Brain

Iron build-up in the lung cells and tissues is associated with worse asthma symptoms and lower lung function, according to new research published in the European Respiratory Journal [1].

The researchers say that the study, which includes data from asthma patient samples and mouse models, is the first to definitively show a relationship between iron build-up in the lung cells and tissues and the severity of asthma.

Experimental models also showed that iron build-up in the lungs triggers immune system responses that are typical in asthma and lead to worsening of the disease. This includes effects like increased mucus secretion and scarring of the lungs, which result in narrowing of the airways and making breathing difficult.

Iron is an essential mineral that we get from food or from supplements, which helps the body to make the red blood cells that carry oxygen around our bodies. Iron absorption is tightly regulated at the whole body, organ and cell levels to keep our iron stores balanced and maintain health. When too much iron is absorbed by cells it can lead to a build-up of iron within the cells.

Jay Horvat, Associate Professor of Immunology and Microbiology at the University of Newcastle and Hunter Medical Research Institute, Australia, is the lead author of the study. He explained: "Our organs and tissues need iron to support oxygen flow and normal enzyme activity, but infections in the body also need iron to thrive. Because of this, our immune system has ways of hiding iron minerals within cells where infections cannot access the iron. This can result in a build-up of iron in the cells and tissues of nearby organs.

"There is evidence that irregular iron absorption and abnormal iron levels are linked to lung disease. We know that both high and low iron levels are reported in asthma, but it is not clear whether iron build-up in the lungs contributes to disease development. We sought to build on this by investigating the link between iron and asthma, to better understand whether increased or decreased iron levels in the lung cells makes the disease worse."

The researchers used a combination of asthma patient samples and experimental models to investigate irregular iron absorption into lung cells and to assess how lung cell iron levels affect disease severity. First, the researchers assessed airway cell iron levels in 11 severe and 12 mild-to-moderate asthma patients and compared their iron levels with 12 healthy people who did not have asthma. Asthma severity was determined by how much air a person could breathe out in one second and based on the frequency of experiencing asthma symptoms.

Researchers at the University of Newcastle, Australia, collected airway cell samples from participants using biopsy, a medical procedure that involves taking a small sample of lung tissue to be examined under a microscope, and using a bronchoscope 'wash', where a thin tube is inserted in to the mouth or nose to pass a small amount of salty water into a certain part of the lung. The liquid is sucked back out through the tube and then tested.

This data was supplemented by high-quality lung cell samples collected via bronchial brushing, where a small, stiff-bristle brush is passed through the bronchoscope tube into the lungs, which brushes along the inside of the airways to collect cells. These samples were collected from 39 severe and 29 mild-to-moderate asthmatics and 29 healthy people as part of the wider data collection for the Europe-wide U-BIOPRED project [2].

The researchers conducted multiple tests to asses iron levels in the airway cell samples and found that iron levels outside of the lung cells were lower in asthma patients compared with healthy people; iron levels were also significantly lower in severe asthmatics compared with mild-to-moderate asthmatics.

In contrast, iron levels within the lung cells were markedly higher in the bronchoscope 'wash' samples of mild-to-moderate and severe asthmatics compared with healthy people. The difference in lung cell iron levels between severe asthmatics compared with mild-to-moderate asthmatics was not significant, but the analyses showed that having high levels of iron in the lung cells and less iron outside of cells was associated with more severe airflow obstruction.

Taken together, the results show that lower iron levels outside of cells and higher iron levels within cells were both associated with lower lung function and worse asthma.

Professor Horvat explained the results: "We showed that lung function was lowest among patients with the highest levels of iron build-up in their airway cells and tissues. As lower iron levels outside of cells and higher iron levels within cells were both associated with worse lung function, we think that the immune system's role in 'hiding' iron minerals within the lung cells may be contributing to asthma severity. However, data from the patient samples is not able to confirm this relationship, and the symptoms of increased iron in lung cells were not clear."

Next, the researchers carried out lab tests using two different mouse models to investigate the effects of increasing lung cell iron levels on asthma severity. In one of the experimental models conducted over an eight-week period, one group of mice was exposed to iron overload through diet and another group were fed a normal low-iron diet. After eight weeks, liver and lung tissues were collected from the mice for further analysis and airway inflammation was measured. In a separate genetic model, the researchers triggered iron overloading in the lung cells of mice that were fed a normal iron diet, to assess the effects on the lungs.

The analyses showed that increasing the lung cell iron levels caused inflammatory cell responses such as increased mucus secretion and scarring in the airways, which the researchers say leads to worsening of asthma. Professor Horvat explained: "In humans, mucous secretion and lung scarring narrows the airways, causing airflow obstruction and breathing difficulties. These symptoms are common in asthma and other chronic lung diseases, and our data shows that increasing iron in the lung cells and tissues led to an increase in these effects.

"Our tests were well controlled to ensure that mice were not exposed to pathogens or other factors that might influence asthma, so we are confident that the data clearly demonstrates the link between increasing lung cell and tissue iron levels and these immune system responses."

The researchers say the findings offer great potential for the development of asthma treatments that target irregular iron absorption in the lung cells and tissues, but more research is needed to determine why there is increased absorption in the lungs of asthmatics. Professor Horvat said: "This study should not be interpreted as high lung iron levels being related to iron intake from diet or use of supplements. We still know so little about how iron intake and the way the body regulates iron can affect iron levels in lung cells and tissues, but we hope this data will encourage more funding for research that investigates the role and therapeutic use of iron in asthma, as targeted treatments, dietary iron or supplement use could improve patient outcomes."

The research team are now investigating ways to modify the iron storage process in lung cells, and whether it is possible to alter the number of the cells that are responsible for iron absorption into the lung cells. They hope to develop these approaches into therapies for not only asthma, but also for rare lung diseases like idiopathic pulmonary fibrosis.

Christopher Brightling, Chair of the European Respiratory Society's Science Council and Clinical Professor in Respiratory Medicine at the University of Leicester, UK, was not involved in the research. He said: "This research offers interesting data to suggest that more iron is absorbed into lung tissue in people with asthma, and that this is associated with disease severity. Further research needs to confirm this finding and investigate this process, which could possibly lead to new therapies. It is important to note that the research does not suggest high iron levels in the lungs is because of diet.

"People who are living with asthma should not avoid iron-rich foods based on this research. To manage their condition most effectively, people with asthma should continue to eat a balanced diet that includes their recommended daily level of iron, and they should use the medications prescribed by their doctors and try to lead an active lifestyle."

Researchers from the Zepler Institute for Photonics and Nanoelectronics at the University of Southampton have demonstrated a new leap in hollow-core fibre performance, underlining the technology's potential to soon eclipse current optical fibres.

Hollow-core fibres replace conventional glass cores with gas or a vacuum to enable unique properties including faster light speed and reduced sensitivity to environmental variations.

The novel technology, which is being advanced in the Zepler Institute's renowned Optoelectronics Research Centre (ORC), is believed able to reach lower loss and higher data transmission capacity than all-solid glass fibres, with current research accelerating models toward this peak performance.

Southampton researchers and collaborators are presenting the latest findings in San Diego this week in two high profile post-deadline papers at OFC 2020, the world's largest optical fibre communication conference.

The newest hollow-core fibres attenuate the light traveling through it by 50% less than the previous record, reported only six months ago. The maximum transmission length at which data can be relayed in such revolutionary fibres has also doubled.

Thanks to an innovative design proposed at the ORC, in the space of 18 months the attenuation in data-transmitting hollow-core fibres has been reduced by over a factor of 10, from 3.5dB/km to only 0.28 dB/km within a factor of two of the attenuation of conventional all-glass fibre technology. At the same time, the maximum transmission distance at which large bandwidth data streams can be transmitted through an air-core has been improved by over 10 times, from 75 to 750km.

Professor Francesco Poletti, Head of the ORC's hollow core fibre group, says: "Transmitting light in an air core rather than a glass core presents many advantages which could revolutionise optical communications as we know them. These latest results further reduce the performance gap between hollow core fibre and mainstream optical fibre technology, and the whole team is really excited by the prospect of the additional significant improvements that seem possible, according to modelling.

Latency, which is the round-trip time for communications, is becoming as important as bandwidth for the new digital economy. Network latency creates a delay between sensing and its response, causing sickness in AR/VR users, loss of fidelity in remote surgery and accidents in autonomous systems. These fibres deliver a vital 30% reduction in round-trip data transmission times and could enable the next generation of connected real-time digital applications, from smart manufacturing and advanced healthcare to the entertainment."

The considerable improvements in attenuation and transmission distance demonstrated in these two works open up the possibility to target longer reach distances, edging close to the 1,000km span of typical long distance long haul terrestrial data transmission links.

Southampton researchers are pushing the boundaries of hollow-core performance in several major research programmes, including the European Research Council funded LightPipe and the Engineering and Physical Sciences Research Council (EPSRC) funded Airguide Photonics.

The team are working in close collaboration with one of the leading groups in advanced optical communications at the Politecnico di Torino, led by Professor Pierluigi Poggiolini, and ORC spinout Lumenisity.

Growing fruit and vegetables in just 10 per cent of a city's gardens and other urban green spaces could provide 15 per cent of the local population with their 'five a day', according to new research.

In a study published in Nature Food, academics from the Institute for Sustainable Food at the University of Sheffield investigated the potential for urban horticulture by mapping green spaces and grey spaces across the city.

They found that green spaces including parks, gardens, allotments, roadside verges and woodland cover 45 per cent of Sheffield - a figure similar to other UK cities.

Allotments cover 1.3 per cent of this, while 38 per cent of green space comprised of domestic gardens, which have immediate potential to start growing food.

The interdisciplinary team used data from Ordnance Survey and Google Earth to reveal that an extra 15 per cent of the city's green space, such as parks and roadside verges, also has potential to be converted into community gardens or allotments.

Putting domestic gardens, allotments and suitable public green spaces together would open up 98m2 per person in Sheffield for growing food. This equates to more than four times the 23m2 per person currently used for commercial horticulture across the UK.

If 100 per cent of this space was used for growing food, it could feed approximately 709,000 people per year their 'five a day', or 122 per cent of the population of Sheffield. But even converting a more realistic 10 per cent of domestic gardens and 10 per cent of available green space, as well as maintaining current allotment land, could provide 15 per cent of the local population - 87,375 people - with sufficient fruit and veg.

With just 16 per cent of fruit and 53 per cent of vegetables sold in the UK grown domestically, such a move could significantly improve the nation's food security.

The study also investigated the potential for soil-free farming on flat roofs using methods such as hydroponics, where plants are grown in a nutrient solution, and aquaponics, a system combining fish and plants. These techniques could allow year-round cultivation with minimal lighting requirements, using greenhouses powered by renewable energy and heat captured from buildings, with rainwater harvesting for irrigation.

Flat roofs were found to cover 32 hectares of land in Sheffield city centre. While equivalent to just 0.5m2 per person, the researchers believe the high-yielding nature of soil-free farming means this could make a significant contribution to local horticulture.

The UK currently imports 86 per cent of its total tomato supply - but if just 10 per cent of the flat roofs identified within the centre of Sheffield became soil-free tomato farms, it would be possible to grow enough to feed more than eight per cent of the population one of their 'five a day'. This increases to more than 60 per cent of people if three quarters of the flat roof area is utilised.

Dr Jill Edmondson, Environmental Scientist at the University of Sheffield and lead author of the study, said: "At the moment, the UK is utterly dependent on complex international supply chains for the vast majority of our fruit and half of our veg - but our research suggests there is more than enough space to grow what we need on our doorsteps.

"Even farming a small percentage of available land could transform the health of urban populations, enhance a city's environment and help build a more resilient food system."

Professor Duncan Cameron, co-author and Director of the Institute for Sustainable Food at the University of Sheffield, said: "It will take significant cultural and social change to achieve the enormous growing potential of our cities - and it's crucial that authorities work closely with communities to find the right balance between green space and horticulture.

"But with careful management of green spaces and the use of technology to create distribution networks, we could see the rise of 'smart food cities', where local growers can support their communities with fresh, sustainable food."

The Institute for Sustainable Food at the University of Sheffield brings together multidisciplinary expertise and world-class research facilities to help achieve food security and protect the natural resources we all depend on.

Experts have stressed an urgent need to find alternatives to wormers and anti-ectoparasitic products used widely on cattle, following the findings of a study just published in Environmental Toxicology and Chemistry.

Researchers from the University of Sussex looked at a body of published evidence into the environmental impact of anthelmintics -- products used as wormers and anti-parasitic agents and widely applied across the world. They found that, across all drug classes, the products were having a devastating impact on dung beetles - species that are vital prey items for a range of bat and bird species.

The study conducted by Domhnall Finch and Professor Fiona Mathews also found that some of the products actively attracted adult dung beetles, before impairing the development of their larvae.

Fiona Mathews, Professor of Environmental Biology at the University of Sussex, said: "When compared with controls, we found that dung samples from cattle treated with these products had about a third fewer dung beetle larvae.

"What's particularly worrying is that the beetles actually seemed to be more attracted to treated dung but, because of the toxicity of the chemicals, their larvae have poor survival rates and face impaired development.

"Over time, this reduces the number of dung beetles which is troubling news for a range of bird and bat species - for which dung beetles are key prey items.

"Many of these species are already listed as vulnerable so any decline in prey availability is a serious concern."

Dung beetles are commonly preyed upon by the serotine bat, noted as Vulnerable to Extinction on the new British Red List; the greater horseshoe bat, protected under European Law because of its perilous conservation status right across Europe; and the Nightjar and the Chough, both of which are protected by the Wildlife and Countryside Act 1981. The Nightjar has been given an amber UK conservation status.

The study, published in the journal Environmental Toxicology and Chemistry, highlighted the particularly negative impact on dung beetle larvae of pour-on treatments - the most common form of application. It also revealed that one of the most widely used products, the anti-parasitic agent Ivermectin, is extremely toxic. These treatments are available for purchase in most EU countries without the involvement of a veterinarian.

But the authors stress that more research is needed into the other treatment types and newer drugs in order to determine the exact effects of each.

The results are particularly timely as they come just a few months after the government announced that it would not be funding extensions to higher-tier organic stewardship agreements in England. This means that farms who currently avoid the use of insecticides will be faced with a difficult choice moving forward.

Prof. Mathews explained: "Many farmers are now facing a gap in their income as they have to make new applications. Sticking to an insecticide-free approach may not be economically attractive compared with switching to conventional systems where the routine use of anti-parasitic agents is normal. Once applied, the residues can remain in the soil -- affecting a wide range of invertebrates -- for months."

"Some of these farms are also critical for British wildlife, particularly rare bats, and the introduction of chemicals could really impact their numbers - as demonstrated in our study."

Dung beetles themselves provide important ecosystem services for farmers. By ensuring that dung is cleared from pasture quickly, they help to control pest flies and also allow for rapid grass regrowth through nutrient cycling, soil aeration and dung removal. The presence of dung beetles has also been shown to reduce the prevalence of cattle nematode infections by 55 to 89% (Fincher 1975) and pest flies by 58% (Benyon et al. 2015). In the UK alone, these services are estimated to exceed £350M per year.

Domhnall Finch, doctoral student at the University of Sussex, said: "Dung beetles are an overlooked but hugely important part of our landscape.

"Studies have proven that they can help to reduce the prevalence of worm infections in cattle, which is ironic when we consider that they're now under threat from chemical products which essentially do the same thing.

"While more research is needed to determine the effects of newer agents, our work has clearly shown that those chemicals which are present in pour-on treatments have a long-lasting negative impact.

"There is an urgent need to find alternatives."

The laboratory directed by Arne Skerra, Professor of Biological Chemistry, has its focus on designing artificial binding proteins for therapeutic applications. The laboratory's current research findings are paving the way for the development of new types of binding proteins for biological sugar structures, which play a significant role in cancer as well as infectious diseases.

Recognizing biological sugar structures

"The recognition of specific sugar molecules, or so-called carbohydrates, is of vital importance in many biological processes," Prof. Skerra explains. Most cells carry a marker consisting of sugar chains which are attached to the outside of the cell membrane or to the membrane proteins, thus enabling the body to identify where these cells belong or whether certain cells are alien. Pathogens also have sugar structures of their own, or they can bind to these.

Proteins, which perform a wide range of functions within cells, generally have only low affinity to sugars. Thus, their molecular recognition poses a challenge. The reason: water molecules look similar to the sugar molecules, meaning that they are basically hidden in the aqueous environment of the cells. Prof. Skerra's research group therefore set out to design an artificial binding protein with a peculiar chemical composition which makes it easier to bind to biological sugar structures.

A boric acid group implemented into a protein as amino acid

Amino acids are the building blocks of proteins. As a rule, nature only uses 20 amino acids in all living organisms. "Using the possibilities opened up by synthetic biology, we have employed an additional artificial amino acid," reports researcher Carina A. Sommer.

"We have succeeded in incorporating a boric acid group, which exerts intrinsic affinity to sugar molecules, into the amino acid chain of a protein. In doing this, we have created an entirely new class of binding protein for sugar molecules," Sommer explains. This artificial sugar-binding function is superior to natural binding proteins (so-called lectins) both in strength and with regard to possible sugar specificities.

"The sugar-binding activity of boric acid and its derivatives has been known for nearly a century," says Prof. Skerra. "The chemical element boron is common on earth and has low toxicity, but so far has largely remained unexplored by organisms."

"By using X-ray crystallography, we have succeeded in unraveling the crystal structure of a model complex of this artificial protein, which allowed us to validate our biomolecular concept," explains scientist Dr. Andreas Eichinger.

The next step: towards medical application

Following approximately five years of fundamental scientific research, the findings from Prof. Skerra's laboratory can now be applied to practical medical needs. Prof. Skerra points out: "Our results should not only be used to support the future development of new carbohydrate ligands in biological chemistry, but should also pave the way for creating high-affinity agents for controlling or blocking medically-relevant sugar structures on cell surfaces."

Such a "blocking agent" could be used for conditions in which strong cell growth is evident or when pathogens are attaching themselves to cells, for example in oncology and virology. If we are successful in blocking the sugar-binding function and in slowing down the progress of a disease, this would give the patient's immune system sufficient time to mobilize the body's natural defense.

BUFFALO, N.Y. - Soft corals at three sites in the U.S. Virgin Islands were able to recover from the destructive effects of nearly back-to-back Category 5 storms in 2017, but the story of these apparently hardy communities of colorful marine life is part of a larger, rapidly shifting narrative surrounding the future of coral reefs, according to a new study led by a University at Buffalo marine ecologist.

The recently realized resilience of the soft corals is an important development toward our increasing understanding of these complex ecosystems, but the findings published in the journal Scientific Reports puts that seemingly good news in the context of an ecosystem that is dramatically changing.

"These soft corals are resilient," says Howard Lasker, a professor in the Department of Environment and Sustainability and the Department of Geology, and an expert on the ecology of coral reef organisms.

"But right now in the Caribbean we're seeing a drastic decline of stony corals, and the soft corals are not a simple replacement for what's being lost."

[Click here to see a video of both healthy reefs and reef damage]

Soft corals, also known as octocorals, are branching colonial organisms. The colonies with their impressionistic tree-like appearance sway in ocean currents like trees in a storm. The stony corals, which also form colonies, produce rigid skeletons and create the framework of coral reefs. The living animal sits atop the structure they create, slowly secreting calcium carbonate, essentially limestone, to build up the reef.

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The soft corals are doing fine while the stony corals have declined as much as 40% in recent decades, according to Lasker, whose team examined three reefs on the south shore of St. John (part of the U.S. Virgin Islands) following Hurricanes Irma and Maria, storms that passed within two weeks of one another in September 2017. They compared data from the storm's aftermath with sampling that began in 2014 and continued in 2018.

"The octocoral communities we studied suffered dramatic declines with the passage of these hurricanes. In that sense, they weren't resistant to the effects of severe storms," says Lasker. "However they showed resilience - the ability to recover.

"We found that many colonies were killed, but two years later it hadn't changed the nature of species distribution, and as importantly new colonies were developing making up for the losses" says Lasker.

This pattern of loss and recovery was emblematic historically of stony corals as well, but that's no longer the case for the scleractinians, and Lasker says their soft coral counterparts while providing shelter for many reef animals will not build the hard physical structure of reefs.

"One of the big questions in marine ecology is what we should be doing," says Lasker. "Should we be trying to remediate the damage and attempt to prevent species loss by creating protected environments?"

There is a range of opinions about taking the curator's approach to the reefs, but what certain is that these systems are already dramatically different from descriptions made during the 1950s. And those observations from the '50s stand in obvious contrast to what European explorers would have seen when they encountered the reefs centuries ago.

"Humans are responsible for the changes," says Lasker. "It's really pretty simple: land use, sediments, sewage, agricultural runoff, overfishing, and now climate change."

As the stony corals wane the soft corals are replacing them, but the reason the stony corals aren't recovering comes back to us, according to Lasker.

"It's important to recognize that the resilience we're seeing in these communities may decline with the frequency and intensity of future storms," says Lasker. "This could be a temporary state.

"The real test will come when we examine these areas 10 years down the road."

Certain middle-aged and older adults, especially women who tend to disengage from difficult tasks and goals after they retire, may be at greater risk of cognitive decline as they age, according to research published by the American Psychological Association.

"This study raises questions about how individual differences in motivation and gender may play a role in cognitive declines and points to the potential importance of continuing to engage in mentally stimulating activities in retirement," said lead author Jeremy Hamm, PhD, of North Dakota State University. "This may be a significant challenge for people who have a tendency to let go of goals when they encounter initial obstacles and setbacks."

The study, published in the journal Psychology and Aging, analyzed data from Midlife in the United States, a national longitudinal survey of 7,108 participants aimed at identifying the factors that influence health as people age. Hamm and his team used a subset of 732 participants from the survey to examine the differences in cognitive function between retired adults and similar others who chose to continue working past retirement age. Half of the participants were female and 94% of participants were white.

Previous research has shown that retiring is associated with an increased risk of cognitive decline, but little is known about the motivation factors that could make someone more susceptible to such a decrease, according to Hamm.

"Our premise was that not all those who retire are likely to be at higher risk of decline. We thought that individuals who retire may be more or less at risk, depending on their tendency to disengage from challenging tasks and goals that could otherwise provide a source of mental stimulation," he said.

Researchers measured participants' level of goal disengagement, or people's tendency to lower their ambitions and decrease commitment to personal goals. Participants were asked to rate their level of agreement with statements such as "To avoid disappointments, I don't set my goals too high" and "I feel relieved when I let go of some of my responsibilities" on a scale of one to four.

Participants also took a test by telephone to measure basic cognitive functions, such as memory, reasoning and processing speed.

The study found that retired women who were prone to disengagement had steeper declines in cognitive functioning than their peers who remained employed. However, no differences emerged between retired and working men who were prone to disengagement, whose higher socioeconomic status may have protected them from early declines, according to Hamm.

"Our findings suggest not everyone who retires is at greater risk of cognitive declines. There are many opportunities to engage in mentally stimulating activities in retirement, such as reading or playing word games," he said. "However, personal agency and motivation may come to the fore at this stage of the lifespan since these activities often need to be self-initiated and autonomously maintained."

Their researches on the lamprey brain has enabled researchers at Karolinska Institutet in Sweden to push the birth of the cortex back in time by some 300 million years to over 500 million years ago, providing new insights into brain evolution. The study is published in the scientific journal Nature Ecology & Evolution.

The human brain is one of the most complex structures that evolution has created. It has long been believed that most of the forebrain evolution took place largely in mammals and that the brains of simpler, pre-mammalian animal groups such as fish and amphibians lack a functional cortex. The cortex, which is the outer layer of the brain, controls the more complex cerebral functions like vision and movement and higher skills such as language, memory and emotion.

"We've spent a long time studying brain evolution using the lamprey, which is one of the oldest groups of extant vertebrates," says Sten Grillner, last author of the study and professor of neurophysiology at the Department of Neuroscience, Karolinska Institutet. "Here we've made detailed studies of the lamprey brain, combining neurophysiological analyses with histochemical techniques."

In the study, the researchers show that even the lamprey, which existed hundreds of millions of years before mammals, possesses a detailed blueprint for the development of the cortex, the basal ganglia and the dopamine system - all the vital ingredients of integrative cerebral function.

The researchers also found that the lamprey's cortex has a visual area on which different parts of its visual field are represented. Sensory and motor areas have also been discovered.

"This shows that the birth of the cortex has to be pushed back about 300 million years," says Professor Grillner. "This, in turn, means that the basic plan of the human brain was defined already over 500 million years ago, that's to say before the lamprey branched off from the evolutionary line that led to mammals and humans."

The study shows that all the main components of the human brain are also to be found in the lamprey brain, albeit with much fewer nerve cells in each part.

"That vital parts of the lamprey brain are conserved and organised in the same way as in the human brain was unexpected," he continues. "These findings are crucial to our understanding of how the brain evolved and how it has been designed through evolution."

The relief "Adoration of the Shepherds" by the Italian sculptor Giuseppe Torretti is disfigured by lumpy salt crystals. Now, a research group at the Max Planck Institute for Solid State Research in Stuttgart has established that the calcium acetate hemihydrate that makes up these efflorescences bears a similar structure to the protein collagen. The structural characteristics not only help prevent damage of this kind, but have also provided the researchers with interesting new ideas for bioinorganic chemistry.

The marble relief "Adoration of the Shepherds" is about 300 years old and has certainly had an eventful history. At the end of World War II, it was moved from Berlin to the Soviet Union, where attempts were made to repair the damage it had suffered during the war - including by using glue. In the early 1990s, the work by Giuseppe Torretti (1664-1743) was returned to the Museum for Byzantine Art in Berlin, where specialists removed the glue using ethyl acetate, an ester of acetic acid.

It is precisely this process that appears to have caused chemical changes in the surface, leading to the formation of white, needle-like efflorescences there a few years later. Experts from the Rathgen Research Laboratory in Berlin have identified them as chemical calcium acetate hemihydrate - that is, the calcium salt of acetic acid that also contains water. Over time, in other words, calcium from the marble had bonded with acetate ions from the solvent to form a new salt - and this substance has also been found on other old works of art.

However, it is only now that the compound's crystal structure has been accurately determined. Restorers rely on structural characteristics as reference data so that they can identify corrosion products and explain the underlying process - as well as, ideally, preventing it. To determine the structure of the efflorescences in Torretti's relief, Gerhard Eggert from the Institute of Conservation Sciences at the State Academy of Art and Design, Stuttgart, enlisted the help of Robert Dinnebier, head of the X-ray diffraction group at the Max Planck Institute for Solid State Research in Stuttgart. This is one of only a few groups in the world that specialize in complex structural elucidation even in samples that are only available in powder form and not as a single crystal.

Structural characteristics help prevent corrosion damage

The DFG-funded project "In search of structure" was also successful in determining this structure, revealing that the calcium ions arrange themselves along spiral-shaped chains - in other words, they form helices. The acetate ions, on the other hand, sit between the calcium ions and act as bridges. Altogether, three of these calcium strings wrap around one another in a similar way to the three strands of a plait.

Collagen also forms a triple helix

Helix structures of this kind are not uncommon in living nature. DNA, the molecule that carries genetic material, takes the form of a double helix - that is, a double strand wound into a spiral. According to Dinnebier, however, the structure that has now been identified bears a striking similarity to collagen proteins in particular, such as those found in the connective tissues of our body. "Collagen's amino acid chains also form a triple helix," the crystallographer explains.

However, the Max Planck researchers in Stuttgart could not use sample material from the efflorescences on Torretti's shepherd relief for their structural analysis. "The corresponding X-ray diffraction technique requires quantities that you can't get from an artwork of this kind," explains Sebastian Bette from Dinnebier's working group. The researchers therefore had to synthesize their own calcium acetate hemihydrate, which they did by leaving a calcium acetate solution in a covered terracotta pot at low atmospheric humidity for half a year. Over this time, the solution slowly passed through the pores of the pot wall and crystallized on the outside as calcium acetate hemihydrate. "We were then able to use this powder to carry out the X-ray diffraction analysis," says Bette. This revealed the positions of the individual atoms relative to one another - and therefore the structure of the compound.

An usually large cell

"It's fascinating to discover a helical structural motif in a relatively simple compound such as calcium acetate hemihydrate," says an enthusiastic Robert Dinnebier. In over 30 years of work on structural elucidation using X-ray diffraction, he has seen a lot of crystal structures and is no longer easily surprised. But he was amazed at the triple helix structure that has now been identified.

Apparently, the researchers were also surprised at the unusual size of the unit cell. Crystallographers use this term to refer to the smallest repeating unit of a crystal structure. With a volume of just under 12,000 cubic ångströms, a single unit cell in the analysed substance is several dozen times bigger than the most common unit cells of simple salts and contains 64 calcium ions. "That's an incredibly large number for a relatively simple compound with only three components - namely calcium, acetate and water," says Bette.

On the other hand, Robert Dinnebier now considers the structural similarity to collagen proteins entirely plausible: "Indeed, the most common amino acid in collagen is glycine." As the simplest of all amino acids, this is closely related to acetic acid on the molecular level and therefore also to its salt, acetate. If you replace a hydrogen atom with an amino group in the acetic acid molecule, you get glycine. The researchers in Stuttgart now consider it likely that a helical calcium glycinate also exists. In principle, Dinnebier finds it "fascinating" that these "complex helical structures are quite clearly not limited to amino acid chains. Rather, they can also form elsewhere in certain circumstances."

Possible template for proteins with helical structures

Due to its similarity to collagen, the researchers are now keenly interested in calcium acetate hemihydrate as a substance. Sebastian Bette says: "In evolution, collagen played a key role in the transition from single-celled to multicellular organisms and therefore also in the emergence of tissues." Now, calcium acetate hemihydrate or a potential calcium glycinate could open up entirely new bioinorganic possibilities. "For example, we already know that the DNA double helix can be used as a template to cause other chemical compounds to crystallize in a helical structure," says Bette. "It's no great leap of the imagination to use the demonstrated triple helix as a template for proteins with helical structures, for example."

A group of researchers from Charité - Universitätsmedizin Berlin has discovered a new mechanism of long-lasting pain relief. The cell-signaling protein interleukin-4 induces a specific type of blood cell to produce endogenous opioids at the site of inflammation. The researchers' findings have been published in the Journal of Clinical Investigation (JCI) Insight*.

Peripheral nerve inflammation can lead to chronic pain. The inflammatory response is mediated by a number of blood-derived immune cells. These produce cytokines, cell-signaling proteins which either enhance or reduce inflammation and pain. Thanks to its anti-inflammatory properties, one of these cytokines - known as interleukin-4 (IL-4) - is already being used to treat pain.

The team, led by Prof. Dr. Halina Machelska from Charité's Department of Experimental Anesthesiology on Campus Benjamin Franklin, used an animal model of sciatic pain to study the analgesic mechanisms of IL-4. Initially, a single injection of IL-4 near the inflamed nerve produced pain relief which only lasted for several minutes. When repeated daily, however, injections reduced pain for up to eight days, even in the absence of further IL-4 injections. This resulted from the IL-4-induced accumulation of M2 macrophages, a type of immune system scavenger cell which produces opioids and thereby reduces pain.

Prof. Machelska proposes that not general inhibition of inflammation, but fostering the beneficial properties of the M2 macrophages is most promising to tackle pathological pain. "Our findings are relevant to many immune-mediated diseases, ranging from arthritis to neurodegenerative diseases and cancer."

The M2 macrophages were then isolated from the inflamed nerve and transferred into a different animal, where they also reduced pain. When the researchers studied the isolated cells in greater detail, they found that these cells produced various endogenous opioids, such as endorphin, enkephalin and dynorphin which activated opioid receptors at the site of inflammation. "As these analgesic effects occur at the peripheral nerves, outside the brain, it is possible to prevent undesirable side effects such as sedation, nausea and addiction," explains Prof. Machelska. She adds: "These findings may offer new perspectives in our endeavors to develop alternative pain management options for patients."

Spiral structure is seen in a variety of natural objects, ranging from plants and animals to tropical cyclones and galaxies. Now researchers at the North Carolina Museum of Natural Sciences have developed a technique to accurately measure the winding arms of spiral galaxies that is so easy, virtually anyone can participate. This new and simple method is currently being applied in a citizen science project, called Spiral Graph, that takes advantage of a person's innate ability to recognize patterns, and ultimately could provide researchers with some insight into how galaxies evolve.

Spiral galaxies, like our own Milky Way, make up approximately 70 percent of the galaxies in the nearby Universe. In many of these galaxies the difference in brightness between the winding arms and the inter-arm regions is very subtle, making it challenging for automated methods to measure. Even bright foreground stars can skew the automated analysis of a galaxy. Additionally, patterns in spiral galaxies are easily seen and followed by people but computer algorithms have a harder time determining where spirals begin and end, especially if they aren't continuous.

The Spiral Graph project takes advantage of a time-honored short cut common in art classes -- tracing. Ian Hewitt, Research Adjunct at the NC Museum of Natural Sciences, and Patrick Treuthardt, Assistant Head of the Museum's Astronomy & Astrophysics Research Lab, tested their tracing method on a set of simple model images of spiral galaxies with known windings. They then traced out the spiral structure and measured the winding of the tracings with their own specially designed software, P2DFFT. When they compared their results against other approaches that involved an artificial intelligence program, fitting observed structure with mathematical models, or even directly inputting images into their own measurement software, none produced results as precise and accurate as their tracing method. A paper detailing this comparison appeared online on March 9, 2020. Spiral Graph is available on the Zooniverse.org platform for citizen science projects.

"These human-generated tracings give our software a boost so it can accurately measure how tightly wrapped the structure is," Treuthardt says. "The degree of wrapping of the spiral arms is called the pitch angle. If a spiral pattern has very tightly wrapped arms, it has a small pitch angle. If it the spiral pattern is very open, it has a large pitch angle." Why is pitch angle important? Because it relates to other parameters of the host galaxy that are more difficult and time consuming to measure, such as the mass of the black hole found in the nucleus, or dark matter content of the galaxy. "If we know the pitch angle we can quickly and easily estimate these parameters and identify interesting galaxies for more detailed, follow-up telescope observations," Treuthardt adds.

Hewitt's work on this study, and the Spiral Graph citizen science project, is especially rewarding since he started out as a volunteer working with Treuthardt. Although a long-time amateur astronomer, Hewitt retired from a career in industry to pursue astronomy full time. He later completed a degree in astronomy and began teaching and working on programming projects in the Museum's Astronomy & Astrophysics Research Lab. "It's been really exciting to get a chance to participate in this kind of research, but even better to have a part in enabling others to contribute to the efforts to better understand our Universe," says Hewitt. And with an estimated 6,000 galaxies in their study, enlisting citizen scientists is a must.

Over the last million years, small variations in Earth's orbit continued to trigger and terminate global glaciations, throughout and after the Mid-Pleistocene Transition, according to a new study, which presents a novel high-resolution record of the last 11 deglaciations. Beyond what was possible using existing less well-dated environmental records, the new precisely dated chronology reveals the persistent influence of obliquity and insolation in pacing Earth's glacial-interglacial cycle. The Quaternary - the current period of Earth's history that began a little more than 2.5 million years ago (Ma) - is often characterized by a series of glacial and interglacial periods, which repeatedly set continent-sized ice sheets to ebb and flow like a frozen tide across much of the Northern Hemisphere. Before the Mid-Pleistocene Transition (MPT, 1.25 to 0.7 Ma), Quaternary global glacial cycles repeated roughly every 40 thousand years (ka). However, during the MPT, the pattern of Quaternary glaciation fundamentally shifted and expanded to approximately 100 ka intervals. While it is widely agreed that the 40 ka pre-MPT cycles were driven by the cyclical variation in Earth's orbital tilt or obliquity, orbital forcing theories fail to explain the longer post-MPT glacial-interglacial periods adequately. A central challenge in evaluating orbital theories of Earth's ice age cycles is the inherent chronological uncertainty of the deep-ocean sediment records often used to identify them. Recent studies using precisely dated speleothem records to anchor the ages of glacial terminations recorded in marine sediments as far back about 640 ka, however, suggest that post-MPT intervals are instead collections of shorter, orbitally driven cycles. Using a uranium-lead radiometrically dated Italian speleothem from Italy to constrain the chronology of new high-resolution marine sediment records, Petra Bajo and colleagues expand this record to cover the eleven glaciation-deglaciation events of the last million years. The authors show that the first two post-MPT deglaciation events are separated by two obliquity cycles and conclude that Earth's obliquity remained the main driver of glacial-interglacial cycles throughout the Quaternary - across the MPT and beyond.

WASHINGTON -- Using a single lens that is about one-thousandth of an inch thick, researchers have created a camera that does not require focusing. The technology offers considerable benefits over traditional cameras such as the ones in most smartphones, which require multiple lenses to form high-quality, in-focus images.

"Our flat lenses can drastically reduce the weight, complexity and cost of cameras and other imaging systems, while increasing their functionality," said research team leader Rajesh Menon from the University of Utah. "Such optics could enable thinner smartphone cameras, improved and smaller cameras for biomedical imaging such as endoscopy, and more compact cameras for automobiles."

In Optica, The Optical Society's (OSA) journal for high impact research, Menon and colleagues describe their new flat lens and show that it can maintain focus for objects that are about 6 meters apart from each other. Flat lenses use nanostructures patterned on a flat surface rather than bulky glass or plastic to achieve the important optical properties that control the way light travels.

"This new lens could have many interesting applications outside photography such as creating highly efficient illumination for LIDAR that is critical for many autonomous systems, including self-driving cars," said Menon.

The researchers say the design approach they used could be expanded to create optical components with any number of properties such as extreme bandwidth, easier manufacturability or lower cost.

Questioning the textbook

Conventional cameras, whether used in smartphones or for microscopy, require focusing to ensure that the details of an object are sharp. If there are multiple objects at different distances from the camera, each object must be focused separately.

"The new lens eliminates the need for focusing and allows any camera to keep all the objects in focus simultaneously," said Menon. "Conventional cameras also use multiple lenses to keep different colors of light in focus simultaneously. Since our design is very general, we can also use it to create a single flat lens that focuses all colors of light, drastically simplifying cameras even further."

To focus light, traditional lenses transform parallel light waves into spherical waves that converge into a focal spot. In an important breakthrough, the researchers realized that waves with other shapes could produce a similar effect, vastly increasing the number of possible lens designs.

"In stark contrast to what is taught in optics textbooks, our research has shown that there is more than one way that light transmission is affected by an ideal lens - a concept known as pupil function," said Menon. "This opened essentially infinite possibilities for the lens pupil function, and we searched through these possibilities for one that achieved an extreme depth of focus."

Experimental confirmation

After choosing the best lens design for depth of focus, the researchers used nanofabrication techniques to make a prototype lens. Experiments confirmed that the new lens performed as expected and achieved a depth of focus several orders of magnitude larger than that of an equivalent conventional lens.

The researchers demonstrated the new lens using infrared light and relatively low numerical aperture -- a number that characterizes the range of angles over which the lens can accept or emit light. They plan to extend the lens to larger numerical apertures and to use it with the full visible light spectrum. Work to ensure that the lenses could be mass manufactured is also needed before they could be commercialized.

"This research is a good example of how abandoning traditional notions can enable devices previously considered impossible," said Menon. "It serves as a good reminder to question dictates from the past."

In research published in Nature, an international research group have ended a fifty-year quest by directly observing a quantum phenomenon known as a Kondo screening cloud. This phenomenon, which is important for many physical phenomena such as high-temperature superconductivity, is essentially a cloud that masks magnetic impurities in a material. It was known to exist but its spatial extension had never been observed, creating controversy over whether such an extension actually existed.

Magnetism arises from a property of electrons known as spin, meaning that they have angular momentum aligned in one of either two directions, conventionally known as up and down. However, due to a phenomenon known as the Kondo effect, the spins of conduction electrons--the electrons that flow freely in a material--become entangled with a localized magnetic impurity, and effectively screen it. The strength of this spin coupling, calibrated as a temperature, is known as the Kondo temperature. The size of the cloud is another important parameter for a material containing multiple magnetic impurities because the spins in the cloud couple with one another and mediate the coupling between magnetic impurities when the clouds overlap. This happens in various materials such as Kondo lattices, spin glasses, and high temperature superconductors.

Although the Kondo effect for a single magnetic impurity is now a text-book subject in many-body physics, detection of its key object, the Kondo cloud and its length, has remained elusive despite many attempts during the past five decades. Experiments using nuclear magnetic resonance or scanning tunneling microscopy, two common methods for understanding the structure of matter, have either shown no signature of the cloud, or demonstrated a signature only at a very short distance, less than 1 nanometer, so much shorter than the predicted cloud size, which was in the micron range.

In the present study, the authors observed a Kondo screening cloud formed by an impurity defined as a localized electron spin in a quantum dot--a type of "artificial atom"--coupled to quasi-one-dimensional conduction electrons, and then used an interferometer to measure changes in the Kondo temperature, allowing them to investigate the presence of a cloud at the interferometer end. Essentially, they slightly perturbed the conduction electrons at a location away from the quantum dot using an electrostatic gate. The wave of conducting electrons scattered by this perturbation returned back to the quantum dot and interfered with itself. This is similar to how a wave on a water surface being scattered by a wall forms a stripe pattern. The Kondo cloud is a quantum mechanical object which acts to preserve the wave nature of electrons inside the cloud. Even though there is no direct electrostatic influence of the perturbation on the quantum dot, this interference modifies the Kondo signature measured by electron conductance through the quantum dot if the perturbation is present inside the cloud. In the study, the researchers found that the length as well as the shape of the cloud is universally scaled by the inverse of the Kondo temperature, and that the cloud's size and shape were in good agreement with theoretical calculations. "Thus, we were able experimentally to confirm the original theoretical prediction of the Kondo cloud length which is on the order of micrometers," said Ivan Borzenets of the City University of Hong Kong, who performed the experimental measurements.

According to Michihisa Yamamoto of the RIKEN Center for Emergent Matter Science (CEMS), who led the international collaboration, "It is very satisfying to have been able to obtain real space image of the Kondo cloud, as it is a real breakthrough for understanding various systems containing multiple magnetic impurities. This achievement was only made possible by close collaboration with theorists. The size of the Kondo cloud in semiconductors was found to be much larger than the typical size of semiconductor devices. This means that the cloud can mediate interactions between distant spins confined in quantum dots, which is a necessary protocol for semiconductor spin-based quantum information processing. This spin-spin interaction mediated by the Kondo cloud is unique since both its strength and sign (two spins favor either parallel or anti-parallel configuration) are electrically tunable, while conventional schemes cannot reverse the sign. This opens up a novel way to engineer spin screening and entanglement." Heung-Sun Sim of KAIST, the theorist who proposed the method for detecting the Kondo cloud, also said, "The observed spin cloud is a micrometer-size object that has quantum mechanical wave nature and entanglement. This is why the spin cloud has not been observed despite a long search. It is remarkable in a fundamental and technical point of view that such a large quantum object can now be created, controlled, and detected."

Millions of people worldwide consume water contaminated with levels of arsenic that exceed those recommended by the World Health Organization. This could cause health problems, such as arsenic poisoning, cardiovascular disease and cancer. Microbes in groundwater release arsenic from sediments, and organic matter helps fuel this reaction. Now, researchers reporting in ACS' Environmental Science & Technology have discovered that the type of natural organic matter (NOM) influences the rate and level of arsenic release.

Arsenic occurs naturally in the minerals that make up aquifer sediments. Some species of bacteria can dissolve arsenic- and iron-containing minerals, releasing arsenic into the water. Scientists have tried to simulate this process in the lab by using simple carbon sources, such as acetate and lactate, as food for arsenic-freeing bacteria. However, NOM in groundwater contains more complex carbon sources, such as plant-derived organic matter, amino acids and carbohydrates. Andreas Kappler and colleagues wanted to study how NOM from actual aquifer sediments near the village of Van Phuc, Vietnam (where groundwater is contaminated with high levels of arsenic), influenced arsenic release.

In the field, the team collected sediment samples from the aquifer as far down as 150 feet below ground level. They found more total NOM, and more complex molecules within that NOM, from upper clayey silt layers than from lower sandy sediments. Back in the lab, the researchers placed arsenic-containing minerals and simulated groundwater in test tubes. Then, they added acetate/lactate or NOM from the two layers. At first, they found that acetate/lactate caused bacteria in the sediments to release more arsenic than when they added NOM from the clayey silt or sandy layers. However, after 100 days, the tubes with NOM from the two aquifer layers contained more dissolved arsenic, as well as more diverse microbial communities, than those containing lactate/acetate. Although NOM from the aquifer caused bacteria to release arsenic more slowly than the simple carbon sources, over time it could help free the same amount of or even more arsenic, the researchers say.