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In the last century, Anfinsen showed beyond a doubt that a protein can find its way back to its 'native' three-dimensional structure after it has been placed under 'denaturing conditions' where the protein structure is unfolded. The profound conclusion of his experiments was that apparently the information that governs the search back to the native state is hidden in the amino acid sequence. Thermodynamic considerations then set forth a view where the folding process is like rolling energetically downhill to the lowest point - to the unique native structure. These findings have often been intertwined with the central dogma of molecular biology. Thus, a gene codes for an amino acid sequence, and the sequence codes for a specific structure. 

Enter intrinsically disordered proteins.

The next breakthrough came with the advent of cheap and fast genome sequencing in the wake of the human genome project; once thousands of genomes of various organisms were sequenced, scientists made a staggering discovery - there were lots and lots of genes that coded for proteins with low-complexity. In other words, these proteins did not contain the right amino acids to fold up and experiments confirmed that they remained 'intrinsically disordered'. Also, the human genome turned out to have more than a third of its genes coding for protein disorder!

How to detect protein disorder?

Since disordered proteins are very flexible, they are not amenable to crystallization and therefore no information can be obtained from X-ray diffraction on protein crystals - the approach that has been so pivotal for folded proteins. Instead, these proteins must be studied in solution, and for this purpose NMR (Nuclear Magnetic Resonance) spectroscopy is the most suited tool. In this method, a quantum physical property called 'spin' is measured in a strong magnetic field for each atom in the molecule. The exact precession frequencies of the spins are a function of their environment, and it is exactly this frequency that allows researchers to quantitatively measure to which extent each amino acid is ordered or disordered in the protein.

In their new paper, published on 8 Sept 2020, Dr. Rupashree Dass together with Associate Professor Frans Mulder and Assistant Professor Jakob Toudahl Nielsen have used machine learning together with experimental NMR data for hundreds of proteins to build a new bioinformatics tool that they have called ODiNPred. This bioinformatics program can help other researchers making the best possible predictions of which regions of their proteins are rigid and which are likely to be flexible. This information is useful for structural studies, as well as understanding the biological role and regulation of intrinsically disordered proteins.

READ ALSO:

Empty spaces, how do they make a protein unstable?

How good are protein disorder prediction programmes actually? 

Read more about the results in Scientific Reports: ODiNPred: comprehensive prediction of protein order and disorder by Rupashree Dass, Frans A. A. Mulder & Jakob Toudahl Nielsen

The research was carried out by researchers from Interdisciplinary Nanoscience Center (iNANO) and the Department of Chemistry at Aarhus University. The work was financially supported by VILLUM Fonden.

For further information, please contact

Associate Professor Frans A. A. Mulder Interdisciplinary Nanoscience Center and Department of ChemistryAarhus UniversityEmail: fmulder@chem.au.dk

Journal

Scientific Reports

DOI

10.1038/s41598-020-71716-1

A European guidance document aimed at identifying endocrine disrupting pesticides can--with some modifications--be used to assess other chemicals' endocrine disrupting effects. This is the finding of a new study conducted by the National Food Institute, Technical University of Denmark, and Copenhagen University Hospital.

According to EU regulation, all pesticides must be thoroughly assessed for potential endocrine disrupting effects before they can be approved for use. However, the same rules do not necessarily apply to chemicals that are used for other purposes.

Researchers at the National Food Institute are pointing out that the approval process for chemicals, which are used e.g. as additives in cosmetics or food, can thus overlook chemicals that are harmful to the human endocrine system.

In a new study, the researchers along with colleagues at Copenhagen University Hospital have evaluated whether an existing European guidance document could be used to identify potential endocrine disrupting effects of chemicals that are used for purposes other than plant protection.

The European Food Safety Authority, EFSA, and the European Chemicals Agency, ECHA, developed the guidance document for the purpose of identifying endocrine disrupting pesticides.

"A person who is exposed to a chemical from food or the environment won't care what the chemical is used for if it is harmful to human health," Head of Research Group Terje Svingen at the National Food Institute says.

Butylparaben--a case study

The focus of the study was butylparaben, which can be used to e.g. extend the shelf life of cosmetic creams. The available data for butylparaben is very different from the available data for biocides and pesticides, as the authorities require far fewer studies of additives.

Nonetheless, by using the EU guidance document the researchers were able to conclude that butylparaben has endocrine disrupting effects on humans--in part because university researchers globally have conducted many smaller studies of butylparaben's endocrine disrupting properties.

Guidance document can be applied to a broader spectrum of chemicals

According to the researchers from the National Food Institute and Copenhaven University Hospital, the butylparaben study provides sufficient evidence to propose that the existing guidelines--with some modifications--can be used to identify the endocrine disrupting effects of a much broader spectrum of chemicals than just pesticides. The modifications are intended to facilitate the use of data other than those generated for pesticides.

"Such use of the guidance document could be a first step towards a more harmonized assessment of the endocrine disrupting effects of chemicals, which is independent of the chemical's intended use. In theory, the guidance could be applied to all chemical substances to which humans are exposed," Senior Researcher Julie Boberg at the National Food Institute says.

September 9, 2020 - The ongoing coronavirus pandemic has affected all aspects of healthcare - including sharp drops in educational opportunities for resident physicians in training. In response, urology training programs across the United States joined forces to develop a multi-institutional online video lecture collaboration, according to a special article in Urology Practice, an Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer.

Called "Urology Collaborative Online Video Didactics" - Urology COViD for short - the online lecture series has been a runaway success in the urology world, with thousands of views and overwhelmingly positive reviews from trainees and educators. Lindsay A. Hampson, Assistant Professor of Urology at University of California, San Francisco (UCSF), and colleagues share their experience with the development and initial evaluation of the groundbreaking lecture series.

Urology Programs Team Up to Replace Educational Opportunities Lost to Coronavirus

An overlooked effect of drastic declines in routine clinical care has been the loss of invaluable training opportunities for resident physicians. This may be especially true in surgical specialties such as urology, as many hospitals have only recently started to resume operations other than emergency or urgent surgery.

Spurred by an example from another surgical subspecialty (otolaryngology), the urology residents at UCSF brought the idea to Dr. Hampson. The following day Dr. Hampson conceptualized Urology COViD and reached out to program directors at eight academic training programs: UCSF, University of Washington, University of California-Davis, Stanford University, University of Minnesota, University of Michigan, Northwestern University, and University of Virginia. There was immediate buy-in, with programs across the country facing the same issues with how to train residents during decreased clinical volume and changing educational contexts.

Within a week the UCSF team had created a new website (https://urologycovid.ucsf.edu/) and launched Urology COViD as a "urology-specific collaborative didactic series." Almost immediately, there was a significant influx of collaborating programs from across the country; by the end of the first week of lectures, volunteer faculty had filled all 84 available lecture slots. The following week, a month-long waiting list was filled.

Consisting of a 45-minute lecture followed by a 15-minute question-and-answer session, lectures are delivered live over the Zoom platform in webinar format, including interactive features. All lectures are subsequently posted on the website for viewing via YouTube.

By any measure, Urology COViD has been a smashing success, with lectures delivered by faculty from 35 institutions. The twice-daily webinars have been seen by an average of more than 470 viewers live on Zoom. Within the first two weeks, there were more than 7,000 views of the lecture recordings on YouTube.

More than 90 percent of users leaving feedback on the lecture series and videos have left above average or excellent ratings. More than 80 percent said the series provided a sense of "community connectedness" during a time of social isolation. "All (100 percent) of the viewers surveyed in this study indicated that they would like to see the series continue into the future," the researchers write.

Urology COViD is resuming in September and is expected to provide continued educational opportunities even after the pandemic ends. "There will be a time in the future when we are back in the operating rooms, clinics and lecture halls," Dr. Hampson and colleagues conclude. "We hope that this series can evolve and persist so that these new collaborative educational efforts can outlast the pandemic and continue to provide a source of shared knowledge, resident teaching, and community building for our diverse field."

If evolution selects for the fittest organisms, why do we still have imperfections? Scientists at the Milner Centre for Evolution at the University of Bath investigating this question have found that in species with small populations, chance events take precedence over natural selection, allowing imperfections to creep in.

Recent work by Alex Ho and Laurence Hurst from the Milner Centre for Evolution at the University of Bath analysed the genomes of a wide range of organisms, from mammals to single-celled algae. They compared the genetic instructions used by cells to make proteins - specifically the code at the end of the gene that tells the cell to stop reading, called stop codons.

When making proteins, our DNA is read out in strings, with a stop codon at the end of a string to tell the cell to stop reading. In any given gene, most organisms have a choice of using one of three very similar stop codons, however, one of them (so called TAA) is much better than the others (called TGA and TAG) at making the cell machinery stop.

The researchers, publishing in Molecular Biology and Evolution, looked at why some genes use the less efficient stop codons, when evolution by natural selection should cause most genes to use the more efficient TAA codon.

They found that in species such as humans and other mammals, where populations are relatively small and reproduction is slow, selection favoured TAA in the most highly expressed genes. However mutations creating the less effective stop codons could increase in frequency because of chance events, the roll of the dice being more influential when populations are small. This results in a less efficient stop codon being found more often than would be expected, mostly in the less commonly used genes.

In contrast, in species with large, fast replicating populations, such as yeast or bacteria, chance is less important and so natural selection tended to "weed out" any less favourable mutations, resulting in TAA being very common.

The findings could help the design of new gene therapies for genetic diseases.

Professor Laurence Hurst, Director of the Milner Centre for Evolution, said: "Our total set of DNA seems very much more complicated than that of something like yeast. Humans have lots of enigmatic DNA between our genes and each of our genes can typically make many different products, whereas yeast genes tend to make just one.

"Our work shows that natural selection in humans is not very efficient and so our DNA ends up similar to an ancient rusting motor car - just able to function, with all sorts of bad repairs and accretions built up over time. Yeast instead is more like an organism straight out of the showroom: the perfect machine."

Their results indicate that organisms, such as humans and other mammals, with relatively small population sizes, cannot sustain a perfect state over evolutionary time. It also supports the view that human DNA is error prone and poor quality, not as part of some complex machine for a complex organism, but instead because selection is too weak a force to stop our DNA from deteriorating.

Professor Hurst said: "These results matter because they help us understand that just because something is common, it doesn't mean it is the best. This helps both the understanding of, and therapeutics for, genetic diseases.

"For example, it suggests when making new genes for gene therapy, we should do what yeast do and use the best stop codon: TAA."

A new study from North Carolina State University reports that the rapidly growing field of collegiate esports is effectively becoming a two-tiered system, with club-level programs that are often supportive of gender diversity being clearly distinct from well-funded varsity programs that are dominated by men.

"Five years ago, we thought collegiate esports might be an opportunity to create a welcoming, diverse competitive arena, which was a big deal given how male-dominated the professional esports scene was," says Nick Taylor, co-author of the study and an associate professor of communication at NC State. "Rapid growth of collegiate esports over the past five years has led to it becoming more professional, with many universities having paid esports positions, recruiting players, and so on. We wanted to see how that professionalization has affected collegiate esports and what that means for gender diversity. The findings did not give us reason to be optimistic."

For this qualitative study, the researchers conducted in-depth interviews with 21 collegiate esports leaders from the U.S. and Canada. Eight of the study participants were involved in varsity-level esports, such as coaches or administrators, while the remaining 13 participants were presidents of collegiate esports clubs. Six of the participants identified as women; 15 identified as men.

"Essentially, we found that women are effectively pushed out of esports at many colleges when they start investing financial resources in esports programs," says Bryce Stout, co-author of the study and a Ph.D. student at NC State. "We thought collegiate esports might help to address the disenfranchisement of women in esports and in gaming more generally; instead, it seems to simply be an extension of that disenfranchisement."

"Higher education has been spending increasing amounts of time, money and effort on professionalizing esports programs," Taylor says. "With some key exceptions, these institutions are clearly not putting as much effort into encouraging diversity in these programs. That effectively cuts out women and minorities.

"Some leaders stress that they will welcome any player onto their team, as long as the player has a certain skill level," Taylor says. "But this ignores the systemic problems that effectively drive most women out of gaming - such as harassment. There needs to be a focus on cultivating skill and developing players, rather than focusing exclusively on recruitment."

The drought that hit central and northern Europe in summer 2018 had serious effects on crops, forests and grasslands. Researchers from the European Research Infrastructure Integrated Carbon Observation System (ICOS), including researchers from the University of Göttingen, are showing what effects this had and what lessons can be learned. The results of 16 studies that are currently underway have been published as a special issue in the journal Philosophical Transactions.

The interdisciplinary teams shed light on different aspects of this research. Among many findings, they found that the plants initially benefited from the warm and sunny conditions in spring, but had too little water available for their roots when the summer heatwave started. As a result, grasslands began to dry up and numerous arable areas recorded the lowest yields for decades. The forests protected themselves by greatly reducing their evaporation for several weeks, but this then led to a sharp drop in carbon dioxide uptake. Such effects were observed simultaneously - all the way from Switzerland to the Netherlands and Germany, and from the Czech Republic to Sweden and Finland.

The Bioclimatology Group of the Faculty of Forest Sciences and Forest Ecology at the University of Göttingen contributes to ICOS with a meteorological station in the Hainich National Park. For the last 20 years every 30 minutes, the station has measured the carbon dioxide (CO2) and water vapour exchange between forest and atmosphere. Comparing the data across Europe shows that the area under investigation is one of those most affected by the 2018 drought. "In 2018, the CO2 uptake calculated over the whole year was about 30 percent lower than the average of the past 20 years," says Head of the Group Professor Alexander Knohl. "On some days in the summer of 2018, the forest actually emitted carbon dioxide instead of absorbing it," adds Dr Lukas Siebicke. "In the past 20 years, this has never happened before."

The measurements from the meteorological station in the Hainich National Park are of great international scientific importance for two reasons: it is one of the world's longest time series for such continuous measurements; and it is one of the oldest unmanaged forests in which such measurements of carbon dioxide and water vapour exchange takes place.

ICOS is a European research infrastructure for measuring carbon dioxide fluxes between land, ocean and atmosphere. Across Europe, 140 measuring stations in twelve countries are involved. ICOS stations are subject to a rigorous quality assurance process and provide standardised data that is made freely available for research, teaching and other applications. ICOS provides essential data for the reports of the Intergovernmental Panel on Climate Change (IPCC) and for the decision-making processes within the UN Framework Convention on Climate Change.

As any parent will tell you, no two children behave in exactly the same way. It is part of what makes each individual unique.

So, why do some adolescents take more risks than others?

University of Delaware Biomedical Engineer Curtis Johnson and graduate student Grace McIlvain think they may have an idea.

The part of the brain that makes adolescents want to take risks is called the socioemotional system. The brain's cognitive control center, meanwhile, is what helps prevent adolescents from acting on these impulses.

In a recently published paper in NeuroImage, Johnson and McIlvain suggest that these two centers in the brain physically mature at different rates and that adolescents with large differences in the rate of development between these two brain regions are more likely to be risk-takers. Further, the research team theorizes that it is the brain's fundamental structure that drives these risk-taking and control tendencies.

What makes this study unique is that the UD researchers and their collaborators used a technique called magnetic resonance elastography (MRE) to safely measure the mechanical properties of the brain tissue as a measure of brain development, rather than activation of those two regions.

Elastography is a method of imaging mechanical properties of tissues using a magnetic resonance imaging (MRI) scanner. Simply put, the researchers take snapshots of how the brain deforms -- or bends -- as it is vibrated under low frequencies, and then put those images through a specific algorithm to reverse engineer what is happening. Johnson explained that MRE vibration is safe for all ages and provides less movement than naturally occurs in the brain. It also offers less vibration than other devices designed for children, such as vibrating rockers.

Johnson likened the process to any other material testing and said the research team's knowledge of how tissue deforms helps them interpret what is happening under different vibrations. In adults, MRE techniques have become popular for studying diseases, such as Alzheimer's, with research showing relationships between memory and cognitive performance.

"MRE techniques do not replace other aspects of studying brain development, but they may provide a more sensitive, objective way to look at the brain's wiring," said Johnson, an assistant professor in the Department of Biomedical Engineering.

Mapping adolescent brain development

This is not the first time that researchers have looked at how two brain regions interact to form a certain output. But most of this work has been done using functional MRI (fMRI), where study participants are placed in the scanner and given a real-time task, and the researchers watch which areas of the brain light up to determine what areas of the brain relate to that task.

Johnson's research group was an early pioneer in using MRE techniques to make high-resolution three-dimensional maps that enable scientists to look at specific regions of the brain. The intensity of every 3D pixel in an image has meaning. For example, bright colors indicate high stiffness, which, in this case, indicates a measure of developmental maturity.

Looking at these features of the brain in their work, the researchers found that it wasn't the socioemotional or the cognitive control center alone, but the combination of the two centers of the brain working together at a specific age or point in time that was the definitive factor in risk taking.

"So, there is this period during adolescence where the part of the brain that makes you want to take risks is more mature than the part of the brain that suppresses those impulses," said McIlvain, who began working on the project as an undergraduate summer researcher in 2016 and is now a third-year doctoral student in biomedical engineering.

"If we can identify individuals who are more likely to take risks, based on the biological composition of their brain, or maybe groups of individuals, it might inform strategies for prevention."

Prior to this project, little MRE research had measured brain stiffness in children. Earlier work in 2018 by McIlvain showed the outside of the brain appears softer in adolescents than adults, whereas the inside of the brain appears stiffer in adolescents than adults. According to Johnson, this aligns with the known developmental trajectory where the inside of the brain develops first and the outside, the cortex, develops later.

The work grew out of Johnson's previous collaborative research with Eva Telzer, a psychology professor at University of North Carolina and co-author of the paper, and leverages the advanced MRI capabilities at UD's Center for Biomedical and Brain Imaging. Today, researchers in the Johnson lab develop all aspects of this MRE technique, from how to safely vibrate the head in the scanner to how to write the software to acquire the data to methods for turning the data into images that are translated into mechanical properties.

While the research team's previous work has shown differences in the brain function of typically developing children and those with conditions, such as cerebral palsy, this is the first time the researchers have shown a relationship with function in healthy children. But there are still more questions than answers.

For example, Johnson said currently there are no good measures for saying when the brain is mature or even for how to define brain health. And while the research team has made connections between how stiffness of the adolescent brain's socioemotional system and cognitive control center interrelate and support risk taking, there are other things they don't know, like how these regions of the brain are affected by things like socioeconomic status, early life trauma or early education.

A big focus of the work is making the MRE scan faster. The scan currently takes over six minutes, which can be difficult for children with disabilities or those who are very young.

"We'd like to complete the scan in under a minute -- less time than half a song from a Disney movie -- before a child loses interest and thinks about moving," said Johnson.

Next steps in the research include scanning kids as young as age 5, including those with autism. The hope is to create a robust data set to explore how brain mechanical properties change from age 5 to age 30, generally considered to be the end of adolescence. Among other things, they hope to use this data to better understand how children with disabilities fit into that developmental curve.

"Right now, there is no standard way to diagnose autism, no targeted treatment plan or metrics for measuring whether intervention is helping," said McIlvain, who recently was awarded an National Institutes of Health fellowship to study brain stiffness in children with autism. "If we can understand how the mechanical properties of the brain are affected in someone with autism, we can start to answer some of those questions."

In January 2019, NASA's OSIRIS-REx spacecraft was orbiting asteroid Bennu when the spacecraft's cameras caught something unexpected: Thousands of tiny bits of material, some just the size of marbles, began to bounce off the surface of the asteroid--like a game of ping-pong in space. Since then, many such particle ejection events have been observed at Bennu's surface.

OSIRIS-REx is an unprecedented effort to investigate what makes up asteroids like Bennu and how they move through space. But, as those leaping particles show, the mission has already delivered a few surprises.

"We've been studying asteroids for a long time, and no one had ever seen this phenomenon before--these little particles getting shot off of the surface," said Daniel Scheeres, distinguished professor in the Ann and H.J. Smead Department of Aerospace Engineering Sciences. He leads the radio science team for OSIRIS-REx along with CU Boulder's Jay McMahon.

Now, a series of new studies seeks to recreate and understand the observed particle ejection events, piecing together what happened and why. Scheeres and McMahon are focusing on one question in particular: How might such leaping particles change the long-term fate of Bennu and other asteroids like it?

In research published in the Journal of Geophysical Research: Planets, the duo and their colleagues report that such seemingly small occurrences may add up over time--perhaps even helping to give the asteroid its telltale shape, which is often compared to a spinning top.

"We want to know what that means for the bigger picture of how asteroids live their lives," said McMahon, an assistant professor of aerospace engineering.

The University of Arizona leads science operations for OSIRIS-REx, which was built by the Colorado-based Lockheed Martin. NASA's Goddard Space Flight Center in Maryland manages the overall mission.

Mass loss

McMahon added that the life of some asteroids can be pretty chaotic. One class of these bodies, which scientists call "active" asteroids, loses a significant amount of material on an ongoing basis.

"They're almost a cross between a comet and an asteroid," McMahon said. "They're losing mass, and it's substantial enough that we can see it from Earth."

Until recently, no one knew that the same thing could happen on a much smaller scale. But that's precisely the case on Bennu. One hypothesis suggests that rapid shifts in temperature could be causing the surface of the asteroid to warp and crack, popping off small bits of material. Another study has contended that the ejections could be the result of small meteoroids smacking into Bennu.

Based on OSIRIS-REx's observations, the particles ejected from Bennu can be as big as softballs and hit speeds of about 7 miles an hour. Even more surprising, McMahon said, a small number of these bits of debris seemed to do the impossible: They flew off the surface of Bennu, then orbited the asteroid for several days or longer.

"That shouldn't happen in typical orbital mechanics," McMahon said.

Put differently, basic orbital calculations suggest that all of these particles should do one of two things: Jump off the surface and fall right back down or escape from Bennu's gravity and never come back.

Close misses

To find out why some aren't playing by the rules, McMahon and his colleagues used detailed computer models to track the trajectories of more than 17,000 test particles ejected from Bennu. They discovered a small subset of those seem to get an assist from an unlikely source: the sun.

McMahon explained that as these objects leap off the asteroid, they are exposed to heat and radiation coming from the sun and from Bennu itself--just a little bit, but enough to occasionally give them a slight boost in speed. With the right push, those particles can, essentially, fail at falling.

"The particle gets really close to the surface and just misses," McMahon said. "If it can do that a few times then it can get into a situation where it can live in orbit for quite a while."

In another study published in the same series, a team led by Scheeres and McMahon tried to figure out if ejection events might even influence Bennu's own orbit around the sun--the answer is probably not.

The group did discover something else unusual: When particles eventually land on Bennu's surface, many appear to disproportionately fall near its equator where the asteroid has a distinct bulge. As a result, these events could be reshaping the asteroid over thousands or millions of years by moving mass from its north and south to its middle.

The findings are a prelude to another major event in the life of Bennu. Next month, OSIRIS-REx will get closer to the asteroid than ever before. Once there, the spacecraft will use a retractable arm to grab a sample from the surface and bring it back home.

Scheeres and colleagues expect even more unexpected findings from an already surprising asteroid.

Coauthors on the new study include researchers from the Jet Propulsion Laboratory, Planetary Science Institute, NASA Goddard Space Flight Center, Lockheed Martin, University of Arizona, The Open University and University of Tennessee.

The management of fungal infections in plants and humans could be transformed by a breakthrough in understanding how fungi develop resistance to drugs.

It was previously thought that only mutations in a fungi's DNA would result in antifungal drug resistance. Current diagnostic techniques rely on sequencing all of a fungi's DNA to find such mutations.

Scientists from the University of Edinburgh have discovered that fungi can develop drug resistance without changes to their DNA - their genetic code.

The new research, published in Nature, finds that resistance can emerge in fungi without genetic changes. Instead the fungi exhibit epigenetic changes - alterations that do not affect their DNA - suggesting that many causes and cases of antifungal resistance could have been previously missed.

Each year fungal diseases affect billions of people globally, causing an estimated 1.6 million deaths.

Infections resistant to treatment are a growing problem, particularly in patients with weakened immune systems such as those with HIV. Few effective antifungal drugs exist.

Overuse of agricultural fungicides is also leading to increasing resistance in soil borne fungi. Fungal disease results in the loss of up to a third of the world's food crops annually.

A team of scientists from the University of Edinburgh's Wellcome Centre for Cell Biology studied the emergence of resistance in a yeast, Schizosaccharomyces pombe, by treating it with caffeine to mimic the activity of antifungal drugs.

The team discovered that the resulting resistant yeast had alterations in special chemical tags that affect how their DNA is organized. Some genes became packed into structures known as heterochromatin, which silences or inactivates underlying genes, causing resistance as a result of this epigenetic change.

This discovery could pave the way for new therapies to treat resistant infections by modifying existing epigenetic drugs or developing new drugs that interfere with fungal heterochromatin.

Improved fungicides to treat food crops could limit agricultural losses and also reduce the number of resistant fungal strains in the environment that continue to fuel increased infections in humans.

Professor Robin Allshire, who led the study at the Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, said: "Our team is excited about the possible implications that these findings may have for understanding how plant, animal and human fungal pathogens develop resistance to the very limited number of available and effective antifungal drug treatments."

Sito Torres-Garcia, Darwin Trust of Edinburgh funded PhD student and first author of the paper, said: "Our study shows for the first time that fungal cells can develop drug resistance by altering how their DNA is packaged, rather than altering their DNA sequence."

Dyslexia is a frequent disorder of reading acquisition that affects up to 10% of the population, and is characterised by lifelong difficulties with written material. Although several possible causes have been proposed for dyslexia, the predominant one is a phonological deficit, a difficulty in processing language sounds. The phonological deficit in dyslexia is associated with changes in rhythmic or repetitive patterns of neural activity in a sound-processing region of the brain, the left auditory cortex. Neuroscientists from the University of Geneva (UNIGE) have demonstrated, in a study published in Plos Biology, a causal relationship between brain oscillations at a specific frequency (30 Hz) and the ability to process phonemes that is essential for reading. Using a non-invasive electrical stimulation technique capable of synchronizing neural activity at the stimulation frequency, phonological deficits and reading accuracy could be improved in adults with dyslexia.

Silvia Marchesotti and Anne-Lise Giraud, respectively researcher and professor in the Department of Basic Neurosciences of the Faculty of Medicine at UNIGE, together with their colleagues, investigated the main possible cause of dyslexia: the phonological deficit. "We know that during brain development, when children start to read, some experience tremendous difficulties matching speech sounds with letters " explains Silvia Marchesotti. These specific difficulties are associated with anomalies of neural activity synchronization in the left auditory cortex at the frequency of 30 Hz. The Geneva study demonstrates for the first time that a causal relationship exists between these brain oscillations and the ability to process speech phonemes.

Reading stimulation

Neuroscientists applied the technique of transcranial alternating current stimulation (tACS), which is under investigation in medicine to treat illnesses such as depression. A twenty minute stimulation over the left auditory cortex in 15 dyslexic adults and 15 fluent control readers immediately improved phonological processing and reading accuracy in the dyslexia group. The beneficial effect of stimulation is most pronounced in people with poor reading skills, but neuroscientists have noted a slightly disruptive effect in very good readers.

Towards non-invasive treatments

The Geneva study paves the way for targeted non-invasive therapeutic interventions aimed at improving phonological processing in people with dyslexia. "The next steps for us are to investigate whether normalising oscillatory function in very young children could have a long-lasting effect on the organisation of the reading system," says Silvia Marchesotti.

This study will continue within the new National Center of Competence in Research (NCCR) "Evolving Language." The method will be different, however: instead of using electrical stimulation, neuroscientists will try to obtain equivalent results with neurofeedback, a non-invasive technique that involves teaching self-regulation of brain signals to patients. "The goal remains the same, but the use of an even less invasive method will allow conducting trials with children," says Anne-Lise Giraud, the project leader.

DURHAM, N.C. -- Interactive software that "reads" and analyzes footprints left by black rhinoceroses can be used to monitor the movements of the animals in the wild, giving conservationists a new way to keep watch on the endangered species and help keep it safe from poachers, according to a Duke University-led study.

The software, called the Footprint Identification Technique (FIT), runs on JMP software from SAS and uses advanced algorithms to analyze more than 100 measurements of a rhino's footprint.

Because each rhino's footprint is as distinctive as a human fingerprint, the analyzed images can be archived electronically in a global database of previously collected footprint images for matching.

"If you find a match, you can identify the individual animal who left the mark and, by plotting the locations of all the other places that mark has been seen, track its movements without disturbing it or coming into close enough contact with it for there to be a risk of animal-to-human viral transmissions," said Zoe Jewell, adjunct associate professor at Duke University's Nicholas School of the Environment and principal research associate at the JMP Division of SAS, who co-led the study and is co-creator of FIT.

"It's a cost-effective approach that not only protects the health of the rhino and the human, but also brings a centuries-old tracking skill into the 21st Century," she said.

Jewell and her colleagues are now working with Namibia's Ministry of Environment, Forestry and Tourism to train wildlife conservationists, land managers, local guides and anti-poaching agents how to use FIT.

The scientists published their peer-reviewed study describing the technology's effectiveness for monitoring the endangered rhinos on Aug. 14 in the open-access journal PeerJ.

Namibia is home to an estimated 2,000 black rhinos, or about 90% of the species' total population worldwide. Though legally owned by the government, the animals are dispersed geographically on private lands across the country.

Stepped up government policing in recent years has significantly slowed the rate of loss due to poaching, but between 30 and 50 of the animals are still slain each year for their horns, which can sell for more than $60,000 a kilogram on the Asian black market, where they are used in traditional medicine or displayed as a symbol of wealth and success.

"You essentially have these animals with horns worth $100,000 or more that disappear from sight into the Namibian backcountry, making them an almost irresistible target for poachers. Authorities often don't know a rhino that's gone missing has been poached until they find its bones or carcass," said Jewell.

FIT allows the animals to be monitored three different ways, allowing scientists, managers, guides or anti-poaching patrols to use it as best meets their individual needs and constraints, she said.

In the simplest option, the heel pattern on a digital image of the footprint is compared to images already in the FIT database to search for a match. This use is well-suited to situations where a random footprint is found in the wild.

The FIT software can also do a survey of footprints throughout the protected area and take measurements from each print to estimate the number of rhinos in that area. This can be useful information for calculating resource needs - the number of patrol vehicles, for instance - to monitor the animals effectively.

In the most advanced option, each individual rhino can be tracked and matched to its unique footprint using both FIT and heel-patterns. This creates an interactive library that anti-poaching patrols can use to search for animals at the highest risk, including those known to frequent areas under threat from poachers or those whose footprints haven't been showing up in recent years.

"FIT is a distillation of the traditional ecological skills of the expert trackers who have lived and worked with in Africa for many years," said Sky Alibhai, also an adjunct associate professor at Duke's Nicholas School and principal research associate at the JMP Division of SAS, who co-led the study and co-developed the FIT technology with Jewell. "Using FIT allows their skills to be used effectively in conservation. This can benefit whole communities."

RIVERSIDE, Calif. -- A new theory about the nature of dark matter helps explain why a pair of galaxies about 65 million light-years from Earth contains very little of the mysterious matter, according to a study led by a physicist at the University of California, Riverside.

Dark matter is nonluminous and cannot be seen directly. Thought to make up 85% of matter in the universe, its nature is not well understood. Unlike normal matter, it does not absorb, reflect, or emit light, making it difficult to detect.

The prevailing dark matter theory, known as cold dark matter, or CDM, assumes dark matter particles are collisionless, aside from gravity. A newer second theory, called self-interacting dark matter, or SIDM, proposes dark matter particles self-interact through a new dark force. Both theories explain how the overall structure of the universe emerges, but they predict different dark matter distributions in the inner regions of a galaxy. SIDM suggests dark matter particles strongly collide with one another in a galaxy's inner halo, close to its center.

Typically, a visible galaxy is hosted by an invisible dark matter halo -- a concentrated clump of material, shaped like a ball, that surrounds the galaxy and is held together by gravitational forces. Recent observations of two ultra-diffuse galaxies, NGC 1052-DF2 and NGC 1052-DF4, show, however, that this pair of galaxies contains very little, if any, dark matter, challenging physicists' understanding of galaxy formation. Astrophysical observations suggest NGC 1052-DF2 and NGC 1052-DF4 are likely satellite galaxies of NGC1052.

"It is commonly thought that dark matter dominates the overall mass in a galaxy," said Hai-Bo Yu, an associate professor of physics and astronomy at UCR, who led the study. "Observations of NGC 1052-DF2 and -DF4 show, however, that the ratio of their dark matter to their stellar masses is about 1, which is 300 times lower than expected. To resolve the discrepancy, we considered that the DF2 and DF4 halos may be losing the majority of their mass through tidal interactions with the massive NGC 1052 galaxy."

Using sophisticated simulations, the UCR-led team reproduced the properties of NGC 1052-DF2 and NGC 1052-DF4 through tidal stripping -- the stripping away of material by galactic tidal forces -- by NGC1052. Because the satellite galaxies cannot hold the stripped mass with their own gravitational forces, it effectively gets added to NGC 1052's mass.

The researchers considered both CDM and SIDM scenarios. Their results, published in Physical Review Letters, indicate SIDM forms dark-matter-deficient galaxies like NGC 1052-DF2 and -DF4 far more favorably than CDM, as the tidal mass loss of the inner halo is more significant and the stellar distribution is more diffuse in SIDM.

The research paper has been selected as an "editors' suggestion" by the journal, an honor that only a select few papers receive each week to promote reading across fields.

Yu explained tidal mass loss could occur in both CDM and SIDM halos. In CDM, the inner halo structure is "stiff" and resilient to tidal stripping, which makes it difficult for a typical CDM halo to lose sufficient inner mass in the tidal field to accommodate observations of NGC 1052-DF2 and -DF4. In contrast, in SIDM, dark matter self-interactions could push dark matter particles from the inner to the outer regions, making the inner halo "fluffier" and enhancing the tidal mass loss accordingly. Further, the stellar distribution becomes more diffuse.

"A typical CDM halo remains too massive in the inner regions even after tidal evolution," Yu said.

Next, the team will perform a more comprehensive study of the NGC 1052 system and explore newly discovered galaxies with novel properties in an effort to better understand the nature of dark matter.

Using innovative computer-based approaches, researchers have developed protein inhibitors that block the interaction between the SARS-CoV-2 virus and human cell receptor ACE2. In cell culture, the most potent of these inhibitors could neutralize virus infection, paving the way for their use in therapies that could be delivered more easily than antibodies. SARS-CoV-2 infection generally begins in the nasal cavity. The monoclonal antibodies in development as treatments for COVID-19 are not ideal for intranasal delivery, however, as antibodies are large and often not extremely stable. Small proteins that bind tightly to the SARS-CoV-2 spike and block the interaction with the human cellular receptor ACE2 may allow direct delivery through intranasal administration. Previous work in rodents has shown that intranasal delivery of small proteins designed to bind tightly to an influenza protein could provide protection against infection. Here, using novel approaches to identify new, higher-affinity binding modes with the SARS-CoV-2 spike's receptor binding domain (RBD), Longxing Cao, David Baker and colleagues developed a series of inhibitors - optimized in their amino acid sequences for targeted binding, folding and stability - that bound to distinct regions of the RBD surface surrounding the ACE2 binding site. When they evaluated their inhibitors in cell culture, several bound with particularly high affinities to SARS-CoV-2 and two neutralized the virus, preventing infection. The small proteins were stable after 14 days at room temperature, addressing concerns associated with cold storage needs required for some antibodies and vaccine candidates. These "minibinders" provide starting points for SARS-CoV-2 therapeutics, the authors say. After further development, they could be used in a gel for nasal application, or for direct delivery into the respiratory system by nebulization. "We will be exploring alternative routes of delivery in the months ahead as we seek to translate the high potency neutralizing proteins into SARS-CoV-2 therapeutics and prophylactics," they write. They also address the utility of their computational design-based approach for preparing against future pandemics.

Brazilian red propolis found in beehives along the coast and mangroves in the Northeast region contains two substances with anti-cancer properties. In laboratory tests, they considerably reduced the proliferation of ovarian, breast, and brain cancer cells.

In a study published in the Journal of Natural Products, researchers at the Universities of São Paulo (USP) and Campinas (UNICAMP) report their discovery of the two anti-cancer substances as well as six novel polyphenols with structures previously unknown to science. Polyphenols are beneficial natural compounds with anti-oxidant properties. They include flavonoids and tannins, and can be found in plants, cereals, and wine.

"Two of the eight substances isolated for the first time from red propolis displayed cytotoxic properties in ovarian cancer, breast cancer, and glioma cells. We performed in vitro tests on these three types of tumor because they are resistant to many different drugs and hence hard to treat. The cells in question have a well-known mechanism that overexpresses a protein responsible for barring drugs. This is why they're drug-resistant. Our tests showed that the substances in red propolis circumvented the mechanism, showing their potential to reduce tumors," said Roberto Berlinck, a professor in the University of São Paulo's São Carlos Institute of Chemistry (IQSC-USP) and a member of the steering committee of the São Paulo Research Foundation - FAPESP Research Program on Biodiversity Characterization, Conservation, Restoration and Sustainable Use (BIOTA-FAPESP).

The discoveries resulted from a study within the scope of BIOTA-FAPESP, coordinated by Berlinck, and from a Thematic Project coordinated by Ronaldo Pilli.

Library of natural products

According to Berlinck, red propolis polyphenols are a novel class of anti-cancer compounds that inhibit tumor growth and induce tumor cell death. "In one of our tests they outperformed a well-known chemotherapy drug [doxorubicin]," he told.

Natural products are among the main sources of new cancer drugs. Hence the importance of bioprospecting studies such as this one, demonstrating the beneficial effects of the substances concerned. Previous research described the bactericidal, anti-fungal, anti-inflammatory, and immunomodulatory properties of red propolis.

"Bees produce propolis to protect the hive, so it's no accident that the resin is bactericidal and anti-fungal," Berlinck said. "This had been reported previously by researchers who analyzed raw red propolis. In our study, we proved the anti-cancer effects of specific substances isolated from red propolis."

Red propolis is rarer than green, yellow, or brown propolis. Brazil is one of the world's largest producers of propolis. Red propolis is found in several states of Northeast Brazil. In Alagoas, for example, it is produced by honeybees (Apis mellifera) that feed on the reddish resin exuded by the coin vine Dalbergia ecastaphyllum.

"We plan to investigate how the bees process this tree resin," Berlinck said. "Do they modify it to make propolis or use it as is?"

However, he added, polyphenols are not considered promising candidates for drug development. "Polyphenols, unfortunately, bind to all sorts of proteins, whereas a drug needs to target a specific protein," he said. "This may be why red propolis is active in so many ways. It can influence several different systems."

At the height of the COVID-19 pandemic in April, a 14-year-old boy was admitted to the emergency department at Nemours Children's Health System in Delaware with mysterious symptoms in what would later be identified as one of the first cases of multisystem inflammatory syndrome in children (MIS-C) in the U.S. His care and retrospective diagnosis have been published in Progress in Pediatric Cardiology as a timely case study linking COVID-19 to the highly dangerous syndrome which is rare in children and causes inflammation of the heart, lungs and other vital organs.

"There are lessons to be learned from this case, the most critical being to maintain your suspicion if there are several plausible diagnoses," said Deepika Thacker, MD, senior author of the paper and pediatric cardiologist with Nemours Children's Health System. "This allowed us to remain vigilant and adapt treatment as we went, based on the signals and symptoms we were seeing."

Prior to reports from Europe about similar cases in children, the patient presented to the emergency department with a four-day history of fever, fatigue, and abdominal pain. He initially tested negative for COVID-19 and was admitted to the general pediatric ward. But his condition quickly deteriorated, with severe diarrhea, increasingly high fever, and a quickly spreading rash that further escalated to chest pain, fluid in the lungs, and decreasing heart function.

The seemingly unconnected presentation of symptoms made several diagnoses appear possible. While being treated in the cardiac intensive care unit, the patient had to be intubated and placed on mechanical ventilation. During his 12-day hospital stay, he was treated with penicillin, ceftriaxone, epinephrine, phenylephrine, milrinone, intravenous immune globulins, and high-dose aspirin to cover the wide variety of possible conditions. Only after discharge, an antibody test showed he had had COVID-19.

Based on the team's experience with this patient and others, as well as data from other centers, Nemours' physicians developed a clinical pathway for early recognition and treatment of MIS-C to speed the diagnosis and care of children with this new presentation of COVID-19.

"In the three months since this patient was in critical care, we have learned so much about diagnosing and treating this novel presentation of COVID-19 in children," said Thacker. "This information-sharing has undoubtedly saved lives."

This first patient recovered, as have all 15 patients treated with MIS-C at Nemours Children's Health System in Delaware. Moving forward, the cardiology team will continue to follow up with patients who have experienced MIS-C for at least one year to understand the long-term impact of this acute condition.