Culture

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."

Nightclubs and bars must create a supportive environment that cracks down on unwanted sexual attention and allows women to enjoy their nights out, according to a new study.

Increasing numbers of women are prepared to speak back to sexual harassment whilst enjoying a night out with female friends by confronting the men responsible and telling them clearly and robustly that their behaviour is unacceptable.

But researchers say that such a response - which they dub 'feisty femininity' - is complex and can result in backlash. It, therefore, needs businesses within the Night Time Economy to take seriously unwanted encounters in order to foster safer venues and help to end gendered violence.

Researchers from the Universities of Birmingham and Liverpool worked with colleagues at Liverpool John Moores University to explore women's navigation of unwanted sexual attention when in bars and nightclubs. They published their findings in Feminist Criminology.

They conducted focus groups with young women in Liverpool and discovered two broad forms for unwanted sexual attention when women went out: 'the pick-up routine', which men used to start sexual encounters; and 'showing off for the lads', where males engaged in undermining and abusive interactions with women for the purpose of impressing their male friends.

Encountering 'the pick-up routine' tended to prompt the use of 'diplomatic' rejection responses, which were carefully constructed in order to manage a potentially aggressive reaction. In contrast, 'showing off for the lads' approaches were more likely to spark a robust 'feisty' rebuttal from the targeted woman.

Article author Dr. Clare Gunby, from the University of Birmingham's Institute of Applied Health Research, commented: "Young people, globally, are starting to demand accountability for sexist structures and norms, partly due to the re-emergence of feminism and activism on University campuses and beyond.

"Women practicing 'feisty femininity' overtly resist unwanted encounters and this approach can arguably play a role in ending gendered violence. However, such responses may expose women to risks and place the labour of managing unwanted incidents onto women directly.

"Indeed, our participants felt that staff in nightclubs and bars did not take their concerns around safety seriously. Hence, women's informal strategies for dealing with unwanted attention become especially important because more formal lines of recourse often remain unavailable.

"Venues must, therefore, play a key role in creating a safe environment that makes it clear that unwanted sexual aggression will not be tolerated. There must be a multipronged approach across the Night Time Economy to addressing sexual violence."

The study sheds light on women's navigation of unwanted sexual attention when in bars and nightclubs - about which little is known, especially in the UK context. In addition to 'feisty femininity', the researchers found that women had developed three other risk management solutions:

'Emotion management' - offering a tactful and diplomatic explanation for their lack of interest (in order to mitigate negative reactions when rejecting men).

'Men as protector' - specifically going out with male friends or using a boyfriend (actual and mythical) to reduce the likelihood of an unwanted encounter.

'From individualism to camaraderie among the girls' - cutting an evening short, moving to another venue, laughing off unwanted attention or stepping in to stop men from exploiting drunken friends and strangers.

"There was a shared reticence to report unwanted incidents to venue staff or police as women felt that any report would be shrugged off and that no one would care due to the perceived normality of such practices when out in bars and nightclubs," Dr. Gunby notes.

"The lack of formal sanction for such behaviours could arguably play a role in their maintenance, prompting women to fill this gap by taking it upon themselves to monitor friends and strangers."

Developing new medicines and understanding how they target specific organs often gives a crucial advantage in the fight against human diseases. An international team led by researchers at the European Molecular Biology Laboratory and Cellzome, a GSK company, has developed a technology to systematically identify drug targets in living animals. In their results, published in Nature Biotechnology on Jan. 20, the scientists mapped protein-drug interactions in rat organs and blood. Their research opens pathways in drug discovery, fundamental biology, and personalized medicine.

When a drug binds to a protein, the structure of the protein gets tighter and only unfolds at higher temperatures. In this study, Mikhail Savitski - team leader and head of the Proteomics Core Facility at EMBL Heidelberg - and his team, together with a team at Cellzome melted proteins to observe their properties. They were able to get insights into the interactions between multiple proteins, or between proteins and drugs.

"For the first time, we can systematically map drug-protein interactions in a mammalian organism. This global view of the drug targets and potential side-effects is a huge step in drug discovery," explains Mikhail Savitski. By comparing the unwinding temperatures of proteins, the researchers determined which drug connected with which protein.

In 2014, Savitski and Cellzome presented their new thermal profiling technique for the first time, allowing scientists to study cell cultures with heat. While this technology advanced the field, cultured cells differ strongly to a living organism.

The method now published represents a significant advancement for translational research because biological changes can be directly monitored in an organ by measuring protein interactions and activation of cellular pathways. In drug discovery, the ability to monitor the engagement of the pharmacological target in a living organism is fundamental for achieving therapeutic efficacy.

To demonstrate their technique's capabilities, the scientists scanned all proteins in rat liver, lung, kidney, and spleen. Their results provided novel insights into the interactions of proteins and revealed potential drug targets. "For the first time, we can study protein interactions in different tissues of living organisms and how they are affected by external conditions. Our technique could significantly improve our understanding of human diseases and aid the development of successful treatments," says Nils Kurzawa, EMBL scientist in the Savitski group.

The study was led by Rodrigo Ramos Catharino, a professor in UNICAMP's School of Pharmaceutical Sciences.

In experiments with a human prostate adenocarcinoma cell line (PC-3), the scientists found that Zika inhibits tumor cell proliferation even when inactivated by high temperature. Results of their research, which is supported by São Paulo Research Foundation - FAPESP, have been published) in Scientific Reports.

"The next step in the investigation involves tests in animals. If the results are positive, we plan to look for companies with which to partner on clinical trials," said Catharino, who also works as principal investigator for UNICAMP's Innovare Biomarker Laboratory.

The research project coordinated by Catharino began in 2015, when the link between the Zika epidemic and the rising number of microcephaly cases in Northeast Brazil was discovered. After studies confirmed that Zika can infect and destroy neural progenitor cells, which are precursors of the various types of brain cells in the fetus, Catharino decided to determine the effects of the virus on glioblastoma cells. Glioblastoma is the most common and aggressive type of central nervous system cancer in adults (read more at agencia.fapesp.br/27166).

The positive in vitro results obtained by the UNICAMP group were confirmed in an animal model by scientists at the Human Genome and Stem Cell Research Center (HUG-CELL), a Research, Innovation and Dissemination Center (RIDC) supported by FAPESP and hosted by the University of São Paulo - USP (read more at agencia.fapesp.br/27677).

"Because it's been confirmed that Zika is sexually transmitted and prefers infecting reproductive cells, we now want to test its effectiveness against prostate cancer," Innovare laboratory team member Jeany Delafiori told Agência FAPESP. Catharino is Delafiori's PhD thesis advisor.

The research is also supported by the Obesity and Comorbidities Research Center (OCRC), another of FAPESP's RIDCs, in this case hosted by UNICAMP.

Persistent inflammation

In another recent study published in Scientific Reports, Catharino and his group reported the identification of markers of neurological inflammation as many as two years after birth in the saliva of babies born with microcephaly to mothers diagnosed with Zika during pregnancy.

"This shows that Zika induces inflammation that lasts a long time, persisting even after the virus has been completely eliminated from the organism," Catharino said. "The 'wild' version of the virus [without inactivation] could therefore have undesirable effects and won't be usable therapeutically."

The researchers therefore decided to determine whether Zika retains the capacity to destroy tumor cells after inactivation. The experiments were performed with a viral lineage obtained from samples isolated from a patient infected in the northeastern state of Ceará in 2015. After cultivation in the laboratory, the virus was fused with a nanoparticle and heated to 56 °C for one hour to suppress its infection potential.

The next step was to expose cultured PC-3 (prostate cancer) cells to the inactivated virus for 24 or 48 hours and then compare these treated cells with tumor cells that had not been exposed to the pathogen.

"We observed a selective cytostatic effect [inhibition of cell growth and division] in PC-3 cells. In the analysis performed after 48 hours, the cells in contact with the inactivated virus were found to have grown 50% less than the control cells," Delafiori said.

To investigate how Zika alters tumor cell metabolism, the cultured cells were analyzed with a mass spectrometer, a device that acts as a kind of molecular scale, identifying and sorting elements present in biological samples according to their mass.

To process the large volume of data obtained by mass spectrometry, the researchers performed a multivariate statistical analysis known as PLS-DA (partial least squares discriminant analysis), which pinpointed 21 markers capable of describing how the virus affects tumor cell metabolism and inhibits cell proliferation.

"For example, we identified lipid markers involved in stress and cellular death processes, such as ceramides and phosphatidylethanolamine," Catharino said. "These and other reported markers explain the lipid remodeling induced by the particle and the disruption of metabolic pathways involving molecules such as porphyrin and folic acid, thus contributing to cell stress and the observed antiproliferative effect."

According to Catharino, these 21 metabolites can be used to pursue a better understanding of the biochemical changes triggered by the virus and to identify therapeutic targets, revealing prospects for further research.