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Kyoto, Japan -- A staple in every science classroom is the periodic table of elements, and for many it is their first introduction to the vast mysteries of the natural world.

Now physicists from Kyoto University have unveiled a new table that provides a different perspective on the building blocks of the universe. While the traditional table is based on the behavior of electrons in an atom, this new table is based on the protons in the nucleus.

"The periodic table of the elements is one of the most significant achievements in science, and in its familiar form it is based on the shell structure of electron orbitals in atoms," explains Yoshiteru Maeno, one of the co-developers of the new table.

"But atoms are comprised of two types of charged particles that designate each element: electrons orbiting the core and protons in the core itself."

The team's new 'Nucletouch' table -- also available as a 3D model -- was announced recently in the journal Foundations of Chemistry.

Over 150 years have passed since Dmitri Mendeleev discovered the periodic law that lead him to propose the classic periodic table. He even had the foresight to add space for elements that were still unknown in his time.

"Fundamentally, it comes down to the electrons in each atom. Atoms are considered to be stable when electrons completely fill their 'shell' of orbits around the nucleus," continues Maeno.

"So-called 'noble gases', inert elements such as helium, neon, and argon, rarely react with other elements. Their most stable electron numbers are 2, 10, 18, 36, and so on."

Maeno decribes these as atomic 'magic numbers', and importantly the same principle can also be applied to protons. Imagining that protons in a nucleus exist in 'orbits' may seem like a stretch, but the discovery of the concept was awarded the 1963 Nobel prize in physics.

Protons have different stable magic numbers: 2, 8, 20, 28, and so on. Among these are familiar elements such at helium, oxygen, and calcium. The Nucletouch table places these 'magic nuclei' at its center, providing a new perspective on the elements.

"Similar to electrons, when nuclear orbits are filled with protons, they form stable nuclei, analogous to the noble-gas elements," says collaborator Kouichi Hagino.

"In our nuclear periodic table, we also see that nuclei tend to be spherically-shaped near the magic numbers, but deformed as you move away from them."

The team made the table to highlight alternative ways to illustrate the laws of nature, and hopes that enthusiasts and academics alike will find something to enjoy and learn from this fresh new look at an old friend.

A re-analysis of dinosaur skulls from northern Alaska suggests they belong to a genus that lived over a broad latitudinal range extending into the Arctic.

The plant-eating, broad-beaked dinosaurs that lived in northern Alaska some 69 million years ago belong to the genus Edmontosaurus, and not to the genus recently proposed by scientists in 2015. The finding suggests this group of dinosaurs existed over a broad latitudinal range, extending from northern Colorado all the way up into the Arctic.

The research was conducted as part of a Perot Museum of Nature and Science's project, joined by Hokkaido University and Okayama University, and published in the journal PLOS ONE.

The Liscomb Bonebed quarry in northern Alaska is rich in dinosaur fossils belonging to the family Hadrosauridae. Biological classifications, or taxonomy, of the hadrosaurid dinosaur found there has puzzled scientists since the 1980s. Scientific consensus eventually classified them as the genus Edmontosaurus, until a group of scientists proposed that the Alaskan hadrosaurids represent a unique genus and species, and named Ugrunaaluk in 2015. However, other scientists questioned the validity of the taxon.

The incompleteness and the immaturity of the Alaskan hadrosaurine fossils make their classification difficult. To overcome this problem, Ryuji Takasaki, former Ph.D. student at Hokkaido University, and his colleagues in Japan and the US specifically examined skull bones. This minimized danger of mixing bones of the two hadrosaurid clades known from the same site: Hadrosaurinae and Lambeosaurinae. Bones from body parts of immature hadrosaurine and lambeosaurine dinosaurs cannot be readily distinguished from each other.

The team compared the skull bones of Hadrosaurinae with those of other hadrosaurines, especially with known Edmontosaurus from lower latitude North America. They found enough evidence to suggest that the Liscomb Bonebed hadrosaurine bones previously named Ugrunaaluk are likely to represent an immature form of the genus Edmontosaurus.

"We recommend the conservative approach of referring them to Edmontosaurus until further discoveries of more mature individuals from the area can resolve the issue," says Takasaki.

Clarifying the taxonomy of the Liscomb Bonebed hadrosaurines can help scientists understand how they lived and evolved. "Re-attribution of the Alaskan hadrosaurines to Edmontosaurus suggests they lived over a broad range of latitudes extending from northern Colorado to northernmost Alaska," says Takasaki. The few anatomical differences among Edmontosaurus, despite of their broad range, suggest they did not evolve much in order to adapt. A small temperature gradient over that area at that time could be one reason to establish the small differences, according to the researchers.

Moreover, Yoshitusugu Kobayashi at Hokkaido University Museum, a co-author of this paper, recently named a new genus species Kamuysaurus japonicus in Hokkaido, Japan, which belongs to Edmontosaurini as Edmontosaurus does. "Taken these studies together, this group of hadrosaurs, the Edmontosaurini, were widely distributed in the northern circum-Pacific region, meaning that they were incredibly successful dinosaurs," Kobayashi commented. "It's fascinating to think they likely used the ancestral Bering Land Bridge between Asia and North America for migration in a manner similar to mammoths, woolly rhinoceroses, and early humans."

POSTECH Professor Seung-Ki Min’s joint research team identifies the mechanism behind the reduction in precipitation after volcanic eruptions

Volcano-induced El Niño amplifies the reduction in precipitation. Safety of geoengineering that mimic volcanoes is not guaranteed.

Climate change is occurring all over the globe as 1°C increase in Earth’s surface temperature has led to the sea level rise, abrupt melting of the Arctic sea ice, and the increase in extreme weather events such as heat waves, droughts, and floods. To accurately predict the anthropogenic climate changes under the increase in greenhouse gases, it is important to understand the effects of natural factors such as solar and volcanic activities. A recent study has shown how global precipitation decreases when volcanoes erupt in the tropics.

Professor Seung-Ki Min and Dr. Seungmok Paik of Division of Environmental Science and Engineering at POSTECH and researchers from the French National Centre for Scientific Research, Swiss Federal Institute of Technology in Zurich, and University of Edinburgh have released new findings that the El Niño induced by volcanic eruptions plays a key role in the decrease in global precipitation. So far, studies have shown that volcanic activity reduces precipitation across the globe, but its specific mechanism had been unclear. These research results were recently published in Science Advances, a sister journal of Science.

During the two to three years following Mount Pinatubo’s eruption in 1991, the average global temperature fell by about 0.2 degrees. This is because the massive dust including sulfur dioxide emitted by the eruption reflected the light from the sun and blocked its heat from reaching the Earth’s surface. Volcanic activities, along with this cooling effect, reduce the global terrestrial precipitation but its amplitude greatly varies depending on climate model simulations. For the first time, the joint research team confirmed that the main factor for the drop in precipitation after volcanic eruptions is the difference in El Niño’s response.

El Niño is a natural climate variability that occurs every three to eight years, with weakened trade winds in the equatorial Pacific Ocean and warmer sea surface temperatures in the equatorial eastern Pacific, causing extreme weather conditions across the globe including drought and heavy rains. Under El Niño’s influence, precipitation reduction occurs especially in the global monsoon regions, including Southeast Asia, India, South Africa, Australia and northern South America.

The team compared several climate model simulations and found that El Niño appeared in the year following a volcanic eruption in most models, with a significant drop in precipitation around the global monsoon region. In particular, the strength of El Niño was different for each simulation, and the stronger the El Niño, the more pronounced the reduction in precipitation occurred. The research team also found that the stronger the volcanic forcing and the greater the warm water volume in the western Pacific Ocean, a stronger El Niño developed, which in turn intensified the reduction in precipitation.

Public parks are many things to many people: a space devoid of domestic chores and patriarchal expectations, a spot to cultivate friendship or love, a place where you can experience a feeling of freedom that is absent elsewhere, an opportunity to &laquovisit» trees from a country you have not seen in a long time, a way of being part of a group while sitting alone on your bench - or even the perfect setting for running a small business to help you get by. Public parks are all this and much more if we're to believe the inhabitants of four Asian mega-cities - Chennai, Singapore, Manila and Shanghai - who were interviewed as part of a recently-published study. Green spaces, we learn, do much more than simply benefit biodiversity and health: they also meet numerous other essential human needs that open the door to sustainable well-being, a concept based on a combination of personal well-being and the necessities of sustainable development.

"There are many theories that try to define human well-being,» begins Marlyne Sahakian, a professor in the Department of Sociology in UNIGE's Faculty of Social Sciences and the study's first author. &laquoInstead of using subjective notions such as happiness, we used a list of nine 'protected needs' that has recently been developed by colleagues from the University of Basel. These needs correspond to what society can offer the population through the public sector. This list of protected needs is the result of an analysis of the scientific literature and was validated among the Swiss population and by panels of experts."

The nine capital needs

In concrete terms, the list is made up of the following nine items: (1) the availability of goods that satisfy vital needs; (2) turning your own idea of everyday life into reality; (3) living in a pleasant environment; (4) growing as a person; (5) self-determination; (6) doing activities that you value; (7) being part of a community; (8) taking part in decisions about the future of society; and (9) being protected by society.

Armed with this list, researchers from the four Asian cities, co-signatories of the study, asked residents about their use of public parks and the benefits they derived from them. An analysis of their responses first showed that ordinary people can assess their well-being using these protected needs, making the distinction between what they need and what they want. "This suggests that meeting human needs is a societal goal that can be discussed by diverse groups of people around the world," says Professor Sahakian before adding: "This has implications for city planning measures designed to ensure everyone's sustainable well-being for today and tomorrow. In the cities of South Asia in particular, parks - which offer a naturally cool, shaded microclimate - are a precious alternative to other leisure spaces, such as air-conditioned shopping centres."

Inclusion rather than exclusion

The research, which was supported by the Swiss Network for International Studies, also found that the use of green spaces fulfils all the protected needs to a certain degree. Three of these needs (3, 4 and 7) however, have a score that is significantly higher than the others.

"Going to the park is a social activity that requires more than just a green space, argues Professor Sahakian. People do different kinds of things in parks to meet the same need, such as exercising, chatting with other people, reading a book, meeting a group or learning about biodiversity. These are very inclusive spaces, where there is ready access for everyone, unlike what happens in shopping centres, which can operate quite a strong form of social segregation. In the immediate context of a post-COVID-19 environment, where public spending will probably be more limited than before, it is all the more important to maintain the infrastructure of the parks (water access points, toilets, trails, etc.) and to ensure access so that they can continue to meet everyone's needs."

When people are highly confident in a decision, they take in information that confirms their decision, but fail to process information which contradicts it, finds a UCL brain imaging study.

The study, published in Nature Communications, helps to explain the neural processes that contribute to the confirmation bias entrenched in most people's thought processes.

Lead author, PhD candidate Max Rollwage (Wellcome Centre for Human Neuroimaging at UCL and Max Planck UCL Centre for Computational Psychiatry & Ageing Research) said: "We were interested in the cognitive and neural mechanisms causing people to ignore information that contradicts their beliefs, a phenomenon known as confirmation bias. For example, climate change sceptics might ignore scientific evidence that indicates the existence of global warming.

"While psychologists have long known about this bias, the underlying mechanisms were not yet understood.

"Our study found that our brains become blind to contrary evidence when we are highly confident, which might explain why we don't change our minds in light of new information."

For the study, 75 participants conducted a simple task: they had to judge whether a cloud of dots was moving to the left or right side of a computer screen. They then had to give a confidence rating (how certain they were in their response), on a sliding scale from 50% sure to 100% certain.

After this initial decision, they were shown the moving dots again and asked to make a final decision. The information was made even clearer the second time and could help participants to change their mind if they had initially made a mistake. However, when people were confident in their initial decision, they rarely used this new information to correct their errors.

25 of the participants were also asked to complete the experiment in a magnetoencephalography (MEG) brain scanner. The researchers monitored their brain activity as they processed the motion of the dots.

Based on this brain activity, the researchers evaluated the degree to which participants processed the newly presented information. When people were not very confident in their initial choice, they integrated the new evidence accurately. However, when participants were highly confident in their initial choice, their brains were practically blind to information that contradicted their decision but remained sensitive to information that confirmed their choice.

The researchers say that in real-world scenarios where people are more motivated to stand by their beliefs, the effect may be even stronger.

Senior author Dr Steve Fleming (Wellcome Centre for Human Neuroimaging at UCL, Max Planck UCL Centre for Computational Psychiatry & Ageing Research and UCL Experimental Psychology) said: "Confirmation bias is often investigated in scenarios that involve complex decisions about issues such as politics. However, the complexity of such opinions makes it difficult to disentangle the various contributing factors to the bias, such as wanting to maintain self-consistency with our friends or social group.

"By using simple perceptual tasks, we were able to minimise such motivational or social influences and pin down drivers of altered evidence processing that contribute to confirmation bias."

In a previous, related study, the research team had found that people who hold radical political views - at either end of the political spectrum - aren't as good as moderates at knowing when they're wrong, even about something unrelated to politics.

Because the neural pathways involved in making a perceptual decision are well understood in such simple tasks, this makes it possible for researchers to monitor the relevant brain processes involved. The researchers highlight that an understanding of the mechanism that causes confirmation bias may help in developing interventions that could reduce people's blindness to contradictory information.

Max Rollwage added: "These results are especially exciting to me, as a detailed understanding of the neural mechanisms behind confirmation bias opens up opportunities for developing evidence-based interventions. For instance, the role of inaccurate confidence in promoting confirmation bias indicates that training people to boost their self-awareness may help them to make better decisions."

A recent study among 3- to 7-year-old children showed that children's motor skills benefitted if a child was older and participated in organised sports. Additionally, the study provided information about the importance of temperament traits for motor skills. More specifically, traits such as activity and attention span persistence were found to be positively associated with motor skills. This was a rather novel result, as the association between motor skills and temperament during early childhood is not yet widely understood.

In essence, motor skills comprise locomotor, ball and balance skills, all of which are present in everyday life tasks like running, climbing, throwing and drawing. Adequate motor skills enable participation in typical games and types of playing for different ages and developmental phases, for example, in tag, running and ball games.

"Even though motor skills develop as a function of age, skill development still needs to be stimulated consciously," says Donna Niemistö, a PhD student from the Faculty of Sport and Health Sciences, University of Jyväskylä. "Motor skills do not develop without practising, thus skills need reinforcement through repetition of the skills. Motor skill development is greatly supported when the child is moving in multiple ways. In a current study we found more evidence that participation in organised sports can be useful to gain more opportunities to practise and repeat essential movements."

Temperament and its traits refer to a child's biological and individual characteristics, such as the biological way of reacting to one's surroundings. Temperament is rather stable over time. To date, there have been only a handful of studies concerning young children's motor skills and temperament traits, even though in older age groups, more research is already available.

"Children who tend to have an active type of temperament, as well as children who show persistency when faced with challenges can be motivated and persistent in learning and rehearsing motor tasks. Therefore, these findings were expected and logical. A child with an active temperament can react more rapidly. Consequently, the child will get more opportunities to move along with increased repetitions. Without noticing, the child will also gain more opportunities to perform motor tasks."

Additionally, the capacity to maintain attention is equally important for skill acquisition.

"To learn new skills, one must be able to concentrate and maintain focus even though the skill may, at first, feel challenging or even difficult," continues Niemistö.

Both temperament traits can influence the development of motor skills. Therefore, it is important that parents as well as early educators and teachers are aware of these individual factors in case they want to encourage and support their children's motor skill development.

"For example, there is no need to emphasize for an active child to be more active," Niemistö explains. "However, with an active child, a parent could guide the child to maintain focus and attention, despite possible distractions in the surroundings."

Motor skills were assessed with two internationally well-known measurements. The first assessment tool measured the locomotor and ball skills and the second one the balance and coordination skills of the child. As the chosen assessment tools measured divergent aspects of motor development, differences between associated factors related to motor skills were also found.

"The development of balance and coordination skills was better in those children who were described as more emotionally regulated," says Niemistö. "On the other hand, locomotor skills were better in children whose parents had higher educational level and the development of ball skills benefitted if children had free access to sport facilities in nearby surroundings."

The Skilled Kids study, conducted at the University of Jyväskylä from 2015 to 2017, had a geographically representative study sample of 945 children and their families from 37 different childcare centres in Finland. Children's temperament traits and participation in organized sports were assessed using a parental questionnaire.

What is the origin of the asteroids Bennu and Ryugu, and of their spinning-top shape? An international research team led by Patrick Michel, a CNRS researcher at the Laboratoire Lagrange (CNRS/Observatoire de la Côte d'Azur/Université Côte d'Azur) and Ronald-Louis Ballouz from the University of Arizona, proposes an answer to this question in an article published in Nature Communications on May 27, 2020. Numerical simulations of large asteroid disruptions, such as those that take place in the asteroid belt between Mars and Jupiter, show that during such events, fragments are ejected and then reaccumulate forming aggregates, some of which have a spinning-top shape. The simulations also show that Bennu and Ryugu may have formed from the disruption of the same parent asteroid even though their levels of hydration are different. The scientists conclude that the overall properties of these asteroids could directly result from the disruption of their parent body. The analysis of return samples from Ryugu and Bennu by the Hayabusa2 (JAXA) and OSIRIS-REx (NASA) spacecraft will allow us to verify this by measuring precisely their composition and by determining their formation age.

University of Vaasa (Finland) researchers propose a model that is capable of explaining 87 percent of cryptocurrency bankruptcies after only one month of trading. It could potentially serve as a screening tool for investors keen to boost overall performance of cryptocurrency investment portfolios by avoiding investing in unreliable cryptocurrencies.

Nowadays there are thousands of cryptocurrencies available. Interestingly, only a small percentage are actively traded, whereas the vast majority appears to be either inactive or have already failed. Default risk is one of the risks associated with investing in digital assets like cryptocurrencies. The question arises which factors help to predict whether a cryptocurrency will eventually go bust.

A recently published research article from Klaus Grobys and Niranjan Sapkota from the University of Vaasa in the well-known journal Applied Economics addresses this question.

In their study, the researchers examined all available 146 Proof-of-Work-based cryptocurrencies that started trading prior to the end of 2014 and tracked their performance until December 2018. They found that about 60 percent of those cryptocurrencies were eventually in default. The model of their study reveals four interesting factors that could be precursors to whether or not a coin will succeed.

The first factor is a coin's first-day performance. Specifically, how an Initial Coin Offering (ICO) performs on the first day coins are made public appears to be an indicator of long-term success. The study finds some evidence that those coins achieving the most long-term success also had the best first-day performances.

The second factor is a coin's pre-mining activity which takes place prior to the ICO launch. The study's findings indicate that a high level of activity raises a red flag. Even if excessive pre-mining doesn't necessarily guarantee failure, it raises suspicions of a potential bait-and-switch - often referred to as 'pump and dump'.

The third factor that might play an important role is developer anonymity. The study provides evidence for that 79 percent of all defaulted cryptocurrencies are developed by anonymous developers. Interestingly, a correlating statistic indicates that 58 percent of new coin developers choose to remain anonymous.

Finally, the study also shows that rewards and supply matter as there appears to be a correlation between longevity and two other factors: lower minimum rewards and coin supply. This result is rather puzzling when considering how critical coin mining is to the sustainability of any cryptocurrency. Specifically, without mining, a cryptocurrency network could not be maintained.

"Our study is a first attempt to reveal potential links between factors that could relate to coin success or failure. The links that we established in our study are not necessarily causal and much more research needs to be done on this issue," says Dr. Klaus Grobys from the University of Vaasa.

The drug nimodipine could prevent nerve cells from dying after brain surgery. Pharmacists at Martin Luther University Halle-Wittenberg (MLU), in cooperation with neurosurgeons at University Hospital Halle (Saale) (UKH), have developed a new method that enables the drug to be administered directly in the brain with fewer side effects. Their findings were published in the “European Journal of Pharmaceutics and Biopharmaceutics”.

Brain surgery poses a major threat to nerve cells. Even slight injuries can kill the sensitive cells. The drug nimodipine could help prevent this. It is currently being used to treat cerebral haemorrhages. The drug relaxes blood vessels which can prevent cramping. It also appears to stop nerve cells from dying. The research group led by Professor Karsten Mäder from the Institute of Pharmacy at MLU has now developed a system that enables the drug to be administered directly in the brain. “The neurosurgeons wanted the drug to be applied locally in order to reduce potential side effects,” explains Mäder.

His research group has integrated nimodipine into biodegradable polymer fibres. The fibres are only one to two micrometres thick. They can degrade in the body and the material which they are made of is already widely used in medicine. “If you want to apply something directly to the nerves, it must be well tolerated,” says Mäder. This is because nerve cells are particularly sensitive. So far, the nimodipine-polymer fibres have been tested in the laboratory for stability and their effect on different cell cultures. Mäder’s team of researchers has been able to show that they release the active ingredient at a very constant rate. This is important as it prevents side effects in the case of an overdose.

Professor Christian Scheller’s research group in the Department of Neurosurgery at UKH then tested how they affected various brain cells. The fibres exhibited no toxic effects. Under various stress conditions, such as heat or high salt concentrations, they reduced the number of cell deaths, in some cases drastically. Nerve cells particularly benefited from the treatment. “In the cell systems, we were able to show that the effect was as good as if we had added the active ingredient without the fibres, in other words intravenously,” says Scheller. However, the latter method has several disadvantages: The active ingredient degrades very quickly and has undesirable side effects, as it relaxes the blood vessels not only in the brain but throughout the entire body, including the heart muscles. This can lead to dangerously low blood pressure if the dose is too high. Directly applying it to the brain could minimize these side effects because significantly less of the active ingredient is required.

The fibres could also be used outside the brain, says Scheller, for example in different types of operations where nerves are at risk.

Fitness tracker bracelets and watches provide useful information, such as step count and heart rate, but they usually can't provide more detailed data about the wearer's health. Now, researchers reporting in ACS Applied Materials & Interfaces have developed smart electronic glasses (e-glasses) that not only monitor a person's brain waves and body movements, but also can function as sunglasses and allow users to control a video game with eye motions.

Devices that measure electrical signals from the brain (electroencephalogram; EEG) or eyes (electrooculogram; EOG) can help diagnose conditions like epilepsy and sleep disorders, as well as control computers in human-machine interfaces. But obtaining these measurements requires a steady physical contact between skin and sensor, which is difficult with rigid devices. Suk-Won Hwang and colleagues wanted to integrate soft, conductive electrodes into e-glasses that could wirelessly monitor EEG and EOG signals, ultraviolet (UV) intensity, and body movements or postures, while also acting as a human-machine interface.

The researchers built the glasses' frame with a 3D printer and then added flexible electrodes near the ears (EEG sensor) and eyes (EOG sensor). They also added a wireless circuit for motion/UV sensing on the side of the glasses and a UV-responsive, color-adjustable gel inside the lenses. When the sensor detected UV rays of a certain intensity, the lenses changed color and became sunglasses. The motion detector allowed the researchers to track the posture and gait of the wearer, as well as detect when they fell. The EEG recorded alpha rhythms of the brain, which could be used to monitor health. Finally, the EOG monitor allowed the wearer to easily move bricks around in a popular video game by adjusting the direction and angle of their eyes. The e-glasses could be useful for digital healthcare or virtual reality applications, the researchers say.

Resembling giant mealworms, superworms (Zophobas atratus) are beetle larvae that are often sold in pet stores as feed for reptiles, fish and birds. In addition to their relatively large size (about 2 inches long), these worms have another superpower: They can degrade polystyrene plastic. Now, researchers reporting in ACS' Environmental Science & Technology have linked this ability to a strain of bacteria that lives in the larvae's gut.

Polystyrene is used in packaging containers, disposable cups and insulating materials. When thrown in landfills or littered in the environment, the plastic takes several hundred years to completely break down. Recently, several studies have found that mealworms and superworms can ingest and degrade polystyrene within a few weeks. In mealworms, this ability was linked to a certain strain of polystyrene-degrading bacteria in the worms' gut. Jiaojie Li, Dae-Hwan Kim and colleagues wanted to search for similar bacteria in superworms.

The team placed 50 superworms in a chamber with polystyrene as their only carbon source, and after 21 days, the worms had consumed about 70% of the plastic. The researchers then isolated a strain of Pseudomonas aeruginosa bacteria from the gut of the worms and showed that it that could grow directly on the surface of polystyrene and break it down. Finally, they identified an enzyme from the bacteria, called serine hydrolase, that appeared to be responsible for most of the biodegradation. This enzyme, or the bacteria that produce it, could someday be used to help break down waste polystyrene, the researchers say.

The authors acknowledge funding from the CJ Blossom Idea Lab of the CJ Corporation, the Undergraduate Research Program at Daegu Gyeongbuk Institute of Science and Technology and the INGE funds of Gwangju Institute of Science and Technology.

The abstract that accompanies this paper can be viewed here.

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PHILADELPHIA - Checkpoint inhibitors, a type of immunotherapy, that target myeloid immune cells and slow tumor growth were discovered by a team from the Perelman School of Medicine at the University of Pennsylvania and other institutions. Reporting in Nature Cancer, the researchers showed for the first time in human cells and a mouse model that inhibiting the c-Rel molecule in myeloid cells -- as opposed to lymphoid cells that today's immunotherapies target -- blocked the production of immune suppressor cells and significantly shrank tumors.

Checkpoint inhibitors blocks proteins, called checkpoints, that are made by some types of immune system cells, such as T-cells. These checkpoints help keep immune responses from being too strong, but they often keep T-cells from killing cancer cells. These therapies have changed the cancer landscape by showing survival benefits where traditional therapies, like chemotherapy, may have failed. However, the number of patients who respond to these types of therapies remains limited, pushing researchers to explore a new class of inhibitors.

The team showed that in c-Rel-deficient mice tumor size and weight were reduced by up to 80 percent, and that administering the c-Rel inhibitor drug in another set of mice shrank tumors by up to 70 percent, compared to controls.

The findings not only show the potential of this new immunotherapy, but also point to a previously unknown pathway of cancer's assault on the body involving what are known as myeloid-derived suppressor cells (MDSCs). Cunning tumor cells, the authors found, hijack c-Rel to produce MDSCs that keep the immune system from attacking the cancer. The Penn-developed inhibitor releases that break.

"c-Rel is generally considered to be a promotor of immune responses, not a suppressor. That's why this discovery is surprising and unexpected," said senior author Youhai H. Chen, MD, PhD, a professor of Pathology and Laboratory Medicine in the Perelman School of Medicine. "There are two big takeaways: conceptually, this is a new pathway of cancer development that wasn't known before. And we have shown that a new drug inhibitor targeting this pathway works as well, if not better, than the first generation of checkpoint blockers."

The discovery of c-Rel's role in cancer was serendipitous. Chen's lab was studying c-Rel's role in inflammation and autoimmune diseases when they observed a relationship with MDSCs. Already equipped with a c-Rel mouse model, they decided to follow the thread and investigate whether c-Rel played a role in cancer growth, too, given the known function of MDSCs.

The results, said Chen, whose lab has been studying c-Rel for nearly two decades, were striking.

Beyond significant shrinkage of tumors in mice, in another experiment, the researchers deleted the REL gene, which blocked tumor growth and reduced MDSCs in mice, suggesting c-Rel is required to generate MDSCs. Follow-up genetic sequencing also showed how c-Rel turns on pro-tumor gene signatures that suppress functions of the immune system in MDSCs.

The researchers then tested their c-Rel inhibitor drug in mice and found that it not only reduced tumor growth, but also enhanced the effects of anti-PD-L1 therapy, another checkpoint inhibitor, when given in combination with the c-Rel drug. That one-two punch approach had the strongest suppression of tumor growth.

Combination therapy has become a popular approach for treating cancer patients, especially for those who do not respond well to other treatments. "In patients who respond to anti-PD-L1 treatments, many of them still die after two years," Chen said. "If you could extend lives by adding another effective approach, that would be a big advance."

Using human cells, the team also showed that its c-Rel inhibitor drug blocked the development of MDSCs in vitro, suggesting that inhibition might help eliminate cancer in patients, according to the authors.

Now that the efficacy of the inhibitor has been demonstrated in the preclinical setting, Chen said, the next step will be studies to assess the safety of the drug, before moving on to further studies and clinical trials.

"This represents a new class of checkpoints belonging to a different type of cell in the immune system that could move the field of immunotherapy even further along," Chen said.

During sleep and under anesthesia, we rarely respond to such external stimuli as sounds even though our brains remain highly active.

Now, a series of new studies by researchers at Tel Aviv University's Sackler Faculty of Medicine and Sagol School of Neuroscience find, among other important discoveries, that noradrenaline, a neurotransmitter secreted in response to stress, lies at the heart of our ability to "shut off" our sensory responses and sleep soundly.

"In these studies, we used different, novel approaches to study the filtering of sensory information during sleep and the brain mechanisms that determine when we awaken in response to external events," explains Prof. Yuval Nir, who led the research for the three studies.

The first study, published in the Journal of Neuroscience on April 1 and led by TAU doctoral student Yaniv Sela, calls into question the commonly accepted idea that the thalamus -- an important relay station for sensory signals in the brain -- is responsible for blocking the transmission of signals to the cerebral cortex.

"The shutdown of the thalamic gate is not compatible with our findings," says Sela whose study compares how neurons in different brain regions respond to simple and complex sounds while asleep or awake.

Using rat models, he found that the responses of neurons in the auditory cortex were similar when the rodents were awake or asleep. But when he examined the perirhinal cortex, related to complex conscious perception and memory associations, he found that neurons showed much weaker responses during sleep.

"Basic analysis of sound remains during sleep, but the sleeping brain has trouble creating a conscious perception of the stimulus," Sela adds. "Also, while we found that initial and fast responses are preserved in sleep, those that occur later and require communication between different regions in the cortex are greatly disrupted."

The second study, published on April 8 in Science Advances, finds that the locus coeruleus, a tiny region of the brainstem and the main source of noradrenaline secretions in the brain, plays a central role in our ability to disconnect from the environment during sleep. Led by TAU doctoral student Hanna Hayat at Prof. Nir's lab, the research was conducted in collaboration with Prof. Tony Pickering of Bristol University, Prof. Ofer Yizhar of the Weizmann Institute and Prof. Eric Kremer pf the University of Montpellier.

"The ability to disconnect from the environment, in a reversible way, is a central feature of sleep," explains Hayat. "Our findings clearly show that the locus coeruleus noradrenaline system plays a crucial role in this disconnection by keeping a very low level of activity during sleep."

For the purpose of the research, the scientists used rat models to determine the level of locus coeruleus activity during sleep and which sounds, if any, would be responsible for waking up the rodents.

They found that the rats' varying levels of locus coeruleus activity accurately predict if the animals would awaken in response to sounds. The team then silenced the locus coeruleus activity through optogenetics, which harnesses light to control neuronal activity, and found that the rats did not readily awaken in response to sound.

"When we increased the noradrenaline activity of the locus-coeruleus while a sound played in the background, the rats woke up more frequently in response, but when we decreased the activity of the locus coeruleus and played the same sound in the background, the rats only rarely woke up," says Hayat. "So we can say we identified a powerful 'dial' that controls the depth of sleep despite external stimuli.

"Importantly, our findings suggest that hyperarousal in some individuals who sleep lightly, or during periods of stress, may be a result of continued noradrenaline activity during sleep when there should only be minimal activity."

The third study, published on May 12 in the Proceedings of the National Academy of Sciences (PNAS), led jointly by TAU doctoral student Dr. Aaron Krom of Hadassah Hebrew University Medical Center and TAU doctoral student Amit Marmelshtein, focuses on our response to anesthesia and finds that the most significant effect of loss-of-consciousness is the disruption of communication between different cortical regions.

The study was the fruit of a collaboration between Prof. Nir, Prof. Itzhak Fried and Dr. Ido Strauss of TAU's Sackler Faculty of Medicine and Tel Aviv Sourasky Medical Center, and a team at Bonn University.

"Despite the routine use of anesthesia in medicine, we still do not understand how anesthesia leads to loss of consciousness; this is considered a major open question in biomedical research," explains Dr. Krom.

For the research, the scientists recorded the brain activity of epilepsy patients who had previously shown little to no response to drug interventions. The patients were hospitalized for a week and implanted with electrodes to pinpoint where in the brain their seizures originated. They were then anesthetized for the removal of their electrodes and their neuron activity recorded while they listened to sounds through headphones. They were asked to perform a task until they lost consciousness, which allowed the researchers to examine how their brain activity changed, down to individual neurons, in response to sounds at the very moment they lost consciousness.

"We found that loss-of-consciousness disrupted communication between cortical regions such that sounds triggered responses in the primary auditory cortex, but failed to reliably drive responses in other regions of the cortex," adds Marmelshtein. "This is the first study to examine how anesthesia and loss of consciousness affect sensory responses at a resolution of individual neurons in humans. We hope that our results will guide future research, as well as attempts to improve anesthesia and develop instruments that can monitor the level of consciousness in anesthesia and other states of altered consciousness such as vegetative states and severe dementia."

"These studies advance our understanding of sensory disconnection during sleep and anesthesia," concludes Prof Nir. "Sleep disturbances are a major health issue and are frequent in aging, as well as in neurological and psychiatric disorders. It is important to test if our findings on varying noradrenaline levels can explain hyperarousal that characterizes condition such as anxiety disorders and PTSD, and if so to build on these findings to develop novel methods to improve sleep quality."

More like mom or dad? Human babies always get this curious look in their face combined with the question whom the child resembles most. The answers vary depending on the degree of kinship, gender and the time of assessment. Mandrills, monkeys living in Equatorial Africa, may recognize facial features coding relatedness better than humans. Scientists at the German Primate Center - Leibniz Institute for Primate Research in Göttingen, together with colleagues from the Institut des Sciences de l'Evolution de Montpellier (ISEM), showed by using up-to-date artificial intelligence (AI) that half-sisters, who have the same father look more alike than half-sisters who share the same mother. The paternal half-sisters also have closer social relationships with each other than unrelated mandrills. This result provided the first evidence suggesting that interindividual resemblance has been selected to signal paternal kinship (Sciences Advances).

Throughout the animal kingdom, related conspecifics show similar features. Some are the spitting image of each other. However, whether resemblance between kin merely reflects their genetic resemblance or results from selection to facilitate their recognition is still unknown. A team of scientists led by Marie Charpentier of the ISEM in Montpellier, including Clémence Poirotte and Peter Kappeler of the German Primate Center in Göttingen, used for the first time artificial intelligence (deep learning) to examine the hypothesis that the similarity of the facial features of free-living mandrills is the result of selection. The database consisted of 16,000 portraits of mandrills, taken since 2012 as part of the Project Mandrillus in Gabon. This natural population of mandrills is the only one habituated to the presence of humans. Using a trained algorithm of deep learning, the individuals were first identified and then quantified in terms of facial resemblance. The results were subsequently related to relatedness data of the study animals.

Mandrills live in groups consisting of more than 100 individuals and are characterized by the fact that the females are maternal relatives. They are familiar with each other and remain in the same family throughout their lives. Since reproduction in mandrill groups is mainly monopolized by the alpha male, young mandrills of similar age often have the same father. However, as members of different family groups within the large groups, they should hardly know each other. Nevertheless, half-sisters on the paternal side, as well as half-sisters on the maternal side, interact with each other more often than unrelated animals. "This observation suggests that paternal half-sisters recognize each other as relatives by their facial features. Although maternal and paternal half-sisters share the same degree of genetic relatedness, the facial resemblance is stronger among paternally related females. We suspect that the similarity of facial features between paternal relatives has evolved to facilitate social discrimination and nepotism between kin," says Clémence Poirotte.

Since the outbreak of the COVID-19 pandemic and its rapid spread, the scientific community has been working on developing an effective treatment for the virus responsible for the disease. Finding drugs that can inhibit the infection caused by SARS-CoV-2 is an essential step to finding the vaccine that can definitively bring the spread of the virus to an end. In this regard, the URV's Cheminformatics and Nutrition research group has carried out a computational screening to predict whether there is a medicine authorised for treating another pathology that can inhibit the main protease of the virus (M-pro). This is key to the whole process because this enzyme plays an essential role in the replication of the virus.

The study demonstrates that a human and a veterinary anti-inflammatory drug - Carprofen and Celecoxib - inhibit a key enzyme in the replication and transcription of the virus responsible for COVID-19. The aim of the study was to use computer techniques to analyze whether 6,466 drugs authorized by various drug agencies for both human and veterinary use could be used to inhibit the M-pro enzyme. This enzyme is a protease that is responsible for cutting two polypeptides (generated by the virus itself) and generating a number of proteins that are essential for the reproduction of the virus. Some of the trials coordinated by the WHO against the COVID-19 pandemic also aim to inhibit M-pro using two antiretrovirals such as Lopinavir and Ritonavir (drugs initially designed to treat HIV).

As a result of the study conducted at the URV, it has been predicted that 7 of these 6,466 drugs may inhibit M-pro. The results have been shared with the international initiative COVID Moonshot which has selected 2 of these 7 compounds (i.e., Carprofen and Celecoxib) in order to test their ability to inhibit M-pro in vitro. The results obtained show that at a concentration of 50 μM of Celecoxib or Carprofen, the inhibition of the in vitro activity of M-pro is 11.90 and 4.0%, respectively. Therefore, both molecules could be used as a starting point for further lead optimization to obtain even more potent derivatives.

The study by the Cheminformatics and Nutrition research group from the Biochemistry and Biotechnology Department of the URV has been led by Drs. Gerard Pujadas and Santi Garcia-Vallvé with the collaboration of Drs. Aleix Gimeno, María José Ojeda-Montes and Adrià Cereto-Massagué, the PhD students Guillem Macip and Bryan Saldivar-Espinoza and student Júlia Mestres-Truyol (double degree student in Biotechnology and in Biochemistry and Molecular Biology at the URV). It has been published by the International Journal of Molecular Sciences (IJMS) and is the first to be published worldwide on drug repositioning as inhibitors of SARS-CoV-2 M-pro where computational predictions are experimentally corroborated. The remaining 5 molecules are expected to be selected soon by COVID Moonshot so that their bioactivity can be tested as well.