Culture

An extensive search and testing of current drugs and drug-like compounds has revealed compounds previously developed to fight SARS might also work against COVID-19.

Using the National Drug Discovery Centre, researchers from the Walter and Eliza Hall Institute identified drug-like compounds that could block a key coronavirus protein called PLpro. This protein, found in all coronaviruses, is essential for the virus to hijack and multiply within human cells, and disable their anti-viral defences.

Initially developed as potential treatments for SARS, the compounds prevented the growth of the SARS-CoV-2 virus (which causes COVID-19) in the laboratory.

The discovery, published yesterday in The EMBO Journal, was led by Professor David Komander, Professor Marc Pellegrini, Professor Guillaume Lessene and Dr Theresa Klemm.

At a glance

Australian researchers have identified a molecular target for potential new COVID-19 treatments

A chemical compound, originally discovered to inhibit SARS, shows promise for halting the growth of the COVID-19 virus (SARS-CoV-2)

The discoveries were made by leveraging the capabilities of the National Drug Discovery Centre and ANSTO's Australian Synchrotron, and may underpin the development of new drugs for COVID-19

Targeting a key viral protein

Coronaviruses, including the viruses that cause COVID-19 and SARS, all contain a protein called PLpro, which allows the virus to hijack human cells and disable their anti-viral defences.

Professor Komander said PLpro belonged to a family of proteins called 'deubiquitinases', which his team had studied for the last 15 years in a range of diseases.

"When we looked at how SARS-CoV-2 functions, it became clear that the PLpro deubiquitinase was a key component of the virus - as it is in other coronaviruses, including the SARS-CoV-1 virus, which causes SARS," he said.

"We quickly established the VirDUB program to investigate how PLpro functions and what it looks like. These are critical first steps towards discovering new drugs that could be potential therapies for COVID-19."

Using ANSTO's Australian Synchrotron, the VirDUB team rapidly ascertained how PLpro interacts with human proteins - homing in on a target that could be blocked by new drugs.

Discovering new medicines

The National Drug Discovery Centre was critical to rapidly search for drugs that could block PLpro.

"We scanned thousands of currently listed drugs, as well as thousands of drug-like compounds, to see if they were effective in blocking the SARS-CoV-2 PLpro," Professor Komander said.

"While existing drugs were not effective in blocking PLpro, we discovered that compounds developed in the last decade against SARS, could prevent the growth of SARS-CoV-2 in pre-clinical testing in the laboratory."

The next step is to turn these compounds into drugs that could be used to treat COVID-19, Professor Komander said.

"We now need to develop the compounds into medicines, and make sure they are safe for patients.

"Importantly, drugs that are able to inactivate PLpro may be useful not just for COVID-19 but may also work against other coronavirus diseases, as they emerge in the future."

A strong association between the genes influencing cattle temperament and autism in humans has been discovered by University of Queensland researchers.

UQ genomic expert Professor Ben Hayes said the research by his interdisciplinary team headed by Dr Roy Costilla could lead to improved animal welfare and meat quality.

"The research doesn't mean that cattle have autism; rather that cattle share an overlap of genes with humans which are critical in brain function and response to fear stimuli," Professor Hayes said.

Temperament is an important trait for day-to-day management of cattle.

"We knew that genetic factors were likely influence temperament in cattle and we thought that genes involved in behavioural traits in humans could also influence temperament in cattle.

"We found that genes known to contribute to autism spectrum disorders also influence temperament in cattle."

Professor Hayes said the results were important as it opened the way for research conducted on behavioural traits in humans to shed further light on temperament in cattle.

"As I've found talking to farmers over the years, it can be distressing having an animal that has a poor temperament in the mob, and stirs up all the other cattle putting them into a state of stress.

"If we can identify those animals early, or breed to eliminate them, we can potentially reduce the stress of the whole mob.

"That has great implications for welfare - not only of the cattle but also the people handling the cattle who are less likely to be charged or kicked."

Professor Hayes said there was an association between a calmer temperament in cattle and better meat quality.

"The cattle industry's standard for measuring temperament is 'flight time' - the speed in which cattle move after release from an enclosure," Professor Hayes said.

"What a producer wants is cattle that move calmly and slowly from the enclosure, rather than an animal that charges out in an aggressive or stressed state.

"Our study found flight time is about 35 percent heritable, which is very significant.

"It means you can make a lot of progress by breeding for better temperament - it's about the same as milk production in dairy cattle, and we've made big breeding gains there."

Professor Hayes said the same genes were identified in other genomic research conducted on domestication of foxes.

"The same genes just come up again and again," he said.
"Some DNA variants in those genes are more common in people with autism and, in cattle, some DNA variants in those same genes are found to make the cattle more fearful in new situations and have a reactive temperament."

It's the first time whole genome sequencing has been used to analyse temperament in beef cattle.
Researchers looked at 28 million data points per animal on the 9,000 cattle with temperament records in the initial study, and then validated the results in over 80,000 cattle from Ireland.

Professor Hayes said his team would incorporate the temperament data into a panel of markers available for producers that would also provide breeding values for fertility.

"It means a producer will be able to use a sample of tail hair which contains DNA to quickly get information on the genetic value of their animals for temperament and fertility.
The temperament analysis was conducted primarily in northern cattle Bos indicus breeds and was validated in Bos taurus cattle.

Nara, Japan - Fans of sake, the traditional Japanese alcoholic beverage, may have even more reason to enjoy it now: Japanese scientists have discovered that a mutant strain of sake yeast produces high levels of the amino acid ornithine.

In a study published this month in Metabolic Engineering, researchers from the Nara Institute of Science and Technology and the Nara Prefecture Institute of Industrial Development have revealed that a mutant strain of sake yeast produces 10 times the amount of the amino acid ornithine compared with the parent yeast strain.

Ornithine is a non-protein-making amino acid and a precursor to two amino acids - arginine and proline. It has been found to perform several physiological functions, such as reducing fatigue and improving sleep quality.

"We wanted to obtain sake yeast strains with improved ethanol tolerance," says a first author of this article, Masataka Ohashi. "During sake fermentation, the yeast is exposed to high concentrations of ethanol, which impedes yeast cell growth, viability and fermentation. Increased ethanol tolerance in sake yeast strains could improve ethanol production and reduce fermentation time."

To find ethanol-tolerant yeast strains, the researchers isolated mutants that accumulated proline, which can alleviate ethanol toxicity, using a conventional mutagenesis (i.e., one that doesn't involve genetic modification). They also conducted whole genome sequencing analysis, and performed brewing tests with sake yeast strains. Then they identified and analyzed a new mutation in a gene that encodes a variant of N-acetyl glutamate kinase that increases intracellular ornithine level.

"We previously constructed self-cloning industrial yeast strains that accumulate proline to increase ethanol tolerance and productivity of yeast," explains Prof. Hiroshi Takagi, a corresponding author. "But those yeasts have not been yet acceptable to consumers because they're considered to be genetically modified, even though a self-cloning yeast has no foreign genes or DNA sequences - they only have yeast DNA."

The researchers successfully isolated non-genetically modified yeasts that produced 10 times the amount of ornithine compared with the parent strain, which is widely used in Japanese sake breweries, and the sake brewed with them contained 4-5 times more ornithine.

The results of this study will contribute to the development of improved yeast strains for production of high levels of ornithine, and the strain obtained in this study could be readily applied to sake, wine, and beer brewing. Ornithine-accumulating yeast strains could also be used in the production of ornithine-rich dietary supplements made from these yeasts and their products.

Prof. Takagi also describes "There are two major purposes for breeding of industrial yeast: improvement of fermentation ability with enhanced tolerance to environmental stresses during fermentation processes and diversity of product taste and flavor with modified metabolic pathways. In yeast, amino acid metabolisms vary under different growth environments and the metabolic styles form a complicated but robust network. The elucidation of metabolic regulatory mechanisms and physiological roles for amino acids is important fundamental research for understanding life phenomenon. The yeast is reliable and safe in food production, and thus the development of novel strains that overproduce 'functional amino acids' such as ornithine, proline and branched-amino acids, would greatly contribute to food-related industries."

Milan, 27 August 2020 - DNA three-dimensional structure is determined by a series of spatial rules based on particular protein sequences and their order. This was the finding of a study recently published in Genome Biology by Luca Nanni, PhD student in Computer Science and Engineering at Politecnico di Milano, together with Professors Stefano Ceri of the same University and Colin Logie of the University of Nijmegen.

The first author of the study Luca Nanni said: "Our study's greatest innovation lies in having identified precise rules for the disposition of CTCF proteins. The beauty and simplicity of CTCF's grammar shows us how nature and evolution produce regularity and incredibly ingenious and functional systems." "Knowing these rules allow CTCF sequences to be engineered to obtain the desired DNA three-dimensional structure. For example, it should be possible to make two disconnected genes interact. Moulding DNA structure will open doors to the creation of pharmaceuticals for the treatment of diseases such as cancer."

The DNA molecule, which would be about two metres long if completely unrolled, wraps itself based on a complex system that maintains its accessibility and correct reading to reside in the cell's nucleus. Crucial in the study of the three-dimensional structure of the genome are topological domains, which are thought to aggregate DNA zones with similar roles and behaviour. For example, genes with similar function are likely to reside in the same topological domain. Nanni continued: "We focused on some specific DNA sequences that encode for the CTCF protein." "This protein isolates portions of DNA creating barriers between the various topological domains. With the help of computer simulations and the creation of a model for classifying these proteins according to their orientation, we identified a surprising regularity in their arrangement along the DNA sequence." The study showed that the orientation and order of these DNA sequences makes it possible to reconstruct topological domains. The human genome compresses following a "grammar" logic comprising CTCF sequences, orientation, and the distance between them.

Simple exercises can help to make people more playful and consequently feel more satisfied with their lives. This has been revealed in a new study by psychologists from Martin Luther University Halle-Wittenberg (MLU) in the journal Applied Psychology: Health and Well-Being. The researchers had participants in an experiment perform a week of exercises to boost their playfulness. They found that the trait can be stimulated and trained - and that this improves a person's mood.

Playfulness is a personality trait that is expressed differently in people. "Particularly playful people have a hard time dealing with boredom. They manage to turn almost any everyday situation into an entertaining or personally engaging experience," explains Professor René Proyer, a psychologist at MLU. For example, they enjoy word games and mental games, are curious, or just like playing around. According to Proyer, this does not mean that these people are particularly silly or frivolous. On the contrary, earlier studies by the researchers from MLU have shown that adults can put this inclination to positive use in many situations: They have an eye for detail, easily adopt new perspectives and can make a monotonous task interesting for them.

Until now it had been unclear whether playfulness could be trained and what effects this might have on people. Therefore, the psychologists from Halle conducted a study on 533 people, teaming up with researchers from the University of Zurich in Switzerland and Pennsylvania State University (USA). Participants were randomly divided into one of three experimental groups or a placebo group. The people in the experimental groups completed one of three daily exercises for seven days. The exercises were intended to boost their playfulness: Before going to bed, they either had to write down three situations from that day in which they had behaved particularly playful, or they were to use their inclination to be playful in an unfamiliar situation, for example in their professional life, and write down that experience. Or they were to reflect more broadly on the playful behaviour they had observed in themselves that day. In contrast, the placebo group received a task that had no influence on the experiment. "All of these methods are based on established interventions of positive psychology," explains Kay Brauer, who is a researcher in Proyer's group.

All groups filled out a questionnaire before and immediately after weeks one, two, four and twelve after the intervention, with which the researchers measured various personality traits. "Our assumption was that the exercises would lead people to consciously focus their attention on playfulness and use it more often. This could result in positive emotions, which in turn would affect the person's well-being," says Brauer. And indeed, the tasks did lead to an increase in playfulness. The researchers also observed a temporary, moderate improvement in the participants' well-being. "Our study is the first intervention study on adults to show that playfulness can be induced and that this has positive effects for them," says Proyer.

The results of the study serve as a starting point for new research questions and practical applications. "I believe that we can use this knowledge in everyday life to improve various aspects," says Proyer. For example, special interventions in the workplace could lead to more fun or a potential to be more innovative at work. Romantic partners could do similar exercises that might increase their satisfaction in their relationship. "This does not mean that every company needs table tennis tables or a playground slide. However, one idea would be to allow employees to consciously integrate playfulness into their everyday work and, as a supervisor, to set an example for this kind of behaviour," concludes Proyer.

The introduction of cigarette-like mentholated 'cigarillos' (mini cigars which are leaf-wrapped) to the UK is helping big tobacco companies to bypass strict public health measures intended to reduce smoking, say researchers.

Writing in the BMJ's Tobacco Control in an article published Thursday 27 August 2020, the team from the University of Bath focus on the introduction and marketing of cigarillo products which mimic cigarette brands, are as dangerous to health, yet are not subject to the same public health measures or taxation.

Whereas the UK has some of the strictest tobacco control legislation in the world for cigarettes and Roll-Your-Own (RYO) tobacco - including restrictions on minimum pack sizes, standardised packaging, and most recently a ban on menthol cigarettes - cigarillos can be sold in small pack sizes, with striking colourful pack designs, and still remain mentholated.

The researchers identify that these products are clearly aimed at cigarette smokers. Earlier this year, in January 2020, one company Japan Tobacco International (JTI) launched 'Sterling Dual Capsule Leaf Wrapped', officially sold as cigarillos but closely resembling previous cigarette products from the same company and with the same brand. Other tobacco companies, Imperial and STG, have since launched similar products suggesting they are also keen to exploit these loopholes.

In March 2020, packs of 10 of these cigarillos were being sold for £4.60, significantly less than half the price of a 20-stick packet of Sterling Dual Capsule cigarettes (purchased for £10.95 in a convenience store). The researchers behind the study say the low pack purchase price is enhancing its consumer appeal, especially for poorer smokers.

Dr Rosemary Hiscock from the Tobacco Control Research Group at the University of Bath, who has been involved in a number of studies evaluating recent tobacco legislation, explains: "Although cigarillos have to carry large pictorial health warnings, they can still be sold in colourful branded packaging, in 10-stick packs, can feature price markings which keep prices low, and can include characterising flavours, like menthol. Cigarettes, by contrast, must be sold in standardised olive-coloured packets of at least 20 sticks featuring the brand name only in a standard font and without any price markings or flavours. Future legislation needs to extend existing rules for cigarettes to all other tobacco products and accessories."

Tobacco tax expert and lead author on the study, Dr Rob Branston from the University of Bath's School of Management adds: "Currently the market for cigarillos in the UK is relatively small, but this could grow rapidly in view of industry efforts to market these products as a new cheaper alternative and this should worry us all given the health impact of a cigarillo is broadly the same as a cigarette. To address this the UK should consider a variety of measures, including urgent adjustments to the tax system so that cigarillos packs can't be sold so cheaply.

"As an immediate first step we would like to see the Treasury extend a minimum excise tax to cigarillos, in order to appreciably raise the pack purchase price. If they are going to be sold as being cigarettes, they should be taxed like it too."

The authors advocate that taxation offers the most immediate way forward; amending UK tobacco regulation is the ideal solution but will take significantly longer to change than taxation and would require public consultation. The recent announcement on the proposed abolition of Public Health England (PHE) likely further complicates any such pro

Intensively tilled soils have lost up to 50% of their original C with the attendant degradation in soil properties and productivity. Restoring the C lost with current conservation practices (i.e., no-till, cover crops) often takes decades. Applying high-C coal combustion residue from sugar beet (Beta vulgaris L.) processing factories, known as char, may rapidly restore soil C and productivity in degraded croplands.

In a recent Journal of Environmental Quality article, researchers in the Nebraska High Plains evaluated soil and crop response to char containing about 30% C applied at different rates ranging from 0 to 67.3 Mg ha-1 to two relatively low C soils (

Findings suggest that this industrial by-product can be a potential strategy to rapidly restore C in degraded agricultural soils, but additional long-term (> 2 years) research with char application exceeding 67.3 Mg ha-1 under different soils and climates is needed to fully understand how char impacts soil properties and crop yields.

Until now, these flows of material had been detected only in other wavelength ranges, such as X-rays or the visible, depending on the phase in which the black hole is consuming its surrounding material. This study provides the first evidence that the winds are present throughout the evolution of the eruption, independently of the phase, and this is a step forward in our understanding of the mysterious processes of accretion onto stellar mass black holes. The article has just been published in Astronomy and Astrophysics Letters, and was chosen as an 'outstanding article' by the journal itself.

X-ray binaries, as their name implies, are binary stars which emit strong radiation in X-rays. They are formed by a compact object, normally a black hole, with a stellar companion. Low mass X-ray binaries (LMXB) have companions with masses equal to, or less than the mass of the Sun. In these systems the two stars orbit at a distance so small that some of the mass of the star falls into the gravitational well of the black hole, forming a flat disc of material around it. This process is called accretion, and the disc, is an accretion disc.

Some X-ray binaries, termed transitory, changed from quiescent states, in which the amount of mass accreting onto the black hole is small and its brightness is too low to detect from the Earth, to eruptive states in which the black hole has an augmented accretion rate, so that the material in the disc heats up, reaching values between one and ten million degrees Kelvin. During these eruptions, which can last from weeks to several months, the system emits a large flux of X-rays, and its brightness increases by several magnitudes.

We still don't know exactly what are the physical processes which occur during these accretion episodes. "These systems are places where matter is subjected to gravitational fields which are among the strongest in the universe, so that X-ray binaries are physics laboratories which nature provides us for the study of compact objects, and the behaviour of the matter surrounding them", explains Javier Sánchez Sierras, a predoctoral researcher at the IAC and the first author of the article.

One of the most important physical processes which scientists need to understand is the ejection of material, or winds, during accretion episodes. According to Teo Muñoz Darias, an IAC research and coauthor of the article, "the study of winds in those systems is a key to understand accretion processes, because the winds can get to expel even more matter than is accreted by the black hole".

Same wind, different states

The article which has just been published in Astronomy and Astrophysics Letters, and which has been chosen by the journal as a "highlight article", presents the discovery of winds from the black hole MAXI J1820+070 in the infrared, during the eruption which took place during 2018-2019. In the past two decades winds have been observed in X-rays during eruption, termed soft in which the radiation emitted by the accretion disc is dominant, showing high luminosity. More recently, the same group at the IAC has discovered at visible wavengths winds in the hard state of accretion which is characterized by the appearance of a jet, which comes out essentially perpendicular to the accretion disc, and which emits strongly at radio wavelengths.

"In the present study -stressed Sánchez Sierras-, we have shown the discovery of infrared winds which are present during both the hard and soft accretion states, during the full evolution of the eruption, so that their presence does not depend on the accretion state, and this is the first time that this type of winds has been observed". The researchers have also been able to show that the kinematic properties of the wind are very similar to those observed in 2019 in the visible range, reaching velocities of up to 1800 km/s.

"These data suggest that the wind is the same for both cases, but its visibility changes wavelength during the evolution of the eruption, which would indicate that the system is losing mass and also angular momentum during the process of the eruption", explains Muñoz Darias. These results are very important to the scientists, because they add a new element to the global picture of the winds in these systems, and represent a step forward towards the goal of completing our understanding of the processes of accretion onto stellar mass black holes.

The first complete dinosaur skeleton ever identified has finally been studied in detail and found its place in the dinosaur family tree, completing a project that began more than a century and a half ago.

The skeleton of this dinosaur, called Scelidosaurus, was collected more than 160 years ago on west Dorset's Jurassic Coast. The rocks in which it was fossilised are around 193 million years old, close to the dawn of the Age of Dinosaurs.

This remarkable specimen - the first complete dinosaur skeleton ever recovered - was sent to Richard Owen at the British Museum, the man who invented the word dinosaur.

So, what did Owen do with this find? He published two short papers on its anatomy, but many details were left unrecorded. Owen did not reconstruct the animal as it might have appeared in life and made no attempt to understand its relationship to other known dinosaurs of the time. In short, he 're-buried' it in the literature of the time, and so it has remained ever since: known, yet obscure and misunderstood.

Over the past three years, Dr David Norman from Cambridge's Department of Earth Sciences has been working to finish the work which Owen started, preparing a detailed description and biological analysis of the skeleton of Scelidosaurus, the original of which is stored at the Natural History Museum in London, with other specimens at Bristol City Museum and the Sedgwick Museum, Cambridge.

The results of Norman's work, published as four separate studies in the Zoological Journal of the Linnean Society of London, not only reconstruct what Scelidosaurus looked like in life, but reveal that it was an early ancestor of ankylosaurs, the armour-plated 'tanks' of the Late Cretaceous Period.

For more than a century, dinosaurs were primarily classified according to the shape of their hip bones: they were either saurischians ('lizard-hipped') or ornithischians ('bird-hipped').

However, in 2017, Norman and his former PhD students Matthew Baron and Paul Barrett argued that these dinosaur family groupings needed to be rearranged, re-defined and re-named. In a study published in Nature, the researchers suggested that bird-hipped dinosaurs and lizard-hipped dinosaurs such as Tyrannosaurus evolved from a common ancestor, potentially overturning more than a century of theory about the evolutionary history of dinosaurs.

Another fact that emerged from their work on dinosaur relationships was that the earliest known ornithischians first appeared in the Early Jurassic Period. "Scelidosaurus is just such a dinosaur and represents a species that appeared at, or close to, the evolutionary 'birth' of the Ornithischia," said Norman, who is a Fellow of Christ's College, Cambridge. "Given that context, what was actually known of Scelidosaurus? The answer is remarkably little!"

Norman has now completed a study of all known material attributable to Scelidosaurus and his research has revealed many firsts.

"Nobody knew that the skull had horns on its back edge," said Norman. "It had several bones that have never been recognised in any other dinosaur. It's also clear from the rough texturing of the skull bones that it was, in life, covered by hardened horny scutes, a little bit like the scutes on the surface of the skulls of living turtles. In fact, its entire body was protected by skin that anchored an array of stud-like bony spikes and plates."

Now that its anatomy is understood, it is possible to examine where Scelidosaurus sits in the dinosaur family tree. It had been regarded for many decades as an early member of the group that included the stegosaurs, including Stegosaurus with its huge bony plates along its spine and a spiky tail, and ankylosaurs, the armour-plated 'tanks' of the dinosaur era, but that was based on a poor understanding of the anatomy of Scelidosaurus. Now it seems that Scelidosaurus is an ancestor of the ankylosaurs alone.

"It is unfortunate that such an important dinosaur, discovered at such a critical time in the early study of dinosaurs, was never properly described," said Norman. "It has now - at last! - been described in detail and provides many new and unexpected insights concerning the biology of early dinosaurs and their underlying relationships. It seems a shame that the work was not done earlier but, as they say, better late than never."

Prof. DONG Zhenchao and Prof. HOU Jianguo from University of Science and Technology of China (USTC) of Chinese Academy of Sciences (CAS) improved the spatial resolution from 8 nm to ~8 Å of photoluminescence imaging. It realized sub-molecular resolution with single molecule photofluorescence imaging for the first time.

This study was published in Nature Photonics on August 10.

To reach atomic resolution with light has always been one of the ultimate goals in nano-optics. The advent of scanning near-field optical microscopy (SNOM) kindled hopes for the goal.

Prof. DONG and his colleagues successfully demonstrated sub-nanometer scale spatial resolution in the single-molecule Raman spectroscopy imaging with local enhancement effect of a nanocavity plasmon field in a study in 2013.

However, unlike the Raman scattering process, fluorescence will be quenched in the very immediate vicinity of metals which stops the resolution development of SNOM at around 10 nm.

The radiation properties (fluorescence) of molecules in the metal nanocavity are directly affected by the photon density of the nanocavity , and the photon density of the nanocavity is closely related to the structure of the probe tip. Therefore, it is the key to modify the structure of the probe and the electronic state of the molecules in the nanocavity to avoid the fluorescence quenching and achieve high-resolution photofluorescence imaging.

DONG's team further fine-tuned the plasmon nanocavity, especially in the fabrication and control of the atomic-level structure of the probe tip. They constructed an Ag tip apex with an atomistic protrusion and matched the nanocavity plasmon resonance with the effective energy of the incident laser and molecular luminescence.

Then, the researchers used an ultra-thin dielectric layer (three-atom-thick NaCl) to isolate the charge transfer between the nanocavity molecules and the metal substrate, achieving sub-nanometer resolution of the single-molecule photoluminescence imaging.

They found that with the probe approaching the molecule, even if their distance is less than 1 nm, the intensity of photoluminescence continues increasing monotonously. And the fluorescence quenching disappears completely.

Theoretical simulations showed that when the atomistic protrusion tip and the metal substrate form a plasmon nanocavity, the resonance response of the nanocavity plasmon and the lightning rod effect of the atomistic protrusion structure would have a synergistic effect. The synergistic effect generates a strong and highly localized electromagnetic field compressing the cavity mode volume to below 1 nm3, which greatly increases the localized photon density of states and the molecular radiation decay rate. These effects not only inhibit the fluorescence quenching, but also realize sub-nanometer-resolution photoluminescence imaging.

To achieve sub-nanometer spatial resolution, the size of the tip and the distance between the tip and the sample must be on the sub-nanometer scale.

The researchers further realized sub-molecular-resolved photoluminescence hyperspectral imaging with spectral information, and demonstrated the effects of local plasmon-exciton interaction on fluorescence intensity, peak position and peak width on the sub-nanometer scale.

This research achieved the long-awaited goal of using light to analyze the internal structure of molecules in SNOM, and provided a new technical method for detecting and modulating the localized environment of molecules and light-matter interactions on the sub-nanometer scale.

The reviewers of Nature Photonics say that this paper will be an important article in its field, which has guiding significance for carrying out ultra-sensitive spectroscopic microscopy research with atomic-scale light.

SEATTLE (August 27, 2020) - A new study projects that 3.1 billion people will still lack effective health service coverage in 2023, with 968 million of those residing in South Asia. This falls short of the World Health Organization (WHO) goal of 1 billion more people benefiting from universal health coverage (UHC) between 2019 and 2023.

Universal health coverage is defined as all people receiving quality health services without incurring financial hardship. The paper, part of the Global Burden of Disease study, was published today in the international medical journal The Lancet. Researchers focused only on measuring service coverage, developing a new framework to capture how well countries align health services with the needs of the population and how well or poorly those services contribute to people's health.

"Universal health coverage is more than just access to health care," said Dr. Rafael Lozano, the senior author of the study and Director of Health Systems at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington School of Medicine. "Measuring access is necessary but not sufficient to capture health outcomes. By striving to capture potential health gains, we hope to better diagnose and address challenges that impede the ultimate objective of UHC: improving health for all people and leaving no one behind."

Using 23 indicators, the researchers assessed effective coverage by country on a scale of 1-100 and measured progress between 1990 and 2019. Globally, UHC effective coverage performance improved by nearly 15 points over that time period, but large variations remained across countries and regions, ranging from over 96 to below 25. Japan had the highest effective coverage score (96.4) in 2019, followed by Iceland, Norway, Switzerland, and San Marino. The Central African Republic, Somalia, Chad, Guinea, and Vanuatu had the lowest performance on UHC effective coverage.

Sub-Saharan Africa had accelerated gains since 2010 compared to other regions, nearly doubling average annual improvement between 2010 and 2019 compared to 1990-2010. Zimbabwe, eSwatini, the Democratic Republic of the Congo, Guinea-Bissau, and South Africa had the fastest growth in effective coverage performance.

The researchers also found that many countries lagged on performance for non-communicable diseases, compared to communicable diseases and reproductive, maternal, and child health. Globally, non-communicable diseases accounted for a greater proportion of potential health gains in 2019.

However, in some countries, like Kenya, Namibia, and Rwanda, causes beyond non-communicable diseases still have a high level of disease burden (e.g., HIV) and are an important area for policymakers and practitioners to prioritize. The different scenarios highlight the value of measuring effective service coverage, which can help inform UHC priorities that align with a country's health needs and evolve with those needs over time, rather than a one-size-fits-all approach to service coverage.

The study did not measure the financial risk protection component of UHC, but the researchers did look at per capita health spending by country. While they found that increased spending could be important for many countries to improve UHC effective coverage performance, efficiencies in health systems are also an important component.

Health spending and its relationship to universal health effective coverage is also explored in IHME's recently published report on global health financing. Countries with high performance relative to spending levels included Peru, Rwanda, South Korea, Cyprus, and Costa Rica. The United States, Central African Republic, Turkmenistan, and Saudi Arabia were among those countries with low performance relative to spending levels.

"We are seeing countries with varied performance at the same level of spend - an indicator that money spent on health is not being translated as efficiently as it could into gains in UHC effective coverage," said Dr. Christopher Murray, IHME Director and a senior author on the study. "For most countries, increased health spending alone is unlikely to deliver on ambitious UHC targets. Improving alignment of health systems with population health needs and bolstering efficiencies, along with more money, will likely result in faster and more sustained gains."

The study was completed prior to the COVID-19 pandemic but provides an important benchmark for measuring the impact of the pandemic and progress on UHC in years to come. It also highlights the value of effective data systems.

"Whether it's a rapidly spreading virus or persistent gaps in health service delivery, establishing and maintaining strong data systems are crucial to identifying health needs and effectively responding to them so that all people, within a country and around the world, have the opportunity to live full, healthy lives," said Nancy Fullman, a PhD student in global health at the University of Washington and one of the study's lead authors.

The link between influenza and serious heart conditions just grew stronger.

A CDC study looking at more than 80,000 adult patients hospitalized with flu over eight seasons found that sudden, serious heart complications were common, occurring in 12% of patients, or 1 in 8.

"Previous to our study, there had been suggestions between the link, but our study shows just how common it is," said lead author Eric Chow, an infectious diseases fellow at University of Washington School of Medicine.

The study, published Aug. 25 in the Annals of Internal Medicine, underscores the importance of getting a flu shot early.

"There are few respiratory viruses we have a vaccine for," he said. "Our team motto is 'Get a flu shot.'" Chow previously worked as an epidemic intelligence service officer, or "disease detective," for influenza at the Centers for Disease Control and Prevention.

The study found that 5% of patients hospitalized with the flu had a cardiac complication despite having no documented underlying conditions.

In the last month, there have been cases of otherwise healthy athletes showing signs of heart complications after recovering from COVID-19. For example, 27-year-old Florida State basketball player Michael Ojo, who recovered from COVID-19, died of an apparent heart attack at a practice.

Chow said he is not surprised this is happening to healthy people who have been infected with SARS-CoV-2, the virus that causes COVID-19. The virus can cause damage to the lungs and other organs, including the heart. Inflammation makes hearts vulnerable to potentially fatal arrhythmias during vigorous exercise.

In this study of adults hospitalized with flu, 12% had acute heart complications. Of these, 30% were admitted to the ICU and 7% died while in the hospital.

The CDC recommends that everyone 6 months and older get a flu vaccine every flu season. According to the CDC, flu vaccination is always considered important for people at high risk of developing serious flu complications, including people with heart disease. Flu shots are approved for people with heart disease, but people with heart disease should not receive the live attenuated influenza vaccine (LAIV, also known as the nasal spray flu vaccine). However any intramuscular flu shot, such as any inactivated or recombinant influenza vaccine, would be appropriate.

The northern quoll, one of Australia's most adorable and endangered native carnivores, appears to be adapted to dramatically different landscapes - which may be key to the species' survival.

University of Queensland PhD candidate Pietro Viacava co-led a study that found similarities between northern quoll skulls across a 5000 kilometre range, which has raised hopes scientists will be able to cross-breed isolated populations.

"Northern quolls are in danger - a lot has been thrown at them," Mr Viacava said.

"They've been victims of a devastating cane toad invasion, increases in bushfires and habitat fragmentation, all while facing stiff competition from other carnivores such as dingoes and cats.

"The problem we are facing with conserving the northern quoll is that there may be too little genetic diversity in these handful of remaining populations, scattered across Australia.

"If we cross-bred them, we might run the risk that they wouldn't be ideally suited to these diverse environments.

"Their skulls, for example, might not be properly adapted to eat local prey, as it differs across Australia.

"Luckily, this doesn't seem to be the case - these quolls seem to be incredibly versatile."

The research team used a technique known as 'geometric morphometrics' to characterise skull shape variation in museum specimens of northern quolls.

They looked for shape differences between populations, or whether environmental conditions coincided with changes in skull shape.

Dr Vera Weisbecker from the Flinders University College of Science and Engineering supervised the study, and said the results appeared to be a win for northern quoll conservation.

"Quoll skull shapes were mostly similar across their entire range, although the shapes did vary with the size of the animals," Dr Weisbecker said.

"This means, for example, that a quoll skull from Pilbara region in WA looked nearly the same as a similar-sized one from south-eastern Queensland, 5000 kilometres apart.

"Although other parts of the animal's body and genetic factors need to be considered, we will most likely be able to breed animals from different populations for conservation without losing adaptations to feeding."

However, there is also a much less positive potential explanation for the results.

"Scientists have long suspected that marsupial mammals - such as quolls, kangaroos and koalas - are seriously limited in the degree to which they can adapt their skull and skeleton," Dr Weisbecker said.

"This is because newborn marsupials require a specifically shaped snout to be able to latch onto the mother's teat.

"In that case, what we see may actually be a serious limitation on the ability of quolls to adapt, rather than the much more hopeful multipurpose solution we propose."

To further explore this possibility, the team is now looking at how closely related species of antechinus - smaller quoll relatives - differ in skull shape.

Children and teenagers are less likely than adults to develop severe Covid-19 or die from the disease, according to the world's largest study of hospital patients with Covid-19.

Obesity, Black ethnicity and being under one month old are factors that increased the risk of a child being admitted into intensive care with the condition, the report said.

The findings also identify new symptoms of a severe inflammation syndrome that significantly increases the risk of children with Covid-19 needing intensive care.

Researchers are calling for the WHO's definition of Multisystem Inflammatory Syndrome in Children (MIS-C) to be updated to help doctors identify more children with the condition and improve their treatment.

The team led by researchers from the Universities of Edinburgh and Liverpool, Imperial College London and the Royal Hospital for Children, Glasgow, recruited 651 children and young people aged 19 years or less who had been admitted to hospital with Covid-19.

The study is led by ISARIC4C - a global group of clinicians working to prevent death from respiratory disease - and involved 138 hospitals across England, Wales and Scotland. The ISARIC4C Covid-19 study includes two thirds of all people admitted to hospital with the disease.

The findings suggest that it is rare for young people to end up in hospital with Covid-19. They make up less than one per cent of participants in the ISARIC study.

The typical age of children hospitalised was five-years-old. Some 42 per cent of patients had at least one other condition, the most common included neurological conditions and asthma.

The number of children and young people who died from Covid-19 was relatively low - six in total - when compared with adult deaths.

Three children who died were newborn babies born with other severe health problems. The other three children were aged 15 to 18 years old and also had profound health issues.

Some 18 per cent of hospitalised children and young people were admitted to intensive care. Experts say children most at risk of needing intensive care were those under one month old and those aged 10 to 14 years old. Similar to adults, obesity and Black ethnicity were also found to be risk factors.

The study also identified 52 patients who had MIS-C an inflammatory syndrome. The researchers found that these children were five times more likely to be admitted to intensive care.

The symptoms usually seen in those with MIS-C include conjunctivitis, a rash or gastrointestinal problems such as abdominal pain, vomiting and diarrhea.

The study found new Covid-19 symptoms in children with MIS-C. These include headaches, tiredness, muscle aches and a sore throat.

The study also found that the number of platelets - a component of the blood involved in clotting - was much lower in the blood of children with MIS-C than in those without the condition.

The combination of symptoms and low platelets may be important in identifying children with MIS-C who may become more unwell, experts say.

This research was funded by UK Research and Innovation (UKRI) and by the Department of Health and Social Care through the National Institute for Health Research (NIHR) as part of the UK Government's Covid-19 rapid research response.

Dr Olivia Swann, lead author and Clinical Lecturer in Paediatric Infectious Diseases at the University of Edinburgh, said: "Researchers often want to call attention to large numbers of patients in their studies, however, we want to highlight that children made up only a fraction of a percent of all Covid-19 admissions across the UK in our study and that severe disease was rare."

Professor Calum Semple, Professor in Child Health and Outbreak Medicine and Consultant Respiratory Paediatrician at the University of Liverpool, said: "The diligent work of our colleagues working in Child Health and the NIHR Clinical Research Network across the UK has led to this report which is the largest and most detailed description of covid-19 and MIS-C in children and young people. We have provided new understanding about MIS-C which will help manage this rare but serious condition, but parents can now be reassured that severe covid-19 is very rare in children."

Dr Louisa Pollock, Consultant in Paediatric Infectious Disease at the Royal Hospital for Children, Glasgow, said: "Parents should be reassured by this study which confirms very few children were seriously affected by Covid-19. As children return to school, and over the winter months, it is important we continue to monitor Covid-19 in children."

Professor Fiona Watt, Medical Research Council Chief Executive, said: "This is a significant study involving 138 hospitals across England, Wales and Scotland showing that children and teenagers are less likely than adults to develop severe COVID-19 or die from the disease. Indeed, the findings suggest it is rare for young people to end up in hospital with COVID-19.

"However, while the overall the risk for young people is lower, the added risks of obesity and ethnicity are shared with adults. We need to understand this, and also why a very small number of children are suffering from an inflammatory syndrome. Obviously the goal is to ensure that everyone who develops COVID-19 has the most appropriate treatment."

An international group of hearing specialists has released a new set of recommendations emphasizing that cochlear implants should be offered to adults who have moderate to severe or worse hearing loss much more often than is the current practice. The group hopes the recommendations help increase usage of such devices, potentially improving hearing and quality of life for millions worldwide.

The consensus statement, published Aug. 27 in JAMA Otolaryngology, was developed by a panel of 31 hearing experts representing more than a dozen countries. Craig A. Buchman, MD, the Lindburg Professor and head of the Department of Otolaryngology-Head & Neck Surgery at Washington University School of Medicine in St. Louis, led the panel.

Unlike hearing aids, which amplify sound for people who retain some ability to hear, cochlear implants help people hear by directly stimulating the auditory nerve.

The committee of hearing experts, which includes otolaryngologists and audiologists, said that the estimated 50 million people living with hearing loss severe enough to negatively affect quality of life could benefit from cochlear implants. The recommendations also are intended to raise awareness among primary care doctors and other health-care providers who potentially could diagnose hearing loss and refer patients to hearing specialists.

"Even though cochlear implants have been approved by the Food and Drug Administration since 1985, less than 10% of adults who could benefit from them actually receive one of these devices," Buchman said. "There may be a misconception that cochlear implants are only for young children born with profound hearing loss. But these devices can be extremely effective for adults who have lost hearing later in life. Adults who have difficulty talking on the phone, for example, are probably candidates for a cochlear implant."

Buchman also said adults and their doctors may turn to hearing aids because they assume such devices will solve the problem and help avoid what is perceived by many to be a major surgery.

"Cochlear implants can be implanted in an outpatient procedure that typically takes about an hour," Buchman said. "It's a safe procedure and highly effective. In addition, hearing aids only work for those who need some amplification. But as hearing diminishes, people start to lose clarity as well. Making unclear speech louder doesn't help with comprehension -- people start to sound like the teacher who mumbles in the Charlie Brown cartoon. At that degree of hearing loss, a cochlear implant is the recommended intervention because it can restore clarity."

The consensus paper reports 20 statements that the panel of experts voted to include in the document. The recommendations, which were arrived upon following a review of scientific literature on cochlear implants, cover seven categories for adults with moderate to severe or worse hearing loss in both ears. They focus on:

Awareness of cochlear implants.

Best practice guidelines for diagnosing hearing loss.

Best practice guidelines for cochlear implant surgery.

Clinical effectiveness of cochlear implants.

Factors linked to outcomes after cochlear implant surgery.

Relationship between hearing loss, depression, social isolation and dementia.

Cost implications for cochlear implants.

Buchman said another possible barrier to wider adoption is that hearing loss is surprisingly difficult to diagnose. Primary care offices do not always have the specialized equipment used to test hearing, and patients are adept at finding ways to cope with diminishing ability to hear.

"During a one-on-one checkup, it's actually quite easy for doctors to miss even severe hearing loss," Buchman said. "Hearing loss can happen gradually, and people may not notice the degree to which they are relying on lip reading and the context of what they can hear to compensate for what they're missing. But to compensate for lost hearing successfully, they need to have face-to-face interactions."

"If you are a doctor having a wellness visit with a patient, a simple way to screen for hearing loss is to go to the sink and wash your hands," he said. "With the water running and your back to the patient, try asking a few questions. If the patient doesn't respond in that situation, it's appropriate to start a conversation about hearing loss with him or her and discuss whether formal hearing tests are appropriate."

Hearing loss has been associated with social isolation, depression and dementia. Though research is ongoing to understand the role of hearing loss in these problems, Buchman and his colleagues said strong evidence suggests that improving hearing can have a significant impact on quality of life.

"Research indicates that hearing loss is the single largest modifiable risk factor for dementia, and cochlear implants can perhaps lessen that risk," he said. "We hope these recommendations will eventually lead to formal clinical practice guidelines. Such guidelines could increase access to cochlear implants worldwide, address disparities in care, and lead to improved hearing and quality of life for adults living with debilitating hearing loss."