Culture

Small organic molecules, including the amino acids that form the 'building blocks' of proteins in living cells, fragment to form ions under the impact of high-energy radiation such as electron beams. A new study published in EPJ D has now shown what happens when electrons collide with one amino acid, glutamine. The extent of the damage and the nature of the ions formed are both affected by the energy of the colliding electrons. This work arises from a collaboration between experimental physicists led by Alexander Snegursky at the Institute of Electron Physics, Uzhgorod, Ukraine and theoreticians led by Jelena Tamuliene at Vilnius University, Vilnius, Lithuania.

The damaging effect of very high-energy radiation on human tissue is well-known from disasters such as the nuclear accidents at Chernobyl and Fukushima. However, the long-term effects experienced by survivors of such disasters, including an increased risk of cancer, are partly caused by the impact of rather lower-energy radiation. The groups chose to study the effect of electron impact on amino acids because they are less widely studied in this context than DNA.

Snegursky and his colleagues used mass spectrometry to measure the mass-to-charge ratio and thus determine the nature of chemical fragments produced when one biologically important amino acid, glutamine, was bombarded with uniform electron beams with different radiation doses. Meanwhile, the theoretical team modelled the electronic and geometric structures of glutamine and its fragments using quantum mechanics. The observed fragmentation patterns differed according to the radiation dose that the molecules received, and the experimental results were largely borne out by the simulations. The study authors believe that this basic research will have implications for understanding the effect of ionising radiation on human cells, improving the selectivity of radiotherapy beams for cancer cells, and even, perhaps, understanding the origin of life.

Vision is fundamentally based on the perception of contrast. When light conditions change, the eye needs a certain period of time to adapt and restore its ability to estimate contrast correctly. These processes are relatively well understood. However, researchers at Johannes Gutenberg University Mainz (JGU) have now discovered a mechanism employed by the fruit fly Drosophila melanogaster that broadens our understanding of visual perception. Their results explain why the eye can correctly evaluate contrast, even in suddenly changing light conditions. "Fruit flies can do this because they have nerve cells in their visual system that react to luminance. These nerve cells make it possible for the flies to adjust their behavior when visual stimuli dynamically change," explained Professor Marion Silies, head of the research project at JGU.

Sensory systems of living organisms have evolved in a way that they tend to note changes rather than absolute sensory inputs. "For example, you might well forget that you're wearing a necklace during the day, but if an insect lands on your skin you feel it immediately," added Silies. Vision works in the same way, as it is adaptable and designed to respond to changes in the environment. Many nerve cells respond to contrasts rather than to luminance itself. That is why many animals have visual systems that work particularly well at dawn, at dusk, in daylight, or in a rapidly changing environment.

The performance of photoreceptors in the retina plays a key role in both vertebrates and invertebrates. These photoreceptors ensure that contrast is detected regardless of the background luminance. However, this retinal adaptation alone cannot explain the mechanism that copes with sudden changes, such when, for example, an animal moves rapidly or when viewing an object moving from bright sunlight into a shadow. In such cases, background luminance can change within milliseconds.

Contrast-sensitive lamina neurons alone are not enough / Luminance acts as a corrective signal

During their investigation of Drosophila, Professor Marion Silies and her team of neuroscientists have focused on the processes that take place directly downstream of the photoreceptors in the nervous system. They paid particular attention to the pathways involving the lamina neurons that are specialized to detect an increase or decrease in contrast. "Here, we uncovered a luminance-sensitive pathway in the Drosophila visual system. Contrast-sensitive neuronal responses alone are insufficient to account for behavioral responses to changing visual stimuli, arguing for the presence of a corrective signal that scales contrast-sensitive responses when background luminance suddenly declines," the authors write in their article for Current Biology. "We have been able to show that information about luminance acts as a corrective signal which intervenes when it suddenly goes dim. This implies that information about luminance is needed in order to accurately recognize contrasts," added lead author Madhura Ketkar. To date, it had been assumed that the relative contrast conveyed by other lamina neurons was alone necessary in order to see accurately in rapidly changing light conditions, making it possible to correctly compute visual responses when, for instance, a football moves from light into the shade.

L3 neurons are sensitive to brightness and particularly active in low light conditions

The neurobiologists were able to demonstrate this by measuring the calcium signals in the nerve cells with the help of two-photon microscopy. This technique enabled them to determine the activity of individual nerve cells in live fruit flies. "Our measurements showed that there are cells which react to luminance and not contrast," emphasized Silies. The team confirmed these findings by behavioral experiments in which the flies were made to walk on a small air-cushioned ball in front of a dynamically changing background. "We were also able to clearly demonstrate that these luminance-sensitive cells are necessary for the fly to respond when the background quickly turned dim," Silies continued. When L3 lamina neurons were not active, there was no appropriate behavioral response.

The researchers have thus identified a new mechanism that explains how correct image processing occurs in dynamically changing light conditions. Sensitivity to contrast alone is not sufficient to account for behavioral responses to visual stimuli. The researchers conclude that light intensity, the primary input signal for the visual system, is also a crucial factor for correctly controlling behavioral responses to visual inputs. They propose that this is a general visual processing strategy that is also likely to be used by the human eye.

Since 2019, Marion Silies has been Professor of Neurobiology at the Faculty of Biology and a Fellow of the Gutenberg Research College (GRC) at Johannes Gutenberg University Mainz.

The number of overweight children has increased significantly. In addition to psychological problems, chronic diseases such as diabetes, high blood pressure and joint wear and tear are on the rise. Some food and beverage companies have signed a voluntary commitment at EU level to restrict advertising of foods high in fat, sugar and salt to children. A study by scientists at the University of Bonn shows: The number of corresponding commercials aimed at children decreased in Germany once this agreement had been put in place, but the companies also exploit loopholes. The results have now been published in the journal Food Policy.

How effective is the self-regulation initiative of food and beverage companies, which was initiated in 2007? Has the number of commercials for high-fat, high-sugar and high-salt foods targeted at children decreased since then? These and other questions were investigated by researchers from the Department of Agricultural and Food Market Research at the Institute for Food and Resource Economics at the University of Bonn. "Under the terms of the EU Pledge, each food company was initially largely free to determine for itself which levels of fat, sugar and salt should not be advertised to children," says doctoral student Stefanie C. Landwehr. These criteria were later standardized throughout Europe, but they are still set by companies and not by an independent scientific body.

Viewing 88 hours of commercials

As part of the study, the authors recorded a total of 88 hours of advertising with 3047 commercials for beverage and food products on specific dates in October 2011 and 2014. Based on a code book Stefanie C. Landwehr determined whether the respective commercial was aimed at children (697 clips) or adults, taking into account the context and tone of the advertising messages. In addition, the researcher investigated the nutritional values for each food product that was advertised in a child-friendly manner and classified whether or not it was in line with the harmonized advertising guidelines of the self-regulation initiative.

She also evaluated the products according to the OFCOM criteria. This nutrient profile developed by the UK's Office of Communications is used, among other things, as the basis for the statutory restriction of TV food advertising to children in the UK. In their investigations, the scientists differentiated between food and beverage companies that have signed the EU Pledge and those that have not. They also analysed which factors influence whether a food commercial meets the criteria of the EU Pledge or the OFCOM criteria.

At first glance, the self-regulation initiative of the food and beverage industry shows considerable impact: "In October 2014, and therefore shortly before the harmonization came into force, almost all commercials on children's television met the self-imposed criteria," reports Landwehr. In addition, commercials aimed at children considerably declined. "The voluntary commitment of the corporations is a step in the right direction," adds Prof. Dr. Monika Hartmann. However, the companies' self-selected criteria for regulating advertising are not stringent enough. "The UK has with the OFCOM nutritional profile much stricter requirements for regulating food advertising to children." When these criteria are applied the picture is no longer quite so positive. Moreover, the voluntary nature of the initiative reduces the potential effect because not all food companies take part.

Corporations partly exploit loopholes in the regulatory framework

Furthermore, according to the findings of the researchers food and beverage companies that are signatories to the voluntary commitment also exploit loopholes. In fact, there is still a considerable amount of child-friendly advertising for problematic products during adult TV broadcasting hours, even though the programs are often also watched by children. "When it comes to child targeted commercials, it would therefore be desirable for the guidelines to apply to all programs and not only to children's programs," says Landwehr.

It is now technically possible to hold groups of atoms at temperatures that are only a few hundredths of a degree above absolute zero. This so-called 'ultracold gas' loaded in an optical lattice is an extremely powerful platform to study quantum mechanical phenomena including phase transitions, due to the excellent control of experimental parameters, such as potential depths, inter-particle interaction strengths and lattice parameters. Sk Noor Nabi from Zhejiang University in Hangzhou, China and colleagues in the Indian Institute of Technology, Guwahati, India, have studied the phase transition between the Mott insulating (MI) and superfluid (SF) states of such a gas in a time-dependent synthetic magnetic field. Their results, published in EPJ B, show that the energy spectrum of the gas loses symmetry in the fluctuating magnetic field. This is observed in the disappearance of the striking 'Hofstadter's butterfly' effect seen in the energy spectrum under a constant magnetic field.

The physics of an ultracold gas - put another way, of interacting, neutral bosons at close to absolute zero - can be described mathematically with the Bose-Hubbard model. Using this theory, Nabi and his co-workers modelled a neutral ultracold gas in a synthetic magnetic field with a magnetic flux that varied over time. Plotting the phase diagrams at different time points and for different values of magnetic flux showed some quite dramatic changes in the shape of the boundary between the MI (insulating) and SF (zero viscosity) states. Thus, the stability of the MI phase and hence the critical location of the phase transition depends upon the particular choice of time dependent gauge field. They also showed that the symmetry of the energy spectrum under a constant magnetic field was lost once time dependence was introduced, leading to the disappearance of the characteristic Hofstadter's butterfly pattern.

The Bose-Hubbard model is important for the study of quantum entanglement, which has many applications in quantum information theory. Therefore, studies like this one - which may on the surface seem rather obscure - may come to have 'real world' applications when quantum computers become practicable.

3D printers working in the millimeter range and larger are increasingly used in industrial production processes. Many applications, however, require precise printing on the micrometer scale at a far higher speed. Researchers of Karlsruhe Institute of Technology (KIT) have now developed a system to print highly precise, centimeter-sized objects with submicrometer details at a so far unmatched speed. This system is presented in a special issue of Advanced Functional Materials (DOI: 10.1002/adfm.201907795).

To demonstrate not only the speed, but also the reliability of their setup, the researchers have printed a lattice structure of 60 cubic millimeters in size with details down to the micrometer scale. It contains more than 300 billion voxels (a voxel is the 3D counterpart of a pixel or 2D picture element). "We have by far outperformed the record reached by 3D-printed aircraft wings. This is a new world record," says Professor Martin Wegener, Spokesperson of the Cluster of Excellence "3D Matter Made to Order" (3DMM2O), within which the system was developed.

For this type of 3D printing, the beam of a laser passes a liquid photoresist in a computer-controlled manner. The material located in the focus of the laser only is exposed and hardened. "The focal points correspond to the nozzles of an inkjet printer, the only difference being that they work three-dimensionally," Vincent Hahn, first author of the publication, says. In this way, highly precise filigree structures can be produced for various applications, such as optics and photonics, material sciences, bioengineering, or safety engineering. Typically, several hundred thousands of voxels per second have been produced with a single laser light spot so far. This means that it was nearly a hundred times slower than graphical inkjet printers, which impeded many applications so far. Scientists of KIT and Queensland University of Technology (QUT) in Brisbane/Australia have now developed a new system within the 3DMM2O Cluster of Excellence. Using special optics, the laser beam is divided into nine partial beams that focus on a focal point each. All nine partial beams can be used in parallel and, thanks to improved electronic control, they can be moved precisely much more rapidly than ever. This and some other technical improvements made the researchers reach 3D printing speeds of about 10 million voxels per second, which corresponds to the speed reached by graphical 2D inkjet printers. KIT will continue research and development work in this area. "After all, 3D printers will be used to print not just one page, but thick volumes," Hahn says. This will also require progress in chemistry. For example, more sensitive photoresists are needed to generate more focal points at the same laser output.

Producing thin-film solar modules requires much less energy than conventional wafer-based Si PV modules, and therefore their energy payback time is much shorter. Chalcopyrite-structured compounds of copper, indium, gallium, and selenium (CIGSe) are an important class of materials for thin-film PV, because CIGSe absorbs incident light much better than silicon, and so a very thin layer grown on a substrate via coevaporation suffices to convert light into electrical energy efficiently.

Efficiency up to 22,6 percent

The European Sharc25 research project approached the challenge of optimizing the conversion efficiency of CIGSe thin film technology from multiple angles, combining theoretical modelling, experimental characterization, and sharing of technological expertise between several leading research groups throughout Europe. During the project, the efficiency of CIGSe solar cells produced within the consortium rose from 21.7 to 22.6 percent.

One focus of the project was to understand the positive effects of post-processing with the alkali elements potassium, rubidium, and cesium. This post-processing changes the chemical and electronic surface properties of the CIGSe absorber. In addition, the alkali atoms migrate from the surface into the grain boundaries between the CIGSe grains, which improves the electronic properties of the thin film. The recombination of charge carriers in the bulk CIGSe is reduced, among other effects. This beneficial effect is observed for CIGSe layers prepared at various temperatures and on different substrates.

Know-how for European industries

Eleven research institutions from eight countries, including an HZB team headed by Prof. Marcus Bär, collaborated on the EU Sharc25 project. An important goal was to secure Europe's pioneering role in the field of thin-film PV. "It is certainly a competitive advantage to be able to address questions related to applied materials research and to the development of industry-oriented devices using advanced research tools. To do so efficiently, we learn in such large EU projects. This represents a significant advantage and preserves the crucial edge in knowledge and know-how", says Bär.

Excessive and obsessive exercise is very harmful to health, this being particularly pronounced for persons suffering from eating disorders. Based on electronic diaries, a team of researchers of Karlsruhe Institute of Technology (KIT) and the University of Freiburg has now uncovered for the first time psychological mechanisms underlying pathological exercise. Their results allow the conclusion to be drawn that persons with eating disorders use exercise to regulate depressive mood and negative thoughts relating to their eating disorders. The study is published in Psychotherapy and Psychosomatics (DOI: 10.1159/000504061).

It is undisputed that exercise promotes health. Excessive and obsessive exercise, however, may become an "addiction" in the extreme case and cause illness. There is sufficient evidence that this unhealthy exercise is particularly pronounced for persons suffering from eating disorders. For the first time, a team of researchers of KIT's Institute of Sports and Sports Science (IfSS) and the University of Freiburg has now uncovered psychological daily mechanisms underlying this pathological form of exercise. The method used for the study is referred to as ambulatory assessment. It records human experience and behavior in daily life and has been developed and used by experts of IfSS. "The main idea consists in the fact that we have to study the human species in its natural habitat in order to understand human behavior," says Professor Ulrich Ebner-Priemer, Head of the Mental mHealth Lab of KIT.

The study was based on specifically developed, activity-triggered electronic diaries on smartphones. "With these electronic diaries, we studied the dynamic interaction of physical exercise and psychological variables in everyday life," explains Markus Reichert, who works in the group of Professor Ebner-Priemer at KIT and is the first author of the study together with Dr. Sabine Schlegel of the University of Freiburg. "Thanks to this technology, it was possible to specifically request subjective self-reports in case of conspicuous exercise episodes and to generate a high statistical variance of data."

Using this method, physical activity of 29 patients with eating disorders and 35 healthy controls was recorded objectively and constantly by an accelerometer, e.g. movement sensor, in daily life for a period of seven days. The accelerometer was connected to a smartphone via bluetooth, an installed app triggered requests for reports when measurements were below or above certain activity thresholds. In addition, the test persons were asked to report their subjective state of condition before and after exercise.

The researchers found that exercise of patients with eating disorders was preceded by declining mood. This effect was not found for healthy controls, who rather felt full of energy prior to exercise. After exercise, patients with eating disorders had a better mood than the healthy controls and their average mood, they felt more relaxed, and less pressure of having to be slim. Altogether, they were more satisfied with their body. However, this effect persisted for a limited period of time ranging from one to three hours depending on the test person.

The results reported by the authors in Psychotherapy and Psychosomatics allow the conclusion to be drawn that patients with eating disorders use exercise to regulate depressive moods and negative thoughts relating to their eating disorders. "To cope with difficult emotional states and negative body experience, they get exercise, probably also due to lacking alternative strategies at such times," Markus Reichert explains. "It is quite obvious that the positive effects of exercise enhance unhealthy exercise. Feeling relieved after sports leads to renewed exercise when the effect declines. This may result in a vicious circle, in which more and more exercise is needed to feel good," say Markus Reichert and Professor Almut Zeeck, coordinator of the study at the university hospital of Freiburg.

According to Zeeck, these findings have major implications for therapy and further research. In therapy, sports might be used specifically and in precise doses to positively influence the mood and body experience of people suffering from eating disorders. It will be of crucial importance, however, to convey alternative action strategies to the patients in order to prevent unhealthy, excessive exercise. Here, latest technologies, such as day-to-day intervention on smartphones, might help. "This opens up new perspectives for therapeutic interventions that reach patients in their everyday life and may represent an important supplement to ambulatory psychotherapy," Zeeck says.

The cover for issue 5 of Oncotarget features Figure 2, "Survival curves in the KRAS, EGFR, and niche mutations cohorts," by Aramini, et al.

Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET.

The multivariable analysis showed that:

Niche mutations had higher mortality than EGFR mutations
KRAS mutations had higher mortality than EGFR mutations, and
Niche mutations presented similar mortality to KRAS mutations.

Niche mutations exhibited an increased risk of death when compared with EGFR mutations and a similar risk of death when compared with KRAS mutations.

Dr. Beatrice Aramini from the Division of Thoracic Surgery in Department of Medical and Surgical Sciences at the University of Modena and Reggio Emilia in Modena Italy said in their Oncotarget Research Paper, "In the last century, carcinoma of the lung has progressed from an uncommon and obscure disease to the most common cancer in the world, and the most common cause of death from cancer."

In addition to these somatic mutations, which are the most frequent, other mutations in several genes have been discovered, including BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET mutations.

Moreover, the prevalence of the RET mutation in adenocarcinoma was estimated to be 1.7%, and the prevalence of DDR2 mutation in lung cancer was 2.2%.

With regard to treatment, discoveries of gene mutations have allowed the development of targeted therapies, which are considered more effective for survival than chemotherapy in patients with advanced mutated disease.

Considering the potential aggressiveness of niche mutations in this context, the technological advances of next-generation sequencing, which is currently used in clinical practice, represents a precise approach to identifying a large panel of mutations in oncologic patients.

The Armini Research Team concluded, "The correct selection of mutations will be helpful in terms of the greater efficacy of treatment in association with better prognosis and a higher quality of life for oncologic patients."

Up to 10% of patients who are hospitalized or undergo surgery will experience acute kidney injury (AKI), and as many as 50% of patients in intensive care units will meet the criteria for AKI, the National Kidney Foundation has determined. Some of these patients will progress to kidney failure within months.

Physician-Scientists and other researchers at Rush University Medical Center, in collaboration with colleagues at other institutions, have revealed a new treatment target that may help change the outcome for patients at risk of AKI. The results were published Jan. 29 in The New England Journal of Medicine.

"In this study, we found evidence that a specific protein produced by immune cells in the bone marrow, called soluble urokinase plasminogen activator receptor (suPAR,) is a strong risk factor for acute forms of kidney failure, that occur as consequence of general medical procedures," said Jochen Reiser, MD, PhD, a professor at Rush University Medical Center and chairperson of Rush's Department of Internal Medicine. Reiser is senior author of the study.

suPAR has been repeatedly shown to harm kidneys. Chronically elevated blood levels are linked to development of Chronic Kidney Disease (CKD), a paper published by Reiser and colleagues in The New England Journal of Medicine in 2015. Now, the new paper is showing that having elevated suPAR levels is also a risk factor for acute kidney injury - a sudden decline in kidney function that can be a severe side effect of general medical procedures.

"Nephrology has found its global risk molecule: suPAR," said Reiser.

"Any kidney disease, chronic or acute, genetic or acquired, is better off with a lower suPAR level. By looking at suPAR levels in patients, we can possibly prevent damage to healthy kidneys that is often irreversible."

Reiser believes that high suPAR levels will inform physician-patient conversations about preventing kidney disease, just as high cholesterol levels signal the need for lifestyle changes and protective drugs, such as statins, to avert heart attacks and strokes.

Study looked at SuPAR levels in coronary angiography, cardiac surgery and ICU patients

"We have known for some time now of suPAR's important role in kidney disease. Here we show that suPAR is relevant in important clinical situations such as coronary angiography and cardiac surgery, and could be targeted to minimize the risk of AKI," said Salim Hayek, MD, a cardiologist at the Michigan Medicine Frankel Cardiovascular Center and first author of the study.

Reiser, Hayek and colleagues performed a two-pronged investigation of suPAR.

First, they looked at suPAR levels and the risk of acute kidney injury in three clinical settings.

"We collected blood samples from patients about to undergo coronary angiography for suspected heart disease, patients undergoing cardiac surgery, and critically ill patients who had been admitted to the intensive care unit," said David E. Leaf, MD, a co-first author on the study and the director acute kidney injury research at Brigham and Women's Hospital of Harvard Medical School.

The team found that suPAR levels independently predicted risk of AKI in each of these clinical settings. If a person had higher suPAR levels before undergoing coronary angiography or cardiac surgery, or upon admission to the intensive care unit, they were at much greater risk of developing AKI afterwards.

These associations were entirely independent of other clinical characteristics, such as age, gender, race, severity of illness, and baseline kidney function. The team divided patients into quartiles based on how high their suPAR levels were and compared outcomes for patients across quartiles.

They found that risk of AKI increased steadily with increasing suPAR levels, with an increase of 3.5 to four times the risk of AKI for those in the highest quartile compared to the lowest. High SuPAR levels consistently predicted AKI in these patients, with levels above 3,000 picograms per milliliter doubling the risk of AKI. In total, the study included 4,769 patients.

Second phase of study found higher suPAR led to worsening kidneys in mouse models

These findings led the researchers to the second phase of the study. They employed mouse models of acute kidney injury to investigate whether high suPAR is actually a contributing cause of the complication. When the mice were exposed to contrast used in patients undergoing coronary angiography, the researchers found that higher levels of suPAR led to worsening of kidneys compared to mice with normal levels.

"We are studying interventions to alter suPAR levels," said Reiser. "We found that when mice were pretreated with a monoclonal antibody to block suPAR, the researchers managed to reduce the development and the severity of kidney injury."

While the researchers are looking at utilizing treatments and medications already used for other purposes, like statins or immune modulators, they have also sparked the creation of novel humanized suPAR antibodies that once fully developed will be explored in clinical trials.

A new handheld 3D printer can deposit sheets of skin to cover large burn wounds - and its "bio ink" can accelerate the healing process.

The device, developed by a team of researchers from the University of Toronto Engineering and Sunnybrook Hospital, covers wounds with a uniform sheet of biomaterial, stripe by stripe.

The bio ink dispensed by the roller is composed of mesenchymal stroma cells (MSCs) -- stem cells that differentiate into specialized cell types depending on their environment. In this case, the MSC material promotes skin regeneration and reduces scarring.

The project is led by PhD candidate Richard Cheng, under the supervision of Professor Axel Guenther, and in close collaboration with Dr. Marc Jeschke, director of the Ross Tilley Burn Centre, and his team at Sunnybrook Hospital. Their successful in-vivo trials on full-thickness wounds are reported in the journal Biofabrication.

The paper is a major step forward for the team, which unveiled the first prototype of the skin printer in 2018. The device was believed to be the first device of its kind to form tissue in situ, depositing and setting in place in two minutes or less.

"Previously, we proved that we could deposit cells onto a burn, but there wasn't any proof that there were any wound-healing benefits -- now we've demonstrated that," says Guenther.

The current method of care for burns is autologous skin grafting, which requires transplantation of healthy skin from other parts of the body onto the wound.

But large, full-body burns pose a greater challenge. Full-thickness burns are characterized by the destruction of both the outermost and innermost layers of the skin; these burns often cover a significant portion of the body.

"With big burns, you don't have sufficient healthy skin available, which could lead to patient deaths," says Jeschke.

Since 2018, the printer has gone through 10 redesigns, as the team moves towards a design they envision surgeons using in an operating room. The current prototype includes a single-use microfluidic printhead to ensure sterilization, and a soft wheel that follows the track of the printhead, allowing for better control for wider wounds.

Next, Cheng says that they ultimately want to "further reduce the amount of scarring, on top of helping with wound healing. Our main focus moving forward will be on the in-vivo side."

Jeschke believes the handheld skin printer could be seen in a clinical setting within the next five years. "Once it's used in an operating room, I think this printer will be a game changer in saving lives. With a device like this, it could change the entirety of how we practice burn and trauma care."

Can staph microbes lead to cancer?

Microbes are known to affect digestion, mood and overall health, and now Princeton researchers have shown that a shift in the microbiome is linked to cancer -- at least in a threatened subspecies of foxes found only on one island off the California coast.

Their research suggests a several-step process: First, the cat-sized Santa Catalina foxes become infested with ear mites, which change the foxes' microbiome and allow a staph infection to take hold. As Staphylococcus pseudintermedius runs rampant, the antibiotic-resistant infection leads to chronic inflammation of the foxes' ears. In that environment of inflamed tissue, tumors can flourish. The researchers detailed their findings in the journal Molecular Ecology.

"We were really excited to find such clear results," said Alexandra DeCandia, the first author on the paper and a graduate student in the lab of Bridgett vonHoldt, an associate professor of ecology and evolutionary biology at Princeton University. "Everything we found -- reduced species diversity, shifts in community composition, overabundance of potentially pathogenic species -- fit within our expectations."

The project started during conservation efforts on Santa Catalina Island, when researchers noticed that roughly half of the adult foxes had tumors growing in their ears. That's one of the highest tumor rates ever observed in wildlife, prompting immediate follow-up study.

Early work demonstrated a link between ear mite infection and tumor growth. Most researchers theorized that ear mites led to chronic inflammation, ultimately sparking the growth of tumors. DeCandia and vonHoldt's team wanted to know whether the microbiome also played a role in this system.

That focus on diversity within the microbiome makes their work "an excellent example of where the field is going to move in the future," said George Amato, the director of conservation genomics at the American Museum of Natural History, who was not involved in this research. "We've only recently learned how important the microbiome is to an individual's health -- whether it's an animal or a human," he said. "Previously, scientists only examined part of the picture. They certainly weren't looking at microbiomes -- they didn't even have tools to do it. ... By examining that, we've come to understand that a lack of diversity in that microbial community, combined with the genetics of the foxes, best helps us understand not only the threat of this particular disease but other diseases as well. This really is a new paradigm for understanding threats to endangered species."

The threatened Santa Catalina foxes are one of six subspecies of Channel Island foxes (Urocyon littoralis) that live on six of the eight Channel Islands off the coast of southern California. Several of the subspecies, including those on Santa Catalina (U. littoralis catalinae), have made impressive rebounds from the brink of extinction -- with the result that they are all incredibly similar genetically, nearly clones of each other.

The foxes' almost total lack of genetic diversity makes them fascinating research subjects, said DeCandia.

"We typically view genetic diversity as a good and necessary thing," she said. "It keeps organisms healthy -- think of the negative health effects associated with inbreeding -- and helps populations survive unexpected changes to their environment. But despite having almost no genetic variation, these foxes exhibit very few signs of poor health or inbreeding depression. That leads us to wonder whether other forms of diversity -- such as their resident organisms -- become important players in health and immunity. That's why we focused our study on the microbiome and disease in these foxes."

The link between microbes and cancers was an unexpected find, DeCandia said. "When we first set out to do this study, we simply wanted to characterize the microbiome across a few different body sites in the foxes. Just as 19th-century naturalists would charge into a new habitat and catalogue species, we originally intended to catalogue microbes. However, after looking at ear canals more closely, we found there was a lot of variation associated with mite infection status. We then pivoted the paper to focus almost entirely on ear canal microbes associated with mite infection!"

With their collaborators from the Catalina Island Conservancy, they swabbed dozens of foxes to collect microbes, then extracted DNA to determine which microbes were present in all of their samples -- and in what relative abundances.

"Since microbes exist within a community, relative proportion matters," DeCandia said.

They found that mite-infected ear canals had significantly different microbial communities than uninfected ears. Overall species richness was lower, and relative abundance was skewed toward one bacterial species: S. pseudintermedius, which is common on canids (including dogs) and can become an opportunistic pathogen when communities are disrupted -- such as by an infestation of mites.

The staph microbe then forms antibiotic-resistant biofilms that are "incredibly difficult" for the immune system to eradicate, said DeCandia. As a result, this strain of staph is linked to chronic inflammation in many species.

The researchers are still trying to clarify the cause and effect relationships -- for example, whether the mites bring in the staph microbes or they were present but latent until the mites caused enough structural damage to allow the staph to have a population boom -- but the string of correlations is clear: mite infection is linked to a proliferation of S. pseudintermedius, which is linked to the chronic inflammation associated with tumorigenesis.

One major outstanding question is why, of the six Channel Island fox subspecies, only three have mites and only one -- the Catalina Island foxes -- show significant tumor growth.

The new study reinforces previous research in which members of vonHoldt's lab, including Kennedy Leverett of the Class of 2020, studied changes in the skin microbiome associated with sarcoptic mange, which is caused by a different species of mite. They looked at coyotes, red foxes and gray foxes and found remarkably consistent signatures of microbial disruption that almost exactly matched the island fox study: Infected individuals had reduced microbiome diversity and higher abundance of S. pseudintermedius.

"Considered together, these two studies suggest that this microbial species is an important player in canid microbiomes and may function in a number of diseases," DeCandia said.

EAST LANSING, Mich. - Researchers at Michigan State University's Precision Health Program have helped develop a fascinating new method for detecting the density of proteins in the blood - a method that could vastly improve the rate at which diseases are detected and diagnosed.

The method, called "magnetic levitation," or MagLev, had previously been used to separate different types of particles in solutions, arranging them in groups based on their relative densities rather than weight. Now, two new studies by Precision Health's Morteza Mahmoudi, assistant professor, and Ali Akbar Ashkarran, research associate, illustrate how the method also can be applied to human blood plasma - the liquid component of blood. Plasma contains many types of proteins that perform a multitude of functions in the body.

"When we put something in liquid, it separates into sediment by weight," Mahmoudi said. "But another force - the magnetic force ¬- can cancel out weight and levitate the proteins. This permits us to much more precisely define the density of proteins in solution."

Being able to accurately measure the density of proteins in the body is important since proteins play important roles in both health and disease states. For example, lipoproteins transport fats to cells, antibody proteins play roles in immunity and coagulation proteins help blood clot. Current methods to measure density of proteins in liquid are unreliable and often destroy the fundamental properties of the proteins.

In the first study, published in Analytical Chemistry, the team applied the MagLev technique in a small tube containing magnetic nanoparticles into which plasma proteins had been introduced. Over a three-hour period, the team observed the emergence of a number of distinct bands representing various forms of proteins.

"The proteins created specific shapes when they were levitated," Mahmoudi said. "It looks like a 'smiley face' of layers."

Measuring the density of the bands, the team arrived at two noteworthy findings. The first was that there was no correlation between the density of a protein and its molecular weight, which came as a surprise since it goes against conventional thinking. The other was that the average density of proteins was much lower than previous studies had suggested.

The mechanism by which the proteins separate into layers by density isn't totally clear, but it may be due to structural differences and/or protein-to-protein interactions.

"The findings are of crucial importance, as protein density is being used to define proteins' physical properties, including their 3D structures," Mahmoudi said. "In addition, the accurate density of proteins enables us to design safer and more efficient therapeutic agents, such as nanomedicine."

So, the MagLev method isn't just a fun research tool - it has exciting clinical implications. The particular "signature" of an individual's plasma proteins might tell a doctor much about a patient's health status.

Indeed, this is what Mahmoudi and Ashkarran laid out in the second study, published in Advanced Healthcare Materials. They tested the MagLev method clinically by comparing the plasma of healthy people to that of people who abuse opioids. From image analysis, they found distinct and reliable differences in the spectrum of plasma proteins of healthy individuals and those who abuse opioids.

For instance, donors abusing opioids had higher levels of certain variants of hemoglobin, a finding that corresponds to previous literature indicating higher levels of hemoglobin in the blood and in the brains of people.

The method holds particular promise for diagnostics, a potentially lengthy process that can delay treatment. Mahmoudi said he and his team are currently working on using MagLev to identify other types of chronic disease, like multiple sclerosis and cancer, where accurate diagnosis is critical and in many cases lifesaving.

"There are four subtypes of MS, but diagnosis is currently based on the patient's behavior, symptoms, and his or her response to treatment," Mahmoudi said. "There is no biomarker or MRI test to diagnose the different subtypes at the early stages. Correctly diagnosing the type of MS is critical, since it dictates which type of treatment is appropriate. We hope this MagLev method will give clinicians a technique to define the subtypes."

The team is also looking at whether MagLev can be used in diagnosing cancer, where early detection can affect survival rates.

"If we can use the technique to detect cancer sooner, many more cancers could be treated successfully," Mahmoudi said. "Studies show that many types of cancers can be cured if they get detected at the early stages. The real problem is late detection."

If you're concerned about rising health care costs and overwhelming medical bills, you're not alone. According to statistics reported in 2019:

Approximately 30% of an average health care bill is paid for out of pocket by the patient (Association of Credit and Collection Professionals International).

About 67% of Americans are either very worried or somewhat worried about unexpected medical bills, compared to only 41% who are concerned about not being able to pay their rent or mortgage (Kaiser Family Foundation).

Of 1,000 patients surveyed, 64% said they delayed or neglected seeking medical care in the previous year because of concerns about high medical bills (20/20 Research).

More than 25% of 5 million consumers surveyed had delinquent debt on their credit reports, with 58% of that liability coming from medical bills (U.S. Consumer Financial Protection Bureau).

In an effort to help address this growing national problem, two physicians at Johns Hopkins Medicine, Simon Mathews, M.D., and Martin Makary, M.D., M.P.H., have proposed five quality measures for medical billing. The metrics are detailed in an article in the Feb. 4, 2020, issue of The Journal of the American Medical Association (JAMA).

"In recent years, patient care and outcomes have been significantly improved by applying quality science to medicine, benchmarking the performance of both health care providers and facilities, yet there are no standardized metrics for billing quality," says Makary, professor of surgery at the Johns Hopkins University School of Medicine and an authority on health care quality.

"We hope that our proposal will be the first step toward achieving the goal of national billing quality standards," says Mathews, assistant professor of medicine and head of clinical innovation at Johns Hopkins Medicine's Armstrong Institute for Patient Safety and Quality.

The Billing Quality 5-Star Rating System that Matthews and Makary propose includes the following measures (shown as published in the JAMA article):

Itemized bills - Are patients routinely provided an itemized bill with items explained in plain English?

Price transparency - Are patients provided real prices for common "shoppable" services when they ask?

Service quality - Can patients speak with a billing representative promptly about a concern they have about their bill and be informed of a transparent review process?

Suing patients - For patients who have not entered into a written agreement specifying a price for a medical service, does the institution sue patients to garnish their wages, place a lien on their home or involuntarily withdraw money from a patient's income tax return?

Surprise bills ­- Are out-of-network patients paying out of pocket expected to pay more than the region-specific, reference-based price [a price outside of that set by traditional insurance carriers]?

and

Are patients billed for complications stemming from National Quality Forum (NQF) serious reportable events?

The NQF is a non-profit organization that promotes patient protections and health care quality through measurement and public reporting. In 2009, it established the first list of serious reportable events (also known as "never events"), a set of largely preventable and harmful clinical practices and behaviors --such as operating on the wrong part of the body or having to remove a foreign object left behind during surgery -- that should never occur.

"Given the wide variation in both pricing and collection practices by hospitals, measures of billing practices are needed," the authors stated in the JAMA article. "Billing quality is a type of medical quality."

The authors also write that "... metrics of billing quality could be used to create public accountability for U.S. hospitals" and that "... incorporating measures of billing quality into reports of overall hospital quality could provide patients with a more complete assessment of a given medical center or practice."

"Financial toxicity -- the difficulties a patient has related to the cost of medical care -- is a medical complication," Makary says. "Taking care of a patient means taking care of the whole person."

Odense, Denmark - As a sixth mass extinction sends shock waves through whole categories of species, modern zoos and aquariums stand as leading sources of conservation funding and safe havens for populations deemed threatened in the wild.

Collectively, members of the World Association of Zoos and Aquariums (WAZA) attract 10% of the planet population and contribute with more than $350 million annually to conservation programs in the wild, making them the world's third largest funder after World Wildlife Fund (WWF) and The Nature Conservancy.

But how do zoos and aquariums address the growing need for funding programs as more populations face threats due to climate change, disease, human encroachment, and disease?

The answer begins with you, the visitor, according to research published today in international journal Nature Communications. Zoos and aquariums that see more visitors also contribute more funding to conservation activities on site and in the wild. Which leaves zoo and aquarium directors asking the same question that these researchers asked: What compels people to come? Is it the large, iconic species of mammals? Or is it more?

The study, "A system wide approach to managing zoo collections for visitor attendance and conservation in the wild," conducted by researchers at Trinity College Dublin, the National University of Ireland, Galway, University of Southern Denmark and global non-profit Species360, finds that - yes - attendance is higher at zoos where large, iconic animals like rhinos, tigers, and bears reside.

"Our findings show that charismatic animals in the care of accredited zoos and the visitors that come to see them, are helping to make a difference by driving much needed conservation actions", says co-author Associate Professor and specialist in species conservation, Dalia Conde, University of Southern Denmark and lead of the Conservation Demography section at the Interdisciplinary Center on Population Dynamics (CPop). She is also Director of Science at Species360.

However, according to Conde the zoos and aquariums can do more:

"By holding 16% of the planet's threatened species, with an unmatched knowledge on animal biology, medicine, welfare, and high number of visitors, they are uniquely positioned to help avert one of humanities major crises".

She expresses the enormous power of these communities by saying:

"In contrast with the past five mass extinctions in the Earth's history, the current extinction crisis is human driven. This is good news, because it means we are in a position to solve it! And zoos and aquariums still have much room to reach their full conservation potential."

Co-author Dr. Kevin Healy, co-author of the study and Lecturer at the National University of Ireland, Galway, adds:

"While having big charismatic animals is one way to gather an audience, having a more unusual collection of species is an alternative way to drive gate receipts and with them conservations fund" .

An example could be a collection of many different butterfly species or threathened amphibians.

This was found by modelling the relationships between attendance, animals, conservation, and other factors for 450 zoological institutions worldwide.

Several factors, including size and variety of species, influence attendance and conservation funding at zoos and aquariums, according to the study published Natural Communications and authored by researchers at Trinity College Dublin, the Center on Population Dynamics at University of Southern Denmark, University of St. Andrews, and National University of Ireland, Galway, and Species360.

The study provides "global evidence to suggest that zoos don't need to compromise their economic viability and entertainment value in order to have a significant value to conservation." said co-author of the study, Yvonne Buckley, Professor of Zoology at Trinity College Dublin.

"Zoos and aquariums attract more than 700 million people annually around the world. That's an unparalleled audience for conservation education," said co-author Andrew Mooney, PhD Candidate in Trinity's School of Natural Sciences.

Central to the study's findings is the Species360 Zoological Information Management System (ZIMS), which has grown to one of the largest sets of wildlife data worldwide. Over 1,200 zoos and aquariums in 99 countries use ZIMS to curate and share information on thousands of animals in their care. ZIMS data analysis, in turn, is a key source for scientists working with organisms such as IUCN Species Survival Commission, the Convention on International Trade in Endangered Species (CITES), and the Wildlife Trade Monitoring Network (TRAFFIC), to sustain populations, improve animal welfare, fight illegal trade, and more.

Association of Zoos and Aquariums (AZA) together conduct 115 different reintroduction programs, more than 40 of which are designed to bolster populations of species listed as threatened or endangered under the Endangered Species Act.

Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Their study, published today in eLife, reveals that cAMP shifts the type of immune system t-helper (Th) cells created in response to a threat by repressing gene transcription by key proteins. The findings may help scientists develop new ways of manipulating the immune system to treat diseases.

Th cells help the immune system identify infections and flag infected cells for destruction by killer T-cells. Previous studies had shown that low cAMP levels cause the immune system to produce more Th2-type cells, while high cAMP levels boost the production of Th17 cells. "In the current study, we dissected the molecular mechanisms by which cAMP levels regulate these Th responses," says lead author Jihyung Lee, Assistant Project Scientist in Medicine at the University of California San Diego School of Medicine (UC San Diego), US.

Lee and the team showed that treating cells with cAMP reprograms Th2 cells to Th17 cells. It does this by suppressing IRF4 and KLF4, two transcription factors that turn on the genes needed to produce Th2 cells. The team then verified this by showing that mice genetically engineered to lack IRF4 have more Th17 cells. Treating these mice with IRF4 restored their Th2 cell levels.

"Our findings identify a new role for cAMP in immune system flexibility and may suggest new therapeutic approaches to control immune responses," says senior author Eyal Raz, Director of the Center for Immunology, Inflammation, and Immune-mediated Disease at Guangzhou Medical University, China, and Emeritus Professor of Medicine at UC San Diego School of Medicine. "For example, drugs that boost cAMP levels may help people recover from bacterial infections by boosting the number of Th17 cells. Drugs that decrease cAMP levels may be helpful in treating parasitic infections, which require a more robust Th2 response."

The results also suggest that drugs repressing IRF4 or KLF4 might be useful in, for example, treating blood cancers that emerge from immune cells called B-cells in the bone marrow.