Culture

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.

BOSTON - New research led by investigators at Massachusetts General Hospital (MGH) and Massachusetts Eye and Ear indicates that the blood pressure drug losartan may benefit patients with neurofibromatosis type 2 (NF2), a hereditary condition associated with vestibular schwannomas, or noncancerous tumors along the nerves in the brain that are involved with hearing and balance. The findings, which are published in Science Translational Medicine, are especially important because vestibular schwannomas are currently treated with surgery and radiation therapy (which carry risks of nerve damage), and no drug is approved by the U.S. Food and Drug Administration to treat these tumors or their associated hearing loss.

"Developing effective therapeutics to preserve hearing function in patients with NF2 is an urgent unmet medical need. The greatest barrier to managing NF2-related auditory impairment is our incomplete understanding of how schwannomas cause hearing loss," says co-senior author Lei Xu, MD, PhD, an investigator in the Steele Laboratories for Tumor Biology within the MGH Department of Radiation Oncology. A previous report showing that scarring, or fibrosis, exists in schwannomas and correlates with hearing loss prompted the team to test whether a drug that blocks fibrosis might be effective.

Losartan blocks a component of the renin-angiotensin system, which is involved not only in regulating blood pressure but also in stimulating fibrosis and inflammation. The entire class of angiotensin-targeting drugs, which includes losartan, has been shown to reduce collagen accumulation in cardiac and kidney fibrotic disease. Using a mouse model of NF2, Xu and her colleagues found that losartan treatment had several effects on vestibular schwannomas and the brain: It reduced inflammatory signaling and swelling and thus prevented hearing loss, and it increased oxygen delivery to enhance the effectiveness of radiation therapy (which may help lower the radiation dose needed to control tumor growth and limit radiation-associated toxicities).

In preparation to translate these findings into the clinic, co-senior author Konstantina Stankovic, MD, PhD, former chief of the Division of Otology and Neurotology at Massachusetts Eye and Ear, now Bertarelli Professor and Chair of the Department of Otolaryngology - Head and Neck Surgery at Stanford University School of Medicine, examined patient samples and data. Her team found that vestibular schwannomas associated with poor hearing had more pronounced inflammatory signaling than tumors associated with good hearing. This inflammatory signaling in tumors was capable of directly damaging cochlear cells that are essential for hearing. Also, patients with vestibular schwannoma who took losartan or other drugs in its class experienced no progression in hearing loss, unlike patients on other or no antihypertensive drugs. This study illustrates the advantages offered by an integrated approach and teamwork that spans basic research, translational investigation and clinical care.

The findings support the need for a prospective clinical trial of losartan in patients with NF2 and vestibular schwannomas. "As one of the most commonly prescribed drugs for hypertension, the safety and low cost of losartan warrants rapid translation of our research to patients with vestibular schwannomas to try to prevent tumor-induced sensorineural hearing loss," Stankovic says.

We sleep on average one third of our time. But what does the brain do during these long hours? Using an artificial intelligence approach capable of decoding brain activity during sleep, scientists at the University of Geneva (UNIGE), Switzerland, were able to glimpse what we think about when we are asleep. By combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), the Geneva team provides unprecedented evidence that the work of sorting out the thousands of pieces of information processed during the day takes place during deep sleep. Indeed, at this time, the brain, which no longer receives external stimuli, can evaluate all of these memories in order to retain only the most useful ones. To do so, it establishes an internal dialogue between its different regions. Moreover, associating a reward with a specific information encourages the brain to memorise it in the long term. These results, to be discovered in the journal Nature Communications, open for the first time a window on the human mind in sleep.

In the absence of tools capable of translating brain activity, the content of our sleeping thoughts remains inaccessible. We however do know that sleep plays a major role in memory consolidation and emotional management: when we sleep, our brain reactivates the memory trace built during the day and helps us to regulate our emotions. "To find out which brain regions are activated during sleep, and to decipher how these regions allow us to consolidate our memory, we developed a decoder capable of deciphering the activity of the brain in deep sleep and what it corresponds to", explains Virginie Sterpenich, a researcher in the laboratory of Professor Sophie Schwartz in the Department of Basic Neurosciences at UNIGE Faculty of Medicine, and the principal investigator of this study. "In particular, we wanted to see to what extent positive emotions play a role in this process."

During deep sleep, the hippocampus - a structure of the temporal lobe which stores temporary traces of recent events - sends back to the cerebral cortex the information it has stored during the day. A dialogue is established which allows the consolidation of memory by replaying the events of the day and therefore reinforce the link between neurons.

Combining MRI, electroencephalography and artificial intelligence

To conduct their experiment, the scientists placed volunteers in an MRI in the early evening and had them play two video games - a face-recognition game similar to 'Guess Who?' and a 3D maze from which the exit must be found. These games were chosen because they activate very different brain regions and are therefore easier to distinguish in the MRI images. In addition, the games were rigged without the volunteers' knowledge so that only one of the two games could be won (half of the volunteers won one and the other half won the second), so that the brain would associate the game won with a positive emotion.

The volunteers then slept in the MRI for one or two hours - the length of a sleep cycle - and their brain activity was recorded again. "We combined EEG, which measures sleep states, and functional MRI, which takes a picture of brain activity every two seconds, and then used a 'neuronal decoder' to determine whether the brain activity observed during the play period reappeared spontaneously during sleep", Sophie Schwartz explains.

Even when asleep, the brain likes rewards

By comparing MRI scans of the waking and sleeping phases, the scientists observed that during deep sleep, the brain activation patterns were very similar to those recorded during the gaming phase. "And, very clearly, the brain relived the game won and not the game lost by reactivating the regions used during wakefulness. As soon as you go to sleep, the brain activity changes. Gradually, our volunteers started to 'think' about both games again, and then almost exclusively about the game they won when they went into deep sleep", says Virginie Sterpenich.

Two days later, the volunteers performed a memory test: recognising all the faces in the game, on the one hand, and finding the starting point of the maze, on the other. Here again, more the brain regions related to the game were activated during sleep, better were the memory performances. Thus, memory associated to reward is higher when it is spontaneously reactivated during sleep. With this work, the Geneva team opens a new perspective in the study of the sleeping brain and the incredible work it does every night.

The COVID-19 pandemic halted the in-person wintertime survey of wolves and moose on the island for the first time in 63 years. Consequently, there are no estimates of wolf or moose abundance for 2021, and the next estimates are scheduled in February 2022. But though the Isle Royale Winter Study didn't happen quite as planned, researchers were still able to visit the remote national park in the spring.

Now, fieldwork has resumed and Michigan Technological University researchers have already uncovered new information about these two iconic wildlife populations. In particular, wolves produced at least two litters of pups, and moose appear poised for decline.

In the Isle Royale Winter Study, Michigan Tech researchers share other significant developments about curating the world's largest moose bone collection, advances in understanding of wolf foraging behavior and the nutritional health of the moose population.

Key points:

The Isle Royale wolf population is likely growing. "We recovered footage of a group of four wolf pups taken in January 2021 by remote cameras at the east end of Isle Royale," said Sarah Hoy, research assistant professor in Michigan Tech's College of Forest Resources and Environmental Science (CFRES). "Additionally, observations of tracks and scats left by wolf pups last fall at two different locations suggest that there were probably two different litters of pups living at the east end of the island in September 2020."

Wolves are specialized foragers. "Wolf foraging behavior seems driven by minimizing the risks associated with killing large prey, like moose, even when the differences in vulnerability among individual moose might seem relatively subtle compared to when predators are choosing between different prey species," Hoy said.

Nutritional stress stacks the deck against moose, which holds significant implications for how moose will handle a warming climate. "We found that the nutritional health of moose was importantly influenced by how hot it is during the summer, and also by how deep the snow is in winter," Hoy said. "Moose tended to be more nutritionally stressed during winters with deep snow, which may be because deeper snow makes it more difficult for moose to move around and find food."

The moose population is likely declining. "Moose really struggled to find enough food this past winter," Hoy said. "Because there have been such large numbers of moose on the island over the last five years and moose ate branches faster than the trees can recover and replace them, the amount of food available to moose during winter has been getting progressively worse each year since 2017.

Winter ticks are worse than usual this year, as evidenced by moose with very little fur left in spring -- having scratched or bitten off almost all of their winter coats in an effort to rid themselves of the blood-sucking parasites. This is significant because blood loss to ticks can exacerbate the detrimental effects of food shortage. Despite the mild winter, depleted food supplies and ticks made life harder for the island's moose this year.

GAINESVILLE, Fla. --- Two fossil teeth from a distant relative of North American gophers have scientists rethinking how some mammals reached the Caribbean Islands.

The teeth, excavated in northwest Puerto Rico, belong to a previously unknown rodent genus and species, now named Caribeomys merzeraudi. About the size of a mouse, C. merzeraudi is the Caribbean's smallest known rodent and one of the region's oldest, dating back about 29 million years.

It also represents the first discovery of a Caribbean rodent from a North American lineage, a finding that complicates an idea that has persisted since Darwin - that land-dwelling mammals colonized the islands from South America. The presence of C. merzeraudi in Puerto Rico suggests a second possibility: Some species may have rafted from North America.

The tiny rodent joins two other types of animals, an extinct rhinoceros-like species and bizarre, venomous shrews known as Solenodons, as the only known examples of Caribbean land-dwelling mammals with North American roots.

"This discovery demonstrates that overwater dispersal from North America was also a potential pathway to the Caribbean," said study co-author Jorge Velez-Juarbe, associate curator of mammalogy at the Natural History Museum of Los Angeles County. "This challenges what we thought we knew about the origins of Antillean terrestrial mammals."

While Caribbean ecotourism brochures generally don't feature splashy images of rats, the islands were once home to a rich representation of rodents, including spiny rats, chinchillas, rice rats and hutias - all descendants of South and Central American forebears.

Fossil and molecular evidence suggest these rodents arrived in the islands in multiple waves over time, though how they got there - whether by scurrying over an ancient land bridge, island-hopping or rafting - has been hotly contested. The paucity of fossils from the early years of the Caribbean Islands further obscures the picture of the region's past biodiversity.

Caribeomys merzeraudi's teeth were so unusual that researchers initially struggled to discern what kind of animal they had come from, said study co-author Lazaro Vinola Lopez, a doctoral student in vertebrate paleontology at the Florida Museum of Natural History.

"We didn't know what it was for several months," he said. "We wondered whether this could be some other rodent from the Caribbean or even some kind of strange fish. It was so puzzling because they're not similar to anything else we had found in that region."

The team eventually pinpointed several tooth characteristics that are hallmarks of rodents known as geomorphs, a group that includes kangaroo rats, pocket mice and gophers. Caribeomys merzeraudi is the first geomorph found outside North America.

An exceptionally thick layer of tooth enamel, among other features, sets C. merzeraudi apart from its relatives and could indicate these rodents belonged to a distinct West Indian branch that evolved in isolation over several million years, Vinola Lopez said.

Scientists found the teeth while screen-washing sediment collected from a river outcrop in San Sebastian, a site that has yielded fossil sharks and rays, fish, turtles, a gharial, sea cows and the oldest known frog in the Caribbean, a coqui. In 2019, the team excavated fossil evidence of two large chinchillas, which likely grew up to 30 pounds. These South American rodents once shared Puerto Rico with the humble C. merzeraudi, which weighed less than a quarter pound.

Today, hutias, bats and Solenodons are the "last survivors of what was once a much more diverse group of Caribbean mammals" that included sloths and primates, Velez-Juarbe said.

Discovering C. merzeraudi opens up the tantalizing possibility that Caribbean mammals with North American origins may not be as exceptional as previously thought, Vinola Lopez said. But there's only one way to find out: "Go back to the locality and see what else we can find."

New Rochelle, NY, July 14, 2021-Firsthand reports from nurses in correctional facilities detail the challenges they faced during the COVID-19 pandemic. These firsthand accounts are reported in a special issue on correctional nursing in the Journal of Correctional Health Care. Click here (https://www.liebertpub.com/toc/jchc/27/2) to read the issue now.

Karen Monsen, PhD, RN, School of Nursing, University of Minnesota, and colleagues present the Omaha System COVID-19 Response Guidelines, which provide evidence-based pandemic response interventions used in correctional nursing. The guidelines are illustrated with examples from correctional nursing practice.

Also in this special issue is an article titled "Leadership in Correctional Nursing: The First Step" by Jennifer Clifton, DNP, College of Nursing, University of Utah. "The first step in developing leadership skills requires introspection and contemplation," she says. She guides nurses through the development of a Personal Professional Philosophy Statement, which should have two components: one's core beliefs and values; and the values of the profession.

Brenda Baker, PhD, RNC, presents "Mothering and Incarceration: A Conceptual Model Supporting Maternal Identity." The model "focuses on four areas of influence for women who experience incarceration: the community before incarceration, individual characteristics, carceral experience, and the post release community for reentry and reunification of the family," states Dr. Baker. "The most significant implication of the conceptual model is ending the intergenerational influences of incarceration on children."

"Correctional nurses, once considered invisible to the public and to other professionals because they serve patients who reside behind bars, are understanding more about their own practice," says Deborah Shelton, PhD, RN, Guest Editor of the special issue. "Correctional nurses are participating in larger numbers on boards and in professional activities to form consensus about the future of nursing. They are claiming their place as leaders."

Indiana Jones hates snakes. And he's certainly not alone. The fear of snakes is so common it even has its own name: ophidiophobia.

Kibret Mequanint doesn't particularly like the slithery reptiles either (he actually hates them too) but the Western University bioengineer and his international collaborators have found a novel use for snake venom: a body tissue 'super glue' that can stop life-threatening bleeding in seconds.

Over the past 20 years, Mequanint has developed a number of biomaterials-based medical devices and therapeutic technologies - some of which are either licensed to medical companies or are in the advanced stage of preclinical testing.

His latest collaborative research discovery is based on a blood clotting enzyme called reptilase or batroxobin found in the venom of lancehead snakes (Bothrops atrox), which are amongst the most poisonous snakes in South America.

Taking advantage of this clotting property, Mequanint and the international research team designed a body tissue adhesive that incorporates the special enzyme into a modified gelatin that can be packaged into a small tube for easy, and potentially life-saving, application.

"During trauma, injury and emergency bleeding, this 'super glue' can be applied by simply squeezing the tube and shining a visible light, such as a laser pointer, over it for few seconds. Even a smartphone flashlight will do the job," said Mequanint, a Western engineering professor.

Compared to clinical fibrin glue, considered the industry gold standard for clinical and field surgeons, the new tissue sealant has 10 times the adhesive strength to resist detachment or washout due to bleeding. The blood clotting time is also much shorter, cutting it in half from 90 seconds for fibrin glue to 45 seconds for the new snake venom 'super glue.'

This new biotechnology translates to less blood loss and more life-saving. The super-sealant was tested in models for deep skin cuts, ruptured aortae, and severely injured livers - all considered as major bleeding situations.

"We envision that this tissue 'super glue' will be used in saving lives on the battlefield, or other accidental traumas like car crashes," said Mequanint. "The applicator easily fits in first aid kits too."

In addition, the new snake venom 'super glue' can be used for suture-free, surgical wound closures.

Snake extract-laden hemostatic bioadhesive gel cross-linked by visible light was published today in the journal Science Advances. For the discovery, Mequanint collaborated with bioengineers, scientists and medical practitioners at the University of Manitoba and Army Medical University in Chongqing, China.

"The next phase of study which is underway is to translate the tissue 'super glue' discovery to the clinic," said Mequanint.

Penn State College of Engineering researchers set out to develop technology capable of localizing and imaging blood clots in deep veins. Turns out their work may not only identify blood clots, but it may also be able to treat them.

The team, led by Scott Medina, assistant professor of biomedical engineering, published its results in Advance Healthcare Materials.

"Deep vein thrombosis is the formation of blood clots in deep veins, typically in a person's legs," said Medina. "It's a life-threatening blood clotting condition that, if left unaddressed, can cause deadly pulmonary embolisms -- when the clot travels to the lungs and blocks an artery. To manage DVT, and prevent these life-threating complications, it's critical to be able to rapidly detect, monitor and treat it."

The challenge, according to Medina, is that current diagnostic imaging methods lack the resolution required to precisely pinpoint potential breeding grounds for clots and monitor the clots in real time. DVT can sometimes present as swelling and aching in a person's leg, which can then be examined via ultrasound.

"Ultrasound isn't great for diagnosing DVT," Medina said. "It can tell you that a region of fluid flow may look odd, which might be related to a clot -- but maybe not. You follow up with blood tests to look for specific factors, and, together, you might be able to diagnose a clot."

Once a clot is diagnosed, a clinician may order either pharmaceuticals to help break it apart or a procedure that involves snaking a probe to the clot to grab it and physically remove it from the body. The pharmaceuticals may not be enough to break the clot apart, though, or they could trigger bleeding issues elsewhere in the body, while the procedure option is invasive and carries risks, including potential infection.

To better identify the location, composition and size of clots, which informs how to treat them, Medina and his team used a particle approach they developed in 2017. Called nanopeptisomes (NPeps), the particles comprise a shell around a droplet of fluorine-based oil similar to liquid Teflon. The surface of the shell holds a molecule that finds and binds a protein on the surface of activated platelets, a key cellular component of clots.

"The particles bind to the surface of the clots, we apply the ultrasound, and the droplet turns to gas and forms a bubble under the shell," said Medina. "It gives an excellent contrast for imaging. The bubbles appear exactly where the clots are forming."

But, Medina said, a mystery unfolded as they tested their technique. To analyze how to diagnose and treat clots, the researchers first induce clots in bovine veins by injecting an enzyme that triggers clot formation.

"The enzyme induces clot formation generally 100% of the time -- but when we applied the particles, we only saw clot formation about 30% of the time," Medina said. "We had to wonder: were the particles not only binding to the clots, but somehow breaking them down?"

The team tested its hypothesis, but the researchers would lose the bubble signal after 15 minutes of ultrasound every time.

"We think that once our particles start to decorate the clot, they saturate the surface and inhibit the mechanisms of further clot growth," said Medina. "And under the ultrasound, the particles are disrupting the clot or inhibiting its mechanism to persist. While we don't understand the underlying mechanism yet, it's clear that these particles can image and help treat clots in real time."

The researchers plan to continue investigating how the particles are disrupting the clots, as well as develop more control over how the particles behave.