Brain

Analysis by national consortium, OUTBREAK, highlights how urinary tract infections (UTIs) are becoming more persistent and harder to treat, resulting in more people being admitted to hospital where they require longer stays and more costly medicines.

OUTBREAK managing director Assoc. Prof. Branwen Morgan said drug-resistant UTIs were the canary in the coal mine for a growing number of antibiotic-resistant germs spreading in our community, animals and environment.

"Drug-resistant infections are a global health threat but this is the first time we've been able to connect the overuse and misuse of antibiotics to the health and economic impact of a single disease," Assoc Prof. Morgan said.

"UTIs affect 1 in 2 Australian women and 1 in 20 men in their life-time, currently resulting in more than 2.5-million GP appointments, 100,000 emergency department visits and 75,000 hospital stays each year.

"We found that UTIs already cost Australia's health system $909 million per year, not including indirect costs such as lost productivity. If we do nothing to stop the rise of antibiotic-resistance, that figure could easily hit $1.6 billion by 2030.

"Those figures are very conservative and don't take into account the increasing numbers of people with UTIs, so realistically it could cost much, much more than that."

The calculations were devised using a combination of national and regional data from the Illawarra Shoalhaven Local Health District (ISLHD) for the number of UTI patients presenting to their doctor, the emergency department, the number hospitalised and proportion requiring intensive care, as well as local antibiotic resistance trend data.

ISLHD infectious diseases staff specialist Dr Simeon Crawford said the potential costs to the economy and our way of life were extraordinary.

"We can see the alarming multi-billion-dollar impact of antibiotic-resistance across the entire health system nationally," Dr Crawford said.

"As more and more germs acquire drug-resistance mechanisms, the burden will rise inexorably. We can't afford to be complacent."

Dr Crawford said a greater variety and volume of information was needed to fight the growing resistance of UTIs to antibiotics.

"Connecting data from different sources will help us to predict and manage the problem," he said. "With the right information we can use antibiotics in a more targeted way; saving lives, saving money and protecting the effectiveness of these invaluable medicines for as long as possible."

Distinguished Professor Antoine van Oijen, from the University of Wollongong, said the proliferation of drug-resistant bacteria was a slow-moving but serious threat.

"COVID-19 is a very powerful example of how one untreatable virus can bring economies to their knees," Prof. van Oijen said.

"But drug-resistant bacteria are a bigger, more pervasive problem in health settings and throughout the community."

British economist Lord Jim O'Neill, who led a landmark review into antibiotic resistance, said the OUTBREAK report was an excellent example of what could be done to determine the costs and consequences of UTIs.

"I love that the role of diagnostics is at the centre of their recommended approach to dealing with the UTI challenge, which I have long since argued is quite possibly the single most important way of reducing the inappropriate demand for antibiotics," Lord Jim said.

Adjunct Professor Anna George, a former Australian ambassador and multilateral negotiator, said COVID-19 had shown how a public health threat could undermine entire economies.

"Consumer behaviour is unpredictable when public health is under threat and that disruption flows through to every business - from multinationals to solo operators," she said.

Ms George said the economic and health consequences of drug-resistant bacteria spreading through the food chain was an emerging challenge, including for Australia food producers and exporters and an issue currently being negotiated in the international food standard setting agency, Codex.

"In the case of UTIs, the bacteria may have a food-borne origin that includes meat and fresh produce," she said.

Read the full report on the cost of UTI superbugs in Australia: https://bit.ly/2Uo2x9W

Watch more: https://youtu.be/wWfpTBUBmmg

Scientists have discovered an extremely rare species of cymothoid from the mouth of a museum specimen of a deep-sea shark caught from the East China Sea, suggesting its wide distribution around the globe.

Cymothoids are a family of isopods (a type of crustacean) that are ectoparasites of fish. Some species in this family are also known as tongue-biter or tongue-eating louse (e.g., Cymothoa exigua).

Assistant Professor Ryota Kawanishi and Dr. Shinpei Ohashi from Hokkaido University have reported the discovery of an extremely rare species of cymothoid, Elthusa splendida, from the East China Sea. Their paper, published in the journal Species Diversity, expands the range of this species to almost the opposite sides of the Earth.

Cymothoids are a diverse family of more than 300 species of parasites, and parasitize a wide variety of fish, from freshwater to the deep sea. A recent study into the genetics of the family has shown that it is highly likely that they evolved in the deep sea and diversified. A number of deep sea cymothoids, however, are poorly studied, primarily due to the difficulty of deep sea sampling.

Elthusa splendida is the least studied of all deep sea cymothoids. Only five specimens have ever been cataloged and described, in 1981. Those specimens were recovered from a Cuban dogfish, a deep-sea shark, which was captured off southern Brazil in the western South Atlantic. No additional specimens have been reported since then.

In the current study, the scientists discovered the specimen of Elthusa splendida while processing fish specimens at the Fisheries Science Center, Hokkaido University Museum (HUMZ), Hakodate. The specimen was found in a Japanese spurdog, also a deep-sea shark, that had been collected from the East China Sea in June 2003 and preserved in formalin. The scientists confirmed the identification of the specimen by comparing the morphological features of the specimen with the original description of the species. The unique feature that defines Elthusa splendida is the presence of four pits on the first pereonite (first segment behind the head); this feature was examined using a computerized 3D measurement system. DNA sequencing was not used for identification as the sequence of the original specimen is unknown.

This discovery is important as it shows the distribution of Elthusa splendida extends from two locations that are almost antipodal to each other -- almost as far as it is physically possible to be on the planet. The scientists suggest that other species of deep sea cartilaginous fish in the genus Squalus (to which both the Cuban dogfish and the Japanese spurdog belong) can potentially serve as hosts for this parasite. They have also confirmed that Elthusa splendida is rare among other Elthusa species in parasitizing the mouth of the host, rather than the gills; furthermore, even among those cymothoids that parasitize the mouth, Elthusa splendida is one of the rare species that attach to the palate.

This study indicates that there is much that remains to be investigated when it comes to deep sea cymothoids. The scientists also propose using existing specimens of fish in museums across the world to reveal the distribution of cymothoids; from a broader perspective, this work suggests the hidden value of museum natural history collections in studying parasites.

Materials consisting of inorganic and organic components can combine the best of two worlds: under certain circumstances, the so-called MOFs - short for metal-organic frameworks - are structured in the same order as crystals and are at the same time porous and deformable. This opens up the prospect of intelligent materials for energy-saving technical applications. However, so far only a few flexible MOFs have been identified.

A research team from Ruhr-Universität Bochum (RUB) and Technical University of Munich (TUM) has used experiments and simulations to find out by what means MOFs can be rendered flexible and why: they tricked the system by using clever chemical manipulations to enable a variety of energetically similar arrangements in the crystalline order.

The application potential of MOFs was first discovered around 20 years ago, and almost 100,000 such hybrid porous materials have since been identified. There are great hopes for technical applications, especially for flexible MOFs.

As shock absorbers, for example, they could react to sudden high pressure by closing their pores and losing volume, i.e. deforming plastically. Or they could separate chemical substances from each other like a sponge by absorbing them into their pores and releasing them again under pressure.

"This would require much less energy than the usual distillation process," explains Rochus Schmid. However, only a few such flexible MOFs have been identified to date.

MOFs under pressure

In order to get to the bottom of the underlying mechanisms within such materials, the Munich team has carried out a more detailed experimental analysis of an already widely known MOF. To this end, the researchers subjected it to uniform pressure from all sides, while observing what goes on inside using X-ray structure analysis.

"We wanted to know how the material behaves under pressure and which chemical factors are the driving force behind the phase transitions between the open-pored and closed-pore state," says Gregor Kieslich.
The experiment showed that the closed-pore form is not stable; under pressure the system loses its crystalline order, in short: it breaks down.

This is not the case with a variant of the same basic structure: if the team attached flexible side chains of carbon atoms to the organic connecting pieces of the MOF that protrude into the pores, the material remained intact when compressed and resumed its original shape when the pressure decreased. The carbon arms turned the non-flexible material into a flexible MOF.

The secret of phase transformation

The Bochum team investigated the underlying principles using computer chemistry and molecular dynamics simulations. "We have shown that the secret lies in the degrees of freedom of the side chains, the so-called entropy," outlines Rochus Schmid. "Every system in nature strives for the greatest possible entropy, to put it simply, the greatest possible number of degrees of freedom to distribute the energy of the system."

"The large number of possible arrangements of the carbon arms in the pores ensures that the open-pored structure of the MOF is entropically stabilized," Schmid continues. This facilitates a phase transformation from the open-pored to the closed-pore structure and back again, instead of breaking down when the pores are squeezed together as would be the case without the carbon arms."

In order to calculate such a large system comprised of many atoms and to search for the many possible configurations of the arms in the pores, the team developed a precise and numerically efficient theoretical model for the simulation.

The key result of the study is the identification of another chemical option to control and modify the macroscopic response behaviour of an intelligent material by a thermodynamic factor. "Our findings open up novel ways to specifically achieve structural phase transformations in porous MOFs," concludes Gregor Kieslich.

Osaka, Japan - Many plants, including legumes, make naturally occurring chemicals called saponins. For example, the medicinal plant licorice produces the saponin glycyrrhizin, a potent natural sweetener that also has antiviral and other pharmacological activity. Soyasaponins, found in soybeans, have anticarcinogenic and antioxidant properties.

But exactly how plants make these useful products was unclear. Now a research team at Osaka University, in collaboration with National Agriculture and Food Research Organization (NARO), RIKEN, and Chiba University, has uncovered a vital link in the complex biochemical pathway for saponin synthesis. Their discovery paves the way for improving the commercial production of these high-value products. The team recently published the study in Nature Communications.

Osaka University researchers Soo Yeon Chung and Hikaru Seki, with collaborators in NARO (Masao Ishimoto et al.), RIKEN, and Chiba University, studied co-expression gene network of saponin synthesis using technologies including gene cloning and sequence comparisons, coupled with biochemical analyses in mutants and genetically modified plants of a model legume species. They discovered a new enzyme in the CSyGT family that are similar in structure to the enzymes producing cellulose in plant cell walls. Unexpectedly, they showed that the new member of the family was responsible for a key step in saponin synthesis, where a sugar molecule is attached to the triterpenoid backbone. This discovery challenged the generally accepted view that a different class of enzyme was probably involved in this step.

They went on to insert the gene for the newly discovered CSyGT enzyme, along with genes for other steps in the biochemical pathway, into yeast cells. The engineered cells successfully produced glycyrrhizin from simple sugars, indicating a potential route for industrial manufacture of valuable saponins by growing yeast cells on a large scale.

"Our multi-disciplinary team showed, for the first time, that this type of enzyme is important in saponin synthesis," says corresponding author Toshiya Muranaka. "Our results fill a gap in previous knowledge and also challenge the accepted view of how this pathway for biosynthesis operates."

"We showed that yeast cells can make glycyrrhizin when we insert the necessary plant genes," explains Chung. "This offers the prospect of new ways to produce these valuable substances commercially, and to generate completely novel types of saponin that might have further beneficial applications in medicine or the food industry." Seki adds, "producing the chemicals in cell cultures would also reduce the need to deplete natural plant resources and so help to meet the vitally important Sustainable Development Goals."

Projections of atmospheric and oceanic processes in the Red Sea are informing the design of sustainable megacities being planned and built along its shores.

The Red Sea is a vital natural and economic resource both for the region and the world. Rapid population and industrial growth along the coast, along with the rising threats of global warming, have highlighted the need to build sustainable cities and maintain a healthy marine ecosystem. Saudi Arabia generates nearly one-fifth of its income from tourism, shipping, agriculture and fishing in the Red Sea, and gets 90 percent of its freshwater from desalinated seawater. These industries all rely upon atmospheric and oceanic conditions, which form part of a complex climate system about which very little was previously known.

An international team led by Ibrahim Hoteit, Professor of Earth Sciences and Engineering at KAUST, has combined expertise in weather, oceans, waves, air pollution, marine ecosystems and data visualization to create an all-in-one climate modeling system for the Red Sea region, using satellite and surface observations to refine the output. "By building expertise in a region instead of a discipline, we can understand circulation, ecosystems and climate in the Red Sea like never before," says Hoteit.

The system, which was built on a supercomputer at KAUST, has generated the first high-resolution oceanic and atmospheric analyses of the region for the past 40 years, which revealed how natural processes in the Red Sea connect with the earth's climate. "We were surprised to see the Indian monsoon's role in seasonally reversing the overturning circulation in the Red Sea," says Hoteit. "It has helped explain unusual summer chlorophyll blooms in the southern Red Sea."

The modeling system can predict numerous processes, including ocean and atmospheric circulation patterns, marine ecosystem behavior, the spread of air pollution and the potential path of an oil spill. This is already providing essential information to academia, government and industry in Saudi Arabia, supporting research into Red Sea biodiversity hotspots, environmental policymaking, renewable energy projects and flood protection. For example, their reconstruction of extreme wave heights along the shoreline guided the design of the sea wall that will protect the newly built King Abdullah Economic City.

Hoteit's team continue to enhance the system's performance and expand its capabilities, with a particular focus on forecasting at the seasonal timescale and high spatial resolution simulations of urban environments. "We want to turn this into an easy-to-use, online visualization tool to support local authorities and industry in solving environmental problems in the region," he says.

New measurements reveal a surprising increase in the amount of dense water sinking near Antarctica, following 50 years of decline.

Dense water formed near Antarctica, known as Antarctic Bottom Water, supplies oxygen to the deep ocean. Bottom water also forms part of the global network of ocean currents that influences climate by storing heat and carbon dioxide in the ocean. Changes in bottom water formation can therefore impact global climate and deep ocean ecosystems.

The study, led by Dr Alessandro Silvano from the University of Southampton and CSIRO and published in the journal Nature Geoscience, documents an increase in the supply of bottom water to the deep Indian and Pacific Oceans. "Over the past 50 years of oceanographic campaigns we have seen a reduction in the amount of dense water reaching the deep ocean' Dr Silvano said. "This trend was mysteriously interrupted in 2018."

The research found that unusual wind patterns near Antarctica changed ocean currents in the Ross Sea where bottom water is formed. The changes in wind and currents increased the amount of ocean cooling and freezing. The extra cooling and freezing, in turn, increased the density of water that sinks into the deep ocean, producing additional dense bottom water.

"We found that an unusual combination of two climate phenomena drove the renewal of bottom water formation: an extreme El Niño event occurring at the same time as stronger and southward-shifted westerly winds," said Dr Silvano. "These results show how remote forcing can influence Antarctic processes and climate."

Co-author Annie Foppert, from the Australian Antarctic Program Partnership and CSIRO's Centre for Southern Hemisphere Oceans Research, said, "Evidence suggests the gradual decline in bottom water formation over the past five decades probably resulted from increased melt of the Antarctic Ice Sheet. The surprising rebound in recent years shows how extreme climate events can temporarily reverse long-term trends in Antarctic climate."

"In the future, we expect the accelerating melt of the Antarctic Ice Sheet to reduce the formation of bottom water" said Dr Silvano. "But climate extremes like those that drove the recent rebound in bottom water formation are also projected to become more common if greenhouse gas emission by human activities continue at current rates."

"Further work is needed to understand how these competing factors will affect bottom water formation in a warming climate."

Long-term variability in the 'abundance' of a macro-organism could provide fundamental information for evaluating its evolution, its responses to climate changes and human impact, enabling management and preservation strategies. Biological monitoring in aquatic systems has provided evidence of long-term variability in the abundance of macro-organisms. However, almost all such records span less than a century; there are none which span centuries or more. Aquatic bottom sediments have provided records of species abundance on longer time scales, although previous studies addressed marine fish species using fossil remains (mainly fish scales) and reconstructed abundance for only seven fish taxons. Thus, there remains a distinct lack of information on long-term changes in abundance for many marine fish species and other macro-organisms in aquatic systems.

This study focused on an approach using sedimentary DNA which is a potentially powerful tool for reconstructing lengthy records of fish species. We first tested the existence of fish DNA in the marine sediment sequences in a Japanese bay. Then we tested the utility of sedimentary DNA in reconstructing past fish abundance by comparing fish sedimentary DNA concentrations with fish scale concentrations and landing data.

Sediment core samples collected from Beppu Bay in the Seto Inland Sea, Japan, were used to quantify sedimentary DNA of three major fish species (Japanese anchovy, Japanese sardine, and jack mackerel) by applying quantitative Polymerase Chain Reaction (qPCR) methods. The result showed that the DNA of these fish species were detected in sediment sequences spanning the last 300 years. Observed temporal changes in fish DNA concentrations on decadal and centennial time scales are consistent with those of landings in Japan for all three species and with those of sardine fish scale concentrations. Thus, sedimentary DNA could be used to track decadal-centennial dynamics of fish abundance in marine.

Using environmental DNA is a widely accepted approach for biological monitoring that is easy, fast and inexpensive without the need for taxonomic expertise for the physical identification of a species. However, such monitoring started only recently; the data collection interval not being less than 10 years. In contrast, the use of sedimentary DNA is expected to instantly obtain lengthy retrospective monitoring data of abundance if the water has a sedimentary basin in which DNA is continuously deposited and stably preserved. This approach has not been used because it remains unclear whether sedimentary DNA concentrations reflect the abundance of an aquatic species. Our findings suggest that the use of sedimentary DNA is a viable technique for tracking past changes in fish abundance, and also could be used to reconstruct the abundance of macro-organisms inhabiting water. Sedimentary DNA technology could support monitoring efforts during the 21st century as a potential tool for decifering the long-term dynamics of macro-organisms before the monitoring started or at a place lacking lengthy monitering observations.

Nowadays, cannabidiol is a star component, not only in the world of cosmetics, but also in pharmaceutics and nutrition due to its antioxidant properties and its therapeutical potential. It is a natural molecule that comes from medicinal cannabis and that, despite being derived from it, is not a psychoactive compound, meaning that it has no effect upon the nervous system.

In spite of its successful sales, we still do not know how cannabidiol acts upon different skin cells in order to unleash its antioxidants. A collaborative partnership with the University of Cordoba and the University of Dundee demonstrated for the first time that cannabidiol induces the expression of heme oxygenase 1, an enzyme with antioxidant and anti-inflammatory properties, in the main cells on the top layer of the skin, called keratinocytes. This is done by reducing or silencing the protein that suppresses it, known as BACH1.

"Once we described the whole working mechanism, we have continued our partnership, making modifications to the cannabidiol molecule in order to try to improve its properties that fight against skin diseases", explains Immunology Professor Eduardo Muñoz, who is in charge of the BIO-304 "Immunopharmacology and Molecular Virology" research group at the University of Cordoba.

Hence, the international research team designed new molecules that, besides inhibiting the BACH1 protein, activate the NRF2 protein. This protein controls the way that certain genes are expressed. These specific genes help to protect cells against oxidative stress such as HMOX1, the one that encodes heme oxygenase 1, but also many others that work independently from BACH1.

So, the newly designed molecules that are derived from cannabidiol have double antioxidant activity: on the one hand, they supress BACH1 and with it, they induce the expression of heme oxygenase 1 and on the other, they activate NRF2, which also induces the expression of heme oxygenase 1, in addition to other antioxidant genes. "When combining the inhibition of BACH1 with the activation of NRF2, the result is a very potent antioxidant and anti-inflammatory response and better therapeutic effects", says Eduardo Muñoz.

This action mechanism is very interesting for skin disease treatments such as atopic dermatitis and epidermolysis bullosa, a very rare disease on which there is little research. What is more, this molecule has great potential to be used in cosmetics due to its antioxidant properties.

In addition to the University of Dundee in Scotland and the University of Cordoba, the companies Emerald Health Biotechnology, in the field of developing new medicine, and Innohealth Madrid (acquired by Evonik Industries AG), which specializes in dermo-cosmetics made from natural ingredients, have also collaborated on this research. Both companies were set up stemming from the BIO-304 research group at the University of Cordoba.

Based on these studies, the research team will continue to modify the molecules in order to improve their properties and, further down the road, perform studies on animal models in order to understand its therapeutical potential for skin diseases and other inflammatory diseases.

Rechargeable lithium-ion batteries (LIBs) are considered the best hope for next-generation battery technology, thanks to their long-life cycle, high specific power and energy density. However, they have not met the ever-increasing demands of emerging technologies such as electric vehicles. Li-Se battery technology is increasingly considered a real alternative to LIBs because of its high theoretical volume capacity and much higher conductivity.

In the first study of its kind, published by the Nature Communications journal, engineers from Surrey's Advanced Technology Institute (ATI), in collaboration with the team at University Technology of Sydney detail how they used a single-atom catalyst to create highly effective cathodes for Li-Se batteries. They demonstrate that their batteries have a superior rate capability and outstanding long-term cycling performance.

The Surrey team used to delicately control Zeolitic Imidazolate Framework (ZIF) particles that were placed on the surface of polystyrene spheres. The core-shell of the ZIF was then converted into a hollow structured carbon material.

Through further fine-tuning, the team from the ATI successfully produced atomic cobalt electrocatalyst, nitrogen-doped hollow porous carbon, nitrogen-doped hollow porous carbon and cobalt nanoparticles. By embedding selenium in hollow structured carbon particles, carbon/selenium composites were produced.

The atomic cobalt electrocatalysts were used as cathode materials for Li-Se batteries and clearly showed superior electrochemical performance including a superior rate capability (311?mA?h?g?1 at 50?C) and excellent cycling stability (267?mA?h?g?1 after 5000 cycles with a 0.0067% capacity decay per cycle at a current density of 50?C) with the Coulombic efficiency of ~100%.

Dr Jian Liu, one of the lead authors and Reader (Associate Professor) of Energy Materials at the ATI, said:

"We truly believe that our atomic cobalt-doped synthesized material can pave the way for Lithium Selenium batteries to be the go-to battery technology for future generations. While our results are incredibly encouraging, there is still some way to go to make our dream of high-capacity, sustainable battery technology a reality."

Professor Ravi Silva, Director of the ATI at the University of Surrey, said:

"We are incredibly proud of the highly creative and excellent work that Dr Liu's team has produced - a piece of research that may be a defining moment for sustainable battery technology development."

(Boston)--Researchers from Boston University School of Medicine (BUSM) have identified that a peptide, pituitary adenylate cyclase-activating mediator of compulsive consumption of alcohol. In addition, they have discovered that this protein acts in an area of the brain called the Bed Nucleus of the Stria Terminalis, or BNST, a region involved in fear, anxiety and stress responses, to exert these effects.

Alcohol use disorder or AUD is a chronic relapsing brain disorder characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational or health consequences. An estimated 15 million people in the U.S. have AUD. Approximately 5.8 percent or 14.4 million adults in the U.S. ages 18 and older had AUD in 2018, including 9.2 million men and 5.3 million women.

Comparing two experimental models, the researchers observed anxiety-like behavior and spontaneous compulsive alcohol drinking among the alcohol dependent models when compared to control models that were not alcohol dependent. The researchers believe these observations suggest that during withdrawal the brain's stress system gets recruited and is responsible for a negative emotional state that drives compulsive alcohol drinking through a negatively reinforced mechanism. "In other words, what we know from the literature and was confirmed by this study is that the negative reinforced mechanism consists of the insurgence of anxiety during withdrawal (which we call "dark side") which in turn drives compulsive drinking as a form of paradoxical self-medication," explained co-corresponding author Pietro Cottone, PhD, associate professors of pharmacology and psychiatry at BUSM.

During withdrawal the alcohol-dependent models show increased levels of the stress neuropeptide PACAP selectively in the BNST, compared to control models. This observation led the researchers to administer an experimental drug that blocks the effects of PACAP directly into the BNST of both the alcohol-dependent model and the controls. "We found that this treatment was able to completely block both the high anxiety-like behavior and the compulsive ethanol drinking of ethanol-dependent models without affecting behavior in the control models," said co-corresponding author Valentina Sabino, PhD, associate professors of pharmacology and psychiatry at BUSM.

According to the researchers, these results provide further evidence that alcohol addiction, as many other forms of addictive disorders, is rooted in a negatively reinforced mechanism. "Compulsive alcohol drinking is mainly driven by a withdrawal-dependent negative emotional state. In this context, we found a new key player, PACAP, driving the negative reinforcing properties of alcohol and which can be targeted for the development of pharmacological therapies," added Cottone.

Fossil bones collected in the early 1990s on Henderson Island, part of the Pitcairn Group, have revealed a new species of Polynesian sandpiper.

The Henderson Sandpiper, a small wading bird that has been extinct for centuries, is described in an article in the Zoological Journal of the Linnean Society published last week.

The newly-described bird is formally named Prosobonia sauli after Cook Islands-based ornithologist and conservationist Edward K Saul.

A team of researchers from New Zealand, Australia, Denmark, Switzerland, the Netherlands and China, led by Canterbury Museum Research Curator Natural History Dr Vanesa De Pietri, described the Henderson Sandpiper from 61 fossilised bones cared for by the Natural History Museum at Tring in England.

Canterbury Museum Visiting Researcher Dr Graham Wragg collected the bones from caves and overhangs on Henderson Island in 1991 and 1992 during the Sir Peter Scott Commemorative Expedition to the Pitcairn Islands.

Prosobonia sauli is the fifth known species of Polynesian sandpiper. All but one of the species, the endangered Tuamotu Sandpiper (Prosobonia parvirostris), are extinct.

"We think Prosobonia sauli probably went extinct soon after humans arrived on Henderson Island, which archaeologists estimate happened no earlier than the eleventh century," says Dr De Pietri.

"It's possible these humans brought with them the Polynesian rat, which Polynesian sandpiper populations are very vulnerable to."

DNA of the living Tuamotu Sandpiper and the extinct Tahiti Sandpiper (Prosobonia leucoptera), which is known only from a skin in the Naturalis Biodiversity Center in the Netherlands, was used to determine how Polynesian sandpipers are related to other wading birds.

"We found that Polynesian sandpipers are early-diverging members of a group that includes calidrine sandpipers and turnstones. They are unlike other sandpipers in that they are restricted to islands of the Pacific and do not migrate," says Dr De Pietri.

Comparisons with the other two extinct Polynesian sandpiper species, the Kiritimati Sandpiper (Prosobonia cancellata) and the Mo'orea Sandpiper (Prosobonia ellisi), are complicated. These birds are known only from illustrations primarily by William Wade Ellis, an artist and Surgeon's Mate on Captain James Cook's third expedition, who probably saw the birds alive in the 1770s.

Compared to the Tuamotu Sandpiper, its geographically closest cousin, the Henderson Sandpiper had longer legs and a wider, straighter bill, indicating how it foraged for food. It probably adapted to the habitats available on Henderson Island, which are different to those on other islands where Polynesian sandpipers were found.

Henderson Island is the largest island in the Pitcairn Group, in the middle of the South Pacific Ocean. It has been uninhabited since around the fifteenth century and was designated a World Heritage Site by the United Nations in 1988.

Dr Paul Scofield, Canterbury Museum Senior Curator Natural History and one of the study's co-authors, says Henderson Island is home to a number of unique species, a handful of which are landbirds like the Henderson Sandpiper.

"The island is really quite remarkable because every landbird species that lives there, or that we know used to live there, is not found anywhere else," he says.

Dr De Pietri says the study shows the need to protect the one remaining Polynesian sandpiper species, the Tuamotu Sandpiper.

"We know that just a few centuries ago there were at least five Polynesian sandpiper species scattered around the Pacific. Now there's only one, and its numbers are declining, so we need to ensure we look after the remaining populations."

Elite runners need a specific combination of physiological abilities to have any chance of running a sub-two-hour marathon, new research shows.

The study is based on detailed testing of athletes who took part in Nike's Breaking2 project - an ambitious bid to break the two-hour barrier.

Professor Andrew Jones, of the University of Exeter, said the findings reveal that elite marathon runners must have a "perfect balance" of VO2 max (rate of oxygen uptake), efficiency of movement and a high "lactate turn point" (above which the body experiences more fatigue).

The VO2 measured among elite runners shows they can take in oxygen twice as fast at marathon pace as a "normal" person of the same age could while sprinting flat-out.

"Some of the results - particularly the VO2 max - were not actually as high as we expected," Professor Jones said.

"Instead, what we see in the physiology of these runners is a perfect balance of characteristics for marathon performance.

"The requirements of a two-hour marathon have been extensively debated, but the actual physiological demands have never been reported before."

The runners in the study included Eliud Kipchoge, who took part in Breaking2 - falling just short of the two-hour target - but later achieving the goal in 1:59:40.2 in the Ineos 1:59 challenge.

Based on outdoor running tests on 16 athletes in the selection stage of Breaking2, the study found that a 59kg runner would need to take in about four litres of oxygen per minute (or 67ml per kg of weight per minute) to maintain two-hour marathon pace (21.1 km/h).

"To run for two hours at this speed, athletes must maintain what we call 'steady-state' VO2," Professor Jones said.

"This means they meet their entire energy needs aerobically (from oxygen) - rather than relying on anaerobic respiration, which depletes carbohydrate stores in the muscles and leads to more rapid fatigue."

In addition to VO2 max, the second key characteristic is running "economy", meaning the body must use oxygen efficiently - both internally and through an effective running action.

The third trait, lactate turn point, is the percentage of VO2 max a runner can sustain before anaerobic respiration begins.

"If and when this happens, carbohydrates in the muscles are used at a high rate, depleting glycogen stores," Professor Jones explained.

"At this point - which many marathon runners may know as 'the wall' - the body has to switch to burning fat, which is less efficient and ultimately means the runner slows down.

"The runners we studied - 15 of the 16 from East Africa - seem to know intuitively how to run just below their 'critical speed', close to the 'lactate turn point' but never exceeding it.

"This is especially challenging because - even for elite runners - the turn point drops slightly over the course of a marathon.

"Having said that, we suspect that the very best runners in this group, especially Eliud Kipchoge, show remarkable fatigue resistance."

The testing, conducted in Exeter and at Nike's performance centre in Oregon, USA, provided a surprising experience for a group of amateur runners in the UK.

"We tested 11 of the 16 runners at Exeter Arena a few years ago," Professor Jones said.

"Some local runners were there at the time, and it was a real eye-opener for them when a group of the world's best athletes turned up.

"The elite runners were great - they even joined in with the local runners and helped to pace their training."

A major technical challenge for any practical, real-world quantum computer comes from the need for a large number of physical qubits to deal with errors that accumulate during computation. Such quantum error correction is resource-intensive and computationally time-consuming. But researchers have found an effective software method that enables significant compression of quantum circuits, relaxing the demands placed on hardware development.

Quantum computers may still be far from a commercial reality, but what is termed "quantum advantage"-the ability of a quantum computer to compute hundreds or thousands of times faster than a classical computer-has indeed been achieved on what are called Noisy Intermediate-Scale Quantum (NISQ) devices in early proof-of-principle experiments.

Unfortunately, NISQ devices are still prone to lots of errors that accumulate during their operation. For there to be any real-world application of quantum advantage, the design of a fully operational large-scale quantum computer with high error tolerance is required. Currently, NISQ devices can be engineered with approximately 100 qubits, but fault-tolerant computers would need millions of physical qubits at the very least to encode the logical information with sufficiently low error rates. A fault-tolerant implementation of quantum computational circuits not only makes the quantum computer larger, but also the runtime longer by orders of magnitude. An extended runtime itself in turn means the computation is even more susceptible to errors.

While advances in hardware may address this resource gap, researchers from the National Institute of Informatics (NII) and Nippon Telegraph and Telephone Corporation (NTT) in Japan tackled the problem from the software development side by compressing quantum circuits in large-scale fault-tolerant quantum computers, potentially reducing the need for hardware improvements.

"By compressing quantum circuits, we could reduce the size of the quantum computer and its runtime, which in turn lessens the requirement for error protection," said Michael Hanks, a researcher at NII and one of the authors of a paper, published November 11 in Physical Review X.

Large-scale quantum computer architectures depend on an error correction code to function properly, the most commonly used of which is surface code and its variants.

The researchers focused on the circuit compression of one of these variants: the 3D-topological code. This code behaves particularly well for distributed quantum computer approaches and has wide applicability to different varieties of hardware. In the 3D-topological code, quantum circuits look like interlacing tubes or pipes, and are commonly called "braided circuits. The 3D diagrams of braided circuits can be manipulated to compress and thus reduce the volume they occupy. Until now, the challenge has been that such "pipe manipulation" is performed in an ad-hoc fashion. Moreover, there have only been partial rules for how to do this.

"Previous compression approaches cannot guarantee whether the resulting quantum circuit is correct," said co-author Marta Estarellas, a researcher at NII. "One has to be very careful to check its correctness every time one of these compression rules is applied. This is an important issue, as such a task is as hard as running the whole quantum circuit."

The research team proposes the use of ZX-calculus as a language for this intermediate stage of compilation. ZX-calculus is a 2D diagrammatic language (using diagrams and imagery instead of words) developed in the late 2000s expressly to allow an intuitive representation of qubit processes. More importantly, it comes with a complete set of manipulation rules.

In their paper, the researchers harness ZX-calculus by discovering the translation relations between ZX-calculus and the components of the braided circuit. The researchers have shown that these two representations of logical gate circuits can be mapped to one another by identifying a new interpretation that had been hidden within ZX-calculus all along.

The ZX-calculus language can apply a set of transformation rules to alter the structure of the circuit without altering its underlying mathematical meaning (and thus its operation) and therefore ensuring its correctness. By altering that conceptual structure carefully, the volume of the circuit can be minimized, achieving considerable compression rates once this new structure is mapped to the actual braided quantum circuit.

Applying this technique, the researchers report compression reductions of up to 77 percent, equivalent to a 40 percent reduction compared to the best previous efforts.

"The compression method and its further development could deliver realization of a real-world fault-tolerant quantum computer years ahead of schedule," said William J. Munro, a research scientist at NTT, who also contributed to the research.

"Interestingly, it could also be the foundation of future operating system development," said Kae Nemoto, Director of the Global Research Center for Quantum Information Science at NII. "It could still take many years for these software developments to be implemented in fully-scalable quantum computers, but our method could save a great deal of effort associated with hardware development in the meantime."

Scientists from the Skoltech Center for Design, Manufacturing, and Materials (CDMM) have developed a method for designing and manufacturing complex-shaped ceramic bone implants with a controllable porous structure, which largely enhances tissue fusion efficiency. Their research was published in the journal Applied Sciences.

Ceramic materials are resistant to chemicals, mechanical stress, and wear, which makes them a perfect fit for bone implants that can be custom-made thanks to advanced 3D printing technology. Various porous structures are used to ensure effective cell growth around the implant. For tissue fusion to be more efficient, the pores should have a size of several hundred microns, while the implants could be bigger than the pores by several orders of magnitude. In real life, an implant with a specific porous structure should be custom-designed in a very short time-frame. Conventional geometric modeling with the object representation limited to its surface does not work here due to the complex internal structure of the implant.

Skoltech scientists led by Professor Alexander Safonov modeled the implants using a Functional Representation (FRep) method developed by another Skoltech Professor, Alexander Pasko. "FRep modeling of microstructures has a wealth of advantages," comments Evgenii Maltsev, a Research Scientist at Skoltech and a co-author of the paper. "First, FRep modeling always guarantees that the resulting model is correct, as opposed to the traditional polygonal representation in CAD systems where models are likely to have cracks or disjointed facets. Second, it ensures complete parametrization of the resulting microstructures and, therefore, high flexibility in the fast generation of variable 3D models. Third, it offers a diversity of tools for modeling various mesh structures."

In their research, the scientists used the FRep method to design cylindrical implants and a cubic diamond cell to model the cellular microstructure. CDMM's Additive Manufacturing Lab 3D-printed ceramic implants based on their design and tested them under axial compression.

Interestingly, the new method enables changing the porous structure so as to produce implants of different densities to accommodate the patients' individual needs.

MIT chemists have determined the molecular structure of a protein found in the SARS-CoV-2 virus. This protein, called the envelope protein E, forms a cation-selective channel and plays a key role in the virus's ability to replicate itself and stimulate the host cell's inflammation response.

If researchers could devise ways to block this channel, they may be able to reduce the pathogenicity of the virus and interfere with viral replication, says Mei Hong, an MIT professor of chemistry. In this study, the researchers investigated the binding sites of two drugs that block the channel, but these drugs bind only weakly, so they would not be effective inhibitors of the E protein.

"Our findings could be useful for medicinal chemists to design alternative small molecules that target this channel with high affinity," says Hong, who is the senior author of the new study.

MIT graduate student Venkata Mandala is the lead author of the paper, which appears in Nature Structural and Molecular Biology. Other authors include MIT postdoc Matthew McKay, MIT graduate students Alexander Shcherbakov and Aurelio Dregni, and Antonios Kolocouris, a professor of pharmaceutical chemistry at the University of Athens.

Structural challenges

Hong's lab specializes in studying the structures of proteins that are embedded in cell membranes, which are often challenging to analyze because of the disorder of the lipid membrane. Using nuclear magnetic resonance (NMR) spectroscopy, she has previously developed several techniques that allow her to obtain accurate atomic-level structural information about these membrane-embedded proteins.

When the SARS-CoV-2 outbreak began earlier this year, Hong and her students decided to focus their efforts on one of the novel coronavirus proteins. She narrowed in on the E protein partly because it is similar to an influenza protein called the M2 proton channel, which she has previously studied. Both viral proteins are made of bundles of several helical proteins.

"We determined the influenza B M2 structure after about 1.5 years of hard work, which taught us how to clone, express, and purify a virus membrane protein from scratch, and what NMR experimental strategies to take to solve the structure of a homo-oligomeric helical bundle," Hong says. "That experience turned out to be the perfect training ground for studying SARS-CoV-2 E."

The researchers were able to clone and purify the E protein in two and half months. To determine its structure, the researchers embedded it into a lipid bilayer, similar to a cell membrane, and then analyzed it with NMR, which uses the magnetic properties of atomic nuclei to reveal the structures of the molecules containing those nuclei. They measured the NMR spectra for two months, nonstop, on the highest-field NMR instrument at MIT, a 900-megahertz spectrometer, as well as on 800- and 600-megahertz spectrometers.

Hong and her colleagues found that the part of the E protein that is embedded in the lipid bilayer, known as the transmembrane domain, assembles into a bundle of five helices. The helices remain largely immobile within this bundle, creating a tight channel that is much more constricted than the influenza M2 channel.

Interestingly, the SARS-CoV-2 E protein looks nothing like the ion channel proteins of influenza and HIV-1 viruses. In flu viruses, the equivalent M2 protein is much more mobile, while in HIV-1, the equivalent Vpu protein has a much shorter transmembrane helix and a wider pore. How these distinct structural features of E affect its functions in the SARS-CoV-2 virus lifecycle is one of the topics that Hong and her colleagues will study in the future.

The researchers also identified several amino acids at one end of the channel that may attract positively charged ions such as calcium into the channel. They believe that the structure they report in this paper is the closed state of the channel, and they now hope to determine the structure of the open state, which should shed light on how the channel opens and closes.

Fundamental research

The researchers also found that two drugs -- amantadine, used to treat influenza, and hexamethylene amiloride, used to treat high blood pressure -- can block the entrance of the E channel. However, these drugs only bind weakly to the E protein. If stronger inhibitors could be developed, they could be potential drug candidates to treat Covid-19, Hong says.

The study demonstrates that basic scientific research can make important contributions toward solving medical problems, she adds.

"Even when the pandemic is over, it is important that our society recognizes and remembers that fundamental scientific research into virus proteins or bacterial proteins must continue vigorously, so we can preempt pandemics," Hong says. "The human cost and economic cost of not doing so are just too high."