Culture

Single-cell RNA sequencing has revealed a subset of cells that could provide protection from a rare, but severely debilitating and fatal, lung disease. The findings were published by Nagoya University researchers and colleagues in the European Respiratory Journal. Further research could lead to new therapeutic strategies for the disease, called idiopathic pulmonary fibrosis (IPF).

Approximately 15 in every 100,000 people worldwide develop IPF. Its prognosis and five-year survival rate can be worse than many types of cancer. It involves the development of scar tissue on the lung, impairing gas exchange and making it difficult to breath. The disease currently has no cure and scientists do not know exactly what causes it.

"Our research, led by a collaborative team from Nagoya University in Japan and Yale University in the US, found a special cell population of protective fibroblasts in lungs of people with IPF," says Nagoya University's Naozumi Hashimoto, who specializes in respiratory medicine.

The team examined around 250,000 cells from lung tissue belonging to 29 normal and 32 IPF lungs. The examinations involved sequencing the RNA of each individual cell to find which genes they expressed. The analysis pinpointed one specific subset of fibroblast cells that were significantly more prevalent in IPF lungs than in normal ones. Fibroblasts are the most common type of cell in the supportive tissue in and around organs. This particular subset of fibroblasts produced a protein called meflin.

Interestingly, these meflin-producing fibroblasts were mainly found within acute focal lung lesions on the edges of dense scarring. The surrounding dense scar tissue contained very few of these cells.

Turning off meflin and inducing lung fibrosis in mice triggered cell aging, which led to more extensive pulmonary fibrosis than would have been expected. This process was counteracted in laboratory-studied cells by inserting the gene that codes for meflin.

"We anticipate that our discovery will promote better understanding of the unsolved disease mechanisms of IPF and ultimately lead to the development of novel therapies for lung fibrosis," says Hashimoto.

The team next plans to further investigate how meflin protects lungs from fibrosis and if meflin-positive cells can be used to diagnose and treat IPF.

INDIANAPOLIS -- Nursing homes throughout the United States have been devastated by the COVID-19 pandemic with many perceptions and misperceptions but little documentation about what has happened on a day-by -day basis to residents in these facilities. A study from Regenstrief Institute and Indiana University School of Medicine research scientists is one of the first to describe and identify patterns in the course of COVID-19 in the typically frail individuals who reside in nursing homes.

Much has been written about number of deaths, vaccine uptake and other topics related to the impact of COVID on nursing homes, yet prior to the Regenstrief-IU School of Medicine study, there has been little known about how the disease has clinically affected individuals residing in nursing homes. A full understanding of the disease burden and trajectories of COVID-19 in nursing home residents - those who died and those who survived COVID - will aid medical and public health professionals immediately, will help them prepare for outbreaks of variants and may inform efforts to confront outbreaks of other diseases.

"When the COVID outbreak occurred, we [physicians who care for nursing home residents] didn't know, because we weren't armed with knowledge or clinical experience, what to expect - who would do well and who wouldn't," said Regenstrief Institute Research Scientist Kathleen Unroe, M.D., senior author of the study. "This is a population that by their very need to reside in a nursing home, has complex medical conditions and is at high risk. And it's a different population than younger adults. For example, some older adults may not experience fever in response to infection; persons with dementia may be unable to report symptoms."

The researchers studied the electronic medical records (EMRs) of 74 nursing home residents infected with COVID of whom half were women, 57 percent were Caucasian and 43 percent were African American. One third (25) died; with 23 of the deaths considered related to COVID-19 infection. Hypertension was the most common comorbidity (81 percent) followed by dementia (51 percent), diabetes (50 percent) and non-dementia mental illness (43 percent). The most common symptoms were fever, hypoxia (low oxygen level in the blood), anorexia, and fatigue/malaise. None reported headaches. The duration of symptoms was extended, with an average of more than three weeks.

The 74 nursing home residents with COVID-19 infection appeared to fall into four disease trajectory categories:

minimal to no symptoms (17)

residents who survived but experienced significant symptoms (32),

residents who died after a rapidly progressive course (less than seven days) (5)

residents who died after a prolonged course with significant symptom burden (20)

"For many of nursing home residents who survive COVID-19, the duration of symptoms is long and arduous; most will survive the disease but may not get back to baseline," said Dr. Unroe. "The effect of COVID on nursing home residents goes beyond the mortality numbers we saw."

To date, there are no effective antidotes against most virus infections. An interdisciplinary research team at the Technical University of Munich (TUM) has now developed a new approach: they engulf and neutralize viruses with nano-capsules tailored from genetic material using the DNA origami method. The strategy has already been tested against hepatitis and adeno-associated viruses in cell cultures. It may also prove successful against corona viruses.

There are antibiotics against dangerous bacteria, but few antidotes to treat acute viral infections. Some infections can be prevented by vaccination but developing new vaccines is a long and laborious process.

Now an interdisciplinary research team from the Technical University of Munich, the Helmholtz Zentrum München and the Brandeis University (USA) is proposing a novel strategy for the treatment of acute viral infections: The team has developed nanostructures made of DNA, the substance that makes up our genetic material, that can trap viruses and render them harmless.

DNA nanostructures

Even before the new variant of the corona virus put the world on hold, Hendrik Dietz, Professor of Biomolecular Nanotechnology at the Physics Department of the Technical University of Munich, and his team were working on the construction of virus-sized objects that assemble themselves.

In 1962, the biologist Donald Caspar and the biophysicist Aaron Klug discovered the geometrical principles according to which the protein envelopes of viruses are built. Based on these geometric specifications, the team around Hendrik Dietz at the Technical University of Munich, supported by Seth Fraden and Michael Hagan from Brandeis University in the USA, developed a concept that made it possible to produce artificial hollow bodies the size of a virus.

In the summer of 2019, the team asked whether such hollow bodies could also be used as a kind of "virus trap". If they were to be lined with virus-binding molecules on the inside, they should be able to bind viruses tightly and thus be able to take them out of circulation. For this, however, the hollow bodies would also have to have sufficiently large openings through which viruses can get into the shells.

"None of the objects that we had built using DNA origami technology at that time would have been able to engulf a whole virus - they were simply too small," says Hendrik Dietz in retrospect. "Building stable hollow bodies of this size was a huge challenge."

The kit for a virus trap

Starting from the basic geometric shape of the icosahedron, an object made up of 20 triangular surfaces, the team decided to build the hollow bodies for the virus trap from three-dimensional, triangular plates.

For the DNA plates to assemble into larger geometrical structures, the edges must be slightly beveled. The correct choice and positioning of binding points on the edges ensure that the panels self-assemble to the desired objects.

"In this way, we can now program the shape and size of the desired objects using the exact shape of the triangular plates," says Hendrik Dietz. "We can now produce objects with up to 180 subunits and achieve yields of up to 95 percent. The route there was, however, quite rocky, with many iterations."

Viruses are reliably blocked

By varying the binding points on the edges of the triangles, the team's scientists can not only create closed hollow spheres, but also spheres with openings or half-shells. These can then be used as virus traps.

In cooperation with the team of Prof. Ulrike Protzer, head of the Institute for Virology at TUM and director of the Institute for Virology at the Helmholtz Zentrum München, the team tested the virus traps on adeno-associated viruses and hepatitis B virus cores.

"Even a simple half-shell of the right size shows a measurable reduction in virus activity," says Hendrik Dietz. "If we put five binding sites for the virus on the inside, for example suitable antibodies, we can already block the virus by 80 percent, if we incorporate more, we achieve complete blocking."

To prevent the DNA particles from being immediately degraded in body fluids, the team irradiated the finished building blocks with UV light and treated the outside with polyethylene glycol and oligolysine. The particles were thus stable in mouse serum for 24 hours.

A universal construction principle

Now the next step is to test the building blocks on living mice. "We are very confident that this material will also be well tolerated by the human body," says Dietz.

"Bacteria have a metabolism. We can attack them in different ways, " says Prof. Ulrike Protzer. "Viruses, on the other hand, do not have their own metabolism, which is why antiviral drugs are almost always targeted against a specific enzyme in a single virus. Such a development takes time. If the idea of simply mechanically eliminating viruses can be realized, this would be widely applicable and thus an important breakthrough, especially for newly emerging viruses.

The starting materials for the virus traps can be mass-produced biotechnologically at a reasonable cost. "In addition to the proposed application as a virus trap, our programmable system also creates other opportunities," says Hendrik Dietz. "It would also be conceivable to use it as a multivalent antigen carrier for vaccinations, as a DNA or RNA carrier for gene therapy or as a transport vehicle for drugs."

A new study finds that resilience is a dynamic process, rather than a fixed trait - and suggests this may have significant ramifications for the business world.

"Organizations are interested in cultivating a resilient workforce, because they want people who are able to remain committed to an organization and its goals over time," says Patrick Flynn, corresponding author of the study and an assistant professor of human resources management at North Carolina State University's Poole College of Management.

"Our work here does a couple things," Flynn says. "First it finds that resilience is more of a process than a characteristic. Second, it identifies some of the characteristics that can contribute to that process in a meaningful way. Taken together, we think the findings can inform recruitment, hiring, operations and training practices."

At the heart of the study is the idea that resilience fluctuates, because it encompasses the way that an individual responds to a variety of circumstances over time.

"It's impossible to assess dynamic resilience at any given moment," Flynn says. "Dynamic resilience is demonstrated across time. How does people's behavior change over time? What influences that? Those are the sorts of questions we wanted to answer with this study."

To that end, researchers worked with 314 members of a university marching band. Study participants were surveyed weekly for 12 weeks. The surveys were designed to collect data on individual participants and their emotional and personal characteristics. To assess how resilience is functioning in individuals over time, the researchers also asked study participants about their commitment to the marching band as an organization, as well as their feelings of "burnout" - specifically, emotional exhaustion related to their work in the organization.

"Tracking the trajectories of commitment and burnout helped us see how resilience played out in real world terms," Flynn says.

The researchers found that, on average, emotional exhaustion increased over time and commitment decreased over time. However, there were factors that influenced those effects.

For example, experience within the organization exacerbated the effects of emotional exhaustion and decreased commitment. In other words, newcomers appeared to be more resilient over the study period.

The researchers also found that people who scored higher on assessments of emotional stability were better able to maintain higher levels of commitment.

Lastly, the researchers also looked at the trajectory of each individual's commitment to the organization to see if it predicted "retention." They found that positive commitment trajectories were associated with a greater likelihood of both planning to return to the organization for another year and then subsequently doing so.

"One takeaway here is that annual employee surveys may not be the best way to assess employee resilience and commitment to an organization," Flynn says.

That's because annual surveys provide snapshots, while resilience is a dynamic process that fluctuates.

"Since resilience affects things like employee retention, which are important to a company's bottom line, we really need to be touching base with employees more often," Flynn says.

The work also shows that resilience can wear down over time, even if people are only exposed to mild stressors.

"Chronic stress can wear down resilience, with ramifications for employee retention and, in all likelihood, job performance," Flynn says.

"However, we also feel that thinking about resilience as a dynamic process creates opportunities to foster resilience in employees not only through recruitment, but through training, and even job design. In short, it's not as simple as hiring the right person and assuming things will work out. Fostering resilience is going to be an ongoing task for management and human resources professionals."

The mitochondrion has garnered quite the reputation for its role as the "powerhouse of the cell." These tiny, but mighty organelles play various life-sustaining roles, from powering our own cells and organs to fueling chemical and biological processes. But when they aren't working properly, a number of rare diseases can occur.

Mitochondrial diseases are a group of debilitating genetic disorders that affect one in 5,000 people throughout the world, most of them being children. Along with these diseases come a variety of health concerns including, but not limited to, heart disease, developmental and cognitive disabilities, respiratory issues, poor growth, and even premature death. As of this moment, there is no cure.

But recent work published in the journals Mitochondrion and BMC Molecular and Cell Biology by Aloka Abey Bandara, a research associate professor in the Department of Biomedical Sciences and Pathobiology in the Virginia-Maryland College of Veterinary Medicine, and his team offers mitochondrial disease patients and their parents a glimmer of hope.

Along with a team of Virginia Tech researchers across Blacksburg and Roanoke, Bandara has successfully created live cell models that mimic mitochondrial disease cells. These cells will lay the groundwork for drug studies and future studies into mitochondrial diseases.

"Our cell models will allow us to see what exactly happens to the cells and its processes when a child develops mitochondrial disease. In addition to these factors, we will be able to conduct further study into the toxicity and effectiveness of novel drug candidates," said Bandara, who is also an affiliated faculty member of the Fralin Life Sciences Institute.

Our bodies produce life-sustaining energy from the food we eat and the air we breathe. Oxygen and nutrients, like glucose, travel throughout the body's organs, tissues, and cells until they arrive at their final destination: the mitochondria. When the nutrients reach the inner membrane of the mitochondria, a unique series of protein complexes, called the electron transport chain, kicks into gear.

Through a series of reactions, the electron transport chain is able to remove electrons from the nutrients and push them through the mitochondrial membrane, which forms a gradient of protons. When this happens, the body generates adenosine triphosphate, better known as ATP, a molecule that carries energy within cells.

"Sometimes, you can see disruptions or mutations within the electron transport chain proteins," said Bandara. "As a result, the protein complexes cannot transport electrons, and then energy production is disrupted. Almost all organs of the organism will be affected - heart, eyes, and muscles - and they will not be able to function correctly."

The electron transport chain is composed of five protein complexes, or groups of proteins. Complex I and Complex II are two protein complexes that are primarily responsible for removing electrons from the nutrients. If they fail to do their duty, the whole electron transport chain fails, and the body cannot produce ATP.

Mitochondrial disease patients can have defects in either Complex I or Complex II. Patients who have Complex I disruptions typically have neurological problems, such as seizures and abnormal brain functions. Those with Complex II disruptions can develop many other diseases and are more likely to develop several cancers.

Although researchers are able to pinpoint where exactly the defects are located, creating treatments for these mitochondrial diseases has been a challenge. Therapies, vitamins, and dietary adjustments have been able to help alleviate symptoms and slow down the progression of disease; but, mitochondrial disease, itself, does not have a cure. Therefore, new drugs need to be created, tested, and refined.

Bandara hopes that his cell lines will not only support upcoming research, but also the patients and their families, who are experiencing the mitochondrial disease and all of its impacts firsthand.

"The parents are often helpless because they cannot just go to the pharmacy and get a drug," said Bandara. "Hopefully, they can see that Virginia Tech is taking huge leaps to find a cure for these diseases. Maybe they can feel that they are not alone anymore - that the universities, the government, and science are fighting with them."

In order to test drug candidates, researchers must first create cellular models, which act as artificial "sick" cells. Cellular models are an excellent tool for drug discovery because mitochondrial disease can be studied without actually needing to extract cells from patients.

To create cells that mimic mitochondrial disease, Bandara had to "knock-out" portions of the genome that create the coding for Complex I and Complex II using CRISPR/Cas9 technology.

First, researchers identified the portion of the genome that needed to be deleted. Then, they designed a piece of RNA that made that point its "home base." The RNA then "guided" an enzyme called Cas9 to its home base on the gene. Cas9 is then able to bind to that point and "cut" it.

After this process was completed, Bandara ran genomic sequencing to confirm that the portion was successfully deleted from the genome. Over several months of hard work, Bandara and his team created two mutant cell lines, one with Complex I removed, and the other without Complex II.

Bandara is one of the very few researchers on Virginia Tech's Blacksburg campus to use the CRISPR/Cas9 technology to treat mitochondrial disease.

After the mutant cell lines were created, Bandara ran them through a disease model, where he tested the functions of the "sick" cell line against the "parent" cell line, which is composed of healthy cells. Through close analysis, Bandara confirmed that the sick cells consumed far less oxygen, grew very slowly, and did not produce enough ATP for the cells to function properly - the three trademarks of cells with mitochondrial disease.

Once they confirmed that the knockout cell lines properly simulated the cellular dysfunctions of mitochondrial disease, they were able to test a newly developed drug called Idebenone. With this treatment, Bandara showed that cell growth and oxygen consumption can be restored to a certain extent.

These cell lines were the product of a fruitful collaboration of experts from the Department of Human Nutrition, Foods, and Exercise and the Virginia Tech Carilion School of Medicine.

The construction of mutant cell lines was guided and supported by David Brown, a former associate professor in the Department of Human Nutrition, Foods, and Exercise in the Virginia Tech College of Agriculture and Life Sciences, now the senior director of scientific and technical innovation at Stealth BioTherapeutics, a Boston-based biotechnology company.

From this work, the team has received two provisional patents for their cells. One of the cell lines has already been patented and licensed to a pharmaceutical company, which will develop new therapies for individuals suffering from mitochondrial diseases.

These cells have been made available for global use by interested researchers and pharmaceutical companies through Ximbio, the world's largest nonprofit specializing in life science research tools of all types.

"Cell models of mitochondrial Complex I and II defects carry high societal and economic impact as models for testing drug candidates in a cost- and time-effective manner for the treatment of mitochondrial dysfunction," said Justin Perry, a Virginia Tech graduate, and now a business development manager at Ximbio.

The pandemic has taught us that almost all companies have to sell on the internet. Bots are a technology that facilitates e-commerce. They are digital assistants that can answer customer queries about products that are sold or help to locate them, as well as supporting customers in the purchasing process. "In whatever language; and moreover, chatbots never get tired: They're available 24 hours a day, 365 days a year", said Jordi Cabot, the Universitat Oberta de Catalunya (UOC) researcher who created Xatkit, a company specialized in their development. This technology has existed for some time in big companies and is now also helping improve the digital competitiveness of SMEs. Indeed, the introduction of bots is expanding: this type of artificial intelligence already generates over 40% of the traffic on the internet.

Xatkit is a new UOC spin-off which offers pre-trained bots for e-commerce. Once installed in the shops, they read the products that are sold and are automatically set up to begin to help the customers who arrive. They are also prepared to continue learning by themselves. "Our bots can do any task that a human salesperson would do, from recommending products or showing offers to notifying the shop when clients ask for a product that they are not currently offering", said Cabot.

The pandemic has taught us that almost all companies have to sell on the internet. Bots are a technology that facilitates e-commerce. They are digital assistants that can answer customer queries about products that are sold or help to locate them, as well as supporting customers in the purchasing process. "In whatever language; and moreover, chatbots never get tired: They're available 24 hours a day, 365 days a year", said Jordi Cabot, the Universitat Oberta de Catalunya (UOC) researcher who created Xatkit, a company specialized in their development. This technology has existed for some time in big companies and is now also helping improve the digital competitiveness of SMEs. Indeed, the introduction of bots is expanding: this type of artificial intelligence already generates over 40% of the traffic on the internet.

Xatkit is a new UOC spin-off which offers pre-trained bots for e-commerce. Once installed in the shops, they read the products that are sold and are automatically set up to begin to help the customers who arrive. They are also prepared to continue learning by themselves. "Our bots can do any task that a human salesperson would do, from recommending products or showing offers to notifying the shop when clients ask for a product that they are not currently offering", said Cabot.

Beyond e-commerce: digital assistants using text or the phone

Digital assistants do not just simulate human conversations on chat windows (so-called chatbots), but can also be used to answer telephone calls or comments made on websites or social media in any language. At present, Xatkit creates bots that can understand and speak in English, Spanish and Catalan.

The technological improvement of bots means that these assistants can currently engage in "complex conversations and process management tasks, processing customers' requests", explained Jordi Cabot. This technology allows customer service costs to be optimized. Cabot, a member of the research faculty at ICREA and leader of the research group SOM Research Lab of the UOC's Internet Interdisciplinary Institute (IN3), who developed Xatkit with Gwendal Daniel, a researcher from his group, indicated that the key to the development of digital assistants is that they have a specialized platform to define their functionalities and guarantee the quality of the training of the bot, testing and monitoring the behaviour in order to improve its effectiveness.

Bots created with open-source software

The Xatkit team works with open-source software, making it easy for clients to set up the digital assistants. Its platform is committed to integrating state-of-the-art technology in processing and understanding natural language to optimize the quality of the conversations. In addition to understanding what the client says, Xatkit summarizes and automatically translates texts, and also analyses the feelings of the buyers. "The bot can figure out whether the client is annoyed and adapt its answer to the situation", explained Jordi Cabot.

From research to entrepreneurship

The initiative of the UOC researchers to develop conversation bots began as a research project but, unlike other research, "we thought that, in view of the subject and the innovation behind it, it could help many organizations and have a bigger social impact", indicated Cabot. Thus, the creation of this new spin-off from the UOC's research activity allows the research group's technological expertise on digital assistants to reach the market. "Xatkit takes advantage of the state-of-the-art technology that we generate in the research to develop more innovative solutions and the research team learns from the application of the technology in real cases, thanks to the creation of the company", said the researcher.

"We recommend combining the role of researcher with that of entrepreneur, because this improves the quality and impact of the research", according to Cabot and other researchers in an article published for the 8th International Virtual Workshop on Software Engineering Research and Industrial Practice. Faced with the lack of more investment by industry in R&I, the experts said that as researchers they can "become the partners that companies need, and thus moreover bring the ideas of the research to the market".

The researchers are committed to promoting open resources, strengthening the triangle of collaboration between research, SMEs - as technology suppliers - and end clients - which could be big corporations -, or as a fruitful relationship which provides real cases of technological development. "If as researchers we don't find the appropriate SME to collaborate with our research, we create it, like we did with Xatkit", they concluded.

Spin-offs from UOC research activity

At present the UOC has four spin-offs. Before Xatkit, it created Immersium Studio, specialized in the development of immersive technology (virtual, augmented and mixed reality); Care Respite, with the Universitat Autònoma de Barcelona, specialized in dependent people monitoring technology for carers; and Open Evidence, an international quantitative consultancy that promotes operating strategies and models for decision-making processes through data-based computational intelligence.

The Xatkit project won the jury award at Spin UOC 2021, the UOC's annual entrepreneurship, innovation and knowledge transfer programme, promoted by the Hubbik platform.

The Xatkit project (Massive Generation of chatbots on-demand, ref. 2019 INNOV 00001) is supported by the Department for Universities and Research in the Government of Catalonia's Ministry of Business and Knowledge and receives funding from the European Regional Development Fund (ERDF).

Xatkit supports sustainable development goal (SDG) 9: Build resilient infrastructure, promote sustainable industrialization and foster innovation

The RUDN University chemists have discovered a reaction for the synthesis of acetimidamides, heterocyclic compounds with biological activity that can be used for the synthesis of hormones, anti-inflammatory and other medical drugs. The reaction goes in one step with an efficiency of up to 96%. The results are published in the journal Molecules.

Traditional chemical synthesis goes in several stages and requires the isolation and purification of intermediates at each stage. It is not efficient and not environmentally friendly as it increases the loss of substances and the consumption of solvents, and there is a problem of waste disposal. Therefore, modern chemistry is trying to replace multi-stage reactions with multicomponent ones, in which several compounds react to form a product in a single stage. Reactions with isocyanides are the most popular in multicomponent chemistry. Isocyanides are organic compounds with high reactivity. RUDN University chemists have discovered a new three-component reaction with isocyanides that results in a heterocyclic compound with biological activity, acetimidamides. They contain a fragment of indole, which is used for the synthesis of hormones, indomethacin, and other drugs. This work is a development of the famous Ugi reaction.

"Isocyanide-based multicomponent reactions play an outstanding role in the syntheses of heterocycles, biologically relevant compounds and for diversity-oriented synthesis. In the case of the famous Ugi reaction, isocyanide interacts with iminium salt generated in situ. The potency of methods, based on the Ugi reaction, increases with the possibility of subsequent modification or cyclization of obtained products of multicomponent reaction. This is promising from the point of view of medical chemistry", said Nikita Golantsov, PhD, Professor of the Department of Organic Chemistry of the RUDN University.

Apart from isocyanides, the new three-component reaction involves a 3-arylidenindoleninium salt and an amine. In total chemists used 8 salts and 13 amines. To choose the optimal reaction conditions, they tested 6 types of solvents, alternated the reaction time and temperature. After the reaction was completed, the chemists isolated the final product by treatment with a saturated baking soda solution followed by chromatography and studied its composition and structure using various methods, including nuclear magnetic resonance (NMR) spectroscopy.

In total, the RUDN University chemists obtained 16 acetimidamides. When using isocyanoacetic ester, imidamides were further cyclized with the formation of an imidazolone fragment. Thus, a series of 19 imidazolones containing an indole substituent was synthesized. The most suitable solvent was acetonitrile. It allowed to minimize the formation of by-products. After three hours at a temperature of 20?, the reaction yield (the ratio of the actual mass of the product obtained to the theoretical one), was 75%. And after 12 hours, the output reached 96%. Chemists tried to accelerate the reaction by increasing the temperature, but this attempt was unsuccessful due to a tar formation and an increase in the amount of the by-product.

"These reactions furnish a new practical synthetic approach to a series of compounds with a privileged indole scaffold, which are prospective choices for seeking new physiologically active compounds", said Nikita Golantsov, PhD, Professor of the Department of Organic Chemistry of the RUDN University.

Scientists have uncovered a way to control many genes in engineered yeast cells, opening the door to more efficient and sustainable production of bio-based products.

The study, published in Nucleic Acids Research by researchers from DSM's Rosalind Franklin Biotechnology Center in Delft, the Netherlands, and the University of Bristol, has shown how to unlock CRISPR's potential for regulating many genes simultaneously.

Baker's yeast, or Saccharomyces cerevisiae to give it it's full name, is considered as a workhorse for biotechnology. Not only has it been used for producing bread and beer for thousands of years, but today it can also be engineered to produce an array of other useful compounds that form the basis of pharmaceuticals, fuels, and food additives. However, achieving optimal production of these products is difficult, requiring the complex biochemical networks inside the cell to be rewired and extended through the introduction of new enzymes and the tuning of gene expression levels.

Klaudia Ciurkot, first author of the study and an EU-funded industrial PhD student based at DSM stated: "To overcome the challenges of optimising S. cerevisiae cells for bio-production, we explored the use of a less widely employed CRISPR technology based on the Cas12a protein. Unlike the Cas9 protein that is more commonly used, Cas12a can be rapidly programmed to interact with sequences that are responsible for controlling gene expression and easily targeted to many different sequences at the same time. This made it an ideal platform for carrying out the complex gene regulation often required for producing industrially relevant compounds."

She went on to add: "What was particularly exciting for me was that this study is the first to demonstrate Cas12a's ability to control gene expression in S. cerevisiae and through joint research across DSM and the University of Bristol, we were able to figure out the rules for how this system is best designed and used."

Thomas Gorochowski, a co-author on the work and Royal Society University Research Fellow based in the School of Biological Sciences at the University of Bristol further stated: "It is hugely exciting that Cas12a has been shown to work so well for gene regulation in the yeast S. cerevisiae, an organism that has huge industrial importance. In addition, the systematic approach we have taken to pull apart and analyse the many difficult aspects of the system, act as a firm foundation for future optimisation."

In addition to analysing how the Cas12a-based system is best engineered, the scientists went on to show its use in robustly controlling the production of β-carotene - an industrially important compound used in production of food additives and nutraceuticals.

René Verwaal, senior author and Senior Scientist at DSM ended by stating: "By demonstrating the capabilities of this system to control the biosynthesis of β-carotene, we have opened the gates to its broader application for other key bio-based products. I cannot wait to see how our system is used to develop more sustainable production platforms for everyday products we all rely on."

According to the World Health Organization, a third wave of COVID infections is now all but inevitable in Europe. A COVID tracker developed by IIASA researcher Asjad Naqvi, aims to identify, collect, and collate various official regional datasets for European countries, while also combining and homogenizing the data to help researchers and policymakers explore how the virus spreads.

While many comparisons have been made between the COVID-19 pandemic and similar events in history, one thing sets this pandemic apart from others: the unprecedented amount of knowledge and data that is constantly being generated to understand how the pandemic is unfolding. For a high-income region like Europe, the quality of information made available on a daily basis is exceptionally high compared to the rest of the world. Using this information to make comparisons between different European countries is however not a simple task.

Almost all European countries make COVID-19 data available in the form of maps and trend graphs, but access to data behind these visualizations varies from country to country, with most allowing some form of access to regional data, while others do not release this information publicly. European countries also tend to define regions differently. The European Commission and Eurostat - the statistical office of the European Union - for instance, use homogenous units known as Nomenclature of Territorial Units for Statistics (NUTS), where NUTS 0 denotes countries, NUTS 1 are typically provinces, NUTS 2 are districts, and NUTS 3 are sub-districts. In addition, differences in testing practices and how COVID-19 related hospital admissions and deaths are recorded, further complicate the comparison of data. Lastly, not all European countries are part of the European Union, and therefore are not subject to Eurostat reporting or data sharing requirements.

To overcome some of these challenges, IIASA researcher Asjad Naqvi has developed a COVID-19 tracker that presents data on daily COVID-19 cases at the sub-national level for 26 European countries from January 2020 until the present. Although several innovative datasets that collect unique COVID-19 related information, such as the Oxford COVID-19 Government Response Tracker and the Complexity Science Hub (CSH) Tracker have come onto the scene since the start of the pandemic, Naqvi's tracker aims to identify, collect, and collate various official regional datasets for European countries, while also combining and homogenizing the data at the NUTS 3 or NUTS 2 level. This homogenized dataset makes it possible to explore how the virus spreads in terms of cumulative cases, daily cases, and cases per capita in Europe at a daily resolution.

"One of my aims in developing this tracker was to ensure data transparency, while also making the data consistent and ready for analysis. The paper identifies sources of COVID-19 datasets for 26 European countries and how to access each of them. The data set currently contains over 0.5 million data points at the NUTS 3 or NUTS 2 level," Naqvi explains.

The tracker's data, which is discussed in a new paper published in the journal Scientific Data, can be merged with country or continent-level datasets, such as primary surveys, data from national statistical offices, or data from Eurostat, to conduct comprehensive analyses on the causes and implications of COVID-19. The paper contains a detailed discussion of data sources in each country, including their strengths and weaknesses, and the raw country-level files are provided in an online repository. According to Naqvi, this is one of the very few datasets that has been continuously updated since August 2020 to provide consistent daily information on a regional level for Europe.

The map, for example, clearly illustrates that Germany, on the whole, insulated itself well against the virus and that Sweden and Czechia were particularly hard hit since the start of the pandemic.

Naqvi notes that the tracker can be used for a host of different research questions. It can, for instance, be mapped onto NUTS-level regional data including various economic, demographic, health, tourism, and labor related indicators, some of which also have a monthly or even a weekly frequency. Since data for individual countries are provided, a detailed country-specific analysis can also be done if regional or micro data are available for analysis. Other datasets catalogued on platforms such as the Oxford COVID-19 Supertracker, provides a range of interesting information on various policies put in place by countries during the pandemic. The tracker data can be combined with several innovative global datasets containing NUTS-level information for European countries. As the data for the tracker has a Creative Commons Attribution 4.0 International License (CC-BY), anyone can access it at any time. The data base will continue to be updated regularly until countries stop publishing regional COVID-19 data.

The Institut Pasteur, in partnership with the French National Health Insurance Fund (CNAM), Santé publique France and the Ipsos Social Research Institute, recently presented the results of the ComCor epidemiological study on circumstances and places of infection with the SARS-CoV-2 virus. The aim of the study was to identify the socio-demographic factors, places visited and behaviors associated with a higher risk of infection with SARS-CoV-2. The study contains two parts:

the first part describes the circumstances of infection of index cases diagnosed positive for SARS-CoV-2 during the curfew period, especially when the person considered as the source of infection is known;
the second part compares the characteristics, behaviors and practices of the index cases with those of a second series of individuals, matched in terms of age, sex, region and population density and period (curfew and lockdown).

Sumarry of results :

Analysis of index cases' circumstances of infection during the curfew period:

44% of infected individuals could identify the person considered to be the source of infection, 21% suspected they had been infected at a specific event, but could not identify the person who was the source of infection, and 35% did not know how they had been infected.

A very large majority (97%) of index cases who responded to this questionnaire self-isolated, but only 54% on symptom onset, and 64% on discovering that they had been in contact with an infected case, where symptoms or discovery of contact with an infected case were the only warning signs.

As regards infections in households (35% of infections where the person considered to be the source was known), most of these adults were infected by their spouses (64% of cases). The fact that children are asymptomatic or present with few symptoms when infected may explain why they were often not identified as the person considered to be the source of the infection.

As regards infections outside households (65% of infections where the person considered to be the source was known), the chief source of infections was family (33%), followed by the workplace (29%), and friends and acquaintances (21%). Meals played a key role in infections among family, friends and acquaintances, and, to a lesser degree, at work. Shared offices were also a major cause of infections in the workplace.

Analysis of factors associated with SARS-CoV-2 infection during the curfew and lockdown periods:

Increased risk of SARS-CoV-2 infection:

- Professions (compared to the medium-risk group of public-sector executives):

Corporate administrative and sales executives

Intermediate health and social workers

Industrial workers

Drivers

- Number of people living in households

- Having children who:

Are looked after by a childminder

Attend a nursery

Attend nursery school (aged 3-5)

Attend middle school (aged 11-14)

Attend high school (aged 15-18)

- Car sharing

- Recent travel abroad

- Participation in a face-to-face meeting:

Professional

Private (friends or family)

- Visits to:

Bars

Restaurants

Gyms

Reduced risk of SARS-CoV-2 infection:

- Professions (compared to the medium-risk group of public-sector executives):

Schoolteachers

Scientists and university lecturers

Intermediate public-sector administrative workers

Civilian employees and public-sector service staff

Corporate administrative employees

Students

Farmers

Male/female homemakers

- Home workers (compared to individuals working face-to-face in offices)

- Bus or tram travel

- Outdoor exercise

- Shopping (in food and clothes stores, etc.)

Study methodology

The "index cases" were adults emailed by the French National Health Insurance Fund (CNAM) to take part in the study based on cases entered in the "Contact-Covid" database of individuals who have tested positive for SARS-CoV-2. IPSOS identified and contacted "control subjects" matched to the index cases by age, sex, region of residence, population density, and period (curfew from October 17, 2020 and lockdown from October 29, 2020).

The index cases and control subjects were asked to complete a self-administered questionnaire concerning their socio-demographic details, places they had visited, and behaviors. The index cases were asked to provide details of the circumstances in which they were infected if known. Two types of analysis were performed. These are presented below.

Analysis of circumstances of infection based on the database of index cases during the curfew period.

Of the 370,000 emails sent out with invitations to take part in the study, 30,330 (8.2%) questionnaires were returned by individuals very likely to have been infected between October 17 and 30, 2020 (the curfew period): 25,644 index cases among non-healthcare workers and 4,686 healthcare workers, who were addressed separately due to potential differences in circumstances of infection.

62% of respondents were women and 72% were aged 29-58 years (only adults were eligible for this study). 55% were resident in conurbations of over 100,000 inhabitants, with large proportions in the Auvergne-Rhône-Alpes and Ile-de-France regions (22% and 21% respectively).

44% of the infected individuals could identify the person considered to be the source of infection and most were aware of their high-risk behavior (failure to wear a mask or socially distance, no measures taken to isolate the person considered to be the source within the household, etc.), 21% suspected they had been infected at a specific event, but could not identify the person who was the source of infection, and 35% did not know how they had been infected.

A very large majority (97%) of index cases who responded to this questionnaire self-isolated, but only 54% on symptom onset, and 64% on discovering that they had been in contact with an infected case, where these were the only warning signs.

As regards infections in households (35% of infections where the person considered to be the source was known), most of these adults were infected by their spouses (64% of cases). The fact that children are asymptomatic or present with few symptoms when infected may explain why they were often not identified as the person considered to be the source of the infection. It was noted that only 51% of individuals considered to be the source of infection within households self-isolated, and of those who did, only 52% did so on symptom onset.

As regards infections outside households (65% of infections where the person considered to be the source was known), the chief source of infections was family (33.1%), followed by the workplace (28.8%), and friends and acquaintances (20.8%). Meals played a key role in infections among family, friends and acquaintances, and, to a lesser degree, at work. Shared offices were also a major cause of infections in the workplace.

Case-control study of the curfew and lockdown periods

For this part of the study, responses to the self-administered questionnaire from 3,426 cases and 1,713 control subjects matched by age, sex, region, population density, and period (curfew or lockdown) were analyzed.

Compared to public sector executives, who are a medium-risk group, administrative and sales executives, industrial workers, drivers, and intermediate health and social workers were at higher risk of SARS-CoV-2 infection during the curfew or partial lockdown. Higher occupancy in households, particularly with children at nursery or school, participation in face-to-face business meetings, car sharing, visits to bars, restaurants and gyms, and participation in private meetings among friends or family were also associated with higher risk.

Schoolteachers, scientists or university lecturers, civilian employees and public sector service staff, corporate administrative employees, students, farmers, male and female homemakers, and people belonging to intermediate public-sector administrative professions were at lower risk of SARS-CoV-2 infection during the curfew or partial lockdown, again compared to public-sector executives. Home working (compared to individuals working face-to-face in offices), bus or tram travel, outdoor exercise, and shopping (in food and clothes stores, etc.), were all associated with a lower risk of SARS-CoV-2 infection during the curfew or partial lockdown.

Of all the circumstances analyzed, the highest proportion of infections (19%) can be attributed to private meetings during the study period.

These results should be treated very cautiously as they only relate to the curfew and lockdown periods, and may be considerably skewed by the study population selected, which only represents a small proportion of all infections, and by the fact that some responses may have been influenced by respondents' knowledge of whether or not they were infected.

Nevertheless, these results are compliant with data from the literature in terms of those already reported in other studies, and are in keeping with our knowledge of SARS-CoV-2 transmission. The places and circumstances of infection are likely to change over the course of the epidemic, and this study may provide a tool for monitoring trends in infection conditions over time. It would be useful to implement this type of monitoring, particularly when certain public or private spaces reopen, to determine whether or not reopening is associated with an increased risk of SARS-CoV-2 transmission.

According to Arnaud Fontanet, Head of the Epidemiology of Emerging Diseases Unit at the Institut Pasteur and Professor at the National Conservatory of Arts and Trades: "This study demonstrates that there is significant risk of SARS-CoV-2 infection during meals and private meetings. It is very important that we minimize this risk during gatherings over the festive period".

A multidisciplinary team of researchers is the first to show combining yeast-expression technology and a novel adjuvant formulation to produce a COVID-19 vaccine candidate is effective against SARS-COV-2 and promises to be easy to produce at large scale and cost-effective, important aspects for vaccinating people worldwide, especially in low- to middle-income countries. Results from the study, which applied lessons learned from the hepatitis b vaccine platform technology, are published online today in Science Immunology.

Researchers from the Yerkes National Primate Research Center (NPRC) at Emory University, Infectious Disease Research Institute (IDRI), 3M and Texas Children's Hospital's Center for Vaccine Development at Baylor College of Medicine paired Baylor's SARS-CoV-2 Receptor Binding Domain (RBD) recombinant protein formulation vaccine candidate with IDRI's aluminum-based formulation of 3M's Toll-like receptor 7 and 8 agonist 3M-052 (3M-052/Alum) to enhance immune response against SARS-CoV-2 and, thus, increase vaccine effectiveness against COVID-19.

"Working with rhesus macaques, we found 3M-052/Alum formulation produced a significant and superior overall immune response than alum alone, a licensed adjuvant," says corresponding author Sudhir Kasturi, PhD. "The superior immune response from our RBD+ 3M-052/Alum vaccine resulted in a significant reduction of SARS-CoV-2 in upper and lower respiratory tracts and a markedly reduced severity of lung disease when compared with unvaccinated animals. We also showed a substantial reduction in virus shedding from the upper airways, which suggests our vaccine may also slow or halt virus transmission," Kasturi continues. Kasturi is an assistant professor in the Emory School of Medicine (SOM) Department of Pathology and Laboratory Medicine and a research assistant professor in Yerkes' Microbiology and Immunology (M&I) division and the Emory Vaccine Center.

The researchers believe their vaccine comprising a recombinant RBD protein with its novel 3M-052 adjuvant formulation may be strongly effective against the emerging variants because the vaccine has the capability to induce both neutralizing antibodies and CD8+ T cells, which can kill the virus if it enters cells. They say this is critical for reducing disease transmission and the virus' impact worldwide.

"Also critical is we showed the vaccine potently reduces the levels of SARS-CoV-2 and limits inflammation by blocking the expansion of pro-inflammatory monocytes, which provides a better understanding of how the vaccine works," says Mirko Paiardini, PhD. "Furthermore, in collaboration with our Emory colleagues Drs. Susan Pereira Ribeiro and Rafick P. Sekaly, we identified via our study a combination of blood markers that predict the virus burden in lungs. Such a diagnostic could potentially help healthcare professionals monitor the disease and adjust treatments for increased effectiveness," Paiardini continues. He is also a corresponding author of the study and an associate professor in the Emory SoM Department of Pathology and Laboratory Medicine as well as a researcher in Yerkes' M&I division.

To the authors' knowledge, their SARS-CoV-2 research is first to report use of a recombinant RBD immunogen and the 3M-052/Alum adjuvant to induce CD8+ T cell responses. The researchers say such T cell responses should be easily translatable from the rhesus monkey model into broad-based protection in humans, especially against emerging SARS-CoV-2 variants.

The researchers vaccinated two groups of five rhesus monkeys each with RBD+alum (Group 2) or RBD+ 3M-052/Alum (Group 3). All animals in these groups received three immunizations over 10 weeks. Based on previous HIV studies, the researchers reasoned a third vaccination could substantially improve the magnitude and quality of neutralizing activity and effectiveness. An additional five rhesus monkeys (Group 1) served as unvaccinated controls for evaluation purposes. The researchers challenged all animals with SARS-CoV-2 (WA1Ä2020 isolate) via a combined intranasal and intratracheal route one month after the third vaccination. The Group 3 animals, which received RBD+ 3M-052/Alum, showed clear advantages in antibody response, neutralizing activity and effectiveness over the Group 2 animals, which received RBD+alum.

Adding to the appeal of the Baylor RBD vaccine candidate is the large-scale production capacity in low- to middle-income countries that use this established yeast-expression platform for producing the hepatitis B vaccine. Such production capacity addresses the ability for transferring this vaccine technology in an effort to improve global health.

"Our results showed producing the RBD recombinant protein using the yeast expression platform would meet the demand for vaccinating communities around the world," says Maria Elena Bottazzi, PhD. We are very excited to see our vaccine candidate is also beneficial in inducing a balanced antibody and CD8+T cells response previously not seen with other protein-based vaccine approaches." Bottazzi is another corresponding author and associate dean of the National School of Tropical Medicine at Baylor and co-director of Texas Children's Center for Vaccine Development.

Study author Peter Hotez, MD, PhD, notes the widespread use and outstanding safety track record of yeast-expressed recombinant protein immunizations offer promise for using this approach to produce and deliver COVID-19 vaccines for global health. Hotez is dean of the National School of Tropical Medicine at Baylor and co-director of Texas Children's Center for Vaccine Development.

The research team also includes Christopher Fox, PhD, IDRI, and Mark Tomai, PhD, 3M.

"Especially because of its cost effectiveness, we believe this vaccine could serve as a great option against emerging SARS-CoV-2 variants as well as an attractive boost to select advanced clinical candidates where repeated vaccination might be a challenge," Kasturi says.

PIWI-interacting RNAs (piRNAs), a class of conserved non-coding small RNAs, are essential for sex determination, defense against viruses, maintaining genome integrity of diverse animal species. The missing of PIWI protein would leads to male-production of sperm. However, many piRNA clusters reside within or close to the heterochromatin, a transcriptional silencing loci. How piRNAs are transcribed remains unknown.

Facing this problem, Prof. GUANG Shouhong and research fellow FENG Xuezhu from University of Science and Technology of China of the Chinese Academy of Sciences (CAS) identified a chromodomain-containing protein, UAD-2, in the model organism Caenorhabditis elegans (C. elegans), and determined the role of UAD-2 in the regulation of gene transcription in heterochromatin regions. This work was published on Proceedings of the National Academy of Sciences of the United States of America (PNAS) on July 6.

In 2019, Prof. GUANG and international collaborators discovered the upstream sequence transcription complex (USTC) and specified its role in the biogenesis process of piRNAs in Genes & Development. Using the USTC complex as a tool, researchers isolated a USTC association-dependent mutant, or uad-2 for short, in which the piRNA foci were depleted, by clonal screening.

Following experiments confirmed that the uad-2 genome was essential for the genesis of piRNAs. In addition, the researchers found that the UAD-2 protein and the USTC complex colocalized with each other in the nucleus, and they were mutually dependent on each other for the proper localization. Thus, the UAD-2 was required in the production of piRNAs by this mutual effect with the USTC complex.

Many piRNA loci overlap with a heterochromatin mark histone called H3K27me3 in C. elegans. The chromodomain in the UAD-2 is one of the major readers of the histone mark, and exogenous experiments proved that the H3K27me3 promoted UAD-2 and USTC focus assembly. Proper modification of H3K27me3 was also recognized as important.

Findings of this work provide a brand-new way for further studies of the transcription of piRNA in heterochromatin region.

Data privacy is an important topic in the digitalised economy. Recent policy changes have aimed to strengthen users' control over their own data. Yet new research from Copenhagen Business School finds designers of cookie banners can affect users' privacy choices by manipulating the choice architecture and with simple changes can increase absolute consent by 17%.

A website cookie banner is the consent management tool that allows users to give their consent to process their personal data. Given the current legal framework, users need to actively provide consent.

The manipulations of the banner can therefore affect the user decision about whether to make an active choice at all and what the outcome of this choice would be, accept or decline consent. The research findings provide empirical evidence that shows people's data privacy decisions can be easily manipulated.

"Choice architecture should be designed to benefit the user to make more informed decisions, which are essential for free markets to work efficiently. Exploiting psychological mechanisms in design, to manipulate users to the benefit of the website owner is problematic," says Associate Professor Jan Michael Bauer from the department of Management, Society and Communication, Copenhagen Business School.

"Detailed user data has become valuable as it allows to better understand customer behaviour and improve the targeting of advertisements. Users and customers deserve and should demand a choice environment that allows their own need satisfaction and not one that benefits the website owner," adds Bauer.

The research highlights that the ability of website owners to manipulate the outcome of user privacy decisions is at odds with the ideals of the ePrivacy Directive and GDPR.

The research paper is published in the Computers in Human Behavior journal.

Privacy manipulation

When the researchers started the project in 2019, there was very little academic research about the impact of cookie banner design elements on acceptance rates. And few guides and rules were available beyond a case ruling about the use of pre-ticked boxes in cookie banners.

The empirical evidence supporting the study's conclusions was gathered through an experiment testing different banner designs on a public website. The researchers analysed how their manipulations affected 1493 user interactions with the cookie banner and the resulting privacy choice, i.e., whether to give or decline consent.

While several official guides on banner design have been published since the experiment was conducted, the researchers argue that website owners remain in a privileged position.

"If they would use their expertise and design skills to elicit their user's privacy preferences in a neutral way, we would potentially welcome this and not have a problem. Nudging users to make a privacy choice is potentially a good thing, manipulating them into providing consent is not and should be opposed," states Bauer.

Protecting user data

Initially, the researchers wanted to create awareness and action by policy makers and acknowledge that the problems of manipulative choice architecture in the digital space - also called dark patterns - remain important topics for debate. They introduce a conceptual distinction between choice-making architecture and choice outcome architecture that might help to have a more structured debate.

"We see this analysis of the choice-making architecture and a choice outcome architecture as a helpful deconstruction of this privacy decision when it comes to protecting user data," says Jan Michael Bauer.

The choice-making architecture captures all elements of the choice environment that might deter or encourage people from/to make a decision - e.g., the complexity of the choice or required effort. The researchers argue there are many cases in which it might be beneficial to nudge people to decide without affecting the outcome (e.g., organ donation and elections). Increasing choice-making is however not the same as nudging people towards one choice outcome.

"In some cases, we might be more confident that selecting one specific option is likely to make users better off and target the choice outcome itself (e.g., cigarettes unhealthy foods). However, interventions that favour a specific outcome is suspect to manipulation and warrants more scrutiny," says Bauer.

Learning about dark patterns

While regulators hopefully catch up with the digital world, the researchers conclude that it will be up to the consumer to detect, avoid and resist manipulative choice architecture.
"One way forward for users and consumers could be to learn about the broader issues surrounding dark patterns and the tricks used in websites and apps to hopefully become less responsive to these manipulations. Even though these manipulations are often subtle, they should be called out," adds Bauer.

"One helpful approach can be to treat aggressive prompts and design element that favour a specific choice outcome as a warning sign to pause and reflect: do I really want to share my data? An issue not limited to data privacy as many websites and online shops gear up with dark patterns in the fight for user attention and to increase sales," concludes Bauer.

Early-life inflammation, such as trauma and viral infections, strongly increases the risk of individual for depression in adulthood, however, the mechanisms are not clear yet.

A team led by Prof. ZHANG Zhi from Division of Life Sciences and Medicine of the University of Science and Technology of China (USTC) of Chinese Academy of Sciences (CAS), collaborating with Prof. XU Lin from CAS, revealed the mechanism by which early-life inflammation induces adolescent depression symptoms. This work has been published in Neuron on July 6th.

Clinically related studies have shown decreased anterior cingulate cortex (ACC) synaptic density and increased inflammation in the brain of depressed patients. Microglial cells are resident immune cells of the brain, and it transforms into reactive states in response to stress challenges. Under the pathological state, activated microglia are the commander of the inflammatory state of the brain tissue, which is closely related to the occurrence and development of depression.

In this work, researchers found that early-life inflammation would lead to the susceptibility of microglial in the ACC to random stress events during adolescent development, and microglia then overengulfed dendritic spines of neurons. This weakened the ability of ACC glutamatergic neuronal (ACCGlu) to fight stress, thus inducing adolescent depression.

To explore the responding and activating model of ACC microglia to stress during mouse development from childhood to adolescence (45 days after birth), researchers established inflammatory model by intraperitoneal administration of lipopolysaccharide (LPS) during the critical time window of mouse brain development (14 days after birth). 6 hours after LPS injection, multiple activation indexes of ACC microglia in mice significantly increased and recovered after 24 hours. Interestingly, during the later development, a series of unpredictable life stress events (such as weaning, caging, noise and fighting) could lead to the re-activation of ACC microglia in LPS mice, being more susceptible than normal mice.

Moreover, before stress, the sharply increase of ACCGlu activity helped mice resist the attack of stress and protect themselves. However, ACC microglia of mice with early-life inflammation were frequently activated by persistent stress in adolescence, and overengulfed the ACCGlu dendritic spines via CX3CR1 signals mediate, consequently reducing the activity of ACCGlu. As a result the body's ability to cope with stress was impaired, which promoted depression in adolescent mice.

If you're regularly out in the fresh air, you're doing something good for both your brain and your well-being. This is the conclusion reached by researchers at the Max Planck Institute for Human Development and the Medical Center Hamburg-Eppendorf (UKE). The longitudinal study recently appeared in The World Journal of Biological Psychiatry.

During the Corona pandemic, walks became a popular and regular pastime. A neuroscientific study suggests that this habit has a good effect not only on our general well-being but also on our brain structure. It shows that the human brain benefits from even short stays outdoors. Until now, it was assumed that environments affect us only over longer periods of time.

The researchers regularly examined six healthy, middle-aged city dwellers for six months. In total, more than 280 scans were taken of their brains using magnetic resonance imaging (MRI). The focus of the study was on self-reported behavior during the last 24 hours and in particular on the hours that participants spent outdoors prior to imaging. In addition, they were asked about their fluid intake, consumption of caffeinated beverages, the amount of time spent outside, and physical activity, in order to see if these factors altered the association between time spent outside and the brain. In order to be able to include seasonal differences, the duration of sunshine in the study period was also taken into account.

Brain scans show that the time spent outdoors by the participants was positively related to gray matter in the right dorsolateral-prefrontal cortex, which is the superior (dorsal) and lateral part of the frontal lobe in the cerebral cortex. This part of the cortex is involved in the planning and regulation of actions as well as what is referred to as cognitive control. In addition, many psychiatric disorders are known to be associated with a reduction in gray matter in the prefrontal area of the brain.

The results persisted even when the other factors that could also explain the relationship between time spent outdoors and brain structure were kept constant. The researchers performed statistical calculations in order to examine the influence of sunshine duration, number of hours of free time, physical activity, and fluid intake on the results. The calculations revealed that time spent outdoors had a positive effect on the brain regardless of the other influencing factors.

"Our results show that our brain structure and mood improve when we spend time outdoors. This most likely also affects concentration, working memory, and the psyche as a whole. We are investigating this in an ongoing study. The subjects are asked to also solve cognitively challenging tasks and wear numerous sensors that measure the amount of light they are exposed to during the day, among other environmental indicators," says Simone Kühn, head of the Lise Meitner Group for Environmental Neuroscience at the Max Planck Institute for Human Development and lead author of the study.

The results therefore, support the previously assumed positive effects of walking on health and extend them by the concrete positive effects on the brain. Because most psychiatric disorders are associated with deficits in the prefrontal cortex, this is of particular importance to the field of psychiatry.

"These findings provide neuroscientific support for the treatment of mental disorders. Doctors could prescribe a walk in the fresh air as part of the therapy - similar to what is customary for health cures," says Anna Mascherek, post-doctoral fellow in the Department of Psychiatry and Psychotherapy of the Medical Center Hamburg-Eppendorf (UKE) and co-author of the study.

In the ongoing studies, the researchers also want to directly compare the effects of green environments vs urban spaces on the brain. In order to understand where exactly the study participants spend their time outdoors, the researchers plan to use GPS (Global Positioning System) data and include other factors that may play a role such as traffic noise and air pollution.