Publisher Health

Göttingen researchers have developed mini-antibodies that efficiently block the coronavirus SARS-CoV-2 and its dangerous new variants. These so-called nanobodies bind and neutralize the virus up to 1000 times better than previously developed mini-antibodies. In addition, the scientists optimized their mini-antibodies for stability and resistance to extreme heat. This unique combination makes them promising agents to treat COVID-19. Since nanobodies can be produced at low costs in large quantities, they could meet the global demand for COVID-19 therapeutics. The new nanobodies are currently in preparation for clinical trials.
Antibodies help our immune system to fend off pathogens. For example, the molecules attach to viruses and neutralize them so that they can no longer infect cells. Antibodies can also be produced industrially and administered to acutely ill patients. They then act like drugs, relieving symptoms and shortening recovery from the disease. This is established practice for treating hepatitis B and rabies. Antibodies are also used for treating COVID-19 patients. However, producing these molecules on an industrial scale is too complex and expensive to meet worldwide demand. Nanobodies could solve this problem.
Scientists at the Max Planck Institute (MPI) for Biophysical Chemistry in Göttingen (Germany) and the University Medical Center Göttingen (UMG) have now developed mini-antibodies (also known as VHH antibodies or nanobodies) that unite all the properties required for a potent drug against COVID-19. “For the first time, they combine extreme stability and outstanding efficacy against the virus and its Alpha, Beta, Gamma, and Delta mutants,” emphasizes Dirk Görlich, director at the MPI for Biophysical Chemistry.
At first glance, the new nanobodies hardly differ from anti-SARS-CoV-2 nanobodies developed by other labs. They are all directed against a crucial part of the coronavirus spikes, the receptor-binding domain that the virus deploys for invading host cells. The nanobodies block this binding domain and thereby prevent the virus from infecting cells.
“Our nanobodies can withstand temperatures of up to 95 °C without losing their function or forming aggregates,” explains Matthias Dobbelstein, professor and director of the UMG’s Institute of Molecular Oncology. “For one thing, this tells us that they might remain active in the body long enough to be effective. For another, heat-resistant nanobodies are easier to produce, process, and store.”
Single, double, and triple nanobodies
The simplest mini-antibodies developed by the Göttingen team already bind up to 1000 times more strongly to the spike protein than previously reported nanobodies. They also bind very well to the mutated receptor-binding domains of the Alpha, Beta, Gamma, and Delta strains. “Our single nanobodies are potentially suitable for inhalation and thus for direct virus neutralization in the respiratory tract,” Dobbelstein says. “In addition, because they are very small, they could readily penetrate tissues and prevent the virus from spreading further at the site of infection.”

Researchers have shown ‘gene drive’ technology, which spreads a genetic modification blocking female reproduction, works in natural-like settings.
The team, led by researchers from Imperial College London, Polo GGB and Liverpool School of Tropical Medicine were able to supress populations of a malaria-carrying mosquito in a year-long experiment mimicking natural environments.
This is the first time a gene drive has been shown to be as effective as expected when tested in challenging ecological conditions over a long timescale. The results are published today in Nature Communications.
Despite the reduction in malaria over recent decades, there were still 229 million cases of malaria in 2019 — an increase on the previous year — and 409,000 deaths.
Co-lead author of the study Dr Drew Hammond, from the Department of Life Sciences at Imperial College London and the Johns Hopkins Malaria Research Institute, said: “The challenges facing malaria elimination have intensified in recent years, due in part to the spread of insecticide resistance and large gaps in funding for parts of sub-Saharan Africa.
“Sadly, researchers estimate that COVID-19 related disruptions may have doubled mortality from malaria in 2020, threatening a setback of several decades.

A pilot study from North Carolina State University has found that a gene associated with autism spectrum disorder (ASD) and pain hypersensitivity may actually decrease itch response. Atopic dermatitis and pain hypersensitivity are both conditions associated with some types of ASD.
The gene in question, contactin associated protein 2 (CNTNAP2), is thought to be linked to a mutation associated with some forms of autism. This gene is found throughout the dorsal root ganglia (DRG), which are clusters of sensory cells located at the root of the spinal nerves. The DRG is the superhighway that transmits sensations of both pain and itch from the skin through the spinal cord to the brain.
“Since atopic dermatitis is often associated with ASD and CNTNAP2 is both linked to pain hypersensitivity in ASD and expressed in almost all DRG sensory neurons, we wondered whether CNTNAP2 might also contribute to itch behavior,” says Santosh Mishra, assistant professor of neuroscience at NC State and author of the study.
Mishra compared itch response in mice with the CNTNAP2 gene to those without it. In the presence of both histamine and non-histamine based stimuli, the CNTNAP2 knock-out mice, or mice without the gene, had a reduced itch response compared to mice with the gene.
“If there is a link between ASD and atopic dermatitis, then mice without a normal CNTNAP2 gene would be expected to have an increased itch response just as they have increased sensitivity to pain,” Mishra says. “There are several possible explanations for this finding, ranging from standard physiological differences between humans and animals to CNTNAP2’s potential role in releasing neuropeptides that could affect this response.
“But we also know that pain can suppress itch sensation and vice versa. Just as some humans with ASD have higher pain sensitivity, so do mice without CNTNAP2. That pain sensitivity may be inhibiting the itch sensation.”
Mishra hopes that this pilot study may pave the way to further exploration of the role of CNTNAP2 in itch.
“The functional role of CNTNAP2 in the neural transmission of itch is unknown,” Mishra says. “While this study sheds light on the possible linkage between ASD and itch, it’s limited because it is primarily based on behavioral, not cellular or molecular, results. Future studies may be required to dissect the molecular underpinnings of CNTNAP2 and itch sensation.”
The study appears in the Journal of Investigative Dermatology and was supported by the National Institutes of Health and NC State seed funding.
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Materials provided by North Carolina State University. Original written by Tracey Peake. Note: Content may be edited for style and length.

A new University of Kentucky College of Medicine study published in the Journal of Biological Chemistry provides foundational information about SARS-CoV-2’s spike protein.
The spike protein is found on the surface of SARS-CoV-2, the virus that causes COVID-19, and is responsible for its entry into host cells. Because of this function, it is the focus of most COVID-19 vaccines including the Pfizer/BioNTech and Moderna mRNA vaccines.
“The spike protein represents one of the most important therapeutic targets for COVID-19,” said study lead Becky Dutch, vice dean for research in the College of Medicine and chair of the Department of Molecular and Cellular Biochemistry. “This study gives scientists a more comprehensive understanding of how the protein works, which is significant to the continued development of vaccines and therapeutics.”
Dutch’s study provides insight into how stable the spike protein is, how it promotes cell-to-cell fusion and how it is modified. Her team examined the effect of mutations in clinical isolates of the virus on protein stability and function. They also observed spike protein synthesis and processing in bat cells to understand if any differences were observed.
The study found that the majority of the spike protein degrades within 24 hours, which provides more understanding about the process of infection and vaccination. Since mRNA vaccines work by giving instructions to our cells to make the spike protein, this finding gives insight into how long the newly made protein will be present.
Dutch’s team also examined the role of key host factors in cell-to-cell fusion. In addition to binding the virus to target cells, the spike protein can cause fusion between the cell it is made in and a neighboring cell, an effect seen in the lungs of COVID-19 patients.
Dutch says there has been relatively little research done on the spike protein’s cell-to-cell fusion or stability, so the study will contribute to giving researchers a full picture of how the proteins are made and how they function.
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Materials provided by University of Kentucky. Original written by Elizabeth Chapin. Note: Content may be edited for style and length.

Twenty-six subjects from a cohort of 80 tested positive for SARS-CoV-2 via nasopharyngeal swab, and all 26 tested positive using gargle lavage (mouthwash), according to new research published in Microbiology Spectrum, the new open-access journal of the American Society for Microbiology. That’s good news, because nasopharyngeal swabbing, currently the gold standard for collecting samples for COVID testing, has a low rate of acceptance due to the discomfort of having a nasal passage swabbed.
The detection method for testing samples used in this study is the highly sensitive real time polymerase chain reaction (RT-PCR). “Our results show that in all cases, where people were positively tested by the gold standard nasal swabbing, one could also detect the virus in gargle lavage by the same RT-PCR method,” said corresponding author Christof R. Hauck, PhD, professor of cell biology, Faculty of Natural Sciences, Department of Biology, University of Konstanz, Germany.
This sampling procedure can be conducted safely in a general practitioner’s office without extra protective equipment for physicians’ staff, as the patients themselves perform the sampling,” said Dr. Hauck. “We usually sent the patients with the gargle solution and sampling container outside.” There, they gargled in front of a window, observed by a physician’s staff member. Thus, “we need not expose trained personnel to the danger of taking samples from so many potentially infected people.”
Study subjects had typical respiratory symptoms or known contact with infected persons. Each received both a nasal swab administered by a professional health practitioner, “which was needed for the regular diagnostic procedure, and each self-performed a gargle lavage,” said Dr. Hauck. “These paired samples were then transferred to the central diagnostic lab, where they were analyzed in parallel, so that the results could be directly compared.”
“Besides performing diagnostics on symptomatic patients, we are involved in regular SARS-CoV-2 surveillance on our university campus, where we test people twice a week. As nasal swabbing is not very pleasant, we were looking for an alternative, and gargle lavage turned out to be highly accepted,” said Dr. Hauck.
“By finding complete congruence of results obtained with paired samples of a sizeable patient cohort, our results strongly support the idea that the painless self-collection of gargle lavage provides a suitable and uncomplicated source for reliable SARS-CoV-2 detection,” said Dr. Hauck.
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Materials provided by American Society for Microbiology. Note: Content may be edited for style and length.

An interdisciplinary team of scientists from Northwestern Engineering and the Massachusetts Institute of Technology has used artificial intelligence (AI) techniques to build new, free, and easy-to-use tools that allow scientists to accelerate the rate of discovery and study of materials that exhibit a metal-insulator transition (MIT), as well as identify new features that can describe this class of materials.
One of the keys to making microelectronic devices faster and more energy efficient, as well as designing new computer architectures, is the discovery of new materials with tunable electronic properties. The electrical resistivity of MITs may exhibit metallic or insulating electronic behavior, depending on the properties of the environment.
Although some materials that exhibit MITs have already been implemented in electronic devices, only fewer than 70 with this property are known, and even fewer exhibit the performance necessary for integration into new electronic devices. Further, these materials switch electrically due to a variety of mechanisms, which makes obtaining a general understanding of this class of materials difficult.
“By providing a database, online classifier, and new set of features, our work opens new pathways to the understanding and discovery in this class of materials,” said James Rondinelli, Morris E. Fine Professor in Materials and Manufacturing at the McCormick School of Engineering and the study’s corresponding primary investigator. “Further, this work can be used by other scientists and applied to other material classes to accelerate the discovery and understanding of other classes of quantum materials.”
“One of the key elements of our tools and models is that they are accessible to a wide audience; scientists and engineers don’t need to understand machine learning to use them, just as one doesn’t need a deep understanding of search algorithms to navigate the internet,” said Alexandru Georgescu, postdoctoral researcher in the Rondinelli lab who is the study’s first co-author.
The team presented its research in the paper “Database, Features, and Machine Learning Model to Identify Thermally Driven Metal-Insulator Transition Compounds,” published July 6 in the academic journal Chemistry of Materials.
Daniel Apley, professor of industrial engineering and management sciences at Northwestern Engineering, was a co-primary investigator. Elsa A. Olivetti, Esther and Harold E. Edgerton Associate Professor in Materials Science and Engineering at the Massachusetts Institute of Technology, was also a co-primary investigator.
Using their existing knowledge of MIT materials, combined with Natural Language Processing (NLP), the researchers scoured existing literature to identify the 60 known MIT compounds, as well as 300 materials that are similar in chemical composition but do not show an MIT. The team has provided the resulting materials — as well as features it’s identified as relevant — to scientists as a freely available database for public use.
Then using machine-learning tools, the scientists identified important features to characterize these materials. They confirmed the importance of certain features, such as the distances between transition metal ions or the electrostatic repulsion between some of them known, as well as the accuracy of the model. They also identified new, previously underappreciated features, such as how different the atoms are in size from each other, or measures of how ionic or covalent the inter-atomic bonds are. These features were found to be critical in developing a reliable machine learning model for MIT materials, which has been packaged into an openly accessible format.
“This free tool allows anyone to quickly obtain probabilistic estimates on whether the material they are studying is a metal, insulator, or a metal-insulator transition compound,” Apley said.
Work on this study was born from projects within the Predictive Science and Engineering Design (PS&ED) interdisciplinary cluster program sponsored by The Graduate School at Northwestern. The study was also supported by funding from the Designing Materials to Revolutionize and Engineer our Future (DMREF) program of the National Science Foundation and the Advanced Research Projects Agency — Energy’s (ARPA-E) DIFFERENTIATE program, which seeks to use emerging AI technologies to tackle major energy and environmental challenges.
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Materials provided by Northwestern University. Original written by Brian Sandalow. Note: Content may be edited for style and length.

Messenger RNA, or mRNA, has been in the news recently as a crucial component of the Pfizer-BioNTech and Moderna COVID-19 vaccines. The nucleic acid looks, for all intents and purposes, like a strand of DNA that has been sliced the long way. It’s what’s known as single-stranded RNA (ssRNA), and it can be found throughout the natural world.
Less common in nature is double-stranded RNA (dsRNA), which has two strands and resembles the well-known DNA double helix. It’s found in some viruses, but for the past few decades, people have been developing synthetic dsRNA for a range of purposes.
Despite our growing familiarity with its potential applications, researchers knew little about a key feature of dsRNA, namely how dsRNA degrades — a particularly important question as one of its most promising applications is in agriculture as a type of pesticide.
Research from the lab of Kimberly Parker, assistant professor of energy, environmental and chemical engineering at the McKelvey School of Engineering at Washington University in St. Louis, has upended common assumptions about the chemical stability of dsRNA that may prove useful to fields from agriculture to medicine. The lab’s findings even may have implications for our understanding of the origins of life. The results were published this summer in the journal Environmental Science & Technology.
“Fundamentally, we are challenging a pervasive assumption that what we know about ssRNA behavior predicts dsRNA behavior,” Parker said.
“The general knowledge is that RNA is less stable than DNA,” Parker said. That’s because the RNA structure has a few extra atoms that causes the nucleic acid to degrade by itself to smaller pieces.

How long do coronaviruses remain infectious on banknotes and coins? Is it possible to become infected through contact with cash? Experts at the European Central Bank, in collaboration with the Department of Medical and Molecular Virology at Ruhr-Universität Bochum, wanted to clarify this question. The researchers led by Professor Eike Steinmann and Dr. Daniel Todt developed a method specifically to test how many infectious virus particles can be transferred from cash to the skin in real-life conditions. Conclusion: under realistic conditions, the risk of contracting Sars-Cov-2 from cash is very low. The study has been published in the journal iScience from 26 July 2021.
Viruses on banknotes and coins
To find out how long Sars-Cov-2 persists on coins and banknotes, the researchers treated various euro coins and banknotes with virus solutions of different concentrations and over several days observed how long infectious virus was still detectable. A stainless-steel surface served as a control in each case. The results are reassuring: while infectious virus was still present on the stainless-steel surface after seven days, on the 10-euro banknote, it took only three days to completely disappear. For the 10-cent, 1-euro, and 5-cent coins after six days, two days and one hour, respectively, no infectious virus was detectable. “The rapid decline on the 5-cent piece is because it’s made of copper, on which viruses are known to be less stable,” explains Daniel Todt.
Artificial skin
The research team developed a new method to study how well the virus is transferred from a surface to the fingertip. They contaminated banknotes, coins and credit-card-like PVC plates with harmless coronaviruses and, under high-security conditions, also with Sars-Cov-2. These surfaces were then touched, while still wet or when already dried, by test subjects with their fingertips or, in the case of Sars-Cov-2, with artificial skin. Cell cultures were then inoculated with the viruses adhering to the fingertips. This allowed the researchers to determine the number of transmitted virus particles that were still infectious.
“We saw that immediately after the liquid had dried, there was practically no transmission of infectious virus,” Daniel Todt summarizes. “Under realistic conditions, infection with Sars-Cov-2 from cash is very unlikely.”
Infection via aerosols or droplets
This observation is consistent with findings of other studies that show in the vast majority of cases, infection occurs via aerosols or droplets. Smear infections via surfaces are almost non-existent. The current study was conducted with the alpha variant of Sars-Cov-2 in addition to the wild-type variant. “We assume that other variants, such as the currently predominant delta variant, also behave similarly,” Eike Steinmann explains. The shelf life of the virus variants studied so far has not differed from that of the original virus.
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Materials provided by Ruhr-University Bochum. Original written by Meike Drießen. Note: Content may be edited for style and length.

Middle-ear infections are a common affliction in early life, affecting more than 80% of children in the U.S. Antibiotics are often employed as a first line of defense but sometimes fail against the pathogenic bacteria that can develop in the middle ear, just behind the eardrum. In a new study, researchers explore the use of microplasma — a highly focused stream of chemically excited ions and molecules — as a noninvasive method for attacking the bacterial biofilms that resist antibiotic treatment in the middle ear.
They report their findings in the journal npj Biofilms and Microbiomes.
Biofilms are communities of microbes that form on surfaces and reproduce, communicate with one another and secrete a slimy adhesive matrix that holds them together. They can be tenacious and harmful, especially when associated with infection.
Plasmas are a form of matter that is neither solid, liquid or gas, said Jungeun (Jenny) Won, a former Ph.D. student in the laboratory of University of Illinois Urbana-Champaign electrical and computer engineering professor Stephen Boppart, who led the research with civil and environmental engineering professor Than H. (Helen) Nguyen and electrical and computer engineering professor J. Gary Eden. Boppart and Nguyen are affiliated with the Carle Illinois College of Medicine and Nguyen is a faculty member in the Carl R. Woese Institute for Genomic Biology at the U. of I.
“Many studies have found that the highly reactive particles or molecules within this plasma can interact with and inactivate bacteria,” said Won, now a postdoctoral researcher at Massachusetts Institute of Technology. She shares first-author status on the new report with former U. of I. postdoctoral researcher Peter P. Sun, a process TD engineer at Intel Corporation.
Previous studies have found that the microplasmas can disrupt the bacterial biofilms that form on various surfaces.

Here’s how to protect your mental health in a culture that values work over well-being.Have you ever felt nervous or afraid to take time off from work to look after your mental health?Marisa Kabas, a writer and political strategist who lives in New York City, recently posed a similar question on Twitter, inspired by Simone Biles, who bowed out of Olympic events this week to protect her mental health.“It was so shocking to so many people,” Ms. Kabas said on Wednesday in an interview. “Because the whole mentality is be strong, and push through the pain.”The tweet drew thousands of responses, many from employees who said they do not disclose the real reason they need time away from work, or feel pressured to lie about it because they are embarrassed. Others said they had never taken a mental health day.As a freelancer who has written prolifically about her health problems, including anxiety and depression, Ms. Kabas said she sometimes wakes up and decides, “I can’t do it today,” and takes the day off, a luxury she didn’t feel she had as an employee.About three-quarters of people in the United States who work for private industry, state or local government have paid sick leave, but surveys suggest that a number of these employees are unlikely to use sick days for mental health reasons or are scared of being punished for doing so.If you’re among the hesitant, experts say it’s time to start thinking about how to protect and prioritize your mental well-being, especially as millions of employees who worked remotely during the pandemic start returning to the office.“You wouldn’t feel bad about taking time off when sick. You shouldn’t feel bad about taking some time off when you’re sad,” said Natalie C. Dattilo, a clinical health psychologist at Brigham and Women’s Hospital in Boston and an instructor of psychiatry at Harvard Medical School. “Your body needs a rest, your brain needs a break.”How do you know if you need a ‘sad day’?There’s no official definition for a “sad day,” also known as a mental health day. Typically, it is paid time off drawn from sick days (or personal days) to help employees who aren’t feeling like their usual selves, offering an opportunity to refresh their minds; do something meaningful; or simply take a break from daily stressors. The “sad day” is only a temporary fix, and not meant to address deeper problems, but sometimes a little time away can make a big difference.Your company may not specify that sick days can be used for this purpose, but “mental health is health,” said Schroeder Stribling, the president and chief executive of the advocacy group Mental Health America. “The two are inseparable.”The signs that you need to take time away from work may not necessarily be obvious, Ms. Stribling said. Indicators include changes in your mood, productivity or ability to concentrate. You may also notice that you are less patient and more irritable than usual, or are having trouble sleeping.You might also have physical symptoms. For example, “if I start getting headaches, that’s a sign of stress for me, and I need to address that with a mental heath day,” Ms. Stribling said.The bottom line: Given the extraordinary stressors of the last year and a half, regardless of your specific symptoms, “if you feel like you might benefit from a mental health day, you have earned one,” said Adam Grant, an organizational psychologist at the University of Pennsylvania’s Wharton business school, whose recent podcast explored the benefits of the “sad day” and the importance of building a culture of compassion within the workplace.Some companies may require employees to provide documentation, such as a doctor’s note, when they use sick days, so make sure you understand what the law says in your region. In New York City, for example, an employee is not required to provide documentation unless more than three consecutive days of sick leave have been used.How do you ask for a mental health day?Your workplace culture and your relationship with your manager will dictate how open you choose to be about why you’re taking time off. You should not feel compelled to divulge more than necessary.“I think sometimes we over-share when we’re anxious or perhaps feel a little bad about having to take time,” Dr. Dattilo said.In most situations, just say that you need to take a sick day, and leave it at that, the experts advised.“I think the safe advice is not to be upfront,” said Andrew Kuller, a clinical psychologist at McLean Hospital in Belmont, Mass. Not everybody values mental health, he added, and “unless you’re close with your supervisor, it is a risk.”But say you work at the type of organization where you can tell the truth without fear of being punished. In that case, you are still under no obligation to reveal why you want to take a sick day. However, if you want to share (or are interested in reducing some of the stigma around mental health) you might approach your manager and say, “I think I would really benefit from taking a day just to recharge a little bit,” Dr. Grant said. “I would like to come back to work with all of my energy.”When employees are mentally and physically exhausted, it affects the quality of their work, their productivity and the people around them, Dr. Grant added.“I think it’s easier to have a conversation about burnout than it is about feeling sad or depressed or anxious, so I would probably play it safe there, and highlight why this is good for the organization, not just good for you,” he said.If you’re feeling up to it, you can also try to assemble a coalition of people within your department who are concerned about mental health fatigue, said Dr. Grant, whose latest book, “Think Again: The Power of Knowing What You Don’t Know,” challenges readers to shift long-held thought patterns. As a group, you can discuss concerns like missed deadlines or errors that might be compounded by burnout, then bring these issues to your manager, who may be motivated to find a solution. That way, you can try to change the system for everyone, including yourself.What do you do during a ‘sad day’?In deciding how to use a mental health day, it helps to think about what brought you to this point in the first place. Do your personal relationships need attention? Are you exhausted from your workload and desperate to disconnect from everything? Did you have a particularly stressful week and want to spend some time decompressing? Maybe it’s a combination of several things.Thinking it through ahead of time will help you use your day in the most helpful way possible. While one person might benefit from a massage or a day of pampering, another person might want to paint or garden. Others will find the most value in reconnecting with friends or family members.The day might also provide an opportunity to rethink your day-to-day activities. “Are they giving you pleasure or meaning?” Dr. Kuller asked.Next, think about ways to take care of yourself on a regular basis, he added, like meditation, yoga or cooking a healthy meal. Make a plan to do more of those things going forward.Whatever you do, don’t spend the day checking your messages or feeling guilty, the experts said.“Self-care is not a selfish act,” Dr. Grant said. “People who are selfless to the point of self-sacrifice end up burning out.”So instead of thinking, “I should be at work right now,” try to reframe your thinking in a more positive way, Dr. Dattilo said. For example, she added, try saying: “It would be great if I could be at work right now. But today is a day that I need to take care of myself, so that’s what I’m going to do.”