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Scientists from The University of Texas Health Science Center at San Antonio have discovered a mechanism by which SARS-CoV-2 exploits changes in metal ion concentrations to disguise itself in the body. Varying concentrations of metal ions — positively charged atoms such as magnesium, manganese and calcium — are observed in hospitalized COVID-19 patients.
“This is a newly described metal-dependent mechanism by which these ions help the virus to evade immune surveillance,” said Yogesh Gupta, PhD, senior author of the research published June 2 in the journal Nature Communications. Dr. Gupta is assistant professor of biochemistry and structural biology at the UT Health Science Center San Antonio and investigator with its Greehey Children’s Cancer Research Institute.
Dr. Gupta and colleagues captured atomic-level snapshots during various stages of camouflaging activity of the coronavirus. It turns out metal ions have an architectural purpose — they form a bridge between viral messenger RNA (which are instructions for encoding the virus) and a protein complex consisting of viral proteins nsp16 and nsp10. The activity is sort of like a scaffold swaying in the wind and workers laying hands on it to steady it.
With the scaffold stabilized, the virus then uses nsp16 to modify its messenger RNA cap into a Trojan horse unrecognizable to the immune system. This tricks the defenses, protects the RNA code from being degraded and enhances viral growth in the body. This activity is required each time the virus multiplies.
The nsp16/nsp10 protein complex stretches itself when the RNA cap is modified, which is a second finding the scientists reported. The stretching is facilitated by metal ion binding.
The understandings gleaned in this research can eventually aid treatment of all coronaviruses.
“The next step is to use this structural knowledge to develop novel therapies to treat COVID-19 and emerging coronavirus infections,” Dr. Gupta said. “We are already studying how imbalances in metal concentrations regulate the host immune response to these infections.”
This research was made possible by the San Antonio Partnership for Precision Therapeutics, the Institute for Integration of Medicine and Science, the Max and Minnie Tomerlin Voelcker Fund, the Cancer Prevention and Research Institute of Texas, UT Health San Antonio and the Greehey Children’s Cancer Research Institute.
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Humans can observe what and where something happens around them with their hearing, as long as sound frequencies lie between 20 Hz and 2,000 Hz. Researchers at Aalto University have now developed a new audio technique that enables people to also hear ultrasonic sources that generate sound at frequencies above 20,000 Hz with simultaneous perception of their direction. The results have been published in Scientific Reports on 2 June 2021.
‘In our study, we used bats in their natural habitat as sources of ultrasonic sound. With our new technique, we can now hear the directions-of-arrival of bat sounds, which means we can track bats in flight and hear where they are — we’re essentially giving ourselves super hearing,’ says Professor Ville Pulkki from Aalto University.
Small devices have been used before to listen to bats but previous versions haven’t allowed listeners to locate the bats, just hear them. With their device the researchers record ultrasound using an array of microphones flush mounted and uniformly distributed on the surface of a small sphere. After the signal has been pitch-shifted to audible frequencies, the sound is played back on the headphones immediately. Currently, the pitch-shifting is performed on a computer, but, in the future, it could be done with electronics attached to the headphones.
‘A sound-field analysis is performed on the microphone signals, and as a result we obtain the most prominent direction of the ultrasonic sound field and a parameter that suggests that the sound comes only from a single source. After this, a single microphone signal is brought to the audible frequency range of human hearing and its single-source signal is played back on the headphones so that the listener can perceive the source from the direction the sound was analysed to arrive,’ Pulkki says.
On top of its popular appeal, the technique has tangible real-world applications.
‘In science and art, people have always been interested in how they could improve their senses. Finding sources of ultrasonic sound is also useful in many practical situations, such as finding leaks in pressurised gas pipes. Minor pipe leaks often produce strong ultrasound emissions not detected by normal hearing. The device allows us to spot the sound source quickly,’ Pulkki explains.
‘Sometimes, damaged electrical equipment also emit ultrasound, and the device could be used for locating faulty equipment faster in places such as data centres,’ he continues.
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High levels of aviation drive global warming, not only through greenhouse gas emissions, but also through additional clouds. This is the conclusion reached by scientists at Leipzig University, Imperial College London and the Institut Pierre-Simon Laplace in Paris. They studied the extent to which cirrus clouds caused by aircraft occurred during the global hard lockdown between March and May 2020, and compared the values with those during the same period in previous years. The study was led by Johannes Quaas, Professor of Theoretical Meteorology at Leipzig University, and has now been published in Environmental Research Letters.
Cirrus clouds, known for their high, wispy strands, contribute to warming the climate. When cirrus clouds occur naturally, large ice crystals form at an altitude of about 36 kilometres, in turn reflecting sunlight back into space — albeit to a small extent. However, they also prevent radiated heat from escaping the atmosphere, and thus have a net heating effect. This is the dominant effect in cirrus clouds.
When the weather conditions are right, condensation trails form behind aircraft. These may persist and spread to form larger cirrus clouds. In this case, their effect on the climate is much greater than that of narrow contrails alone.
The researchers led by Professor Quaas analysed satellite images of clouds in the northern hemisphere, between 27° and 68° North, in the period from March to May 2020. They then compared these with images from the same period in previous years. “Crucially, our studies reveal a clear causal relationship. Since clouds vary considerably depending on the weather, we would not have been able to detect the effects of air traffic in this way under normal circumstances. The period of lockdown due to the COVID-19 pandemic offered a unique opportunity to compare clouds in air traffic corridors at very different traffic levels.
Analysis of the data collected showed that nine per cent fewer cirrus clouds formed during the global lockdown, and that the clouds were also two per cent less dense,” said Professor Quaas. “The study clearly demonstrates that aircraft contrails lead to additional cirrus clouds and have an impact on global warming.” According to Professor Quaas, the data collected confirmed previous estimates based only on climate models: “Our study may improve the ability to simulate these effects in climate models.”
Despite the team’s findings, there has still not been enough research into the impact of aviation on global warming. A European research collaboration involving Professor Quaas’s research group is currently investigating the precise mechanisms in detail. “The tough global lockdown has been helpful in terms of our research. In order to mitigate or even avoid the warming effect on the climate, flight routes could be adapted in the future to avoid cirrus cloud formation, for example by separating flight corridors,” said the Professor of Theoretical Meteorology at Leipzig University.
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Researchers at the Francis Crick Institute have identified a protein that helps tumours evade the immune system and, in certain types of cancers, is linked to a poorer chance of survival. The protein could become a target for future cancer treatments.
A crucial part of the immune system’s response to cancer is a group of white blood cells, called CD8+ T-cells, which kill tumour cells. Before they launch their anti-tumour response, these cells must be told who to attack by another immune cell, called a dendritic cell.
In their study, published in Cell today (2 June), the scientists identified a protein that is present in blood plasma and is also secreted by cancer cells, secreted gelsolin, which interferes with this relay process by blocking a receptor inside dendritic cells. With no instruction passed to the T-cells, the tumours avoid their killer response.
The team analysed clinical data and samples from cancer patients with 10 different types of the disease and found that individuals with liver, head and neck and stomach cancers, who have lower levels of this protein in their tumours had higher chances of survival.*
They also found that blocking the action of this protein in mice with cancer increased their response to treatments including checkpoint inhibitors, a major immunotherapy.
Caetano Reis e Sousa, author and group leader of the Immunobiology Laboratory at the Crick, says: “The interaction between tumour cells, the surrounding environment and the immune system is a complex picture. And although immunotherapies have revolutionised the way certain cancers are treated, there’s still a lot to understand about who is most likely to benefit.

Zebrafish exposed to the leading cannabinoids found in cannabis in the earliest stages of development suffer a significant drop in neural activity later in life, according to a University of Alberta study that has implications for prenatal development in humans.
Richard Kanyo, the lead author on the study and post-doctoral fellow in the Faculty of Medicine & Dentistry, said despite the popular narrative that the health benefits of cannabis are many, it turns out there is a surprisingly large knowledge gap.
“Once the legalization happened, people got really excited about it and there’s a lot of bias in the media about positive effects, so we began wondering about the negative implications,” said Kanyo.
Kanyo teamed up with Declan Ali, a biological sciences researcher in the Faculty of Science, whose lab had an ongoing interest in how certain chemicals and compounds alter development in young animals “when their neurons are contacting each other and trying to communicate.”
For the study, developing zebrafish embryos were left to incubate for 10 hours in a solution containing one of the two main active cannabinoids found in cannabis — tetrahydrocannabinol (THC) or cannabidiol (CBD) — or a combination of these two compounds, immediately after fertilization.
Ali explained that 10 hours represents a period in animal development that includes a stage of development known as gastrulation, when the multiplying cells start to form multiple tissue layers. In zebrafish it happens between five and 10 hours after the egg has been fertilized; in humans it lasts about a week and occurs roughly three weeks after egg fertilization.

Developing vaccines against bacteria is in many cases much more difficult than vaccines against viruses. Like virtually all pathogens, bacteria are able to sidestep a vaccine’s effectiveness by modifying their genes. For many pathogens, such genetic adaptations under selective pressure from vaccination will cause their virulence or fitness to decrease. This lets the pathogens escape the effects of vaccination, but at the price of becoming less transmissible or causing less damage. Some pathogens, however, including many bacteria, are extremely good at changing in ways that allow them to escape the effects of vaccination while remaining highly infectious.
For scientists looking to develop vaccines, this kind of immune evasion has been a fundamental problem for decades. If they set out to develop vaccines against bacterial pathogens, often they will notice that these quickly become ineffective.
Weaponising immune evasion
Now, however, researchers at ETH Zurich and the University of Basel have exploited precisely this mechanism to come up with an effective vaccine against bacteria. They succeeded in developing a Salmonella vaccine that, instead of trying to outright kill intestinal bacteria, rather guides their evolution in the gut to make them a weaker pathogen.
“This allowed us to show that immune evasion is not only a major challenge in vaccine development, but that it can in fact be put to good use in both human and veterinary medicine,” explains ETH Professor Emma Slack. “We can use it to drive the evolution of pathogenic microorganisms in a certain direction — in our case, a dead end.” Slack led the study, which involved many researchers from different groups at ETH Zurich and other institutions, together with ETH Professor Wolf-Dietrich Hardt and Médéric Diard, Professor at the University of Basel’s Biozentrum.
Combination vaccine leads to the goal
In their study, the researchers inoculated mice with a series of slightly different vaccines against Salmonella typhimurium, and observed how the Salmonella in the animals’ guts modified their genes to escape the vaccines’ effects. This let the scientists identify the full spectrum of possible immune evasion mutations in Salmonella typhimurium. Subsequently, the researchers produced a combination vaccine from four Salmonella strains that covered the bacteria’s full spectrum of genetic evasion options.
A surprising immune evasion was driven by this combined vaccine, causing an important Salmonella sugar coating on the surface to atrophy. While the affected bacteria were still able to multiply in the animals’ guts, they were largely unable to infect body tissues and cause disease. This is because the sugar coating is part of the bacteria’s protective coating that shields them from the host’s defences as well as from viruses that often infect and kill the bacteria. In tests on mice, the scientists were able to show that their new vaccine was more effective at preventing Salmonella infections than existing vaccines approved for use in pigs and chickens.
The scientists now plan to use the same principle to develop vaccines against other microorganisms — for example, against antimicrobial-resistant bacterial strains. In addition, it ought to be possible to use the approach in biotechnology and bring about specific modifications in microorganisms by exerting selective pressure through vaccines.
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Materials provided by ETH Zurich. Original written by Fabio Bergamin. Note: Content may be edited for style and length.

It is estimated that during a heart attack, one billion cells in the heart are lost. In the wake of the heart attack, the lost tissue is replaced by scar tissue, which can lead to heart failure, arrhythmia and death. In a new study, researchers from the University of Tsukuba have shown how cells in the scar tissue can be converted to heart muscle cells, effectively regenerating the injured heart.
The injured heart of humans and rodents alike does not have the capacity to regenerate after injury. Therefore, the only way for the heart to heal the wound is to build a scar tissue in the injured area. A longstanding goal in the field has been to find a way to reprogram fibroblasts, cells that produce the connective tissue in a scar, to cardiomyocytes, the working heart muscle cells. By doing so, the lost heart muscle cells could be replaced, effectively preventing the heart from going into heart failure, a heart muscle weakness that can lead to death.
Previous studies have shown that cardiomyocytes appear to be formed by directly injecting a harmless virus carrying a set of cardiac transcription factors, proteins that drive the expression of genes that heart muscle cells need for their development and function, into the heart of rodents after a heart attack. However, the origin and functional significance of these newly formed heart muscle cells has not unequivocally been determined yet.
“Direct cardiac reprogramming holds great potential for cardiac regeneration and the treatment of myocardial infarction,” says lead author of the study Professor Masaki Ieda. “However, when transcription factors are introduced, apparent cardiomyocytes may be formed either by converting fibroblasts to new cardiomyocytes or by fusing fibroblasts with existing cardiomyocytes. The difference is that only the former process, which we call ‘direct reprogramming’, significantly contributes to regeneration. In this study, our goal was to determine how new cardiomyocytes are formed when cardiac transcription factors are introduced after myocardial infarction.”
To achieve their goal, the researchers first generated mice in which all cells emitted red fluorescence. However, the mice were modified in a way that the fibroblasts emitted green fluorescence after treatment with the drug tamoxifen. As a result, when looking at the heart after treatment with tamoxifen, cells that emitted both red and green fluorescence indicated that cell fusion between fibroblasts and cardiomyocytes had happened. Conversely, the presence of green fluorescence indicated that direct reprogramming of fibroblasts to cardiomyocytes had occurred.
Equipped with the tools to tackle their research question, the researchers used a mouse model of heart attack and treated the mice with tamoxifen. While there was no direct reprogramming in a control group, the researchers found 1-1.5% of directly reprogrammed cells when a virus carrying cardiac transcription factors was injected into the mice. Both groups exhibited minimal cell fusion. These results suggest that the main route of generating new heart muscle cells by this method is via reprogramming fibroblasts directly to cardiomyocytes.
“These are striking results that show that fibroblasts can be directly reprogrammed to cardiomyocytes. Our findings demonstrate the exciting potential of direct reprograming as a strategy for cardiac regeneration after myocardial infarction,” says Professor Ieda.
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Treating patients with acute respiratory failure is a constant challenge in intensive care medicine. In most cases, the underlying cause is lung inflammation triggered by a bacterial infection or — more rarely, despite being frequently observed at present due to the corona pandemic — a viral infection. During the inflammation, cells of the immune system — the white blood cells — migrate to the lungs and fight the pathogens. At the same time, however, they also cause “collateral damage” in the lung tissue. If the inflammatory reaction is not resolved in time, this can result in chronic inflammation with permanent impairment of lung function. Together with colleagues from London, Madrid and Munich, a research team at the University of Münster headed by Prof Jan Rossaint and Prof Alexander Zarbock, two specialists in anaesthesiology and intensive care medicine, has gained new insight into the cellular processes involved in bacterial lung inflammation. In a study on mice, the researchers found that the interaction between platelets and certain white blood cells — the regulatory T cells — play a significant role in resolving the inflammation. The study has been published in the Journal of Experimental Medicine.

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Researchers at the University of Eastern Finland have uncovered potential mechanisms by which microRNAs (miRNA) drive atherogenesis in a cell-type-specific manner. Published in the Arteriosclerosis, Thrombosis, and Vascular Biology journal, the study provides novel insight into the miRNA profiles of the main cell types involved in atherosclerosis.
Atherosclerosis is the underlying cause of most cardiovascular diseases and one of the leading causes of mortality in the world. During atherosclerosis, arteries become progressively narrow and thick due to the formation of plaques containing cholesterol deposits, calcium and cells, among other components. Although the role and contribution to atherosclerosis of endothelial cells, smooth muscle cells and macrophages — the main cell types associated with disease progression in the vascular wall — has been previously described, the molecular mechanisms leading to gene expression changes during atherosclerosis in these cell types remain unknown. In particular, the cell-type specific expression and regulation of miRNAs in the disease context has remained unexplored. MiRNAs represent one class of small non-coding RNAs that regulate the protein production by binding to messenger RNAs of protein encoding genes and this way affect cell function and disease progression.
In this study, by integrating different next generation sequencing techniques, the researchers have provided a deeper understanding of the miRNA changes in primary human endothelial cells, smooth muscle cells and macrophages under various pro-atherogenic stimuli, and discovered that the precursor forms of the miRNA (primary miRNAs) were highly expressed in a cell-type specific manner, suggesting distinct regulatory mechanisms on transcriptional level. In contrast, the large majority of mature miRNAs were common to all cell types and dominated by 2-5 abundant miRNA species. Moreover, the researchers uncovered microRNA-messenger RNA networks through which miRNAs could drive cell-type-specific responses. Given that miRNAs play an essential role in maintaining tissue homeostasis and can be dysregulated in pathological states, miRNA therapeutics that manipulate cellular miRNA levels are essential and have already entered clinical trials. Thus, these results are fundamental for the atherosclerosis research community and could serve as the basis for future development of cell-targeted therapeutics.
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Doctors have hoped that antibiotics could benefit patients with chronic lung diseases, but a new study has found no benefit for patients with life-threatening idiopathic pulmonary fibrosis in preventing hospitalization or death.
While there were no statistical benefits for patients with the lung-scarring disease, the new research will prevent unnecessary antibiotic use that could contribute to the growing problem of antibiotic resistance. The nationwide clinical trial — believed to be the largest idiopathic pulmonary fibrosis trial ever conducted — also collected biological samples that will advance the understanding and treatment of the mysterious and ultimately fatal illness.
“We were certainly disappointed in the results. But we remain hopeful that in further downstream analyses, we may yet find groups of patients that were potentially benefiting. In the meantime, this study will make sure that no one takes antibiotics without need,” said researcher Imre Noth, MD, the chief of UVA Health’s Division of Pulmonary and Critical Care Medicine. “We did view the study as great success as an NIH [National Institutes of Health] initiative, in that the pragmatic design, without blinding patients to treatment, led to rapid enrollment, ahead of schedule and basically ahead of budget, showing that large studies can be accomplished in this uncommon disease.”
About Idiopathic Pulmonary Fibrosis
In idiopathic pulmonary fibrosis, scar tissue builds up in the lungs over time, preventing them from supplying adequate oxygen to the body. It typically affects people over age 50, mostly men. Patients typically survive only two to five years after diagnosis, though some live much longer.
Doctors are uncertain what triggers idiopathic pulmonary fibrosis. (“Idiopathic” means “unknown cause.”) However, environmental and genetic factors may play a part, as may lung infections.
Doctors also suspect that changes in the microorganisms that naturally live in our lungs may be a factor. Scientists have increasingly come to appreciate the importance of the tiny organisms that live in our bodies and on our skin. In idiopathic pulmonary fibrosis, the thinking goes, the natural state of the microorganisms in the lungs may become unbalanced — perhaps there are too many of one type or a general loss of variety. Lab work in mice has suggested that antimicrobials may be able to help fix the problem.
To see if antimicrobial treatments could benefit idiopathic pulmonary fibrosis, researchers at 35 sites around the country conducted a randomized clinical trial with volunteers age 40 or older. A total of 513 patients enrolled between August 2017 and June 2019. Half received antimicrobial drugs, choosing between co-trimoxazol or doxycycline, while the other half received the standard care.
After a median follow-up time of 12.7 months, there was no statistically significant benefit from the antimicrobials. The time to both breathing-related hospitalization or death was unchanged.
The findings echoed those of a previous study, and the researchers say the results show that treatment with antibiotics is ineffective and unwarranted as a general treatment for idiopathic pulmonary fibrosis. They do not rule out, however, that it may be useful in a limited number of patients with known disruptions to their lung microorganisms.
“As the largest single study in IPF ever conducted, I think we are going to learn a lot as we look at things more closely. Might our choice of antibiotics have been the right ones? Were there some patients that did better than others? Who should we be targeting for treatment? All things this study will help in the future,” said Noth, a top expert on the disease. “I am heartened and hopeful moving forward as this study teaches us a lot for the next one, and each study gets us closer to better treatments and a cure.”