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Researchers at the Perelman School of Medicine at the University of Pennsylvania have produced a detailed molecular atlas of lung development, which is expected to be a fundamental reference in future studies of mammalian biology and of new treatments for diseases, such as COVID-19, that affect the lungs.

The researchers, who published their study in Science, generated a broad atlas of cell types in the developing and adult mouse lung by measuring the expression of genes in thousands of individual mouse lung cells across the lifespan, covering multiple cell types and stages of maturation, from early development in the womb to adulthood. Analyzing all this data, they predicted thousands of signaling interactions among different cell types in the developing lung, confirmed many of these with functional experiments, and identified several cells and molecular regulators that are critically important for normal lung development.

"This study provides foundational information to guide our understanding of how lung function develops, and how the early postnatal period of life is a time of rapid adjustment in the lungs to optimize gas exchange," said study senior investigator Edward Morrisey, PhD, the Robinette Foundation Professor of Medicine, a professor of Cell and Developmental Biology, and director of the Penn-CHOP Lung Biology Institute at Penn Medicine.

The trove of new data is likely to be valuable in the development of future treatments for early-life lung problems, including insufficient lung development in premature babies. It may also speed the search for better therapies for pneumonia and chronic obstructive pulmonary disease (COPD), two of the leading causes of death worldwide.

The study focused largely on the developmental steps leading to the maturation of alveoli. These delicate sac-like structures in the lungs contain thin, capillary-rich membranes that orchestrate the exchange of carbon dioxide in the bloodstream for oxygen in inhaled air. There are hundreds of millions of alveoli in an average human lung, and the total surface area of their gas-exchange membranes has been estimated as approximately the same as a tennis court's.

Many human diseases, from birth to old age, disrupt these vital structures. Yet the details of how cells emerge and signal to each other to bring about the formation of alveoli in early life have remained largely mysterious.

Morrisey's team used two relatively new techniques called single-cell RNA sequencing and single cell ATAC sequencing to record the expression and accessibility of genes in thousands of individual cells at seven different time-points during lung development in mice. They then analyzed the gene activity in each cell type, at each time point, to predict which cells were making important signaling molecules and which were expressing the receptors that receive those signals. In this way they made a map of predicted interactions among all these cells, from which they could identify key factors in alveolar development. Lastly, they confirmed the activity of two of these pathways, the Wnt and Sonic Hedgehog (Shh) pathway, using genetic mouse models to inactivate their function in specific cell types identified in the single cell experiments.

A novel finding of the study was the identification of a cell type known as the alveolar type 1 epithelial cell (AT1), which was already known to help form alveolar gas exchange interface, as a crucial originator and hub of molecular signals that guide alveolar development. The researchers also determined that another cell type known as the secondary crest myofibroblast (SCMF) plays a key role in guiding the maturation of alveolar structures. Morrisey's team moreover identified several transcription factor proteins--which regulate gene activity--as crucial for normal alveolar development. Some of these findings were also confirmed to occur in the human pediatric lung. The vast new dataset generated by the researchers should empower many future studies, including deeper studies of human lung development.

The molecular details of how alveoli develop will also inform future research aimed at treating disorders that affect these structures. Babies that are born very prematurely often suffer from respiratory distress because their alveoli are not yet fully developed. Pneumonias, which can be caused by bacteria or viruses--including SARS-CoV-2--and can affect anyone from childhood to old age, usually feature a storm of alveoli-damaging immune molecules and immune cells, and the destruction of the alveolar gas-exchange interface. Similarly, COPD, which can result from long-term cigarette smoking, involves chronic inflammation and degeneration of alveolar structures.

"We are hopeful that our study will provide a framework for a better understanding of the molecular pathways that could be harnessed to promote lung regeneration after acute or chronic injury," Morrisey said.

Bone turnover markers, and specifically bone resorption markers, are commonly used to monitor patients' response to pharmacological treatment and adherence.

In 2011, the Joint Committee on Bone Marker Standards of the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) designated Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (ß-CTX) in blood as reference bone turnover markers for bone formation and bone resorption, respectively, in osteoporosis. However, the effective clinical implementation of these recommendations requires the standardization/harmonization of the different commercial assays.

In its latest publication, published in the journal 'Calcified Tissue International', the IFCC-IOF joint Committee has carried out a multicentre evaluation of C-terminal telopeptide of type I collagen (ß-CTX) with the current assays used in clinical laboratories. For the study, four centres (Athens GR, Copenhagen DK, Liege BE and Sheffield UK) collected serum and EDTA plasma samples from 796 patients presenting to osteoporosis clinics.

The study derived regression equations for the interconversion of ß-CTX results assayed on serum and plasma specimens, and between Roche cobas e, IDS iSYS immunoassay platforms and IDS manual ELISA. The study findings and recommendations include:

Significant variation was found between the individual centres;

No useful regression equation could be calculated to harmonize results obtained with the different platforms, mainly because of the large between-centre variations;

Until harmonization is achieved, the IFCC-IOF Committee recommends measuring ß-CTX by the same assay on EDTA plasma, especially for research purposes in large pharmacological trials where samples can be stored for long periods before they are assayed;

It is recommended that patients are followed by the same method and that laboratories identify the assay used for ß-CTX determination on their protocols.

Lead author, Professor Etienne Cavalier, Chair of the IFCC-IOF Committee of Bone Markers (C-BM), stated:

"The ability to monitor bone remodelling markers and in particular ß-CTX would be beneficial in the follow-up of patients undergoing treatment. However, the results of this study show that challenges persist given the large within- and between-assay variation for ß-CTX measurement, particularly in serum. As we continue to work towards harmonization, we hope that our recommendations will be helpful, and that our findings will serve to inform further research towards the harmonization of ß-CTX values between assays. We insist on the importance of using EDTA plasma over serum for ß-CTX measurement to improve short and long-term stability as well as harmonization of the results."

Professor Nicholas Harvey, Chair of the IOF Committee of Scientific Advisors added:

"Together with IFCC, the International Osteoporosis Foundation looks forward to the important next steps which will lead to reliable reference ranges across assays and thus greater capacity for these measures to inform both clinical care and research. The project demonstrates the huge value of such international collaborations in setting the state of the art to improve bone health globally."

An international team of researchers has found that three commonly used antiviral and antimalarial drugs are effective in vitro at preventing replication of SARS-CoV-2, the virus that causes COVID-19. The work also underscores the necessity of testing compounds against multiple cell lines to rule out false negative results.

The team, which included researchers from North Carolina State University and Collaborations Pharmaceuticals, looked at three antiviral drugs that have proven effective against Ebola and the Marburg virus: tilorone, quinacrine and pyronaridine.

"We were looking for compounds that could block the entry of the virus into the cell," says Ana Puhl, senior scientist at Collaborations Pharmaceuticals and co-corresponding author of the research. "We chose these compounds because we know that other antivirals which successfully act against Ebola are also effective inhibitors of SARS-CoV-2."

The compounds were tested in vitro against SARS-CoV-2, as well as against a common cold virus (HCoV 229E) and murine hepatitis virus (MHV). Researchers utilized a variety of cell lines that represented potential targets for SARS-CoV-2 infection in the human body. They infected the cell lines with the different viruses and then looked at how well the compounds prevented viral replication in the cells.

The results were mixed, with the compounds' effectiveness depending upon whether they were used in human-derived cell lines versus monkey-derived cell lines, known as Vero cell lines.

"In the human-derived cell lines, we found that all three compounds worked similarly to remdesivir, which is currently being used to treat COVID-19," says Frank Scholle, associate professor of biology at NC State and co-author of the research. "However, they were not at all effective in the Vero cells."

"Researchers saw similar results when these compounds were initially tested against Ebola," says Sean Ekins, CEO of Collaborations Pharmaceuticals and co-corresponding author of the research. "They were effective in human-derived cell lines, but not in Vero cells. This is important because Vero cells are one of the standard models used in this type of testing. In other words, different cells lines may have differing responses to a compound. It points to the necessity of testing compounds in many different cell lines to rule out false negatives."

Next steps for the research include testing the compounds' effectiveness in a mouse model and further work on understanding how they inhibit viral replication.

"One of the more interesting findings here is that these compounds don't just prevent the virus from potentially binding to the cells, but that they may also inhibit viral activity because these compounds are acting on the lysosomes," Puhl says. "Lysosomes, which are important for normal cell function, are hijacked by the virus for entry and exit out of the cell. So, if that mechanism is disrupted, it cannot infect other cells."

"It's also interesting that these compounds are effective not just against SARS-CoV-2, but against related coronaviruses," Scholle says. "It could give us a head start on therapies as new coronaviruses emerge."

Scientists investigating the genetics of chilli pepper species have discovered a whole host of new chilli hybrids that can be grown by crossing domesticated peppers with their wild cousins. This will allow plant breeders to create new varieties that have better disease resistance and could increase productivity.

Despite their huge world-wide culinary appeal, chillies are relatively difficult to cultivate, being prone to disease and sensitive to growing conditions.

There are 35 species of pepper in the Capsicum family, including five domesticated species. The most well-known of these is C. annuum, which includes several varieties with widely differing shapes and tastes, including bell peppers, jalapeños, New Mexico chiles, and cayenne peppers.

The team of scientists from the World Vegetable Center in Taiwan investigated the genetic relatedness between 38 samples of 15 species of wild and domesticated peppers collected from locations around the world.

Their findings, published in the journal, PLOS ONE, found that breeding compatibility between species was not necessarily connected to how closely related they were to each other.

They also discovered that four species were wrongly characterised.

Lead author of the study, Catherine Parry, collected the data whilst on a six-month work placement at the World Vegetable Center as part of her undergraduate degree in Biology at the University of Bath.

She said: "The main differences between peppers that are grown for culinary purposes and their wild counterparts are that the wild species have much smaller fruits and leaves.

"However, we have large gaps in our understanding of the wild relatives of the Capsicum family.

"It was previously thought that only a narrow range of species could be successfully hybridised for cultivation, but our research has shown that there is a much wider potential number of varieties that could be grown.

"Many of the wild species have better disease resistance and so our findings could be valuable for identifying candidates for future breeding programmes, potentially increasing productivity for food producers and maybe even creating some new flavours to explore too!"

The World Vegetable Center, Taiwan, holds the largest collection of Capsicum genetic material globally.

Dr Derek Barchenger, from the World Vegetable Center and second author on the study, said: "Unlike other crops in Solanaceae, the use of wild relatives in pepper/chilli/chile pepper breeding programs is extremely limited.

"In fact the phylogeny of Capsicum is still not completely resolved.

"There are many important abiotic and biotic stresses to which we lack sources of resistance and tolerance.

"Therefore, we are interested in exploring the wild relatives of Capsicum to identity resistant sources to incorporate into our breeding program.

"This study provides a critical first step in the utilisation of Capsicum wild relatives in breeding by expanding our understanding of genetic and phenotypic similarities and crossability among wild and domesticated species."

Researchers have developed experimental flu shots that protect animals from a wide variety of seasonal and pandemic influenza strains. The vaccine product is currently being advanced toward clinical testing. If proven safe and effective, these next-generation influenza vaccines may replace current seasonal options by providing protection against many more strains that current vaccines do not adequately cover.

A study detailing how the new flu vaccines were designed and how they protect mice, ferrets, and nonhuman primates appears in the March 24 edition of the journal Nature. This work was led by researchers at the University of Washington School of Medicine and the Vaccine

Research Center part of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Influenza virus causes an estimated 290,000-650,000 deaths per year. Available flu vaccines, which need to be taken seasonally, often fail to protect against many circulating flu strains that cause illness, and the threat of another influenza pandemic looms.

"Most flu shots available today are quadrivalent, meaning they are made from four different flu strains. Each year, the World Health Organization makes a bet on which four strains will be most prevalent, but those predictions can be more or less accurate. This is why we often end up with 'mismatched' flu shots that are still helpful but only partially effective," said lead author Daniel Ellis, a research scientist in the laboratory of Neil King. King is an assistant professor of biochemistry at the UW School of Medicine and a researcher at the Institute for Protein Design at UW Medicine.

To create improved influenza vaccines, the team attached hemagglutinin proteins from four different influenza viruses to custom-made protein nanoparticles. This approach enabled an unprecedented level of control over the molecular configuration of the resulting vaccine and yielded an improved immune response compared to conventional flu shots. The new nanoparticle vaccines, which contain the same four hemagglutinin proteins of commercially available quadrivalent influenza vaccines, elicited neutralizing antibody responses to vaccine-matched strains that were equivalent or superior to the commercial vaccines in mice, ferrets, and nonhuman primates. The nanoparticle vaccines--but not the commercial vaccines --also induced protective antibody responses to viruses not contained in the vaccine formulation. These include avian influenza viruses H5N1 and H7N9, which are considered pandemic threats.

"The responses that our vaccine gives against strain-matched viruses are really strong, and the additional coverage we saw against mismatched strains could lower the risk of a bad flu season," said Ellis.

Female adult sockeye from the Fraser River are dying at significantly higher rates than their male counterparts on the journey back to their spawning grounds, finds new UBC research. For every male salmon that doesn't make it to their natal stream, at least two, sometimes three female salmon die.

"This is causing skewed sex ratios in their spawning grounds, something that has been observed in recent years," says lead researcher Dr. Scott Hinch, a professor in the faculty of forestry and head of the Pacific Salmon Ecology and Conservation Laboratory at UBC. "The implications on the health of Fraser River stocks are concerning, particularly as Pacific salmon populations in British Columbia have been declining over the past several decades."

Hinch noted that records in the 1930s and even up to the early 1990s show that for most years, females outnumbered males on spawning grounds. The sex ratios started to change in the early 2000s towards relatively fewer females.

"A combination of environmental stressors could have triggered the shift," he explains. "More females die relative to males when migration conditions are challenging. This happens when the water is too warm, or there is too much turbulence, or when the fish have been handled or released from capture. Stressful events have a larger impact on females."

The trend of higher female mortality when environmental conditions are challenging also was identified in other Pacific salmon species including Coho and Chinook salmon, and in sockeye in other river systems.

Energy, heart function, stress and disease identified as factors

Hinch and his collaborators came up with their finding after reviewing 19 major studies on salmon, including tagging and tracking studies in the field, and laboratory studies. They are proposing four reasons why females are dying at higher rates than males in the studies they reviewed: depletion of energy reserves, reduced cardiac capacity, stress and disease.

"Females have higher heart rates and smaller hearts than males leading to reduced cardiac capacity. Because female gonads are so large compared to males, they have to divert way more blood to them especially as the eggs are developing and this requires even more oxygen supply from the heart, so it's likely that when the migration is difficult, females are not able to get enough oxygen to swim."

Sockeye and other Pacific salmon don't feed during their river migration and the females, more so than the males, can also run out of stored energy reserves earlier. "Females are also more susceptible to stress, and to pathogens, so a combination of factors is likely causing their higher mortality."

In 2019, the Committee on the Status of Endangered Wildlife in Canada (COSEWIC), an independent committee of wildlife experts and scientists, designated 24 salmon populations in southern B.C. as threatened or endangered, including several of the sockeye populations that Hinch and his colleagues studied.

"The conservation and management implications of our findings are significant," says Hinch. "Pacific salmon stocks are important ecologically, but also culturally and as food security to First Nations, and for commercial and recreational fisheries. Salmon fishing in British Columbia supports more than 8,000 jobs and generates over $200 million in tax revenues annually, while commercial fisheries bring in up to $200 million a year. Recreational fishing contributes almost $1 billion in economic impact each year."

Potential solutions

Hinch and his team are recommending actions like adjusting harvest rates to protect female salmon, and ensuring migration routes have fewer obstacles to ensure females are able to complete their migrations. This is a particularly large issue at present as a fishway is now being built at the site of the Fraser River Big Bar landslide, an area that has impeded spawning migrations for the past two years.

"A few years ago we studied the migration of sockeye salmon through the Seton River Dam and Fishway near Lillooet, B.C., and proposed that some small adjustments by BC Hydro to flows at this dam could improve salmon passage, which they did. Female salmon benefitted the most, showing us that basic research can be used to fine-tune our management actions to improve the survival of female salmon."

Hinch and his team acknowledge that more research is needed to fully understand the mechanisms behind the different mortality rates in salmon. But they warn that as rivers continue to warm with climate change, we will see even higher rates of female mortality.

Three-dimensional or "volumetric" images are widely used in medical imaging. These images faithfully represent the 3D spatial relationships present in the body. Yet 3D images are typically displayed on a two-dimensional monitor, which creates a dimensionality mismatch that must be resolved in a clinical setting where practitioners must search a 2D or a 3D image to find a particular trait or target of interest.

To learn more about this problem, Craig K. Abbey, Miguel A. Lago, and Miguel P. Eckstein, of the Department of Psychological and Brain Sciences at University of California Santa Barbara, used techniques from the field of vision science to examine how the observers use information in images to perform a given task. Their research, published in the Journal of Medical Imaging, evaluates human performance in localization tasks which involve searching a 2D or a 3D image to find a target that is masked by noise. The addition of noise makes the task difficult, similar to reading images in a clinical setting.

The images in the study were simulations intended to approximate high-resolution x-ray computed tomography (CT) imaging. The images were generated in 3D and viewed as 2D "slices," and the test subjects in the experiment were able to freely inspect the images, including scrolling through 3D images. Abbey explains, "Many techniques for image display have been developed
but it is not uncommon for volumetric images to be read in a clinical setting by simply scrolling through a ‘stack' of 2D sections." The study aimed to compare components of reader performance in 3D images to 2D images, where scrolling is not possible, to see if subjects are capable of integrating multiple slices into a localization response identifying a target of interest.

A total of eight experimental conditions were evaluated (2D versus 3D images, large versus small targets, power-law versus white noise). The team evaluated performance in terms of task efficiency and classification image technique, which shows how observers use noisy images to perform visual tasks, such as target localization.

According to Abbey, "The somewhat surprising finding of the paper was that the classification images showed almost no evidence of combining information over multiple sections of the image to localize a target that spans multiple sections of the image. The observers are essentially treating the volumetric image as a stack of independent 2D images. This leads to a dissociation in which observers are more efficient at localizing larger targets in 2D images, and smaller targets (that don't extend over many volumetric sections) in 3D images."

The findings warrant further investigation, but they support and help to explain the need for multiple views in 3D image reading, and they provide useful information for modeling observer performance in volumetric images.

Read the open access research article by Abbey, Lago, and Eckstein, "Comparative observer effects in 2D and 3D localization tasks," J. Medical Imaging 8(4), 041206 (2021), doi 10.1117/1.JMI.8.4.041206. The article is part of a JMI Special Series on 2D and 3D Imaging: Perspectives in Human and Model Observer Performance, guest edited by Claudia R. Mello-Thoms, Craig K. Abbey, and Elizabeth A. Krupinski.

Journal

Journal of Medical Imaging

DOI

10.1117/1.JMI.8.4.041206

The more nitrate there is in mothers' drinking water, the smaller the babies they give birth to. But alarmingly, the declining birth weight can also be registered when the women are exposed to nitrate levels below the EU's threshold of 50 milligrams of nitrate per litre.

This is shown by a register-based study of more than 850,000 births in Denmark carried out in a Danish-American partnership led by Professor Torben Sigsgaard from the Department of Public Health at Aarhus University and Professor Leslie Stayner and Dr. Vanessa Coffman from the Division of Epidemiology and Biostatistics at the University of Illinois at Chicago, School of Public Health.

On the basis of Danish registry data, the research group concluded that babies born to mothers whose drinking water contains between 25 and 50 milligrams of nitrates per litre - i.e. from half of the current threshold value up to the maximum limit - on average weigh ten grams less than babies born to mothers with smaller amounts of nitrate in the tap water. Not only did the babies weigh less, they were also slightly shorter, while their head size was unaffected by the amount of nitrate - which is the form of nitrogen run off from the agricultural sector that most frequently appears in groundwater.

According to Professor Torben Sigsgaard from Aarhus University, it is difficult to say whether we should be concerned about public health in areas with high amounts of nitrate:

"The difference in body length and weight doesn't sound like much at first as it's on average only ten grams, but this is not insignificant if the newborn also begins life as underweight for other reasons. Birth weight is generally recognised as having a life-long impact on a person's health and development," says Torben Sigsgaard.

"There is no doubt that the results of the study challenge the threshold value that is in place throughout the Western world, and that any changes will be a bit like turning around a supertanker. But it's important to discuss these results," he adds with reference to the WHO, EU and American authorities who all view drinking water as harmful when the content of nitrates is higher than fifty milligrams per litre.

The study was initiated because it has long been known that very high nitrate concentrations may lead to people being exposed to nitrite. This inhibits the body's ability to absorb oxygen and can lead to the dangerous blue-baby syndrome, or methemoglobinemia to give it its medical name. Nitrate in drinking water is also suspected of causing other chronic diseases, including bowel cancer. Research has also documented how, depending on local geological and geochemical conditions in theearth, the fertiliser used in agriculture more or less percolates down to the groundwater.

"With the study, we've established that there is a need to explore the effect of the low nitrate concentrations in the drinking water, if we're to assess the adequacy of the current threshold values - and this is possible thanks to the unique Danish registers. It wouldn't be possible to carry out corresponding studies on the basis of US data alone, because such data simply doesn't exist," says Torben Sigsgaard.

Sickle cell disease is the most prevalent inherited blood disorder in the world, affecting 70,000 to 100,000 Americans. However, it is considered an orphan disease, meaning it impacts less than 200,000 people nationally, and is therefore underrepresented in therapeutic research.

A team led by Abhishek Jain from the Department of Biomedical Engineering at Texas A&M University is working to address this disease.

"I'm trying to create these new types of disease models that can impact health care, with the long-term goal of emphasizing on applying these tools and technologies to lower health care costs," said Jain, assistant professor in the department. "We strategically wanted to pick up those disease systems which fall under the radar in orphan disease category."

Jain's research is in organ-on-a-chip, where cells from humans can be grown on USB-sized devices to mimic the way the organ would work inside the body. This sort of system is ideal for testing new drug treatments, as drugs cannot be tested on humans, and animal models have not shown to be a good representation of how a patient and disease would interact with a treatment. For sickle cell disease patients, the organ-on-a-chip would also be beneficial because patients can present with mild to severe cases.

Jain works with Tanmay Mathur, a fourth-year doctoral student who trained as a chemical engineer in his undergraduate years. His research focused on microfabrication techniques and simulations, skills he said merged well into the organ-on-a-chip research he now performs in Jain's lab. The team collaborates closely with the Texas Medical Center in Houston.

The work was recently published in the journal Bioengineering & Translational Medicine. Their paper builds off a 2019 publication in the journal Lab on Chip, where the team demonstrated that endothelial cells (cells that line the blood vessels) could be used to model the disease physiology of a patient without having to stimulate the model to perform differently than a healthy vessel.

"Traditionally these cells were not used for disease modeling, so in that way our approach is very novel," Mathur said. "We are one of first to harness these cells and employed them in disease modeling research."

Mathur and Jain demonstrate that these models can be used to differentiate between patients. The first step: build a blood vessel that mimics a patient's vessel. For that the team would need two components -- patient blood and endothelial cells. Collecting the blood involved a simple blood draw. They faced a challenge with the endothelial cells, however. They would need to take a biopsy of the cells or use stem cells to grow their own, neither of which was ideal.

Then they found the answer was in the blood.

"What we learned is within blood samples are some endothelial cells also circulating," Jain said. "We call them blood outgrowth endothelial cells that we can harness very easily. That's what is new about this work. You can get those cells, grow them so that's there's enough in number and then you can make blood vessels."

Now that they could build the vessels, the next step was to see if these models would show how the disease has various biological impacts in different patients. Again, the goal was to be able to test treatments on these models, so the closer they mimiced their human patient, the better.

"We're able to differentiate a very severe sickle cell patient in terms of their phenotype from very mild patients," Mathur said. "Moving forward, we can take a larger population of any sickle cell disease patients and assess them using our organ-chip technology and then categorize them into different groups based on symptoms."

Their findings indicate that these organs-on-a-chip could lead to patient-centric, personalized treatment, improving how clinicians approach this and other cardiovascular diseases.

"When you take it to the field, now it can become a predictive device," Jain said. "Now you do not have to know whether the patient is mild or severe, you can test for that. You can predict if patient is serious and can dictate their therapeutic needs."

The next step is to continue to expand the patient cohort to collect more results. A long-term goal would be to use the patient information collected to develop a database to better predict disease progression.

"You take a history of a lot of these patients and their cardiovascular health with this device, and you can predict which patient might have better chance of having a stroke and you start treating them early on," Jain said.

Mathur said even with future challenges, he looks forward to continuing their research.

"I think even though it may take 10, 15 years, we will at least push forward some of the research that we're doing and get it out in the clinical field," he said. "We are one of the only groups in the world that have started this field of personalized treatment. I feel that our impact is pretty high, and I'm sure we will be able to expand the same treatment to other cardiovascular diseases and attract more attention and deeper insights into the biology that we are looking at."

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, arrived one year ago and turned our lives upside-down.

While worldwide vaccination programs are currently ongoing, we do not yet know for how long the vaccine will provide immune protection against infection, and if the currently approved vaccines can provide protection against the emerging virus variants.

In addition, it appears that vaccines cannot prevent illness for people who have already been infected. In contrast to vaccines, there are currently no effective drugs that act against the virus SARS-CoV-2.

New research by Associate Professor Jasmin Mecinovic and co-workers from the Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, now presents a compound that might provide a basis for the development of drugs against COVID-19.

The work has been recently published in Chemical Communications.

- Our approach is based on mimicking Nature, and the idea is to prevent the virus from entering the body's cells. If the virus does not enter the cells, it cannot survive. Instead, the immune system destroys the viral particles, thus preventing an infection, explains Jasmin Mecinovic.

SARS-CoV-2 belongs to the family of coronaviruses, which are named after their characteristic crown shaped envelope that shields its RNA from being damaged. This crown is made up out of viral spike proteins, which act as the lock-picks used by the virus to break into a host cell.

The SARS-CoV-2 spike protein specifically interacts with an enzyme, called ACE2 receptor, to initiate cell entry and infection.

The ACE2 receptor is found on the surface of cells in many different tissues and is especially common in the lungs. For this reason, SARS-CoV-2 infection leads to (severe) respiratory disease symptoms for many people.

Mecinovic and colleagues have found that peptides (a small part of protein), made to look exactly like the ACE2 receptor can act as a decoy and prevent binding of the of the SARS-CoV-2 spike protein.

- This suggests that molecular decoys based on the ACE2 receptor might be an effective therapeutic to prevent infection by the virus, says PhD student Marijn Maas, the first author of the article.

- Getting a new drug to the market is a long journey. Next step is to continue studying our synthetic peptide - for example by making variations of it to see if we can improve its potency, says Jasmin Mecinovic.

The Event Horizon Telescope (EHT) collaboration, a multinational team of over 300 scientists including two astrophysicists from the University of the Witwatersrand (Wits University), has revealed today a new view of the massive object at the centre of the M87 galaxy: how it looks in polarised light.

This is the first time astronomers have been able to measure polarisation, a signature of magnetic fields, this close to the edge of a black hole. The observations are key to explaining how the M87 galaxy, located 55 million light-years away, is able to launch energetic jets from its core.

"We are now seeing the next crucial piece of evidence to understand how magnetic fields behave around black holes, and how activity in this very compact region of space can drive powerful jets that extend far beyond the galaxy," says Monika Mo?cibrodzka, Coordinator of the EHT Polarimetry Working Group and Assistant Professor at Radboud Universiteit in the Netherlands.

"This work is a major milestone: the polarisation of light carries information that allows us to better understand the physics behind the image we saw in April 2019, which was not possible before," explains Iván Martí-Vidal, also Coordinator of the EHT Polarimetry Working Group and GenT Distinguished Researcher at the Universitat de València, Spain. He adds that "unveiling this new polarised-light image required years of work due to the complex techniques involved in obtaining and analysing the data."

Professor Roger Deane, SARAO/NRF Chair in Radio Astronomy at Wits and his postdoctoral researcher, Dr Iniyan Natarajan, are the only two scientists in the EHT collaboration that are based on the African continent. On 10 April 2019, the collaboration released the first ever image of a black hole, revealing a bright ring-like structure with a dark central region -- the black hole's shadow. Today's results reveal that a significant fraction of the light around the M87 black hole is polarised.

"When unpolarised, the oscillations of the electromagnetic fields have no preferred direction. Filters such as polarised sunglasses or magnetic fields in space, preferentially let the oscillations in one direction pass through, thereby polarising the light. Thus, the polarised-light image illuminates the structure of the magnetic fields at the edge of the black hole," says Natarajan, who was part of the EHT Polarimetry Working Group.

Black holes have long been known to launch powerful jets of energy and matter far out into space. Astronomers have relied on different physical models of how matter behaves near the black hole to better understand this process. The jet emerging from M87's core extends at least 5000 light-years from its centre, the process behind which is still unexplained.

The observations suggest that the magnetic fields at the black hole's edge are strong enough to push back on the hot gas and help it resist gravity's pull. Only the gas that slips through the field can spiral inwards to the event horizon.

To observe the heart of the M87 galaxy, the collaboration linked eight telescopes around the world to create a virtual Earth-sized telescope, the EHT. The impressive resolution obtained with the EHT is equivalent to that needed to measure the size of a cricket ball on the surface of the Moon.

This setup allowed the team to directly observe the black hole shadow and the ring of light around it, with the new polarised-light image clearly showing that the ring is magnetised. The results are published today in two separate papers in The Astrophysical Journal Letters by the EHT collaboration.

"Peering as close as we can to the edge of black holes using cutting-edge techniques is precisely the sort of challenge we relish here at Wits," says Deane, Founding Director of the newly approved Wits Centre for Astrophysics. "We are in a golden era for radio astronomy, and our involvement in projects like the Event Horizon Telescope and the Square Kilometre Array is at the centre of our plan to carry out fundamental research, and train world-class postgraduate students who will become the leading African scientists of tomorrow."

Natarajan was involved in simulating the black hole polarisation observations and was also part of the efforts to calibrate and generate the polarised image. Deane and Natarajan have also written one of the software packages that is being used to simulate black hole observations within the EHT collaboration.

"Our collaboration developed new techniques for analysing the polarisation data, which were validated on simulations before being applied to real observations," says Natarajan.

"Such challenging projects provide the opportunity to develop techniques which later find wider applicability in the community in ways which can pleasantly surprise us."

AMHERST, Mass. - An international team of astronomers, including University of Massachusetts Amherst professors Gopal Narayanan and Peter Schloerb, has just revealed a new view of the massive black hole at the center of a galaxy located 55 million light-years away, known as the M87 galaxy. This new image, captured by the Event Horizon Telescope (EHT) collaboration, shows how M87 looks in polarized light, and is published today in two papers appearing in The Astrophysical Journal (links here and here). It is the first time astronomers have been able to measure polarization, a signature of magnetic fields, this close to the edge of a black hole. The observations are key to explaining how the M87 galaxy is able to launch energetic jets from its core.

"There is a super-massive black hole at the center of almost every galaxy," Narayanan explains. These black holes power the galactic nuclei, which often launches high energy jets from the central parts of the galaxy. Understanding the physics connecting super-massive black holes and galactic jets has been difficult. That is where light polarization comes in.

Light becomes polarized when it goes through certain filters, like the lenses of polarized sunglasses, or when it is emitted in hot regions of space that are magnetized. In the same way polarized sunglasses help us see better by reducing reflections and glare from bright surfaces, astronomers can sharpen their vision of the region around the black hole by looking at how the light originating from there is polarized. Specifically, polarization allows astronomers to map the magnetic field lines present at the inner edge of the black hole. "Magnetic fields and jets have previously been mapped," says Narayanan, "but at lower resolution. Now we can zoom in to the energetic launching regions of these jets with incredible resolution and map the jets in a way that has never been done before."

"We are now seeing the next crucial piece of evidence to understand how magnetic fields behave around black holes, and how activity in this very compact region of space can drive powerful jets that extend far beyond the galaxy," says Monika Mo?cibrodzka, coordinator of the EHT Polarimetry Working Group and assistant professor at Radboud Universiteit in the Netherlands

Astronomers have relied on different models of how matter behaves near the black hole to better understand this process. But they still don't know exactly how jets larger than the galaxy are launched from its central region, nor how exactly matter falls into the black hole. With the new EHT image of the black hole and its shadow in polarized light, astronomers managed for the first time to look into the region just outside the black hole where the interplay between matter flowing in and being ejected out happens. "What's particularly notable about this observation," says Schloerb, "is that by measuring polarization you're really getting at the properties of the magnetic field, which is so important because it helps us understand the basic physics of how galaxies evolve."

To observe the heart of the M87 galaxy, the collaboration linked eight telescopes around the world, including the Large Millimeter Telescope (LMT), jointly operated by UMass and the country of Mexico, and the largest of its kind. Narayanan, who leads UMass's EHT team, built the radio-astronomical receiver for the LMT that helped to gather the data on the M87's black hole. The impressive resolution obtained with the EHT is equivalent to that needed to measure the length of a credit card on the surface of the Moon.

This setup allowed the team to directly observe the black hole shadow and the ring of light around it, with the new polarized-light image clearly showing that the ring is magnetized. The results are published today in two separate papers in The Astrophysical Journal Letters by the EHT collaboration. The research involved over 300 researchers from multiple organizations and universities worldwide.

"Unveiling this new polarized-light image required years of work due to the complex techniques involved in obtaining and analyzing the data," says Iván Martí-Vidal, coordinator of the EHT Polarimetry Working Group and GenT Distinguished Researcher at the Universitat de València, Spain.

"The thing I'm most fascinated about is the follow-up," says Narayanan. "We have even more sensitive receivers now, and with more sensitive instruments we can pull out more details in the magnetic fields. There's even more exciting data and analysis ahead."

Rich false memories of autobiographical events can be planted - and then reversed, a new paper has found.

The study highlights - for the first time - techniques that can correct false recollections without damaging true memories. It is published by researchers from the University of Portsmouth, UK, and the Universities of Hagen and Mainz, Germany.

There is plenty of psychological research which shows that memories are often reconstructed and therefore fallible and malleable. However, this is the first time research has shown that false memories of autobiographical events can be undone.

Studying how memories are created, identified and reversed could be a game changer in police and legal settings, where false memories given as evidence in a courtroom can lead to wrongful convictions.

According to Dr Hartmut Blank, co-author of the research from the University of Portsmouth's Department of Psychology, "believing, or even remembering something that never happened may have severe consequences. In police interrogations or legal proceedings, for instance, it may lead to false confessions or false allegations, and it would be highly desirable, therefore, to reduce the risk of false memories in such settings.

"In this study, we made an important step in this direction by identifying interview techniques that can empower people to retract their false memories."

The researchers recruited 52 participants for a study on 'childhood memories' and with the help of parents, they implanted two false negative memories that definitely didn't happen, but were plausible. For example getting lost, running away or being involved in a car accident.

Along with two true events, which had actually happened, participants were persuaded by their parents that all four events were part of their autobiographical memory.

The participants were then asked to recall each event in multiple interview sessions. By the third session, most believed the false events had happened and - similar to previous research - about 40 per cent had developed actual false memories of them.

The researchers then attempted to undo the false memories by using two strategies.

The first involved reminding participants that memories may not always be based on people's own experience, but also on other sources such as a photograph or a family member's narrative. They were then asked about the source of each of the four events.

The second strategy involved explaining to them that being asked to repeatedly recall something can elicit false memories. They were asked to revisit their event memories with this in mind.

The result, according to Dr Blank, was that "by raising participants' awareness of the possibility of false memories, urging them to critically reflect on their recollections and strengthening their trust in their own perspective, we were able to significantly reduce their false memories. Moreover, and importantly, this did not affect their ability to remember true events.

"We designed our techniques so that they can principally be applied in real-world situations. By empowering people to stay closer to their own truth, rather than rely on other sources, we showed we could help them realise what might be false or misremembered - something that could be very beneficial in forensic settings."

Sight is by far the sense that we humans use the most when navigating an environment. When those who are blind or visually impaired walk alone, they put themselves at great risk of falling or colliding with obstacles, especially when traversing new places. Unfortunately, the number of visually impaired people throughout the world is likely to increase in the near future because of the rapidly aging population. Thus, there is an urgent need for innovative and cost-effective solutions to help visually impaired people navigate safely.

A promising strategy that was first implemented in Japan and then replicated throughout the world is called tactile paving. Inspired by Braille, the reading system of the blind, tactile paving essentially consists of placing textured tiles to form a guiding path that can be felt through the sole or with a cane. With the advent of modern digital technology, researchers worldwide are trying to implement camera-based support systems to help visually impaired or blind people find and stay on tactile paving paths, as well as warn the user of impending obstacles.

However, many challenges remain unsolved in currently available options, which results in limited applicability. "Many existing camera-based approaches for detecting tactile paving depend on filtering color information with fixed thresholds, though this strategy is not reliable in contexts with variable lighting conditions that can cause large changes in color," explains Associate Professor Chinthaka Premachandra from Shibaura Institute of Technology (SIT), Japan. "This problem is made worse by the fact that different places use different color schemes for their tactile paving," he adds.

In an effort to tackle these problems efficiently, Dr. Premachandra and his team have developed a new image processing algorithm that can more accurately detect tactile paving. As described in their latest study published in IEEE Access, their proposed support system consists of a forward-facing depth camera worn around the chest that is connected to a small microcomputer board roughly the size of a credit card. The board continuously executes the image processing algorithm on the data captured by the camera and detects tactile paving. If an obstacle on the tactile paving is detected, the system warns the user through earphones.

The most important part of the system--the image processing algorithm--was the focus of the study. The team's objective was to make the detection of tactile paving independent of pre-defined color thresholds. To this end, they first employed a widely studied technique called the Hough line transform. With it, straight lines in any image can be found, therefore making it relatively easy to find the borders of the tactile paving. Once the tentative borders of the tactile paving are found, the algorithm looks at the distribution of colors in a small area near the center of the path. Through statistical analyses, it determines an appropriate threshold for the current frame to generate an appropriate 'image mask' that marks the tactile paving. Finally, after a few final adjustments to reduce noise are made, the result is an image in which the tactile paving is clearly identified.

The scientists tested their system experimentally using nearly a thousand pictures of tactile paving from around the world. Excited about the promising results, Dr. Premachandra remarks: "The proposed system correctly detected tactile paving 91.65% of the time in both indoor and outdoor environments under varying lighting conditions, which is a markedly higher accuracy than previous camera-based methods with fixed thresholds." Another notable advantage of the system is that it can be implemented in small microprocessor-based circuits, unlike other strategies that required the user to carry a laptop.

With eyes set on the future, Dr. Premachandra and his team are working on increasing the system's processing speed and further improving its accuracy, especially under extreme lighting conditions such as those in the nighttime and when under very bright lights. Hopefully, future progress in cost-effective and practical support systems will make it safer for visually impaired people to walk alone, giving them more freedom and confidence to go to new places.

When invaded by a virus, our body cells launch an alert to neighboring cells to increase their antiviral defenses to prevent the infection from spreading. Some viruses, however, manage to bypass this system by mimicking the host's RNA, preventing them from being detected by the infected cell and avoiding this alert. In the case of SARS-CoV-2, this mimicking uses a protein known as nsp14. This protein is also very important for virus multiplication, a task which is facilitated by its binding to the nsp10 protein, resulting in a protein complex. Interfering with nsp14 binding and with the nsp10-nsp14 protein complex is the aim of the most recent ITQB NOVA research in COVID-19, led by researchers Margarida Saramago, Rute Matos and Cecília Arraiano.

The researchers began by performing the biochemical characterization of the nsp10-nsp14 protein complex, a known therapeutic target. "For the first time, it was possible to identify the amino acids which must be targeted in order to silence this complex", explains Rute Matos. The silencing of nsp14 also "makes it easier for the organism to identify the virus' messenger RNA and to activate the immune system before it replicates", adds fellow researcher Margarida Saramago.

The discovery was only possible due to the collaboration between researchers from an experimental RNA laboratory and scientists from the bioinformatics area, who worked together to characterize the proteins. The construction of the three-dimensional model of the nsp14-nsp10 complex was based on the equivalent SARS-Cov-1 proteins. "It's like doing a facial composite", says bioinformatician Caio Souza, who built the model. With a very clear notion of the shape of the protein, it was possible to predict the most important amino acids. "We have a very detailed map of the target we must attack with future therapies," points out Diana Lousa, fellow bioinformatician and co-author of the study. "By silencing this protein, we will be able to "domesticate" a severe disease and turn it into a cold," explains Cecilia Arraiano, leader of one of the two laboratories involved. "It's as if we turned a wolf into a dog."

This knowledge can now be used to develop antivirals, research which is now being carried out by the team. "Even with the hope of vaccines, it is essential to identify therapies capable of treating the infections that will continue to occur," explains Cláudio M. Soares, Director of ITQB NOVA and co-author of the work. "This type of research must be funded by public institutions," he adds. The scientific paper has been accepted for publication by the Federation of European Biological Societies (FEBS) in "The FEBS Journal".