Culture

A multi-institutional collaboration has revealed that α-solanine, a toxic compound found in potato plants, is a divergent of the bitter-tasting α-tomatine, which is found in tomato plants. The research group included Associate Professor MIZUTANI Masaharu and Researcher AKIYAMA Ryota et al. of Kobe University's Graduate School of Agricultural Science, Assistant Professor WATANABE Bunta of Kyoto University's Institute for Chemical Research, Senior Research Scientist UMEMOTO Naoyuki of the RIKEN Center for Sustainable Resource Science, and Professor MURANAKA Toshiya of Osaka University's Graduate School of Engineering.

It is hoped that these research results can be used in potato breeding as a basis for suppressing the synthetization of poisonous compounds.

These research results were published in the international academic journal 'Nature Communications' on February 26.

Main Points

α-solanine is a toxic steroidal glycoalkaloid (SGA) (*1) found in potatoes.

Tomato's α-tomatine is astringent-tasting SGA that accumulates inside unripe fruits.

Based on their chemical structures, SGAs can be divided into two general classes, solanidanes (*2, e.g.α-solanine) and spirosolanes (*3, e.g. α-tomatine).

The research group revealed that the toxic α-solanine in potatoes is biosynthesized from spirosolane.

They discovered that the dioxygenase DPS (*4) is the key enzyme for this catalytic conversion.

It was also revealed that the α-solanine biosynthesis pathway in potatoes diverged from the spirosolane biosynthesis pathway due to the evolution of DPS.

Research Background

α-solanine is a type of toxic steroidal glycoalkaloid (SGA), which accumulates in the green skin on potato tubers (*5) and in tuber sprouts. SGA is not only found in potatoes but also in other plants of the Solanaceae family, including crops like tomatoes and eggplants. These substances are poisonous to many living things and serve as one of the plants' natural defenses. Low concentrations of SGA in potatoes cause a bitter taste and larger amounts can cause food poisoning. For this reason, biosynthesis research has been conducted with the aim of controlling the accumulation of SGA in potatoes.

Based on their skeletal chemical structures, SGAs can be divided into two general classes, solanidanes and spirosolanes (Figure 1). The potato toxinα-solanine is an example of a solanidane, whereas α-tomatine, which accumulates inside unripe tomatoes, is a spirosolane. It is known that both classes of SGA are biosynthesized from cholesterol. Up until now, several genes that encode the catalytic enzymes in SGA biosynthesis have been discovered and potato and tomato plants share these enzymes in the common pathway of SGA biosynthesis. However, the steps and enzymes involved in the metabolic branch point between solanidane- skeleton and spirosolane-skeleton formation remains an unsolved mystery.

This research group showed that the potato toxinα-solanine is biosynthesized from spirosolane. In a world first, they discovered that the dioxygenase DPS is the key to this conversion.

Research Findings

Potatoes contain the toxic solanidanes α-solanine and α-chaconine. The research group investigated theα-solanine biosynthesis pathway in potato plants. Using genome editing, they disrupted the biosynthetic enzyme gene in potato so that it was unable to produceα-solanine. Feeding α-tomatine (a spirosolane found in tomatoes) to the disruptant resulted in a metabolic conversion to the corresponding solanidane compound. In addition, it was found that this metabolic alteration could be suppressed with a 2-oxoglutarate dependent dioxygenase inhibitor, revealing that a dioxygenase is responsible for the oxidation reaction that synthesizes solanidanes from spirosolanes.

The researchers singled out a 2-oxoglutarate dependent dioxygenase (DPS) gene that was expressed in potato during α-solanine synthesis. To investigate this further, the researchers generated modified plants in which DPS gene expression was suppressed via RNA interference (*7). The solanidane concentrations in these modified potato plants were far lower than in the unmodified group, and spirosolanes accumulated inside the plants in place of solanidanes. Next, the researchers measured the enzymatic activity of DPS by recombining the proteins and expressing them in E. coli. The results revealed the unique catalytic role of DPS in spirosolane's conversion into solanidane (Figure 2). This proved that DPS is the key enzyme responsible for this conversion.

This research revealed that the potato's ability to produce α-solanine came about due to the evolution of DPS, which is responsible for metabolically converting spirosolanes (e.g. α-tomatine) into solanidanes. It is known that tomatoes also have an enzyme for metabolizing spirosolanes. The bitter-tasting α-tomatine is found in unripe tomatoes but is metabolized into the tasteless, non-toxic esculeoside A as the fruits ripen. The catalyst for this reaction is 23DOX (*8), which is also a dioxygenase.

From the relationship between their chromosomal positions and phylogenetic analysis, it was revealed that the α-solanine biosynthase DPS has evolved from the same precursor gene as the non-toxic α-tomatine's catalytic enzyme 23DOX. Thus, it is believed that the evolution of the dioxygenase gene that metabolizes spirosolanes is one of the main drivers of the development of structural and functional variation in SGAs.

Further Developments

Potatoes have been termed a potentially dangerous food because large concentrations of toxic α-solanine can cause food poisoning. It is hoped that these research results can provide a basis for future potato varieties in which the biosynthesis of toxic compounds is suppressed by targeting the DPS gene.

As shown in this research, the evolutionary origins of the structural diversity of SGAs provide clues towards discovering unknown SGA synthesis enzymes involved in biological functions in various plants. Illuminating these functions could pave the way for the molecular breeding of plant varieties that are able to adapt to different stressful environments.

CORVALLIS, Ore. - A novel analysis of encounters between albatross and commercial fishing vessels across the North Pacific Ocean is giving researchers important new understanding about seabird-vessel interactions that could help reduce harmful encounters.

The new research method, which combines location data from GPS-tagged albatross and commercial fishing vessels, allows researchers to accurately identify bird-vessel encounters and better understand bird behavior, environmental conditions and the characteristics that influence these encounters.

"It is hard to conceptualize how often birds encounter vessels in the open ocean, but with this new data, it becomes really apparent," said Rachael Orben, an assistant professor in the Department of Fisheries and Wildlife in Oregon State University's College of Agricultural Sciences and the study's lead author. "Some of these birds are in an environment where they see vessels all the time, while others are in an environment where they rarely encounter vessels."

The findings were just published in the Journal of Applied Ecology. Co-authors include Leigh Torres, an associate professor at OSU's Marine Mammal Institute, and David Kroodsma, director of research and innovation for Global Fishing Watch, a not-for-profit organization dedicated to advancing ocean governance through increased transparency of human activity at sea.

Albatross are large, long-lived seabirds that roam widely over the open ocean. Three albatross species are found in the North Pacific: the black-footed albatross, the Laysan albatross and the short-tailed albatross. All three species are of high conservation concern and the short-tailed albatross is listed as endangered under the Endangered Species Act.

Fishing activity can offer the birds opportunities for foraging, but not without risks, including threat of bycatch. Bycatch is the term for fish, birds or other animals caught unintentionally and includes interactions with fishing vessels and fishing gear.

Researchers have been using biologging, the practice of attaching data recording devices to animals, to track individual bird movements at sea for more than 20 years. But they have not had much access to information about the location of vessels, which is a critical piece to understanding the seabird-fishery interaction puzzle, Torres said.

Torres learned that Global Fishing Watch was processing and making available data from the Automatic Identification System, or AIS, an automatic tracking system that uses transceivers on ships. The data includes information about vessel size, movement, fishing method and more. Access to the data was a "game-changer," she said.

"With their data, you can track individual vessels," Torres said. "You can get precise information about a vessel's location, its size, the type of fishing gear it is using and the flag nation of the ship."

Global Fishing Watch's goals include making commercial fishing on the high seas more transparent to the public, improving fisheries regulation and ensuring sustainability of ocean resources.

"This study represents a new frontier in our ability to understand how fisheries impact marine life," said David Kroodsma, director of research and innovation at Global Fishing Watch. "Vessel tracking data, collected by satellites and processed with machine learning, can be a powerful tool to analyze how biodiversity and fishing vessels interact at sea."

Members of the research team had previously collected albatross tracking data from adult black-footed albatross and Laysan albatross breeding in the Papahānaumokuākea Marine National Monument in the Northwest Hawaiian Islands; Laysan albatross nesting on Oahu, Hawaii; and juvenile short-tailed albatross originating from their colonies in Japan.

The researchers were able to marry data on fishing vessels with tracking data from the GPS-tagged albatross during the same periods to identify and locate where bird-vessel interactions occur throughout the North Pacific Ocean.

When birds are within 30 kilometers of a vessel, the researchers assumed the albatross was aware of the vessel's presence, Orben said. When the bird was within 3 kilometers of the vessel, researchers assumed a close encounter between the two. The research team then modeled the drivers of these close encounters.

"With these models, we can start to understand why birds sometimes do and sometimes don't interact with a fishing vessel," Torres said. "This information can help identify how and when efforts should be made to make sure these interactions don't go wrong for the bird. As we start to identify patterns, we can potentially help mitigate these bycatch events."

Among the researchers' findings:

When birds are in a transit state - where they are traveling directly from one location to another - they are not likely to stop and engage with a vessel. But when they are in a foraging state, they are more likely to stop.

Vessel characteristics, including fishing method and the nation of flag on the vessel did not seem to be factors in whether a bird interacted with a vessel.

In areas where there is a lot of fishing, short-tailed and Laysan albatross associated with fishing vessels more frequently.

Short-tailed albatross were more likely to stay with a vessel for a longer period of time in lighter wind conditions.

"These results indicate that it may be more important to use bycatch mitigation methods from a fishing vessel in low wind conditions," Torres said. "Things like that can help guide efforts to reduce bycatch of seabirds. The best regulations are those that are the least burdensome to fishermen and the most effective."

The analysis framework developed by the researchers could be used to study encounters between fishing vessels and other seabirds or marine mammals. Information gathered through the study of these interactions could help inform fisheries management decisions, as well, the researchers said.

"Our study is really one of the first to look at the fine-scale overlap between fishing vessels and marine animals on the high seas, in international waters," Torres said. "It opens a whole new understanding of the dynamics between animals and vessels. This work can help the fishing community fish better and help these seabirds survive and thrive."

Microswimmers are artificial, self-propelled, microscopic particles. They are capable of directional motion in a solution. The Molecular Nanophotonics Group at Leipzig University has developed special particles that are smaller than one-thirtieth of the diameter of a hair. They can change their direction of motion by heating tiny gold particles on their surface and converting this energy into motion. "However, these miniaturised machines cannot take in and learn information like their living counterparts. To achieve this, we control the microswimmers externally so that they learn to navigate in a virtual environment through what is known as reinforcement learning," said Cichos.

With the help of virtual rewards, the microswimmers find their way through the liquid while repeatedly being thrown off of their path, mainly by Brownian motion. "Our results show that the best swimmer is not the one that is fastest, but rather that there is an optimal speed," said Viktor Holubec, who worked on the project as a fellow of the Alexander von Humboldt Foundation and has now returned to the university in Prague. According to the scientists, linking artificial intelligence and active systems like in these microswimmers is a first small step towards new intelligent microscopic materials that can autonomously perform tasks while also adapting to their new environment. At the same time, they hope that the combination of artificial microswimmers and machine learning methods will provide new insights into the emergence of collective behaviour in biological systems. "Our goal is to develop artificial, smart building blocks that can perceive their environmental influences and actively react to them," said the physicist. Once this method is fully developed and has been applied to other material systems, including biological ones, it could be used, for example, in the development of smart drugs or microscopic robot swarms.

Food scientists from Nanyang Technological University, Singapore (NTU Singapore) have made an antibacterial gel bandage using the discarded husks of the popular tropical fruit, durian.

Known as the "King of Fruits" in Southeast Asia, the durian has a thick husk with spiky thorns which is discarded, while the sweet flesh surrounding the seeds on the inside is considered a delicacy.

By extracting high-quality cellulose from the durian husks and combining it with glycerol - a waste by-product from the biodiesel and soap industry - NTU scientists created a soft gel, similar to silicon sheets, which can be cut into bandages of various shapes and sizes.

They then added the organic molecules produced from baker's yeast known as natural yeast phenolics, making the bandage deadly to bacteria.

Developed by Professor William Chen, the Director of NTU's Food Science and Technology Programme, the innovation was published recently in ACS Sustainable Chemistry & Engineering, a peer-reviewed journal of the American Chemistry Society.

Conventional hydrogel patches are commonly available at pharmacies, usually used to cover wounds from surgery to minimise the formation of excessive scar tissue, resulting in a softer and flatter scar. The patch keeps the skin hydrated instead of drying up when conventional band-aid or gauze bandages are used.

Prof Chen said conventional hydrogel patches on the market are made from synthetic materials such as polymers like polymethacrylate and polyvinylpyrrolidine. Those with antimicrobial properties also use metallic compounds such as silver or copper ions. Such synthetic materials approved for use in biomedical applications are more costly as compared to the new hydrogel made from natural waste materials.

"With the growing threat of antibiotic-resistant superbugs, the world will need multiple alternative ways to prevent infections. An effective way to protect open wounds is with antimicrobial bandages that are biocompatible and safe for prolonged use by humans. This is especially important for diabetic patients suffering from chronic wounds," explained Prof Chen, the Michael Fam Chair Professor in Food Science and Technology at the School of Chemical and Biomedical Engineering.

"By using waste products which are currently discarded in large quantities - durian husks and glycerol - we could turn waste into a valuable biomedical resource that can enhance the speedy recovery of wounds and to reduce chances of infections.

With the husk comprising 60 per cent of the durian it is usually discarded and incinerated, posing an environmental issue. In Singapore, it was reported by Straits Times that 14,300 tonnes[1] of durian (estimated 10 million durians) were imported and consumed in 2017.

Being non-toxic and biodegradable, the organic gel bandage is also expected to have a smaller environmental footprint than conventional synthetic bandages.

Giving an independent comment on this innovation, Associate Professor Andrew Tan, Vice Dean (Faculty) from NTU's Lee Kong Chian School of Medicine, who is an expert in metabolic disorders, said there are existing natural and synthetic hydrogels on the market now, where their usefulness in the healing of some types of wounds are well recognised.

"Hydrogel bandages are known for their non-toxicity, ability to rehydrate the wound bed, and can facilitate autolytic debridement (where the body enzymes and natural fluids act to soften bad tissue and remove it). The innovative and unique part of Prof Chen's current work is the upcycling of the durian rind to obtain cellulose. It's also quite unique given that the thorns of the durian can hurt, but the materials from the rind can heal," Assoc Prof Tan said.

Why antimicrobial wound dressings are needed

Wounds linked to chronic diseases are expected to become a more common health burden, where bacterial infection of skin wounds is a serious risk. The market for wound dressing is estimated to be worth $11.4 billion annually, according to a paper published in the European Polymer Journal (A. Gupta et al, 2019).

The clinical advantage of the new hydrogel bandage is that the natural yeast phenolics embedded will help to prevent the growth of bacteria such as Gram-negative E. coli and Gram-positive S. aureus. and the subsequent formation of biofilms (a layer of slime that can lead to antimicrobial resistance within a bacteria colony).

As a proof of concept, the antimicrobial hydrogels were tested as a wound dressing on animal skin and showed good antimicrobial effects for up to 48 hours.

The new proof-of-concept hydrogel bandage is applied by simply laying it across the wound, just as with existing commercially available silicone gel sheets for wound dressing, the current gold-standard used following cosmetic surgeries to reduce scarring.

Other applications of hydrogels

Organic hydrogels are also useful for wearable, flexible and stretchable electronics, which Prof Chen had demonstrated in a 2019 paper published in Scientific Reports.

Wearable electronics can consist of small sensors that can detect heart rate and physical activities, much like current smart bands. They could aid healthcare workers in monitoring the health of the elderly in remote communities.

To demonstrate the use of organic hydrogels in flexible electronics, a prototype hydrogel that could conduct electrical signals was made with cellulose obtained from Okara - the waste leftover from soybean pulp during the making of soy milk.

"As shown in many of our research papers, fundamental research in food science and technology carries far more interdisciplinary applications in other industries, such as healthcare, biomedical applications and speciality chemicals," Prof Chen added.

"Our innovation is in line with the NTU 2025 strategic plan, where research and innovation are key pillars of focus in tackling some of humanity's greatest challenges. By adopting a waste-to-resource approach and the use of green manufacturing techniques, we have shown that it is possible to reduce consumption of Earth's natural resources, reuse what was thought of as rubbish, and recycle them into valuable products that are useful for mankind."

The team of four NTU researchers took two years to research and publish their findings and is now looking for industry partners who may be keen to take their antibacterial gel bandage to market.

European listed companies in the energy and mining sector provide, to say the least, sparse information on future environmental costs in their annual reports. Researchers believe that stricter guidelines are required as the lack of information may lead to underestimation of environmental liabilities, resulting in that future generations may have to bear the burden of cleanup costs.

"I believe that the future environmental liabilities such as decommissioning costs are often underestimated and few understand the burden these costs might impose on future generations. If, for example, an oil & gas company fails, it costs an incredible amount to clean up after old oil wells and the risk is great that the taxpayers will have to pay the bill. Therefore, it is important that environmental obligations are made visible to investors, lenders and the public so that we can discuss the problem," says Mari Paananen, associate professor of business administration at the School of Business, Economics and Law at the University of Gothenburg.

In fact, as there is no clear claimant for this type of future obligations, there is little demand for information either.

"The International Accounting Standards Board* needs to provide clearer requirements about what information should be included in the annual reports in order to make it possible to assess environmental liabilities. I think that such guidelines would make companies inclined to disclose more information and would also provide, for example, auditors a mandate to demand specific information," says Mari Paananen.

Using a sample of 164 European listed companies active in oil, gas, energy (nuclear power) and mining, Mari Paananen and her research colleagues have analyzed environmental disclosures in annual reports over a twelve-year period. Specifically, the researchers use computerized text analysis, to examine information on environment-related restoration costs in the notes to annual reports. Among other things, they searched for information about the discount rate and estimated time horizon for payments - key information needed to assess the size of environmental liabilities.

"Even though we could see that the disclosure of environmental information in the annual reports has increased over time, companies are, are on average, not very forthcoming with information. Approximately 60 percent of the companies provided information about discount rates and 65 percent disclosed the time horizon for the expected future cash outflow. On the other hand, only just over a third provided information about both," says Mari Paananen.

The researchers also investigated whether the level of disclosure increased when companies faced media exposure focusing on environmental issues or how companies' take responsibility for the environment.

"We clearly saw that if companies were exposed in the media, the environmental information increased and the companies provided more specific disclosure on environmental liabilities in the following annual report. Above all, there was more information if the media used an uncertain or litigious tone," says Mari Paananen.

Bright but disadvantaged students from urban areas are more likely to enter elite UK universities than similar peers from rural communities due to an urban 'escalator effect', according to a new study.

Researchers from the University of Bath analysed data from 800,000 English students commencing university in the years 2008, 2010, 2012, 2014 and 2016.

They found that while in general rural areas had higher overall progression to university than city centres and surrounding areas, when controlling for factors including socio-economic status, age, ethnicity and sex, disadvantaged pupils from rural areas were less likely to progress to one of 27 'top' UK universities.

The authors suggest the difference is due to a 'vortex of influences' including 'social mix effects' in more diverse urban settings, successive urban-centred policy interventions and the targeting of university and third-sector outreach activities to urban areas.

Although the results reaffirmed that social class remains the biggest predictor of progression to a top university, the researchers say the results highlight drawbacks of existing geographic measures used to identify disadvantage, as they do not account for the diverse nature of deprived areas, and therefore universities risk missing disadvantaged students. Instead the use of more sophisticated measures could help universities target under-represented and disadvantaged students more effectively, and the authors call for a co-ordinated strategic approach to ensure that no areas are missed by universities' widening participation programmes.

The paper is published in the British Educational Research Journal.

Jo Davies, who led the research as part of her PhD studies in the Department of Education, said: "There has been a lot of interest and concern about geographic inequalities in education. Our paper shows that whilst social background is still the most important predictor for progressing to an elite university, there may also be further geographic factors compounding access. We believe that the use of Geographic Information System (GIS) mapping methods, as used within our own research, could enable elite universities to target under?represented students more effectively, especially disadvantaged students living in rural areas with otherwise good progression rates."

The research team, from the Department of Education, used data from the Higher Education Statistics Agency (HESA) of 800,000 English students beginning university in the academic years 2008/09, 2010/11, 2012/ 13, 2014/15 and 2016/17.

They were interested in progression to 27 'top' UK universities, comprising the Russell Group plus the Universities of St Andrews, Bath and Strathclyde, comparing rates from each Middle Super Output Area (MSOA) in England. Each MSOA, of which there are 6,791 across England, has a population between 5,000 and 15,000, with a minimum of 2,000 and a maximum of 6,000 households.

By analysing progression to these elite institutions after controlling for a factors including education (state/private school education, tariff point score, number of facilitating subjects studied), socio-economic status, age, ethnicity, sex, distance travelled and academic year, the urban escalator effect emerged.

The research was funded by a University of Bath Research Studentship Award. The University currently funds seven PhD students as part of its programme of research aiming to uncover ways in which participation in higher education can be widened and to ensure that no student who has the ability and desire to go to onto higher education is prevented from doing so because of their background.

Dr Matt Dickson, who leads the overall programme for the University's Institute for Policy Research, said: "This research is a great example of the importance of analysis that goes beyond a descriptive picture to understand the key factors that perpetuate inequalities in higher education access. Rather than a simple rural-urban divide, the reality is much more complex and this has important implications for higher education policy."

These lessons are already being implemented at the University of Bath. For example, alongside its existing programme of Widening Participation initiatives the University recently entered into a partnership with Villiers Park Educational Trust to support students from neglected rural and coastal communities to access top universities, such as Bath, through activities including coaching and mentoring for students.

Prof. ZHAO Jin's research team from University of Science and Technology of China (USTC) has made important progress in the development of Spin-Valley exciton dynamics. The research developed an ab initio nonadiabatic molecular dynamics (NAMD) method based on for the spin-resolved exciton dynamics. The team gained the first clear and complete physical picture of valley exciton dynamics in MoS2 from the perspective of first-principles calculations based on GW plus real-time Bethe-Salpeter equation (GW + rtBSE-NAMD).

It can accurately include many-body effects at the level of first principles and break through the bottleneck of GW+BSE method in time-dependent dynamics. The research results were published in Science Advances.

From investigations on MoS2, the research provides a comprehensive picture of spin-valley exciton dynamics where the electron-phonon (e-ph) scattering, spin-orbit interaction (SOI), and electron-hole (e-h) interactions come into play collectively.

In this work, the team develop an ab initio NAMD method based on GW plus real-time propagation of BSE (GW + rtBSE-NAMD). The SOI is included by using the spinor basis sets, and the e-ph coupling is simulated by combining ab initio MD (AIMD) with real-time BSE. The team used the rigid dielectric function approximation and used GW + rtBSE-NAMD to investigate the spin-valley exciton dynamics in monolayer MoS2.

It is found that the intervalley bright exciton transition induces fast valley depolarization within a few picoseconds, which provide a direct evidence that e-h exchange interaction plays an essential role in the intervalley bright exciton transitions in TMD systems.

The newly developed GW + rtBSE-NAMD method provides a powerful tool to investigate the time- and spin-resolved exciton dynamics.

This method can also be widely applied to other material systems to study important physical problems such as exciton relaxation, lifetime, dissociation, and interaction with defects, opening the door to the field of exciton dynamics in solid materials based on first principles.

When we grow crystals, atoms first group together into small clusters - a process called nucleation. But understanding exactly how such atomic ordering emerges from the chaos of randomly moving atoms has long eluded scientists.

Classical nucleation theory suggests that crystals form one atom at a time, steadily increasing the level of order. Modern studies have also observed a two-step nucleation process, where a temporary, high-energy structure forms first, which then changes into a stable crystal. But according to an international research team co-led by the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab), the real story is even more complicated.

Their findings, recently reported in the journal Science, reveal that rather than grouping together one-by-one or making a single irreversible transition, gold atoms will instead self-organize, fall apart, regroup, and then reorganize many times before establishing a stable, ordered crystal. Using an advanced electron microscope, the researchers witnessed this rapid, reversible nucleation process for the first time. Their work provides tangible insights into the early stages of many growth processes such as thin-film deposition and nanoparticle formation.

"As scientists seek to control matter at smaller length scales to produce new materials and devices, this study helps us understand exactly how some crystals form," said Peter Ercius, one of the study's lead authors and a staff scientist at Berkeley Lab's Molecular Foundry.

In line with scientists' conventional understanding, once the crystals in the study reached a certain size, they no longer returned to the disordered, unstable state. Won Chul Lee, one of the professors guiding the project, describes it this way: if we imagine each atom as a Lego brick, then instead of building a house one brick at a time, it turns out that the bricks repeatedly fit together and break apart again until they are finally strong enough to stay together. Once the foundation is set, however, more bricks can be added without disrupting the overall structure.

The unstable structures were only visible because of the speed of newly developed detectors on the TEAM I, one of the world's most powerful electron microscopes. A team of in-house experts guided the experiments at the National Center for Electron Microscopy in Berkeley Lab's Molecular Foundry. Using the TEAM I microscope, researchers captured real-time, atomic-resolution images at speeds up to 625 frames per second, which is exceptionally fast for electron microcopy and about 100 times faster than previous studies. The researchers observed individual gold atoms as they formed into crystals, broke apart into individual atoms, and then reformed again and again into different crystal configurations before finally stabilizing.

"Slower observations would miss this very fast, reversible process and just see a blur instead of the transitions, which explains why this nucleation behavior has never been seen before," said Ercius.

The reason behind this reversible phenomenon is that crystal formation is an exothermic process - that is, it releases energy. In fact, the very energy released when atoms attach to the tiny nuclei can raise the local "temperature" and melt the crystal. In this way, the initial crystal formation process works against itself, fluctuating between order and disorder many times before building a nucleus that is stable enough to withstand the heat. The research team validated this interpretation of their experimental observations by performing calculations of binding reactions between a hypothetical gold atom and a nanocrystal.

Now, scientists are developing even faster detectors which could be used to image the process at higher speeds. This could help them understand if there are more features of nucleation hidden in the atomic chaos. The team is also hoping to spot similar transitions in different atomic systems to determine whether this discovery reflects a general process of nucleation.

One of the study's lead authors, Jungwon Park, summarized the work: "From a scientific point of view, we discovered a new principle of crystal nucleation process, and we proved it experimentally."

Serotonin, or 5-hydroxytryptamine (5-HT), is a kind of neurotransmitter. 5-HT can regulate multifaceted physiological functions such as mood, cognition, learning, memory, and emotions through 5-HT receptors. 5-HT receptors are a type of G protein-coupled receptor and can be divided into 12 subtypes in humans. As drug targets, they play a vital role in the treatment of schizophrenia, depression, and migraine.

However, the structural and functional mechanisms of 5-HT receptors have been largely unknown.

In a study published in Nature on March 24, Prof. H. Eric XU and Prof. JIANG Yi from the Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences, together with Prof. ZHANG Yan from Zhejiang University, and their collaborators, have clarified the critical role of PtdIns4P and cholesterol in G-protein coupling and ligand recognition as well as the molecular basis of basal activity and the drug recognition mode of 5-HT receptors, by resolving the cryo-electron microscopy (cryo-EM) structures of five 5-HT receptor-Gi complexes.

These five 5-HT receptor-Gi complexes include three with 5-HT1A structures (one in the apo state, one bound to 5-HT, and one bound to aripiprazole, an antipsychotic drug), one with 5-HT1D bound to 5-HT, and one with 5-HT1E bound to the 5-HT1E- and 5-HT1F-selective agonist BRL-54443.

PtdIns4P is one of the major classes of phosphoinositides. In this study, the researchers first identified PtdIns4P as a major phospholipid at the 5-HT1A-G protein interface, which stabilizes the 5-HT1A-G protein complex.

They found that PtdIns4P is sandwiched between two cholesterol molecules surrounding the 5-HT1A receptor, therefore providing a structural basis for the modulation of 5-HT1A signaling by cholesterol and phospholipids.

Researchers also found several structured water molecules that form hydrogen bonds with the apo receptor within the orthosteric binding pocket. Water molecules mimic the polar functionalities of 5-HT in the active apo-5-HT1A-Gi complex, thus revealing the key role of water molecules in sustaining the basal activity of 5-HT receptors.

In addition, the researchers revealed the basis of ligand selectivity and drug recognition in 5-HT receptors. They identified residue at position 6×55 as a key determinant for the BRL-54443 and 5-CT selectivity of 5-HT receptors.

An outward shift of the extracellular end of TM7 in 5-HT1A stabilizes the quinolinone group of aripiprazole, resulting in 5-HT1A's high selectivity for aripiprazole.

A cholesterol molecule was further found to be involved in the stabilization of the aripiprazole pocket and causes aripiprazole to have a higher binding affinity for 5-HT1A.

The observations in this study have wide implications for a mechanistic understanding of 5-HT signaling and for drug discovery targeting the 5-HT receptor family.

The novel label-free assay uses unconventional L and inverse-L shaped pillars of deterministic lateral displacement (DLD) microfluidic technology to quantify and profile immune states of white blood cells (WBCs) by assessing biophysical properties of size, deformation, distribution, and cell count

The assay requires only 20 microlitres (μl) of unprocessed blood and takes just 15 minutes - much faster than existing methods which require up to 15 millilitres (ml) of blood and take at least a few hours to produce results

This new technology measures and profiles the often volatile host immune response, resulting in a more accurate assessment of patient pathophysiology

Current methods for early diagnosis of infection focus on detecting low-abundance pathogens, and are time-consuming, of low sensitivity, and do not accurately reflect the severity of infection

Singapore, 25 March 2021 - Researchers from Critical Analytics for Manufacturing Personalized-Medicine (CAMP), an Interdisciplinary Research Group (IRG) at the Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore, have developed a new label-free immune profiling assay that profiles the rapidly changing host immune response in case of infection, in a departure from existing methods that focus on detecting the pathogens themselves, which can often be at low levels within a host. This novel technology presents a host of advantages over current methods, being both much faster, more sensitive and accurate.

The new assay is described in a paper titled, "Label-free biophysical markers from whole blood microfluidic immune profiling reveals severe immune response signatures", published recently in Small, a weekly peer-reviewed scientific journal covering nanotechnology, and included a pilot study of 85 donors recruited from the National University Hospital (NUH) emergency department. The paper was led by Dr Kerwin Kwek Zeming, senior postdoctoral associate at SMART CAMP, and co-authored by Professor Jongyoon Han, Principal Investigator at SMART CAMP and Professor of Biological Engineering and Electrical Engineering at MIT, and Dr Win Sen Kuan, Research Director, Emergency Medicine Department, NUH.

In many cases, the main culprit behind disease manifestation, severity of infection, and patient mortality is an overly aggressive host immune response. For instance, the Spanish Flu pandemic of 1918 resulted in a disproportionately high number of deaths among otherwise healthy young adults. This has been attributed to the now well-studied phenomenon of cytokine storms, which precipitate the rapid release of immune cells and inflammatory molecules and are brought on by a hyper-aggressive host immune response. In a more recent example, cases of severe COVID-19 infection often result in death via sepsis and a dysregulated immune response, while current risk stratification methods based on age and comorbidity remain a significant challenge and can be inaccurate. Moreover, current Covid-19 testing does not prognose the severity of the immune response and can thus lead to inefficient deployment of resources in healthcare settings.

In cases of acute infection, the status of a patient's immune response can often be volatile and may change within minutes. Hence, there exists a pressing need for assays that are able to rapidly and accurately inform on the state of the immune system. This is particularly vital in early triage among patients with acute infection and prediction of subsequent deterioration of disease. In turn, this will better empower medical personnel to make more accurate initial assessments and deliver the appropriate medical response. This can ensure timely intervention in the emergency department (ED) and prevent admission to the intensive care unit (ICU).

The new assay developed by SMART researchers focuses on profiling the rapidly changing host inflammatory response, which in a hyper-aggressive state, can lead to sepsis and death. A 15-minute label-free immune profiling assay from 20 μL of unprocessed blood using unconventional L and inverse-L shaped pillars of DLD microfluidic technology was developed, functioning as a sensitive and quantitative assay of immune cell biophysical signatures in relation to real-time activation levels of WBCs. As WBCs are activated by various internal or external triggers, the assay can sensitively measure both the extent and direction of these changes, which in turn reflect a patient's current immune response state. As such, the new assay developed by SMART researchers is able to accurately and quickly assess patients' immune response states by profiling immune cell size, deformability, distribution, and cell counts.

Significantly, the new assay provides considerable advantages over existing methods of profiling the immune system and its activity. These include measuring leukocyte gene expression, cell-surface biochemical markers, and blood serum cytokine profile. Notably, these current methods require sample dilution or pre-processing steps, as well as labour-intensive, expensive equipment and antibody labelling procedures. As a result, these methods generally require a few hours, at minimum, to return results. This is a key pain point and drawback in triage and the emergency department, where clinicians need to make accurate clinical assessments as early as possible. The labour- and time-intensive nature of these current methods significantly limits their clinical utility for rapid triage and prevents their wider implementation within the ER or ICU.

In contrast, as this new SMART assay takes only 15 minutes, uses only 20 μL of whole blood, and only requires video capture frame rates of up to 150 fps, there is considerable potential for the technology to be developed into a portable unit that can perform point-of-care blood-sparing assays which could significantly improve the diagnosis and differentiation of patients in the ER and other primary or critical care settings. This application will enable clinicians to be able to quickly identify at-risk patients and take immediate action to mitigate or prevent organ dysfunction and other adverse effects of a hyper-aggressive immune response.

Lead author Dr Kerwin Kwek said, "Our new DLD assay will help address an unmet need in the ER and ICU by significantly reducing waiting time for accurate patient assay results. This could lead to more effective triage decision-making and more appropriate and timely treatment, which are critical to saving lives. More generally, this groundbreaking technology provides new insights into both the engineering of precision microfluidics and clinical research."

Professor Jongyoon Han added, "In the wake of lessons learnt in emergency rooms in hospitals across the world especially during the COVID-19 pandemic, where medical professionals have been faced with making difficult and at times life-or-death decisions in triage, this new technology represents a hugely exciting and significant breakthrough. By reducing the time taken for assay results from hours to a matter of minutes, SMART CAMP's new assay could help save lives as we continue to combat the scourge of pathogens and infectious diseases. The assay will also have wider applications, giving clinicians a new and more effective tool in the ER and ICU."

For almost a century, physicists have been intrigued by the fundamental question: why are complex numbers so important in quantum mechanics, that is, numbers containing a component with the imaginary number i? Usually, it was assumed that they are only a mathematical trick to facilitate the description of phenomena, and only results expressed in real numbers have a physical meaning. However, a Polish-Chinese-Canadian team of researchers has proved that the imaginary part of quantum mechanics can be observed in action in the real world.

We need to significantly reconstruct our naive ideas about the ability of numbers to describe the physical world. Until now, it seemed that only real numbers were related to measurable physical quantities. However, research conducted by the team of Dr. Alexander Streltsov from the Centre for Quantum Optical Technologies (QOT) at the University of Warsaw with the participation of scientists from the University of Science and Technology of China (USTC) in Hefei and the University of Calgary, found quantum states of entangled photons that cannot be distinguished without resorting to complex numbers. Moreover, the researchers also conducted an experiment confirming the importance of complex numbers for quantum mechanics. Articles describing the theory and measurements have just appeared in the journals Physical Review Letters and Physical Review A.

"In physics, complex numbers were considered to be purely mathematical in nature. It is true that although they play a basic role in quantum mechanics equations, they were treated simply as a tool, something to facilitate calculations for physicists. Now, we have theoretically and experimentally proved that there are quantum states that can only be distinguished when the calculations are performed with the indispensable participation of complex numbers," explains Dr. Streltsov.

Complex numbers are made up of two components, real and imaginary. They have the form a + bi, where the numbers a and b are real. The bi component is responsible for the specific features of complex numbers. The key role here is played by the imaginary number i, i.e. the square root of -1.

There is nothing in the physical world that can be directly related to the number i. If there are 2 or 3 apples on a table, this is natural. When we take one apple away, we can speak of a physical deficiency and describe it with the negative integer -1. We can cut the apple into two or three sections, obtaining the physical equivalents of the rational numbers 1/2 or 1/3. If the table is a perfect square, its diagonal will be the (irrational) square root of 2 multiplied by the length of the side. At the same time, with the best will in the world, it is still impossible to put i apples on the table.

The surprising career of complex numbers in physics is related to the fact that they can be used to describe all sorts of oscillations much more conveniently than with the use of popular trigonometric functions. Calculations are therefore carried out using complex numbers, and then at the end only the real numbers in them are taken into account.

Compared to other physical theories, quantum mechanics is special because it has to describe objects that can behave like particles under some conditions, and like waves in others. The basic equation of this theory, taken as a postulate, is the Schrödinger equation. It describes changes in time of a certain function, called the wave function, which is related to the probability distribution of finding a system in a specific state. However, the imaginary number i openly appears next to the wave function in the Schrödinger equation.

"For decades, there has been a debate as to whether one can create coherent and complete quantum mechanics with real numbers alone. So, we decided to find quantum states that could be distinguished from each other only by using complex numbers. The decisive moment was the experiment where we created these states and physically checked whether they were distinguishable or not," says Dr. Streltsov, whose research was funded by the Foundation for Polish Science.

The experiment verifying the role of complex numbers in quantum mechanics can be presented in the form of a game played by Alice and Bob with the participation of a master conducting the game. Using a device with lasers and crystals, the game master binds two photons into one of two quantum states, absolutely requiring the use of complex numbers to distinguish between them. Then, one photon is sent to Alice and the other to Bob. Each of them measures their photon and then communicates with the other to establish any existing correlations.

"Let's assume Alice and Bob's measurement results can only take on the values of 0 or 1. Alice sees a nonsensical sequence of 0s and 1s, as does Bob. However, if they communicate, they can establish links between the relevant measurements. If the game master sends them a correlated state, when one sees a result of 0, so will the other. If they receive an anti-correlated state, when Alice measures 0, Bob will have 1. By mutual agreement, Alice and Bob could distinguish our states, but only if their quantum nature was fundamentally complex," says Dr. Streltsov.

An approach known as quantum resource theory was used for the theoretical description. The experiment itself with local discrimination between entangled two-photon states was carried out in the laboratory at Hefei using linear optics techniques. The quantum states prepared by the researchers turned out to be distinguishable, which proves that complex numbers are an integral, indelible part of quantum mechanics.

The achievement of the Polish-Chinese-Canadian team of researchers is of fundamental importance, but it is so profound that it may translate into new quantum technologies. In particular, research into the role of complex numbers in quantum mechanics can help to better understand the sources of the efficiency of quantum computers, qualitatively new computing machines capable of solving some problems at speeds unattainable by classical computers.

The Centre for Quantum Optical Technologies at the University of Warsaw (UW) is a unit of the International Research Agendas programme of the Foundation for Polish Science,  co-financed from EU resources, obtained from the European Regional Development Fund under the Smart Growth Operational Programme. The seat of the unit is the Centre of New Technologies at the University of Warsaw. The unit conducts research on the use of quantum phenomena such as quantum superposition or entanglement in optical technologies. These phenomena have potential applications in communications, where they can ensure the security of data transmission, in imaging, where they help to improve resolution, and in metrology to increase the accuracy of measurements. The Centre for Quantum Optical Technologies at the University of Warsaw is actively looking for opportunities to cooperate with external entities in order to use the research results in practice.

By clearing forests, burning grasslands, plowing fields and harvesting crops, humans apply strong selective pressures on the plants that survive on the landscapes we use. Plants that evolved traits for long-distance seed-dispersal, including rapid annual growth, a lack of toxins and large seed generations, were more likely to survive on these dynamic anthropogenic landscapes. In the current article, researchers argue that these traits may have evolved as adaptations for megafaunal mutualisms, later allowing those plants to prosper among increasingly sedentary human populations.

The new study hypothesizes that the presence of specific anthropophilic traits explains why a select few plant families came to dominate the crop and weed assemblages around the globe, such as quinoa, some grasses, and knotweeds. These traits, the authors argue, also explain why so many genera appear to have been domesticated repeatedly in different parts of the world at different times. The 'weediness' and adaptability of those plants was the result of exaptation traits, or changes in the function of an evolutionary trait. In this way, rather than an active and engaged human process, certain plants gradually increased in prominence around villages, in cultivated fields, or on grazing land.

Grasses and field crops weren't the only plants to use prior adaptations to prosper in human landscapes; select handfuls of trees also had advantageous traits, such as large fleshy fruits, resulting from past relationships with large browsers. The rapid extinction of megafauna at the end of the Pleistocene left many of these large-fruiting tree species with small, isolated populations, setting the stage for more dramatic changes during later hybridization. When humans began moving these trees they were likely to hybridize with distant relatives, resulting, in some cases, in larger fruits and more robust plants. In this way, the domestication process for many long-generation perennials appears to have been more rapid and tied into population changes due to megafaunal extinctions.

"The key to better understanding plant domestication may lay further in the past than archaeologists have previously thought; we need to think about the domestication process as another step in the evolution of life on Earth, as opposed to an isolated phenomenon," states Dr. Robert Spengler. He is the director of the archaeobotanical laboratories at the Max Planck Institute for the Science of Human History in Jena, Germany, and the lead investigator on this paper.

This publication is a result of archaeologists, geneticists, botanists, and paleontologists contributing insights from their unique disciplines to reframe the way scholars think about domestication. The goal of the collaboration is to get researchers to consider the deeper ecological legacies of the plants and the pre-cultivation adaptations that they study.

Prof. Nicole Boivin, director of the Department of Archaeology at the Max Planck Institute in Jena, studies the ecological impacts of humans deep in the past. "When we think about the ecology of the origins of agriculture, we need to recognize the dramatic changes in plant and animal dynamics that have unfolded across the Holocene, especially those directly resulting from human action," she adds.

Ultimately, the scholars suggest that, rather than in archaeological excavations, laboratories, or in modern agricultural fields, the next big discoveries in plant domestication research may come from restored megafaunal landscapes. Ongoing research by Dr. Natalie Mueller, one of the authors, on North American restored prairies is investigating potential links between bison and the North American Lost Crops. Similar studies could be conducted on restored megafaunal landscapes in Europe, such as the Bia?owieski National Park in Poland, the Ust'-Buotoma Bizon Park or Pleistocene Park in Sakha Republic, Russia.

Dr. Ashastina, another author on the paper and a paleontologist studying Pleistocene vegetation communities in North Asia, states, "these restored nature preserves provide a novel glimpse deep into the nature of plant and animal interactions and allow ecologists, not only to directly trace vegetation changes occurring under herbivore pressure in various ecosystems, but to disentangle the deeper legacies of these mutualisms."

By offering a microscopic "tightrope" to cells, Virginia Tech and Johns Hopkins University researchers have brought new insights to the way migrating cells interact in the body. The researchers changed their testing environment for observing cell-cell interaction to more closely mirror the body, resulting in new observations of cells interacting like cars on a highway -- pairing up, speeding up, and passing one another.

Understanding the ways migrating cells react to one another is essential to predicting how cells change and evolve and how they react in applications, such as wound healing and drug delivery. In a study published in the Proceedings of the National Academy of Sciences, a team formed by Mechanical Engineering Associate Professor Amrinder Nain, graduate researchers Jugroop Singh and Aldwin Pagulayan, and Johns Hopkins Assistant Professor Brian Camley, pivoted from traditional testing methods to more accurately observe how moving cells behave when they encounter one another.

Cells have polarity, a north-south orientation, like common magnets. Polarizing helps a cell orient itself correctly with other cells and also establish a leading and trailing edge - the front and the back ends of the cell in motion. As cells move and divide, their polarities change and shift, a product of the motion of molecules within them. Each cell's motion is controlled by protrusions - tentacles that pull each cell along at the leading edge, controlling its motion - and when migrating cells collide, they tend to repel one another, causing their protrusions to contract inward. Cells form new protrusions away from the collision to change direction and go to new places.

This behavior of changing direction after collisions is called contact inhibition of locomotion, and it brings about a change in the cell's poles. After a collision, the trailing edge becomes the leading edge, thus reversing the migration direction.

Since the 1950s, contact inhibition of locomotion has been observed by placing cells in a flat environment, such as a petri dish. This is unlike the setting of a body, however, where cells move along networks of fibers. To bring their observations closer to the natural environment, the team introduced cells onto a single fiber, a kind of cellular "tightrope." In that setting, they found that cell-cell interaction was entirely different than that of a flat surface. Whereas cells collide on a flat surface, they become far more civil when walking along a fiber. When sharing the tightrope, given nowhere to go, cells tended to move past one another.

Of course, a body is made of many fibers, not just one. To further investigate cellular behavior in its natural environment, the team introduced a second, parallel fiber. Cellular behavior changed again: instead of moving past one another, cells would stick together, moving in pairs with one of the cells changing its poles.

Another change occurred when cells divided. After a new cell was formed from a division, called a "daughter cell," they tended to walk past other cells more often in both configurations. The researchers found that daughter cells moved with increased speed, and this was likely a contributor to their ability to move past more often.

The team was able to recreate these behaviors with a simple model that assumed cells crawled along the fibers and reoriented when they came in contact with another cell's front, and that daughter cells moved faster.

"This cocktail of mechanical engineering, cell biology, physics, and computational modeling reveals cell behaviors not known before," said Nain. "Cells and their environments are complex and constantly changing. Our collaborative work adds a twist to the knowledge of contact inhibition of locomotion, first discovered in the 1950s."

According to Camley, knowing this information furthers understanding into why some drugs work differently in a test on a petri dish than in an animal. The difference in flat-surface behavior versus fiber provides insights that could mean the difference between a impacting a cell with a drug or missing it, given a more holistic view of cellular responses.

"Instead of changing our view about the underlying biology, this shows how physical changes in the cell's environment can alter cell-cell interactions," said Camley. "Scientists often want to figure out how drugs can alter cell-cell interactions -- our results show that it's important to study these in as natural an environment as possible because environment plays a huge role."

Energy models are used to explore different options for the development of energy systems in virtual "laboratories". Scientists have been using energy models to provide policy advice for years. As a new study shows, energy models influence policymaking around the energy transition. Similarly, policymakers influence the work of modellers. Greater transparency is needed to ensure that political considerations do not set the agenda for future research or determine its findings, the researchers demand.

Renewable energies bring many changes, including fluctuations in the energy supply and a more geographically distributed generation system. Despite the myriad uncertainties, politicians must make important decisions around the future development of the energy system. Key issues include the choice of technologies and the location of renewable energy infrastructure, the integration of the electricity, heating, transportation and industry sectors, as well as the balancing of interests of diverse stakeholders and population groups. A team of researchers has studied both the role of computer-based energy models in the political decision-making process and, conversely, how policymakers influence energy modelling.

Energy models inform policy decisions that shape our energy future

The researchers analysed a range of documents, including legislative texts, position papers and progress reports as well as secondary literature on political processes. They also conducted 32 interviews with various actors from politics, science, industry, and non-governmental organisations in Germany, Sweden, Poland, Greece and at the European Union level. "The results of this research clearly show that models help to explore possible energy futures. Their influence on policymaking is growing accordingly: politicians draw on modelling outputs to define energy and climate targets and study policy measures to achieve them," says lead author Diana Süsser.

Likewise, policymakers influence modelling, for example by helping to define research questions and the scope of studies, and by deciding how the results will be used. In interviews, however, policymakers suggested that modelling results were often too general for their purposes and left specific questions unanswered. According to these respondents, models lack transparency, which can undermine the credibility of their results. The respondents said that they would like researchers to engage with them more closely so that models could be developed to address the issues relevant to policy development.

Modelling can help to shape the energy transition

This interest in co-creative cooperation is welcome in principle, says Diana Süsser. Energy models are well-suited to tackle real-world issues and achieve societal impacts. "But it is vital that neither side loses sight of the fact that researchers are committed to generating knowledge, rather than to serving political ends. The transformation of the energy system is a complex challenge and, in terms of scientific policy advice, as much as politicians would like one, there is no 'silver bullet'.

Co-author Johan Lilliestam adds: "Models help us to understand the impacts of possible goals and policy options. What our study has shown is that they are sometimes also used to legitimise policy decisions that have already been made. Transparency, open data and open models are essential in order to protect the credibility of models and to improve their utility for policy advice." The IASS project "Sustainable Energy Transitions Laboratory," (SENTINEL) is developing a modelling framework for user-friendly models to improve cooperation between science and politics. Used properly, energy models can play an important role in the development and design of our future energy system and help us to achieve ambitious energy and climate goals.

This release was removed on April 7, 2021. For more information, please contact Carolyn Unck at Carolyn.unck@kaust.edu.sa.