Culture

Like motley bandits, certain enzymes implicated in cancer and other diseases also annihilate each other. A new study reveals details of their mutual foils in the hopes that these behaviors can be leveraged to fight the enzymes' disease potential.

The bandits are cathepsins, enzymes that normally dispose of unneeded protein in our cells. But in unhealthy scenarios, cathepsins can promote illnesses like cancer, atherosclerosis, and sickle cell disease. Many experimental drugs that inhibit them, while effective, have failed due to side effects that could not be well explained, so researchers at the Georgia Institute of Technology abandoned the common focus on single cathepsins to model three key cathepsins as a system.

The researchers found that the cathepsins, denoted by the letters K, L, and S, not only degrade extracellular structures - proteins outside of cells that support cells - but also cannibalize, distract, and deactivate each other. Cathepsins are proteases, enzymes that degrade proteins, and since the cathepsins are themselves proteins, they can degrade each other, too.

Cathepsin Three Stooges

"Auto-digestion is my personal favorite. Think about it: You take a group of cathepsin Ks, and they eat each other. Why? Because they're just closer to each other than to what they would otherwise eat," said the study's principal investigator Manu Platt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

In disease, cathepsins appear to be like The Three Stooges in a porcelain shop, tearing the shop down while they torment each other. As a result, early on, when the Georgia Tech researchers tried to influence a single cathepsin in the group, outcomes were puzzling, and the researchers felt they might be onto something relevant to past mysterious drug failures.

Through lab experiments and mathematical calculations, they arrived at a computational model that showed how single influences ripple through the system. They published the model as a tool online that other researchers can use to jigger the three cathepsins in group settings, their levels of available targets, and inhibitor chemicals. The tool contrasts cathepsin bungling with cathepsin effectiveness.

The researchers publish their research results in the journal the Proceedings of the National Academy of Sciences in the week of January 20, 2020. The research, which took a systems biology approach, was funded by the National Science Foundation and the National Institutes of Health.

Q&A

How do cathepsins go wrong?

The three cathepsins in this study are best known for their activity in cell organelles called lysosomes under healthy conditions, where they work like molecular woodchippers to cut protein down to amino acids.

"They also serve functions in specific cell types, such as cathepsin S helping the immune system to recognize what to attack and what not to," Platt said.

"Problems happen when cathepsins get overexpressed and end up in the wrong places. They're crazy powerful and degrade the structural proteins elastin and collagen that make up arteries, tendons, the endometrium, and many tissue structures."

"In healthy settings, cathepsin K breaks down old bone to recycle calcium. But when breast cancer comes, those cancerous cells make cathepsin K to destroy collagen around the tumor. And that allows the cells to escape and metastasize to the bone," Platt said.

How is this research relevant to drug development?

"I study cathepsins in illnesses like tendinopathy, endometriosis, atherosclerosis, cancer, and sickle cell disease," Platt said. "So, having a drug on the market to handle cathepsins would be a big deal."

"Many cathepsin inhibitor drugs that have failed clinical trials were very finely targeted but caused big side effects, and some of those cathepsin inhibitor drugs did not even cross-react with other cathepsins they were not targeting - which is usually a good thing - so the cause of the side effects was a mystery," Platt said. "By modeling a system of cathepsins, we think we have a good start toward uncovering that mystery."

"If we don't know how these cathepsins are working with and against each other in complex systems, similar to how they exist in our bodies, then we are going to have a hard time getting anything into the medicine cabinet to inhibit them."

The study floats ideas on new approaches to drug research. For example, cathepsin S could be strategically boosted in situations where it is not the culprit to break down cathepsins K and L.

What can other researchers expect from the online model?

"They can set up their own experiments and make predictions, including what inhibitors will do, so they can test inhibitors at varying strengths in this system," Platt said. "They can ask questions that they can't answer yet experimentally then test the model's predictions in the lab."

The model processes varying inputs into resulting changes in cathepsin levels and outcomes of degradation and indicates whether they have been deactivated or demolished. Scenarios can be exported as a report and a data spreadsheet.

EVANSTON, Ill. --- Northwestern University researchers have added a new dimension to the importance of diversity.

For the first time, physicists have experimentally demonstrated that certain systems with interacting entities can synchronize only if the entities within the system are different from one another.

This finding offers a new twist to the previous understanding of how collective behavior found in nature -- such as fireflies flashing in unison or pacemaker cells working together to generate a heartbeat -- can arise even when the individual insects or cells are different.

Northwestern's Adilson Motter, who led the research, explained that identical entities naturally behave identically -- until they start interacting.

"When identical entities interact, they often behave differently from each other," said Motter, who is a professor of physics in Northwestern's Weinberg College of Arts and Sciences. "But we identified scenarios in which the entities behave identically again if you make them suitably different from each other."

This discovery could help researchers optimize human-made systems, such as the power grid, in which many parts have to remain synchronized while interacting with one another. It also could potentially inform how groups of humans, such as juries, can coordinate to reach a consensus.

The research will publish on Monday, Jan. 20 in the journal Nature Physics. Motter coauthored the paper with Northwestern's Takashi Nishikawa and Ferenc Molnar, a former postdoctoral researcher at Northwestern who is now at Notre Dame University.

This work expands upon Nishikawa's and Motter's 2016 paper, which theoretically predicted the phenomenon.

"It is interesting that systems need to be asymmetric to exhibit behavioral symmetry," said Nishikawa, a research professor of physics in Weinberg. "This is remarkable mathematically, let alone physically. So, many colleagues thought that experimentally demonstrating this effect was impossible."

Motter and his collaborators made the seemingly impossible possible by using three identical electric generators. Each generator oscillated at a frequency of exactly 100 cycles per second. When separated, the identical generators behaved identically.

When connected to form a triangle, their frequencies diverged -- but only until the generators were properly mismatched to have different energy dissipations. At that point, they synchronized again.

"This can be visualized by putting a small lamp between each pair of generators," Molnar explained. "When the generators are identical, the lamp flickers, meaning that the generators are not synchronized. But when the generators' dissipation is tweaked to different levels, the flickering stop, indicating that the generator voltages are oscillating in sync."

The researchers dubbed this phenomenon "converse symmetry breaking" because it represents the opposite of the previously known phenomenon of symmetry breaking, which underlies superconductivity, the Higgs mechanism and even the appearance of zebra stripes.

In symmetry breaking, the dynamical equations have a symmetry that is not observed in the behavior of the system, while converse symmetry breaking concerns situations in which the behavior of the system has a given symmetry only when that symmetry is avoided in the dynamical equations.

"It might seem counterintuitive," Motter said. "But our theory predicts that this is true across many systems, not just electromechanical ones."

Motter's team plans to explore the implications of their findings across social, technological and biological systems. In particular, the team is actively working on the design of a power grid that is more stable while allowing incorporation of an increasing share of energy from renewable sources.

Racial bias and policing made headlines last year after a study examining records of fatal police shootings claimed white officers were no more likely to shoot racial minorities than nonwhite officers. There was one problem: The study was based on a logical fallacy.

The original research counted the numbers of fatal shootings, but never considered how often civilians encounter police officers, an essential ingredient to justifying its central claim.

The findings sparked a fiery debate among other academics, including two professors from Princeton University, who raised mathematical concerns about the study's approach. Today, they published their critique as a letter in the Proceedings of the National Academy of Sciences (PNAS).

The pair -- Dean Knox, assistant professor of politics, and Jonathan Mummolo, assistant professor of politics and public affairs-- outline a number of serious flaws in the original study, which was featured in PNAS on Aug. 6, 2019.

For the original study, researchers from Michigan State University and the University of Maryland compiled data on 900 fatal U.S. police shootings from crowdsourced databases. They then contacted each police department, gathering information about the race of the police officers responsible for each fatality.

The researchers then used the shootings data to predict the race of victims. Specifically, they showed that when the shooting officer was black, the civilian who was shot was more likely to be black than white. And controlling for attributes of the county in which shootings occurred, "the relationship between officer and civilian race was attenuated or eliminated." The authors interpreted these results as evidence that white officers are not biased against black civilians.

Yet, Knox and Mummolo show that the authors' conclusions hinge on the assumption that black and white officers encounter black and white civilians in equal numbers. Knox and Mummolo show this formally, but a simple thought experiment also illustrates the conceptual problem.

Imagine a white officer encounters 90 white civilians and 10 black, while a black officer encounters 90 black civilians and 10 white, both under identical circumstances. If both officers shot five black and nine white civilians, the results would -- according to the reasoning of the original study -- appear to show no racial bias.

However, once encounter rates are taken into account, one would see the white officer shot 50% of the black civilians he or she saw while the black officer shot 5.6%. Therefore, failing to incorporate information on encounter rates masks racial bias.

The data from the original study also only includes records of shootings, ignoring all other police-civilian encounters. And it doesn't take into account that all police officers -- white and nonwhite -- could, in theory, be biased in shooting black men.

These critiques have a number of implications on the way data is collected for research and the benchmarks used for analysis.

"New data on police behavior are coming online all the time, and that is great from a research standpoint," Mummolo said. "But all the data in the world do not negate the need to adhere to basic tenets of statistical theory and causal inference. Studies of racial bias demand the utmost rigor, and when blatant mistakes are made, they need to be quickly corrected. To allow provably false results to stand unchallenged risks confusing the public and lawmakers on one of the most pressing policy issues of our time."

After their critique was initially rejected by PNAS, Mummolo published a Twitter thread highlighting the mathematical problems associated with the original study in August 2019. The team also posted their analysis on the preprint server SSRN.

Responding to the critique, the authors of the original paper released a formal response, stating their claim about the relative probability of white and black officers shooting racial minorities was not supported, but adding that the original findings, "as described in that manuscript, largely stand unchanged."

Knox and Mummolo then appealed the rejection at PNAS, and their critique was accepted.

Marijuana use is on the rise as more states legalize it for medicinal and recreational purposes, and physicians are fielding more questions about its safety.

Although smoking tobacco is responsible for approximately one in four deaths from cardiovascular disease, the effects of smoking marijuana on the heart are not fully understood. Some studies suggest that marijuana can trigger heart attacks and strokes in some users.

Ersilia DeFilippis, MD, a second-year cardiology fellow at Columbia University Irving Medical Center and NewYork-Presbyterian, first became interested in marijuana's effect on the heart a few years ago when studying heart attacks in people under 50. "We noted that 10% of patients in a registry of young heart attack patients had used marijuana and/or cocaine," she says.

DeFilippis and colleagues recently reviewed the medical literature to find out what's known about marijuana's effect on the heart and what's still unknown. Their full report was published Jan. 20 in the Journal of the American College of Cardiology.

Here are five highlights from the review:

2 Million People with Heart Disease Have Used Marijuana

Marijuana is the most commonly used drug of abuse. It's estimated that approximately 90 million American adults have used the drug at least once in their life, and more than 39 million have used the drug in the past year.

Based on responses to the National Health and Nutrition Examination Survey from 2016, DeFilippis and her colleagues estimate that about 2 million adults in the United States who have cardiovascular disease currently use marijuana or have used the drug in the past.

"In addition to the 2 million marijuana users with diagnosed cardiovascular disease, many more may be at risk," DeFilippis says. "With many adolescents and young adults turning to marijuana, it is important to understand the cardiovascular implications they may face years down the line."

Cannabinoids Can Interact with Drugs Used to Treat Heart Disease

Cannabinoids inhibit certain enzymes in the body, which affects the metabolism of many drugs for heart disease, including antiarrhythmics, statins, calcium-channel blockers, beta blockers, and warfarin.

Researchers believe that cannabinoids may increase the activity of these prescribed drugs in the body, though limited data are available to guide physicians in adjusting dose to compensate for marijuana use.

Marijuana's Potency Today Is Higher

The potency of marijuana--the percentage of THC contained in the plant--has steadily increased over the past 30 years, from about 4% in the mid-1990s to 12% in 2014. However, most scientific studies of cannabis tested products with THC levels between 1.5% and 4%.

"Higher potency may translate into greater effects on the conduction system, the vasculature, and the muscle of the heart," DeFilippis says. "It also highlights the need for real-world data given the variety of marijuana products and formulations available for purchase."

THC is the most psychoactive chemical in marijuana, but marijuana also contains more than 100 compounds, called cannabinoids, that are chemically related to THC.

Receptors for cannabinoids are highly concentrated in the nervous system but also can be found in blood cells, muscle cells, and other tissues and organs.

Marijuana May Be Linked to Heart Attacks and Strokes

Studies have identified marijuana smoking as a potential trigger of heart attacks, and marijuana use is not infrequently detected in adults who have experienced heart attacks at an early age (under 50).

A small experimental study found that smoking marijuana can bring on angina (chest pain) more quickly in patients with coronary heart disease compared with smoking a placebo.

Though current evidence for a link between marijuana and heart attacks is modest, it's thought that smoking marijuana may increase cellular stress and inflammation, which are known to be precipitating factors for coronary artery disease and heart attacks.

Cerebrovascular events, including strokes, also have been associated with marijuana use. It's thought that marijuana may induce changes in the inner lining of blood vessels or alter blood flow.

Physicians Should Screen for Marijuana Use

"Although we need more data, the evidence we do have indicates that marijuana use has been associated with coronary artery disease, arrhythmia, cardiomyopathy, and more," DeFilippis says.

"Therefore, asking patients about marijuana use may help in risk assessment. In addition, we know that marijuana use affects the metabolism of many common cardiac drugs. In order to make sure patients are getting therapeutic doses without untoward side effects, it is important for cardiologists to talk to their patients about marijuana use."

Economists working with Professor Marko Sarstedt from Otto von Guericke University Magdeburg are demanding that the same scientific standards be applied to economics and the behavioral sciences in general as are used in the natural sciences. They believe that the inherent uncertainties in measured values must be described and quantified in order to enhance the reproducibility of measurement series. Only in this way can the sources of errors be identified and eliminated.

In a recently published study, the economists investigated why so much research work in the behavioral sciences is not reproducible - or only to a limited extent. They argue that established checklists that are intended to make important aspects of the studies transparent are inadequate. According to the economist and co-author, Professor Marko Sarstedt, in physics no study would pass muster without stating the accuracy of the measurements used. "Although providing corresponding calibration data for the measurement of social phenomena is difficult to conceive of, it is not impossible." In the study the economists advocate transferring concepts from the natural sciences to the behavioral sciences and show, using a sample calculation, what major consequences the allowance for measurement uncertainty can have for a seemingly statistically significant result.

Researchers in the behavioral sciences need to try to incorporate the impact of interference factors directly and fully into their results. "Physicists, engineers, physicians and biologists do this by stating the measurement inaccuracy of their instruments, for example of a thermometer or scale," explains Sarstedt. "Behavioral scientists such as economists and psychologists must do the same when measuring unobservable concepts such as satisfaction and happiness - even if it is difficult."

Whilst physics generally deal with precisely defined and measurable quantities such as lengths, masses and temperatures, concepts such as satisfaction and happiness are not clearly defined and are measured and interpreted differently depending on the team of researchers. But, according to Sarstedt, despite the disparity between the subjects being studied, reproducibility is simply an essential element of science. Only through the repeated confirmation of research results can they be accepted as fact.

"Protocols in physics or biology specify clear guidelines, which even in terms of the rather imprecise subjects being studied in our discipline must be adapted," explains the economist. "As in physics, we need institutions to establish standards for measurements in the behavioral sciences and to quantify uncertainties in standard measurements."

The background to the study is that according to the authors, many areas of social science research find themselves in a replication crisis. In recent years it has not been possible to verify fundamental effects in psychology, management and marketing research in repeated studies under almost identical conditions. Since then, various groups of researchers around the Center for Open Science have made efforts to define standards for empirical studies in order to enhance their reproducibility. From this a variety of checklists have resulted, that are intended to assist researchers in documenting important aspects of their studies and making them transparent.

The study by the authors, Edward E. Rigdon (Georgia State University), Marko Sarstedt (University of Magdeburg) and Jan-Michael Becker (University of Cologne) recently appeared in the renowned journal, Nature Human Behaviour under the title "Quantify uncertainty in behavioral research".

What rules shaped humanity's original social networks? Researchers in Japan developed new mathematical models to understand what conditions produced traditional community structures and conventions around the world, including taboos about incest.

"We think this is the first time cultural anthropology and computer simulations have met in a single research study," said Professor Kunihiko Kaneko, an expert in theoretical biology and physics from the University of Tokyo Research Center for Complex Systems Biology.

Researchers used statistical physics and computer models common in evolutionary biology to explain the origin of common community structures documented by cultural anthropologists around the world.

The earliest social networks were tightly knit cultural groups made of multiple biologically related families. That single group would then develop relationships with other cultural groups in their local area.

In the 1960s, cultural anthropologists documented social networks of indigenous communities and identified two kinship structures common around the world. In areas with hunter-gatherer communities, anthropologists documented direct-exchange kinship structures where women from two communities change places when they marry. In areas with agrarian farming communities, kinship structures of generalized exchange developed where women move between multiple communities to marry.

"Anthropologists have documented kinship structures all over the world, but it still remains unclear how those structures emerged and why they have common properties," said Kenji Itao, a first year master's degree student in Kaneko's laboratory, whose interdisciplinary interests in physics, math and anthropology motivated this research study.

Experts in anthropology consider the incest taboo to be an extremely common social rule affecting kinship structures. The ancient incest taboo focused on social closeness, rather than genetic or blood relationships, meaning it was taboo to marry anyone born into the same cultural group.

Itao and Kaneko designed a mathematical model and computer simulation to test what external factors might cause generations of biologically related families to organize into communities with incest taboos and direct or generalized exchange of brides.

"Traditionally, it is more common for women to move to a new community when they marry, but we did not include any gender differences in this computer simulation," explained Itao.

Simulated family groups with shared traits and desires naturally grouped together into distinct cultural groups. However, the traits the group possessed were different from the traits they desired in marriage partners, meaning they did not desire spouses similar to themselves. This is the underlying cause of the traditional community-based incest taboo suggested by the study.

When the computer simulation pushed communities to cooperate, generalized exchange kinship structures arose. The simulation demonstrated different kinship structures, including the direct exchange basic structure, emerge depending on the strength of conflict to find brides and the necessity of cooperation with specific other communities.

"It is rewarding to see that the combination of statistical physics and evolution theory, together with computer simulations, will be relevant to identify universal properties that affect human societies," said Kaneko.

The current computer model is simple and only included factors of conflict and cooperation affecting marriage, but researchers hope to continue developing the model to also consider economic factors that might cause communities to separate into different classes. With these additions, the theory can hopefully be extended to explore different communities in the modern, global society.

"I would be glad if perhaps our results can give field anthropologists a hint about universal structures that might explain what they observe in new studies," said Itao.

Many bacterial pathogens excrete toxins as soon as they have entered the host in order to suppress its immune response. Researchers at Ruhr-Universität Bochum (RUB) have analysed what happens on the molecular level when the diarrhea pathogen Yersinia pseudotuberculosis switches into attack mode. To this end, they examined so-called RNA thermometers, which signal to the bacteria whether they are in the host.

In collaboration with colleagues from the Helmholtz Institute for Infection Research in Braunschweig, they also showed that bacteria with deactivated RNA thermometers can no longer trigger an infection. The journal PLOS Pathogens reports about the study online on 17. january 2020.

RNA thermometer melts at 37 degrees Celcius

"We knew from previous studies that Yersinia bacteria are very sensitive to temperature changes and recognise that they are in their host on the basis of body temperature," says Professor Franz Narberhaus from the RUB Chair of Microbial Biology. RNA thermometers are responsible for temperature measurement. They are sections in the messenger RNA of many genes that contain the blueprint for disease-causing proteins.

At low temperatures, i.e. outside the host, RNA thermometers prevent the RNA from being read and translated into proteins. Only after successful infection of the warm-blooded host, i.e. at a temperature of around 37 degrees Celsius, do the RNA structures melt. They can then be written into proteins that have a harmful effect on the host. In the current publication, the scientists describe the underlying melting mechanism of the RNA thermometer for one of the toxins of Yersinia pseudotuberculosis, namely the CnfY-Toxin.

Bacteria with non-functional thermometers do not cause illness

PhD student Christian Twittenhoff from Bochum used isolated cell components of the diarrhoea pathogen to show which structure the RNA thermometer for the CnfY toxin assumes and where it melts. The biologist created a model that documents how the thermometer opens. It also shows how the ribosome - the cell component on which the messenger RNA is translated into a protein - docks to the messenger RNA.

In cooperation with the group headed by Professor Petra Dersch, formerly at Helmholtz Institute in Braunschweig, currently at the University of Münster, the researchers moreover demonstrated the role of the RNA thermometer in the disease process. They infected mice with Yersinia bacteria that either had functioning RNA thermometers or inactivated RNA thermometers that could not melt at 37 degrees Celsius. The bacterial strains with modified RNA thermometers were not able to make mice ill. "The results have shown how important very short regulatory RNA sequences can be for the successful course of infection of a bacterium," concludes Christian Twittenhoff, lead author of the study.

Similar mechanisms suspected in other bacteria

Christian Twittenhoff compared the gene of the CnfY toxin with toxin genes of other pathogens using bioinformatic methods. The analysis suggests that other toxin genes might also be regulated by RNA thermometers. "Even though the sequences are very different, we are able to predict which RNA structures are likely to act as thermometers," he explains.

"RNA thermometers function via a very simple mechanism, which has probably proved its efficacy in the course of evolution and has therefore developed many times and independently of each other," assumes Franz Narberhaus. In principle, it is possible to prevent bacterial infection by preventing the melting of such RNA structures. "However, we don't yet know any substances that freeze RNA thermometers in the closed state," continues Narberhaus.

A team of Russian scientists working in cooperation with international colleagues used a new method combining visual microscopic observations and photoemission spectrum registration that can be used to create a map of the physical and chemical state of cell surface. The team studied the cells of the colon bacillus Escherichia coli that are a promising material for the development of nature-like technologies. The study was supported with a grant of the Russian Science Foundation, and the article about it was published in the Results in Physics journal.

Nature-like object studies are an actively developing field of science based on the use of biological materials. Among other things, it includes technologies for the development of nanosized constructions on the basis of biological macromolecules: DNA, protein capsules and conjugators, and nucleoprotein complexes. However, to create such devices scientists need to understand how a biological system functions as a whole, and also to have technologies of such constructions composition and structure fine tuning.

One of the best objects for the development of these technologies are the cells of the colon bacillus E. coli that can be easily cultivated in lab conditions. The bacteria produce ferritin-like proteins called Dps. One of their main functions in a cell is the accumulation of different iron compounds (of fixed shape and not more than 5 nm in size) inside the protein globule. Such molecules can be obtained using a long and relatively quite expensive method of extraction with different means of fractioning. Alternatively, the E. coli cells themselves can work as a factory for controlled production, formation, transportation, and distribution of these proteins with inorganic nuclei. However, the issues of physical and chemical state of iron compounds, as well as their local atomic and electronic constriction within the bacterial cells and on their surfaces remain open. Currently there are no universal direct experimental methods that are precise and chemically sensitive enough for the studies of microparticles on the surfaces of biological objects (e.g. cells).

A team of scientists from Voronezh State University together with their colleagues (including the representatives of Immanuel Kant Baltic Federal University) were the first to study bacterial cells using the PhotoEmission Electron Microscopy (PEEM) method. It allowed the researchers to visually observe individual E. coli cells and potentially to study their surfaces physical and chemical state. The team confirmed that PEEM was qualitatively applicable for this type of research.

"A team from Voronezh State University with the support of Russian Science Foundation used a set of high-resolution research methods including X-ray Photoelectron Spectroscopy and Scanning Electron Microscopy that confirmed the efficiency of the approach used. The results shown by the group hold out a hope for a wider use of PEEM for the bioimaging of cell objects with integrated inorganic nanoparticles. In other words, PEEM can be used to map inorganic inclusions on the cell surface, that is, to gain information on what atoms and in what state are localized on the membrane of a bacterial cell on the microscopic scale. X-ray Photoelectron Spectroscopy technique was applied with the use of the National Research Center Kurchatov Institute storage ring synchrotron radiation" said the head of the project Associate Professor Sergey Turishchev.

"In the future we plan to increase the resolving power of this approach in order to be able to obtain precise data about the surface of single cells or even specific areas on them. Moreover, we'd like to consider the application of this method not only to bacterial cells with quite resistant membranes, but also to eukaryotic cells," commented Sergey Antipov, Associate Professor, the head of the Molecular Biophysics and Bionanotechnologies science group at the School of Life Sciences Immanuel Kant Baltic Federal University.

Information about an artwork has no effect on the aesthetic experience of museum visitors. The characteristics of the artwork itself have a much stronger impact on observers. Psychologists from the University of Basel reached these conclusions in a new study.

Aesthetic experiences involve a complex interaction of modes of perception and cognitive processes: the artworks' properties such as coloring and the content depicted play a role, and so do the individual characteristics of the viewer, their knowledge, and contextual factors such as an artwork's title.

Researchers from the University of Basel led by the psychologists Professor Jens Gaab and Professor Klaus Opwis examined the extent to which an artwork's contextual information influences aesthetic experience in a real exhibition situation. They particularly focused on the question of whether and how various kinds of information affect the aesthetic experience of museum visitors.

Previous research has shown that contextual information can significantly shape perception and experience - for example, wine tastes better to consumers when the price is higher.

Study under real conditions

For the present study, 75 participants visited the Future Present exhibition at the Schaulager Museum in Münchenstein and viewed six paintings by various artists from the Flemish Expressionism era. They were randomly assigned to one of two groups and received either simple descriptive information about the paintings or elaborative, in-depth information, such as an interpretation of the work.

The participants evaluated the intensity of their aesthetic experience in a questionnaire. The researchers also measured the emotions that arose while they viewed the art using psychophysiological data such as heart rate and skin conductance.

The researchers expected that the detailed descriptions would have a stronger effect on the cognitive processes and aesthetic experience than the simple information.

Artworks influence heart rate

The results showed, however, that neither the simple nor the detailed information influenced the aesthetic experience. There was no evidence of differences between the two groups, whether through the subjective evaluation or the physical reactions.

The properties of the artworks themselves, however, did affect the aesthetic experience. The physical reactions were stronger than before the participants began viewing the art, and differed significantly depending on the painting. The artwork that produced the greatest reaction in terms of aesthetic experience was James Ensor's Les masques intrigués from 1930. "Ensor's artworks mostly appear bizarre or absurd; this particular mode of expression may be what led the viewers to provide more extreme evaluations," explains lead author Luisa Krauss.

The study, which was published in the journal Psychology of Aesthetics, Creativity, and the Arts, thereby relativizes the significance of accompanying information and also underscores how the context of the museum influences aesthetic experience. "Museum visitors do not necessarily require information to feel satisfied after visiting an exhibition. The art can speak for itself," says Professor Jens Gaab in summary.

New study shows that peach-fronted conures have a surprisingly advanced talent for collaboration when it comes to finding food. This is important knowledge for biologists working with conservation of wild bird populations.

It is well known that certain mammals and birds live in groups and help each other find food, care for the young, hunt or keep watch.

Now, in a first, a new study describes that a parrot species - the peach-fronted conure - is capable of a very sophisticated form of collaboration: These birds are somehow able to solve a task together with a partner that they can't see.

- It is, as far as we know, the first time this is observed in any animal; a task solved by two individuals who cannot see each other. This reveals how advanced birds can be, says Sara Torres Ortiz, who has studied animal cognition at University of Southern Denmark.

- This teaches us that parrot species in the wild can be expected to work together and that their advanced group dynamics are important for their survival. That is relevant knowledge for biologists working with conservation and improvement of their living conditions, she says.

She did the study while at University of Southern Denmark, together with the colleagues Alejandro Corregidor Castro and Thorsten Johannes Skovbjerg Balsby (University of Aarhus) and Ole Næsbye Larsen (University of Southern Denmark).

The study is published here: https://link.springer.com/article/10.1007%2Fs10071-019-01331-9

The task solved by the peach-fronted conures is based on a traditional method of testing cognitive abilities of birds: Two birds are presented with each end of a string, which - if pulled at the same time - will release a snack. If the birds do not pull the string simultaneously, no snack is released.

This test has successfully been solved by a number of birds, including ravens, rooks, African grey parrots and New Caledonian crows, but that is the limit of their capabilities.

In this case, the research team worked with four peach-fronted conures, presented them with more and more complex collaboration tasks - and observed their surprising talents for solving the tasks.

In the most difficult experiment, the researchers first placed a bird in the test box where it could see its own end of the string. Then they waited a little and let in the second bird behind a wall; thus invisible to the first bird. Now the two birds had to figure out how to pull both ends of the string to get a snack.

- They were generally good at solving the task and only started pulling when both were present and ready. But we do not know exactly how they did it. Our recordings revealed that they produced more vocalisations when they couldn't see their partner, so maybe they exchanged information that way, says Sara Torres Ortiz.

The birds also seemed to have individual approaches to the task. One bird immidiately grabbed its end of the string, but then let it go and only picked it up it again when its partner began pulling the other end of the string. Another bird picked up the string and waited for it to be pulled by the partner.

The four parrots were coupled in 12 different couple combinations and they solved most of the different tests. However, when they got to the fourth and most difficult test, only five out of 12 couples managed to solve more than 40 % of the tasks.

- Being able to wait for a partner 40 pct. of the time is quite impressive. Other birds like African grey parrots, rooks, ravens and New Caledonia crows are not able to wait at all, even when they can see their partner, comments Sara Torres Ortiz.

The researchers recorded the vocalisations of the birds while they collaborated and next step is to analyze these recordings to see if they reflect some kind of communication between the birds.

A team of scientists from Immanuel Kant Baltic Federal University used Raman spectroscopy to study the thrombocytes of patients with cardiovascular diseases and compared their spectra with those of healthy people. The researchers identified informative areas of the spectra and confirmed that Raman spectroscopy was a promising method allowing one to diagnose the diseases associated with changes in thrombocyte activity and also to forecast the efficiency of antithrombotic therapy. A grant for the research was provided by the Russian Science Foundation, and its results were presented at several conferences on medicine and optics: Optics in Health Care and Biomedical Optics IX, 20-23 October 2019, Hangzhou, China, and the 6th Annual European Congress on Clinical and Translational Medicine. 18-20 October, 2019 Vienna, Austria. The results were also published in SPIE Digital Library ? European Journal of Molecular & Clinical Medicine.

Blood consists of a liquid medium called plasma and blood cells suspended in it and performing different functions. Thrombocytes protect our bodies from blood loss in case of an injury. They look like colourless oblate spheroids 2-4 micron in diameter and are produced by red bone marrow. As a rule, thrombocytes remain deactivated; however, when vascular walls are damaged, and cell disintegration products and special molecular "distress signals" are released in the blood, they react with the proteins on the surface of thrombocytes and activate them. When a thrombocyte is activated, it quickly and almost always irreversibly changes its state and shape, increasing its surface area. As a result thrombocytes acquire the ability to stick to each other (this process is called aggregation) and to vascular walls (adhesion). A clot is formed, and serious blood loss is prevented. Moreover, thrombocytes release the so-called growth factor into body tissues surrounding the injury site, making them divide faster.

But blood properties can change in the course of some cardiovascular diseases causing clots (thrombs) to form without any damage to vascular walls. Thrombs can circulate along blood vessels and stick to their walls thus contracting their lumen and making other elements stick to them. This leads to the clotting of vessels, prevents blood flow to tissues and organs, damages their functions, and in case of long oxygen and nutrient deficiency might even cause necrosis. If an artery is clotted in the heart (heart attack) or the brain (stroke), it causes serious health issues and may even be lethal. To diagnose the diseases of this type, doctors pay attention to several blood indicators including the quantity and state of thrombocytes. Current evaluation methods are quite complex and take a lot of time to carry out all reactions. However, as it turns out, to diagnose the state of a patient, one may use the characteristics of thrombocytes.

A team of scientists from Immanuel Kant Baltic Federal University suggested using Raman spectroscopy to diagnose the state of thrombocytes. In the course of Raman spectroscopy a laser beam goes through the studied substance, and then the characteristics of scattered light are compared to its initial indicators. The substance absorbs a part of light, and the frequency of such absorption depends on the composition and structure of the sample. The intensity of the beam in all frequencies is visualized as a chart, and scattering peaks are identified on it. Then the spectral structure of the thrombocyte in question is evaluated.

"Raman spectroscopy is currently being actively studied as a new diagnostic method in many areas of medicine. For example, it can be used to identify the known markers of cardiovascular diseases or to search for new ones. The analysis of thrombocytes and their aggregation ability might become a new efficient and minimally invasive diagnostics method in modern cardiology", said Ekaterina Moiseeva, a postgraduate of the Institute of Medicine, Immanuel Kant Baltic Federal University.

The team suggested that the state of thrombocytes in the blood of patients with cardiovascular diseases could be quickly evaluated using Raman spectroscopy. The participants of the study were volunteers; some of them had healthy hearts and blood vessels, and some suffered from high blood pressure or had survived a heart attack and took antiaggregants (blood thinners). Samples of venous blood were taken from both groups. After that, thrombocytes were extracted from them and placed on a base plate. Then the scientists registered the spectra of single suspended cells and studied their characteristics. The comparison of samples taken from healthy people and cardiovascular patients showed differences in several areas of the spectra. Namely, the intensity of the signal changed in the latter which may indicate changes in the physical characteristics of the lipidic base of thrombocyte membranes

"It is too early to say that the spectra change according to a certain set of rules. We need further studies to classify them and link to specific cell processes. To confirm the results, we plan to collect more research statistics and to identify spectral patterns that might be brought into correlation with the thrombocyte state indicators," said Andrei Zyubin, a senior researcher at the Research and Educational Center "Fundamental and Applied Photonics. Nanophotonics", Immanuel Kant Baltic Federal University.

The results of the study confirmed that Raman spectroscopy could be used to study the changes in the properties of thrombocytes in patients undergoing antiaggregant therapy. This would help doctors not only control the progress of the therapy, but also identify possible risks of cardiovascular diseases.

A team of scientists from Immanuel Kant Baltic Federal University together with their colleagues from NUST MISiS and RWTH Aachen University (Germany) compared different treatments against liver fibrosis and published the results of their study in the Cells journal. In the course of this disease liver tissue is replaced with connective (cicatricial) tissue preventing the organ from its normal functioning. According to the scientists, magnetic nanomaterials may become a basis for a completely new approach to anti-fibrosis treatment and help avoid the issues associated with traditional therapeutic methods.

Fibrosis may affect different body organs. It develops as a reaction to long-time inflammation and is supposed to isolate the inflammation site from surrounding tissues. For example, chronic liver fibrosis may occur if the liver is constantly influenced by toxins, viruses, or metabolic disturbances. Liver damage is caused by the hepatocytes death, the main type of liver cells that secure the functioning of the organ. As hepatocytes die and are replaced with connective tissue cells, liver functions decrease, and if a patient receives no treatment, cirrhosis may develop. Cirrhosis is a fatal illness: patients with it live for 2-4 years and die in excruciating pain. On its early stages fibrosis exhibits no symptoms and is often diagnosed when a patient starts to experience serious liver failure.

Currently, there are few efficient methods for treating liver fibrosis, and all of them work indirectly -- mainly by means of reducing the anti-inflammatory reactions. Scientists are working on new medicinal drugs that would affect the regulatory mechanisms of connective tissue development. The main role in this process is played by hepatic stellate cells, therefore they have been chosen as the targets of the drugs.

Despite the advantages of the new drugs, their targeted delivery remains a complex task. The solution may lie in the use of magnetic nanoparticles as carriers. The most widely spread therapeutic magnetic nanoparticles are based on iron oxide. Their size varies from 1 to 10 nm, which is smaller than any animal cell, and their movements in the body can be regulated using an external magnetic field. In actual practice nanoparticles are never used in their pure form, but are hybridized with other materials, for example, placed inside polymeric capsules on the stage of synthesis. This allows the scientists to regulate the properties of the particles: their charge, stability in the environments with different acidity, ability to penetrate cells, and so on. Hybridizing also reduces their possible toxicity.

Hybrid nanoparticles can be used not only to treat, but also to diagnose liver diseases. If molecules that bind specifically with liver connective tissue cells are placed on the surface of such particles, one can use MRI to visualize the areas of their accumulation and thus identify the sites of cirrhosis. The new method might help the patients avoid painful biopsies that are currently considered a standard procedure in liver fibrosis diagnostics.

"Targeted drug delivery using magnetic nanoparticles is not a new approach; for example, they are currently being clinically tested as the carriers of docetaxel, a drug against prostate cancer. Studies suggest that magnetic nanoparticles can effectively accumulate in the functional tissues of the liver and therefore can be used as drug molecule carriers in the therapy of liver fibrosis. Our laboratory works in the same field: for example, we carry out the tests of 'magnetic tweezers' allowing one to move single cells from one place to another. We are also involved in the synthesis of nanoparticles for biomedical applications," said Valeria Rodionova, the head of the Laboratory for New Magnetic Materials.

Endogenous proteins that play a vital part in allergies and parasitic infection can prevent the immune system from wrongly attacking the body and causing inflamed joints, a study from Karolinska Institutet in Sweden published in the scientific journal PNAS reports. The researchers hope that the results will give rise to new drugs for rheumatoid arthritis.

In protecting us against infections, our immune systems are vital to our survival. Unfortunately, immune cells can sometimes wrongly attack the body, resulting in what are called autoimmune diseases. These diseases are often serious and affect some five per cent of the population. One example is rheumatoid arthritis, in which the patient's immune system attacks the joints, causing inflammation and pain. If scientists are to develop better treatments for such patients, they need to understand in detail how immune cells are regulated.

Researchers at Karolinska Institutet have now discovered that certain proteins called IL-4 and IL-13 can play an important part in preventing autoimmune attacks. The proteins, which are secreted by immune cells in the presence of allergens or parasitic infections, influence the behaviour of a specific type of immune cell called a neutrophil. Neutrophils are commonly the most abundant immune cells found in the actively inflamed joints of patients with rheumatoid arthritis. They are particularly virulent against tissue since they can secrete various fairly non-specific tissue irritants.

Previous research has shown that IL-4 and IL-13 can affect arthritis in experimental models, but exactly how they do so has remained a mystery. The results of this latest study show that these proteins prevent neutrophils from migrating into the inflamed joint. The presence of IL-4 or IL-13 also stimulates an increase in neutrophil surface receptors which have an inhibiting effect on joint inflammation.

"We will continue to study these mechanisms and hope that our work can contribute to the development of treatments for rheumatoid arthritis," says principal investigator Fredrik Wermeling, assistant professor at the Department of Medicine, Karolinska Institutet (Solna).

For their study, the researchers used the CRISPR method to modify selected immune-cell genes in order to understand how they affect cell behaviour. The use of the bacterial CRISPR system as a research method is one of the most significant scientific advances of the past decade.

"The results we obtained using CRISPR were key to quickly understanding how the system under study is regulated," says Dr Wermeling. "I have high hopes that the experimental use of CRISPR will be hugely important to our understanding of how immune-cell behaviour is regulated, and that this can guide us in the development of new efficacious drugs."

More than 30 years ago, the European comet mission Giotto flew past Halley's comet. The Bernese ion mass spectrometer IMS, led by Prof. em. Hans Balsiger, was on board. A key finding from the measurements taken by this instrument was that there appeared to be a lack of nitrogen in Halley's coma - the nebulous covering of comets which forms when a comet passes close to the sun. Although nitrogen (N) was discovered in the form of ammonia (NH3) and hydrocyanic acid (HCN), the incidence was far removed from the expected cosmic incidence. More than 30 years later, researchers have solved this mystery thanks to a happy accident. This is a result of the analysis of data from the Bernese mass spectrometer ROSINA, which collected data on the comet 67P/Churyumov-Gerasimenko, called Chury for short, on board the ESA space probe Rosetta (see info box below).

Risky flight through the comet Chury's dust cloud

Less than a month before the end of the Rosetta mission, the space probe was just 1.9 km above the surface of Chury as it flew through a dust cloud from the comet. This resulted in a direct impact of dust in the ion source of the mass spectrometer ROSINA-DFMS (Rosetta Orbiter Sensor for Ion and Neutral Analysis-Double Focusing Mass Spectrometer), led by the University of Bern. Kathrin Altwegg, lead researcher on ROSINA and co-author of the new study published today in the prestigious journal Nature Astronomy, says: "This dust almost destroyed our instrument and confused Rosetta's position control."

Thanks to the flight through the dust cloud, it was possible to detect substances which normally remain in the cold environment of the comet on the dust particles and therefore cannot be measured. The amount of particles, some of which had never before been measured on a comet, was astonishing. In particular, the incidence of ammonia, the chemical compound of nitrogen and hydrogen with the formula NH3, was suddenly many times greater. "We came up with the idea that the incidence of ammonia in the ROSINA data could potentially be traced back to the occurrence of ammonium salts," explains Altwegg. "As a salt, ammonia has a much higher evaporation temperature than ice and is therefore mostly present in the form of a solid in the cold environment of a comet. It has not been possible to measure these solids either through remote sensing with telescopes or on the spot until now."

Ammonium salt and its role in the emergence of life

Extensive laboratory work was needed in order to prove the presence of these salts in cometary ice. "The ROSINA team has found traces of five different ammonium salts: ammonium chloride, ammonium cyanide, ammonium cyanate, ammonium formate and ammonium acetate," says the chemist on the ROSINA team and co-author of the current study, Dr. Nora Hänni. "Until now, the apparent absence of nitrogen on comets was a mystery. Our study now shows that it is very probable that nitrogen is present on comets, namely in the form of ammonium salts," Hänni continues.

The ammonium salts discovered include several astrobiologically relevant molecules which may result in the development of urea, amino acids, adenine and nucleotides. Kathrin Altwegg says: "This is definitely a further indication that comet impacts may be linked with the emergence of life on Earth."

Amsterdam, January 20, 2020 - A new study published in the Journal of Alzheimer's Disease (JAD) supports a growing body of research that links human exposure to aluminum with Alzheimer's disease (AD). Researchers found significant amounts of aluminum content in brain tissue from donors with familial AD. The study also found a high degree of co-location with the amyloid-beta protein, which leads to early onset of the disease.

"This is the second study confirming significantly high brain accumulation in familial Alzheimer's disease, but it is the first to demonstrate an unequivocal association between the location of aluminum and amyloid-beta in the disease. It shows that aluminum and amyloid-beta are intimately woven in the neuropathology," explained lead investigator Christopher Exley, PhD, Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, UK.

An association between aluminum and amyloid-beta has been suggested for over 40 years. In an earlier study, brain tissue from donors in the United Kingdom diagnosed with familial AD showed significant accumulations of aluminum. To further understand this relationship, in the current study the researchers measured aluminum in the brain tissue of a cohort of Colombian donors with familial AD who shared a specific mutation. The mutation leads to elevated levels of amyloid-beta, early disease onset, and an aggressive disease etiology. The levels were compared with a control set of brain tissues from donors with no diagnosis of neuropathological disease. They also used aluminum-specific fluorescence microscopy imaging to investigate the relationship between aluminum and amyloid-beta in familial AD.

The results were striking. The aluminum content of the brain tissue from donors with the genetic mutation was universally high, with 42% of tissues having a level considered pathologically significant, and the levels were significantly higher than those in the control set. The imaging studies identified aluminum deposits in all brain tissues studied. They were predominantly co-located with amyloid-beta in senile plaques and occasionally in the brain vasculature. Aluminum was also found separately from amyloid-beta in intracellular compartments including glia and neuronal axons. The results strongly suggest that genetic predispositions known to increase amyloid-beta in brain tissue also predispose individuals to accumulate and retain aluminum in brain tissue.

"Compelling localization of aluminum with a central player in AD, amyloid-beta, strengthens the link of aluminum to the pathogenesis of AD," commented George Perry, PhD, Professor of Biology, Semmes Distinguished University Chair in Neurobiology, University of Texas at San Antonio, and Editor-in-Chief of JAD.

"One could envisage increased amyloid-beta in brain tissue as a response to high levels of aluminum content, or that aluminum fosters the accumulation of amyloid-beta," said Dr. Exley. "Either way, the new research confirms my resolve that within the normal lifespan of humans, there would not be any AD if there were no aluminum in the brain tissue. No aluminum, no AD."