other things, the processes of citizens participation, the role of host communities, and press reporting on nuclear waste management in Finland and Sweden.

Since fast radio bursts (FRBs) were first discovered over a decade ago, scientists have puzzled over what could be generating these intense flashes of radio waves from outside of our galaxy. In a gradual process of elimination, the field of possible explanations has narrowed as new pieces of information are gathered about FRBs - how long they last, the frequencies of the radio waves detected, and so on.

Now, a team led by McGill University researchers and members of Canada's CHIME Fast Radio Burst collaboration has established that FRBs include radio waves at frequencies lower than ever detected before, a discovery that redraws the boundaries for theoretical astrophysicists trying to put their finger on the source of FRBs.

"We detected fast radio bursts down to 110 MHz where before these bursts were only known to exist down to 300 MHz," explained Ziggy Pleunis, a postdoctoral researcher in McGill's Department of Physics and lead author of the research recently published in the Astrophysical Journal Letters. "This tells us that the region around the source of the bursts must be transparent to low-frequency emission, whereas some theories suggested that all low-frequency emission would be absorbed right away and could never be detected."

The study focussed on an FRB source first detected in 2018 by the CHIME radio telescope in British Columbia. Known as FRB 20180916B, the source has attracted particular attention because of its relative proximity to Earth and the fact that it emits FRBs at regular intervals.

The research team combined the capacities of CHIME with those of another radio telescope, LOFAR, or Low Frequency Array, in the Netherlands. The joint effort not only enabled the detection of the remarkably low FRB frequencies, but also revealed a consistent delay of around three days between the higher frequencies being picked up by CHIME and the lower ones reaching LOFAR.

"This systematic delay rules out explanations for the periodic activity that do not allow for the frequency dependence and thus brings us a few steps closer to understanding the origin of these mysterious bursts," adds co-author Daniele Michilli, also a postdoctoral researcher in the Department of Physics at McGill.

WHAT:
The experimental antiviral drug MK-4482 significantly decreased levels of virus and disease damage in the lungs of hamsters treated for SARS-CoV-2 infection, according to a new study from National Institutes of Health scientists. SARS-CoV-2 is the virus that causes COVID-19. MK-4482, delivered orally, is now in human clinical trials. Remdesivir, an antiviral drug already approved by the U.S. Food and Drug Administration for use against COVID-19, must be provided intravenously, making its use primarily limited to clinical settings.

In their study, published in the journal Nature Communications, the scientists found MK-4482 treatment effective when provided up to 12 hours before or 12 hours after infecting the hamsters with SARS-CoV-2. These data suggest that MK-4482 treatment potentially could mitigate high-risk exposures to SARS-CoV-2, and might be used to treat established SARS-CoV-2 infection alone or possibly in combination with other agents.

The same research group, located at Rocky Mountain Laboratories, part of NIH's National Institute of Allergy and Infectious Diseases in Hamilton, Montana, developed the hamster model last year to mimic SARS-CoV-2 infection and mild disease in people. The University of Plymouth in the United Kingdom collaborated on these most recent studies.

The project involved three groups of hamsters: a pre-infection treatment group; a post-infection treatment group; and an untreated control group. For the two treatment groups, scientists administered MK-4482 orally every 12 hours for three days. At the conclusion of the study, the animals in each of the treatment groups had 100 times less infectious virus in their lungs than the control group. Animals in the two treatment groups also had significantly fewer lesions in the lungs than the control group.

The scientists determined the MK-4482 treatment doses for this study based on previous experiments performed in mouse models of SARS-CoV-1 and MERS-CoV. In those studies, MK-4482 was effective at stopping the viruses from replicating.

With funding support from NIAID, Emory University's Drug Innovation Ventures group in Atlanta developed MK-4482 (also known as molnupiravir and EIDD-2801) to treat influenza. Merck and Ridgeback Biotherapeutics are now jointly developing and evaluating MK-4482 as a potential COVID-19 treatment. The drug is in Phase 2 and 3 human clinical studies.

A survey of star formation activity in the Orion Nebula Cluster found similar mass distributions for newborn stars and dense gas cores, which may evolve into stars. Counterintuitively, this means that the amount of gas a core accretes as it develops, and not the initial mass of the core, is the key factor in deciding the final mass of the produced star.

The Universe is populated with stars of various masses. Dense cores in clouds of interstellar gas collapse under their own gravity to form stars, but what determines the final mass of the star remains an open question. There are two competing theories. In the core-collapse model, larger stars form from larger cores. In the competitive accretion model, all cores start out about the same mass but accrete different amounts of gas from the surroundings as they grow.

To distinguish between these two scenarios, a research team led by Hideaki Takemura at the National Astronomical Observatory of Japan created a map of the Orion Nebula Cluster where new stars are forming, based on data from the American CARMA interferometer and NAOJ's own Nobeyama 45-m Radio Telescope. Thanks to the unprecedent high resolution of the map, the team was able to compare the masses of the newly formed stars and gravitationally collapsing dense cores. They found that the mass distributions are similar for the two populations. They also found many smaller cores which don't have strong enough gravity to contract into stars.

One would think that similar mass distributions for prestellar cores and newborn stars would favor the core-collapse model, but actually because it is impossible for a core to impart all of its mass to a new star, this shows that continued gas inflow is an important factor, favoring the competitive accretion model.

Now the team will expand their map using additional data from CARMA and the Nobeyama 45-m Radio Telescope to see if the results from the Orion Nebula Cluster hold true for other regions.

The nervous system is the internet of the human body and can in the same way transfer signals over long distances very quickly. Some of the most important elements in this signaling are the axons. They are projections of the nerve cells which send signals to other nerve cells or muscles. For instance, axons that jut out from nerve cells in the spinal cord can be over one meter long.

Researchers from the Faculty of Health and Medical Sciences at the University of Copenhagen have now in a new study examined how signal molecules are transported in the axons.

"We have found out, that the protein Rab2 has to be present and functioning properly in order for the nerve cells to send effective signals between the central nervous system and the body. When we remove the protein in fruit flies we can see that the signal molecules are accumulate in the axons like in a traffic jam," explains visiting researchers Viktor Karlovich Lund from the Department of Neuroscience.

Same or similar mechanism in humans

The researchers investigate the transport of signal molecules in axons because there are multiple illnesses in humans where the transport is inhibited. This is true for neurodegenerative diseases such as Alzheimer's and Parkinson's disease, Amyotrophic lateral sclerosis (ALS) and neuropathy. Changes in the Rab2 gene are also connected to autism spectrum disorders.

Even though one has to be careful drawing conclusions between species, the researchers think that they have good reason to believe that their discovery is also relevant in humans.

"We share around 75 percent of disease-related genes with fruit flies. Beyond that, we know that the genes coding for Rab2 look alike in many different species - they have a high degree of evolutionary conservation. This makes us quite convinced that the same mechanism or one very similar exists in the human nervous system," says Ole Kjærulff, Associate Professor at the Department of Neuroscience.

The glue between cargo and engine

The signaling works by signaling molecules being transferred from one end of the axons to other nerve cells.

"Some types of signals require that the signal molecules first travel very far in the same cell. They are packaged into small organelles with a membrane around them and then they are transported op to one meter or more. This requires a complex machinery where everything needs to run smoothly," says Ole Kjærulff.

Inside the axons the 'cargo' is pulled by motor proteins that can be compared to small locomotives.

"Our best guess is that the Rab2 protein is the link between the motor proteins driving forward and the cargo being pulled. Almost like a molecular glue holding everything together," says Viktor Karlovich Lund.

The researchers hope that their new discovery can be the foundation for new attempts to create drugs targeting neurodegenerative diseases and neuropathy.

A candidate vaccine that could provide protection against the COVID-19 virus and other coronaviruses has shown promising results in early animal testing.

The candidate coronavirus vaccines, created by Virginia Tech's University Distinguished Professor X.J. Meng and UVA Health's Professor Steven L. Zeichner, prevented pigs from being becoming ill with a pig coronavirus, porcine epidemic diarrhea virus (PEDV).

The researchers have recently published their findings in the Proceedings of the National Academy of Sciences.

"The candidate vaccine was developed using an innovative vaccine platform targeting a highly conserved genomic region of coronaviruses," said Meng, a University Distinguished Professor in the Department of Biomedical Sciences and Pathobiology in the Virginia-Maryland College of Veterinary Medicine. "The new vaccine platform utilizes a genome-reduced bacteria to express the coronavirus vaccine antigen on its surface. Such a vaccine platform can be manufactured with low cost in existing facilities around the world, which could meet the pandemic demand."

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.

"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," said Zeichner.

A new vaccine-development approach

The 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 a 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 COVID-19

The team's candidate vaccines take an unusual approach in that it targets a part of the spike protein of the virus, the "viral fusion peptide," that is highly 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 course of the pandemic.

"With the emergence of various SARS-CoV-2 variants, a vaccine targeting a conserved region of all coronaviruses, such as the fusion peptide, may potentially lead to a broadly protective candidate vaccine. Such a vaccine, if successful, would be of significant value against variant virus strains," said Meng, who is also the founding director of the Center for Emerging, Zoonotic, and Arthropod-borne Pathogens in the Fralin Life Sciences Institute at Virginia Tech.

To create their vaccine, the researchers used the new vaccine platform, synthesizing the DNA with the instructions to make the fusion peptide and engineered bacteria to place the proteins on the surface of the bacteria that had a large number of its genes removed, then grew and inactivated the bacteria to make the candidate coronavirus vaccine.

Meng and Zeichner made two vaccines, one designed to protect against COVID-19, and another designed to protect against the pig coronavirus, PEDV. PEDV and SARS-CoV-2, the virus that causes COVID-19, are both coronaviruses, but they are distant relatives. PEDV and SARS-CoV-2, like all coronaviruses, share a number of core 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 U.S. in 2013, it killed millions of pigs in the United States alone.

One advantage of studying PEDV in pigs is the researchers 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 nonnative 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 candidate vaccine against PEDV and the candidate 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.

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.

"Although the initial results in the animal study are promising, more work is needed to refine both the vaccine platform using different genome-reduced bacterial strains and the fusion peptide vaccine target," said Meng. "It will also be important to test the fusion peptide vaccine in a monkey model against SARS-CoV-2 infection."

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.

"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," said Zeichner.

Angiogenesis is a process of new vessel formation that is activated both in physiological (tissue repair, reproduction, etc.) and pathological (myocardial infarction, diabetic retinopathy, cancer, etc.) conditions. The process is carried out by endothelial cells and includes their proliferation, migration and arrangement in tubes. Angiogenesis regulation is precise and is mainly mediated by pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), which in turn promote different signalling pathways leading to an increase of intracellular Ca2+ concentrations.

The researchers from the Cardiovascular Pathophysiology group at the Institute of Biomedicine of Seville (IBiS) focused on precisely this point, demonstrating that the inhibition of certain proteins involved in the pathway's regulation drastically affects the proper development of blood vessels. Specifically, these researchers demonstrated, for the first time, the involvement of SARAF, a SOCE regulatory protein, and Orai1, a subunit that forms the pore of the SOCE channel, in the VEGF-mediated activation of endothelial cells. Likewise, the research group has shown the importance of this Ca2+ pathway in the formation of new vessels and in the development of retinal vascularisation in neonatal mice. Thus, Orai1 and SARAF can be viewed as targets for the design of therapeutic strategies that could control angiogenesis in pathological situations such as cancer or retinopathies, or physiological situations such as post-infarction cardiac neovascularisation.

The study was funded by Spain's Agencia Estatal de Investigación (State Research Agency) and was the result of collaboration with Dr. Rosado of the University of Extremadura, and with Dr. Khatib of the University of Bordeaux - LAMC INSERM 1029, France.

Russian scientists have proposed a theory of phase transformation in polymer gels. It explains the mechanisms of the dramatic reduction in volume of zwitterionic hydrogels when they are cooled. The results are published in the journal Chemical Communications (ChemComm).

Polymer gels have unusual properties, including the ability to absorb water in volumes hundreds of times greater than their own. For example, some hydrogels are capable of holding up to two kilograms of water per gram of dry gel. By changing the temperature or adding solvents, various desired properties can be achieved. This is why polymer gels are used in industry and biomedicine, including for the targeted delivery of medication, creation of artificial skin, children's toys, etc.

If you take a gel containing a high volume of solvent and gradually lower its temperature, when a certain temperature threshold is reached, there will be a sharp decrease in the volume of the gel and a large amount of liquid will be squeezed out of it--the gel will collapse (contract).

The theory of gel collapse was first proposed by the American physicists and chemists Paul Flory and John Rehner, Jr. in 1943 and subsequently developed by the Japanese scientist Tsuyoshi Tanaka. A shortcoming of classical theory is that it does not take into account the peculiarities of the molecular structure of polymer links. The new theory was proposed by a team of Russian scientists consisting of Yury Budkov, Professor at MIEM HSE (HSE Tikhonov Moscow Institute of Electronics and Mathematics), Nikolai Kalikin, a PhD student at the Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, and Andrei Kolesnikov, a research fellow at the Institute of Non-Classical Chemistry in Leipzig. The researchers developed a microscopic theory of polymer gel, each link of which carries an electric dipole --two electric charges equal in magnitude, but opposite in sign.

This molecular structure is most commonly found in zwitterionic polymers, whose units carry both positively and negatively charged ion groups.

The authors have shown that at sufficiently low temperatures it is the electrostatic interaction of polymer units that leads to gel collapse. They also named the main parameters influencing the transition temperature from expanded to contracted state: the dipole moment value (the product of the charge per dipole length) and the ratio of the bond length between adjacent links of the polymer chain to the dipole length.

The latter result is a significant advance in gel theory compared to the classical Flory-Rehner-Tanaka theory, which does not take into account the specific molecular structure of polymer links.

'In practice, we cannot control the molecular properties of polymer links, but thanks to our theory chemists will be able to create polymers with suitable properties in advance and control the collapse temperature,' comments Yury Budkov, professor at MIEM HSE.

The scientists note that the theoretical evaluations made will be useful in modern applications of zwitterionic gels, such as superabsorbents, molecular nanoreactors, antibacterial coatings, electrically conductive membranes for chemical current sources, artificial skin, artificial muscles and others.

Every year, the ChemComm editorial board shortlists young researchers from around the world working in different areas of chemistry and invites them to publish in a special Emerging Investigators issue. This year, Yury Budkov was among the invited young scientists in the field of Theoretical and Physical Chemistry.

Rare diseases are sometimes the most difficult to treat because of a lack of research and fewer participants to study.

An example would be those who have Pompe disease, a genetic condition when a body can't make a protein that breaks down a complex sugar, called glycogen, for energy. Too much glycogen builds up and damages muscles and organs. The disease causes muscle weakness and trouble breathing and can affect the heart and muscles.

In the case of Pompe disease, however, University of Cincinnati researchers have found a newer, more effective treatment for the rare condition that could become the new standard of care.

Hani Kushlaf, MD, an associate professor in both the Department of Neurology and Rehabilitation Medicine and the Department of Pathology and Laboratory Medicine at UC and principal investigator of a study led at UC, will present findings on this new treatment virtually at the American Academy of Neurology on April 20.

Kushlaf, a UC Health physician, says Pompe disease affects about 1 in 40,000 people in the United States. It can impact children, but it can also present later in life as well. Left untreated, it can result in progressive loss of function of muscles in limbs and respiration leading to the need for wheelchair use and respiratory support.

"In this clinical trial, we tested a new drug, or enzyme replacement therapy (avalglucosidase alfa), to see if it was more effective and safer than the currently approved therapy, also an enzyme replacement therapy, in patients with late-onset Pompe disease," he says. "It turns out that it is safer and more effective than the current FDA-approved therapy. This new enzyme will likely become the standard of care for patients with the disease and has already been submitted for Food and Drug Administration approval. This is a big deal for patients with this rare disease, as t-PA was for stroke."

This study was double-blinded, meaning neither the participants nor the researchers knew which treatment was being administered via an infusion. In 51 patients who received the new treatment, researchers saw an improvement in respiratory muscle function, endurance and muscle strength, in addition to an overall better quality of life, when compared to patients on the current standard of care therapy.

"These results are extremely promising for finding a new and effective treatment for this disease," adds Kushlaf, who is also a member of the UC Gardner Neuroscience Institute. "With these results, we can take the next steps in having it used widely in this patient population, improving their outcomes and giving them a better life."

COVID-19 needs no introduction. Last year, the disease, which is caused by the virus SARS-CoV-2, reached every continent across the globe. By the end of March 2021, there had been an estimated 128 million cases recorded with almost three million of these being fatal. As scientists' race to develop vaccines and politicians coordinate their distribution, fundamental research on what makes this virus so successful is also being carried out.

Within the Mathematics, Mechanics, and Materials Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), postdoctoral researcher, Dr. Vikash Chaurasia, and Professor Eliot Fried have been using energy minimization techniques to look at charged proteins on biological particles. Previously they researched cholesterol molecules but when the pandemic hit, they realized that with the methods they had developed could be applied to the new virus. They collaborated with researchers Mona Kanso and Professor Jeffrey Giacomin, from Queen's University in Canada, to take a close look at SARS-CoV-2 and see how the shape of the virus' 'spikes' (which are officially called peplomers) aid its success at spreading so prolifically. Their study was recently published in Physics of Fluids.

"When one envisions a single coronavirus particle, it is common to think of a sphere with many spikes or smaller spheres distributed across its surface," said Dr. Chaurasia. "This is the way the virus was originally modeled. But this model is a rough sketch and over the last year, we've come to learn much more about what the virus looks like."

Instead, Dr. Chaurasia pointed out, the 'spikes' of the coronavirus particle are actually shaped like three small spheres stacked together to form a triangular shape. This is an important consideration because the shape of a viral particle can influence its ability to disperse.

To understand this, imagine a ball moving through space. The ball will follow a curve but, as it does this, it will also rotate. The speed at which the ball rotates is called its rotational diffusivity. A particle of SARS-CoV-2 moves in a similar way to this ball although its suspended in fluid (specifically, tiny droplets of saliva). The rotational diffusivity of the particle impacts how well it can align with and attach itself to objects (such as a person's tissues or cells) and this has been key in its ability to successfully spread from person to person so quickly. A higher rotational diffusivity will mean that the particle shakes and jitters as it follows a trajectory - and thus may have difficulty attaching to objects or efficiently bouncing off an object to continue to move through the air. Whereas a lower rotational diffusivity has the opposite effect.

Another consideration was the charge of each spike. The researchers assumed that each is equally charged. The same charges always repel each other so if there are only two spikes on a particle and they have equal charges, they'll be situated at either pole (as far away from each other as possible). As more equally charged spikes are added, they become evenly distributed across the surface of the sphere. This provided the researchers with a geometrical arrangement from which they could calculate the rotational diffusivity.

Previously, the researchers looked at a viral particle with 74 spikes. For this new study, they used the same particle but switched out the single-bead spikes for the three-bead triangles. When they did this, the rotational diffusivity of the particle was found to decrease by 39%. Moreover, this trend was found to continue with the addition of more spikes.

This was an important finding - having a lower rotational diffusivity means that the virus particles can better align and attach themselves to objects and people. Thus, this study suggests that the triangular shaped spikes have contributed to the success of SARS-CoV-2.

"We know it's more complicated than this," explained Dr. Chaurasia. "The spikes might not be equally charged. Or they might be flexible and able to twist themselves. Also, the 'body' of the particle might not be a sphere. So, we plan to do more research in this area."

An additional interesting feature of this research is its connection to a question asked more than a century ago by physicist J. J. Thomson, who explored how a set number of charges will be distributed across a sphere.

"I find it fascinating that a problem considered more than 100 years ago has such relevance for the situation we're in today," said Professor Eliot Fried. "Although this question was first posed primarily from a standpoint of curiosity and intellectual interest, it has turned out to be applicable in unexpected ways. This shows why we mustn't lose site of the importance of fundamental research."

The scientists at OIST and at Queen's University intend to continue to collaborate on this kind of research to shed light on the success of SARS-CoV-2. The researchers at Queen's University have just been awarded a Mitacs Globalink Research Award to allow for lead author Mona Kanso to travel between Canada and Japan and work more closely with OIST.