Tech

A research team at Tokyo Medical and Dental University (TMDU) find that Wipi3, a protein involved in cellular waste disposal, is crucial for neuronal health

Tokyo, Japan - A little mess never killed anyone, right? Wrong. Researchers at Tokyo Medical and Dental University (TMDU) have recently shown that a build-up of cellular "trash" in the brain can actually cause neurodegeneration, and even death.

Reporting their findings in Nature Communications, the researchers describe how defects in a cellular waste disposal mechanism, called "alternative autophagy", can lead to a lethal build-up of iron and protein in brain cells.

"Cells are constantly clearing out dysfunctional or unnecessary components, which are then degraded and recycled," explains study lead author Hirofumi Yamaguchi. "Autophagy is the process whereby unwanted cellular components and proteins are contained within a spherical doubled-membraned vesicle called an autophagosome, which fuses with an enzyme-filled lysosome to form an autolysosome. The waste material is then broken down and reused by the cell."

This common form of autophagy, called "canonical autophagy", is well characterized and involves a suite of autophagy-related proteins, such as Atg5 and Atg7. More recently though, several Atg5-independent alternative autophagy pathways have also been described, the biological roles of which remain unclear.

After identifying alternative autophagy-related proteins in yeast, the team at TMDU focused on a mammalian ortholog called "Wipi3", which had previously been implicated in canonical autophagy. "When we deleted Wipi3 in a mouse cell line and induced alternative autophagy, we no longer observed the formation of double-membraned autophagosomes or single-membraned autolysosomes, confirming that Wipi3 is essential for alternative autophagy," says Yamaguchi.

Mice containing a brain-specific deletion of Wipi3 demonstrated growth and motor defects most commonly seen in patients with neurodegeneration, with the researchers also noting an accumulation of iron and the iron-metabolizing protein ceruloplasmin in the brain cells of affected mice.

"Iron deposition has been flagged as a possible trigger in various neurodegenerative disorders, and is usually associated with the abnormal accumulation of iron-binding proteins," explains study senior author Shigeomi Shimizu. "Our findings are strong evidence that alternative autophagy, and Wipi3 specifically, may be essential for preventing this toxic build-up of iron."

Interestingly, although Wipi3-deficient and Atg7 (canonical autophagy)-deficient mice showed similar motor defects, they exhibited very different sub-cellular changes, suggesting that alternative autophagy and canonical autophagy act independently to protect neurons. Supporting this, deletion of both Wipi3 and Atg7 in mice was almost always fatal.

The researchers are hopeful that this research could lead to the development of neuroprotective drugs. Preliminary tests indicate that over-expression of Dram1, another alternative autophagy-associated protein, can reverse the effects of Wipi3 deletion, and may form the basis of future therapies for various neurodegenerative diseases. The article, "Wipi3 is essential for alternative autophagy and its loss causes neurodegeneration," was published in Nature Communications (DOI: 10.1038/s41467-020-18892-w).

A new paper from the University of Melbourne reveals how animals use beautiful but unreliable iridescent colours as communication signals. Special adaptations enable animals to control how these shifting colours appear so that they can convey reliable information.

The new work now published in Trends in Evolution and Ecology draws together studies from across the animal kingdom to discover how animals control the appearance of iridescent colors in nature.

"Iridescence is tricky to study because the hue that you see depends on the position of the viewer and the direction of light," said senior author, Dr Amanda Franklin from the School of BioSciences.

"That means that iridescent colors change constantly, so it's hard to see how they can convey reliable information. The number one rule for communication is that the information must be reliable - it's the same for both animals and humans!"

But paradoxically, iridescent colours, like dazzling butterfly wings or dramatic peacock feathers, are widespread in the natural world.

Co-author and PhD student Leslie Ng explains: "By studying how animals detect and process iridescence, we can get a better idea of when iridescence is actually a useful communication signal.

"Reliable iridescent signals usually come with behavioural or physical adaptations that help animals control the visual effect. For example, male Anna's hummingbirds precisely control their courtship flights so that their iridescent throats appear a constant bright pink colour to watchful females."

Dr Franklin said organisms can do beautiful things with light.

"Through evolution, they have adapted microstructures to produce specific effects. Some use microstructures to control the precise angle at which the hue of iridescent colours appears to shift. In this way, they control the information they communicate with color."

Ms Ng said many studies suggest iridescent colours are important for courtship or camouflage but rarely consider how these flashy signals are actually seen by animals. "Because of this, we know very little about how iridescence is processed in the animal's brain."

The detection of iridescent signals also depends on how organisms display their colour patches, and the physical position of both the signaler and viewer. For example, an iridescent colour can be processed differently if it is flashed quickly, or if the colours are fast-moving.

Lead author, Professor Devi Stuart-Fox, said the insights shed new light on the colourful world of animal communication and highlight the challenges of studying accurately how iridescent colours work in nature.

"Nature provides a testing ground for the detection and processing of dynamic and colourful signals," she said. "Understanding how animals reliably use and produce these shifting signals can help the development of bio-inspired iridescent materials designed for human observers."

Osaka, Japan - A team of researchers at Osaka University has developed a nanopowder shaped like seaweed for a water filter to help remove toxic metal ions (Fig. 1). Made of layered sodium titanate, the randomly oriented nanofibers increase the efficacy of cobalt-II (Co2+) ion capture. This work might lead to cheaper and more effective solutions for filtering water that is currently unusable due to hazardous heavy metals or radioactive fallout.

As the global population continues to increase, so will the need for drinkable water. Sadly, many water sources have become contaminated with heavy metals, such as cobalt, from industrial waste or radioactive runoff. Sodium titanate has been widely used to filter out these toxic substances, but its efficiency is not enough. Sodium titanate is generally a two-dimensional layered material, but its crystal structure can vary based on the chemical composition and preparation method. To effectively capture radioactive and/or heavy metal ions, the morphological control of the sodium titanate is very important.

Now, researchers from the Institute of Scientific and Industrial Research at Osaka University have developed a new method to create highly efficient sodium titanate filters. "We used a template-free alkaline hydrothermal process to produce the mats," first author Yoshifumi Kondo says. The researchers found that increasing the hydrothermal synthesis time caused the initially round crystals to become elongated and fibrous, and to form the seaweed-shaped mats consisting of the randomly oriented nanofibers (Fig. 2). This seaweed-like nanoscale morphology increased the surface area of the mats, which improved the removal efficiency of Co2+ during sorption tests.

"Due to the progress of global warming and serious environmental pollution, the need for safe ways to remove radioactive materials and heavy metals from water resources has become even more critical," senior author Tomoyo Goto says. Compared with a commercially available material, the nanostructured sodium titanate mats showed improved performance for capturing Co2+ ions. The method is expected to be applied for other purification systems that remove heavy metals and radionuclides from wastewater (Fig. 3).

The term leukaemia is used to describe a group of malignant diseases of the haematopoietic system, in which precursors of the white blood cells (leucocytes) proliferate uncontrollably. Chemotherapy and radiotherapy are used to destroy the abnormal blood cells, which are then replaced by means of a stem cell transplant. In leukaemia, the transplantation of healthy bone marrow stem cells or haematopoietic stem cells is often the only hope of recovery for patients. The process involves "replacing" all the recipient's blood cells that were previously destroyed by the treatment with donor cells.

However, the MedUni Vienna dermatologists have now found that there are so-called skin-resident and inactive T cells in the endogenous immune system that survive chemotherapy and radiotherapy intact and go on to survive for a further ten years between and beneath the epithelial cells of the skin, while the circulating T cells are destroyed.

"We were able to demonstrate that T cells surviving in the skin tissue are responsible for the inflammatory reaction following a stem cell transplant. These phenomena often occur within the first 100 days and can cause anything from mild eczema through to extensive fibrosis, hardening of the tissue, or blistering on the surface of the skin. In other words, the endogenous T cells attack the recipient (host) following stem cell transplantation." In specialist jargon, the condition is also referred to as Graft versus Host Disease (GvHD), and, for the first time, this study identified an inverse "Host-versus-graft reaction".

There were also cases in which the donor T cells further "supported", and thus intensified, this reaction. Affected patients are treated with cortisone, which causes an additional burden for patients who are already immunosuppressed following the transplantation. The study found that in patients who do not develop graft-versus-host disease, tissue-resident T cells remaining after treatment even proved to be beneficial to the recipient, in that they assumed their role in immune defence and protecting against infection.

In the future, the exemplary study results could lead to new treatment strategies that help to avoid, or at least to minimise, undesirable and violent inflammatory reactions following stem cell transplants by manipulating the recipient's inactive T cells in advance. In addition, the manipulation of tissue-resident T cells might lead to new therapeutic approaches for other chronic inflammatory skin diseases, such as psoriasis or neurodermatitis.

Although it might seem like it, Norway's oil history did not begin with the first major discovery at the Ekofisk field in 1969 by Phillips Petroleum Co. It didn't even begin with the Balder discovery a couple of years earlier, or Norway's claim to large areas in the North Sea in 1963.

A better place to look for a kind of beginning is the end of the 19th century. The story involves one of the richest men of all time, John D. Rockefeller, and his giant company Standard Oil.

It's also the story of how governments in small countries struggle to fight economic giants.

"In the first phase starting in 1890, the Norwegian, Swedish and Danish oil markets were dominated by the large global oil company Standard Oil, which didn't hold back from using rather heavy-handed tactics to control the market," says Professor Espen Storli at the Norwegian University of Science and Technology's (NTNU) Department of Modern History and Society.

This part of Norwegian and Scandinavian oil history has not been studied much so far, but Storli and his colleague Professor Pål Thonstad Sandvik address the period in a recently published article in the Scandinavian Economic History Review.

"Standard Oil's approach is a typical example of how large companies try to gain advantages and monopolies by utilizing their financial power and taking control of the value chains," Sandvik says.

In terms of money, both Standard Oil and the company's famous owner, John D. Rockefeller, had more than enough.

If you don't include royalty and dictators who ruled whole countries, Rockefeller stands out as perhaps the richest person in history. He became the first billionaire in the United States, at a time when an ordinary industrial worker had an annual salary of about US $500. Relatively speaking, Rockefeller was far richer than Amazon's Jeff Bezos, the world's richest living person today.

Ron Chernow's writes the following about Rockefeller in his biography about him:

"He could be extraordinarily violent when he wanted to force competitors to submit. But at the same time he did not exert this pressure casually, and where possible, preferred patience and argumentation rather than intimidation."

Rockefeller's wealth came largely from his oil company Standard Oil, which he helped start in 1870. Through ingenuity, cunning, acquisitions and a not-so-little use of muscle, the company became completely dominant in the national and global oil sector. Eventually, this applied to all parts of the value chain.

At the beginning of the last century, few European countries had known petroleum reserves. In Norway, oil companies therefore competed most for access to the sale of products like kerosene and petrol, and not for extraction rights or other parts of the value chain.

"Product sales are also where the oil companies collide most directly. The need for regulation quickly became clear to the authorities," says Sandvik.

But this task was far from easy for inexperienced politicians and officials. The opponent used varied tactics and had much more experience and money.

In Scandinavia, Standard Oil used the company Det Danske Petroleums Aktieselskab (DDPA) as a pawn. Standard Oil bought into DDPA as early as 1891, and later owned half of the shares.

In practice, DDPA became a subdivision of Standard Oil, because the management in Denmark had to consult with the American company in all important decisions.

The Danes already had a solid position in Scandinavia before Standard Oil came in, but only with American money did things really turn around. Sometimes the methods were ingenious.

For example, DDPA had long-term contracts with sellers of petroleum products. These sellers were not allowed to sell products from suppliers other than DDPA. If the sellers broke these contracts, they had to pay large fines, not to DDPA, but to local charities. This was probably a wise strategy, because protesting against a company that appeared to be running a charity was more difficult.

DDPA and Standard Oil eventually succeeded in taking over large parts of the market, but they never secured a complete monopoly. Actors such as the Europäische Petroleum Union and Pure Oil gave them solid competition at times, even if they were proportionally much smaller companies.

Standard Oil's dominant position gradually became a concern for more than just the authorities and competitors.

"The debate about Standard Oil gradually grew, but it wasn't easy for the authorities to do anything given the company's power. For small countries with limited resources, it was difficult to respond to cartel activities and cooperation between companies that exploited their position in the oil market," says Storli.

But the company wasn't able to hold its position without Norwegian politicians being fully involved.

"Standard Oil's grip on the Scandinavian oil market gradually weakened due to competing companies," Sandvik says.

This was partly due to the fact that the company could not continue operating in the same way following a court decision in the USA.

Standard Oil grew too large, and in 1911 the Supreme Court of the United States had had enough. The court sought to dissolve the company because it had used illegal methods to gain a monopoly-like power over the US oil market. Standard Oil was then split into 34 different companies.

Standard Oil's successors were also big in Scandinavia until 1939, if not as dominant as before. Some of the companies that stemmed from this split are still among the world's largest, such as Amoco, ExxonMobil, Marathon and Chevron.

Rockefeller himself gradually withdrew from business life starting in 1896 and eventually concentrated mostly on philanthropic activities. He died in 1937, almost 98 years old.

The effects of the strong oil dominance at that time are possible to observe even today.

"The oil companies' abuse of market power was exactly what Norwegian politicians wanted to avoid. This basis of experience was important when Norway's parliament passed strict competition legislation and comprehensive regulation of Norwegian natural resources such as hydropower, forests and minerals," says Sandvik.

These regulations would come in handy a few decades later, when Norway itself proved to be sitting on large petroleum riches. Unlike many other countries, the country has largely managed to retain large parts of these riches, to a great extent because the Norwegian authorities already had extensive experience in regulating natural resources.

"Norwegian politicians and bureaucrats were well informed about the phenomenon of market power in the oil industry. This affected how they related to the large foreign oil companies in both the 1960s and 1970s," Storli says.

"Of course, it's always difficult to say where politicians and officials draw their perception of reality from, but it isn't surprising that domestic experiences have been an important factor," he says.

A team of palaeontologists described two amber pieces found in sites in Teruel (Spain) with remains from vertebrates corresponding to the Early Cretaceous. Both pieces have their origins in the same conservation process of resins, described for the first time by the researchers. One of these remains corresponds to the finding of the oldest mammalian hair in amber worldwide, and the remains found in the other piece correspond to dinosaur feathers.

The team, whose results have been published in the journal Scientific Reports, is formed by SergioÁlvarez Parra and Xavier Delclòs, both from the University of Barcelona; Mónica M. Solórzano Kraemer, from the Senckenberg Natural History Museum (Frankfurt, Germany); Luis Alcalá, from Dinópolis (Teruel), and Enrique Peñalver, from the Geological and Minning Institute of Spain (Valencia).

The origin of both pieces is in the resin formed about 105 and 110 million years ago, corresponding to the Early Cretaceous. The cretaceous sites of amber are abundant in the Iberian Peninsula, and its study has provided many findings of global relevance. In particular, Teruel province has many of these sites.

Dinosaur feathers and mammalian hair

One of the pieces was found years ago in the amber site in Sant Just, in Utrillas, and another in Ariñi, in the Santa María mine, both in Teruel. The piece from Sant Just includes remains of dinosaur feathers distributed in the convex surface of amber with a stalactite shape.

The amber from Ariño presents three mammalian hairs with its characteristic microscopic scale pattern, exceptionally preserved. The parallel disposition of the three hairs and their similar proportions allow researchers to identify it as a small lock from a mammal and it corresponds to the oldest finding of hair in amber. "The determination of both findings is very complex, but it is likely for the feather remains to correspond to the extinct birds Enantiornithes, like other feathers in amber. Regarding the lock of hair, we should consider that the surface scale pattern is similar to the current mammalian hair", notes Sergio Álvarez, researcher at the UB and first author of the study. "Ariño was already known for its vertebrate fossils, such as the dinosaurs

Proa valdearinnoensis and Europelta carbonensis, but no-one thought we could find remains from vertebrates included in amber", adds Álvarez.

A new conservation process for resin

In the study, the researchers described for the first time a process they call "pull off vestiture", through which small portions of the feather and fur of a living being are trapped after being in contact with a sticky mass of resin, the necessary amount of time for it to harden.

The dinosaur and the mammal to which the feathers and the lock of hair correspond, respectively, from the studied amber pieces taht were in contact with resin while they were resting or sleeping in or near a tree. Later, with movement, these epidermal structures were torn off. When the resin hardens, the entire structures are removed, but the closer portions are not covered by the resin and are not preserved.

A similar but not identical process has been observed in sticky traps that three of the researchers installed on resin trees in Madagascar. These traps also retained hairs from mammals that touched them although, due to their high stickiness, they quickly ripped them off at minimal contact. "The feature of the process described in this research is that a somewhat long time must pass between the animal's contact with the resin and the pulling off of the vestiture", points out Xavier Delclòs, professor at the Faculty of Earth Sciences and member of the Biodiversity Research Institute (IRBio) of the UB. "Thus, the findings of this study and the new process shed light on the complexity of ecosystems during the Cretaceous," concludes the researcher.

Both amber pieces in the study are in the Palaeontological Museum of Aragon (Fundación Conjunto Paleontológico de Teruel - Dinópolis) and both add more value to the large palaeontological heritage of the province of Teruel.

ABERDEEN PROVING GROUND, Md. -- Scientists from the U.S. Army and MIT's Center for Bits and Atoms created a new way to link materials with unique mechanical properties, opening up the possibility of future military robots made of robots.

The method unifies the construction of varying types of mechanical metamaterials using a discrete lattice, or Lego-like, system, enabling the design of modular materials with properties tailored to their application. These building blocks, and their resulting materials, could lead to dynamic structures that can reconfigure on their own; for example, a swarm of robots could form a bridge to allow troops to cross a river. . This capability would enhance military maneuverability and survivability of warfighters and equipment, researchers said.

These findings, which researchers published in the Science Advances cover story are an example of high-risk exploratory science and technology efforts from the U.S. Army Combat Capabilities Development Command's Army Research Laboratory, said Dr. Bryan Glaz, associate chief scientist in the laboratory's Vehicle Technology Directorate.

Motivated in part by swarms of tiny robots that link together to form any imaginable structure like in the animated movie Big Hero 6, these metamaterials may also enable future high-performance robotics and impact/blast absorbing structures, Glaz said.

Futuristic visions from concept developers with the Army Future Command's Futures and Concepts Center at Fort Eustis, Virginia, directly motivated this work, Glaz said. Researcher pursued this research based on discussions and concepts supported by The U.S. Army Functional Concept for Movement and Maneuver, which describes how Army maneuver forces could generate overmatch across all domains.

The doctrine lays out a series of objectives in the Army S&T investment area for ground combat; one is to develop individual systems capable of 4D transformation, which has the ability to change the system's shape, modality and function. For example, a swarm of unmanned systems will be capable of moving to an obstacle, such as a river, and then forming a structure to span the gap.

Glaz said researchers started out trying to build a bridge made of robots to support this vision, but the work has since evolved into mobile robots made of robots.

"Robots rearranging to form a bridge made of robots, similar to ants, is one embodiment of our concept of structural robotics, which blur the line between active and passive elements and feature reconfigurability. It is still a motivating use case for the system, but we are looking at broader implications for ground robotics which are adaptable, reconfigurable, and resilient," said Dr. Christopher Cameron, an Army researcher. "If a swarm of robots can turn themselves into a bridge, how else can they be rearranged? How do we design and control robots like this?"

The paper addresses the design of modular structures and introduces a system which will enable the Army to build a variety of robots with unique properties like impact energy absorption. The materials researchers designed demonstrated a range of surprising and useful properties including extreme stiffness, toughness and unique couplings between displacement and rotation.

The system, based on cost-effective injection molding and discrete lattice connections, enables rapid assembly of macro-scale structures which may combine characteristics of any of the four base material types: stiff; compliant; auxetic, or materials that when stretched become thicker perpendicular to the applied force; and chiral, or materials that are asymmetric in such a way that the structure and its mirror image cannot be easily viewed when superimposed. The resulting macro-architected materials can be used to build at scales orders of magnitude larger than achievable with traditional metamaterial manufacturing at a fraction of the cost.

The research is a product the ARL Northeast extended site, where Cameron is embedded in tight collaboration with researchers at MIT. Army researchers contributed expertise in large-scale finite element simulation to complement experimental observations, Cameron said.

The next phases of the research will explore the design space created by the system with target applications including modular soft robotics, impact absorbing structures, and rapid construction at the point of demand. Cameron said researchers also want to investigate how traditional, additively manufactured metamaterials might be integrated with this system to create large-scale hierarchical metamaterials, combining strengths across scales.

"This part of our high risk, exploratory research portfolio within the Vehicle Technology Directorate," Glaz said. "In a couple of years we may find there is no major Army advantage to robots-made-robots but right now, we've thought of early Army applications such as rapidly forming bridges as well as air dropping or launching a bunch of smaller robots into a contested area and to test how they come together to form a larger mobile platform that can do useful functions in the aggregated phase."

Researchers from MIPT and the RAS Institute of Problems of Chemical Physics have proposed a simple and convenient way to obtain arbitrarily sized quantum dots required for physical experiments via chemical aging. The study was published in Materials Today Chemistry.

Colloidal quantum dots are nanosized crystals whose size determines the frequency at which they emit and absorb electromagnetic radiation. They are used in solar cells, TV sets, fire alarm systems, and more.

The MIPT Laboratory for Photonics of Quantum Nanostructures conducts research using lead sulfide quantum dots. The conventional approach to their synthesis, known as hot injection, involves mixing two so-called precursors -- compounds containing lead and sulfur -- under particular conditions. This process is controlled using special reagents and equipment to create quantum dots of desired size. However, the synthesis is complex, costly, and it does not yield dots of all requisite sizes.

"If a physicist needed some quantum dots but had no equipment to manufacture them, they used to spend quite a lot of money to commission synthesis or order the products from abroad through a catalog. And you could not buy dots of arbitrary size," said Ivan Shuklov, deputy head of the MIPT Laboratory for Photonics of Quantum Nanostructures. "So we searched for a simple and affordable way to obtain lead sulfide quantum dots that would not require any specialized equipment or skills and would produce dots of any size and therefore precisely the properties needed."

Experimenting with various compounds, the researchers found the quantum dot spectrum to change in the presence of a mixture of oleic acid and oleylamine. Electron microscopy afforded a closer look at what was going on, showing that mixture of the two chemicals to actually reverse the standard synthesis, causing sulfur and lead atoms to retreat back into the solution, gradually reducing dot size. More importantly, the dot size distribution remained the same. In other words, you get basically the same dots you had before introducing the mixture, just that they get smaller and therefore alter their properties.

The standard approach to synthesizing quantum dots also employs oleic acid and oleylamine, but the chemicals are used at different stages. It is their simultaneous application and mutual interaction that turned out to enable controlled crystal aging. That is, the predictable long-term change in crystal properties over time.

"We have proposed a solution that allows an experimenter who has 10-nanometer quantum dots to predictably reduce them to 8 nanometers tomorrow, to 6 nanometers the day after that, and so on. Accordingly, the absorption frequency will change from 2 micrometers to 1.8 micrometers the first time and then to 1.5 micrometers," explained Vladimir Razumov, the head of the Laboratory for Photonics of Quantum Nanostructures at MIPT. "Basically, from one batch of generic colloidal quantum dots, you can produce those with precisely the right size and properties for your needs. With our technique, a physicist with no special equipment other than some test tubes can convert one sample of quantum dots into any size. All it takes is waiting for the dots to 'age' to the appropriate size."

Using x-ray lasers, researchers at Stockholm University have been able to follow the transformation between two distinct different liquid states of water, both being made of H2O molecules. At around -63 Centigrade the two liquids exist at different pressure regimes with a density difference of 20%. By rapidly varying the pressure before the sample could freeze, it was possible to observe one liquid changing into the other in real time. Their findings are published in the journal Science.

Water, both common and necessary for life on Earth, behaves very strangely in comparison with other substances. How water's properties such as density, specific heat, viscosity and compressibility respond to changes in pressure and temperature is completely opposite to other liquids that we know. Consequently, water is often called "anomalous". If water would have behaved as a "normal liquid" we would not exist, since marine life could not have developed. However, it is still an open question: what causes these anomalies?

There have existed a number of explanations to the strange properties of water and one of them propose that water has the ability to exist as two different liquids at different pressures and at low temperatures. If we would be able to keep the two liquids in a glass they would separate with a clear interface in between, as for water and oil (see figure). Ordinary water at our ambient conditions is only one liquid and no interface would be seen in a glass - but on a molecular level, it fluctuates creating small local regions of similar density as the two liquids, causing water's strange behaviour. The challenge has been that no experiment has been possible at the temperatures where the two liquids would co-exist since ice would form almost instantaneously. Up to now it has only been possible to investigate water at these conditions using different types of computer simulations, which has led to a lot of contradicting results depending on the model used.

"What was special was that we were able to X-ray unimaginably fast, before the water froze, and could observe how one liquid transformed to the other", says Anders Nilsson, Professor of Chemical Physics at Stockholm University. "For decades, there has been speculations and different theories to explain these anomalous properties and why they get stronger when water becomes colder. Now we have found that the two liquid states are real and can explain the water strangeness."

"I have studied several forms of disordered ices for a long time with the goal to determine whether they can be considered a glassy state representing a frozen liquid", says Katrin Amann-Winkel, Senior Researcher in Chemical Physics at Stockholm University. "It is a dream come true to see that indeed they represent real liquids and we see the transformation between them".

"We worked so hard for several years to conduct measurements of water under such low temperature conditions without freezing and it is so rewarding to see the outcome", says Harshad Pathak, Researcher in Chemical Physics at Stockholm University. "Many attempts over the world have been made to look for the two liquids by putting water in tiny compartments or mixing it with other compounds but here we could follow it as simple pure water".

"I wonder if the two liquid states as fluctuations could be an important ingredient to the biological processes in living cells", says Fivos Perakis, Assistant Professor in Chemical Physics at Stockholm University. "The new result can open up many new research directions also about water in biological sciences".

"Maybe one of the liquid forms is more prominent for water in small pores inside membranes used to desalinate water", says Marjorie Ladd Parada, Postdoc at Stockholm University. "I think the access to clean water will be one of the major challenges with climate change."

"There has been an intense debate about the origin of the strange properties of water for over a century since the early work of Wolfgang Röntgen", further explains Anders Nilsson. "Researchers studying the physics of water can now settle on the model that water can exist as two liquids in the supercooled regime. The next stage is to find if there is a critical point when the two liquids cross over to become only one liquid, as the pressure and temperature changes. A big challenge for the next few years."

Hydrogen can be produced with renewable energies in a climate neutral way and could make a major contribution to the energy system of the future. One of the options is to use sunlight for electrolytic water splitting, either indirectly by coupling a solar cell with an electrolyser or directly in a photoelectrochemical (PEC) cell. Light-absorbing semiconductors serve as photoelectrodes. They are immersed in an electrolyte solution of water mixed with strong acids or bases, which contains high concentration of protons or hydroxide ions necessary for efficient electrolysis.

However, in a large-scale plant, it would make sense for safety reasons to use an electrolyte solution with a near-neutral pH. Such a solution has a low concentration of protons and hydroxide ions, which leads to mass-transport limitations and poor performance. Understanding these limitations is essential to design a safe and scalable PEC water splitting device.

A team led by Dr. Fatwa Abdi from the HZB Institute for Solar Fuels has now for the first time investigated how the liquid electrolyte throughout the cell behaves during electrolysis: With the help of fluorescent pH-sensor foils, Dr. Keisuke Obata, a postdoc in Abdi's team, determined the local pH value in PEC cells between the anode and cathode during the course of electrolysis. The PEC cells were filled with near-neutral pH electrolytes. The scientists experimentally visualized the decrease of pH at regions close to the anode and the increase of pH at regions close to the cathode. Interestingly, they observed a clock-wise motion of the electrolyte as the electrolysis proceeds. The observation can be explained by buoyancy due to changes of electrolyte density during the electrochemical reaction which leads to convection. "It was surprising to see that tiny changes in electrolyte density (~0.1%) cause this buoyancy effect," says Abdi.

In parallel, Abdi and his team developed a multiphysics model to calculate the convection induced by electrochemical reactions. "We have thoroughly tested this model and can provide now a powerful tool to simulate natural convection in an electrochemical cell with various electrolytes in advance," says Abdi.

For the project Abdi has built up a "Solar Fuel Devices Facility" at HZB, which is part of the Helmholtz Energy Materials Foundry (HEMF), a big infrastructure open to other scientists as well. This study was also performed in collaboration with TU Berlin, within the framework of UniSysCat cluster of excellence.

"With this work we are expanding our materials science expertise with efforts on photoelectrochemical reactor engineering, which is an essential next step for the scale-up of solar fuel devices" says Prof. Dr. Roel van de Krol, who heads the HZB Institute for Solar Fuels.

Staphylococcus aureus (which includes MRSA) is the most prevalent organism isolated from the airways of children with cystic fibrosis (CF), and is treated using antibiotics, but its role in lung disease is poorly understood

Using pig lungs from a butcher and synthetic mucus, researchers from the University of Warwick have shown that S. aureus preferentially colonises mucus, rather than the lung tissue

This sparks an investigation into the best ways to treat S. aureus in patients with Cystic Fibrosis, and in the future could lead to fewer antibiotics being used

For young people with cystic fibrosis, lung infection with Staphylococcus aureus, MRSA, is common and is treated with antibiotics in the hope that this will prevent a decline in lung function. However there has recently been debate over the role S. aureus plays in CF lung disease. Researchers from the University of Warwick have used a new model of CF lungs which could be used to make better decisions about future use of antibiotics.

S. aureus is commonly found on the skin of healthy people, it can cause lung infection and abscess, and is often present in the mucus and sputum of children with cystic fibrosis. When S. aureus - including the antibiotic-resistant form, MRSA - is found in people with CF, it is treated with antibiotics, but exactly how S. aureus affects the lungs in people with this condition is unknown.

Previous research models have often looked at S. aureus in the lungs of mice, however when S. aureus is infected into mouse lungs, abscesses form and abscess are extremely rare in people with CF. In the paper 'An ex vivo cystic fibrosis model recapitulates key clinical aspects of chronic Staphylococcus aureus infection', published in the journal Microbiology, researchers from the School of Life Sciences at the University of Warwick, have found that using left over pig lungs from a butcher, and synthetic mucus that mimics CF lung secretions, that S. aureus tends to aggregate in mucus, not invade the lung tissue as it does in mice.

To see if they could find a better way to mimic human CF lungs, and decrease the use of animal testing, the researchers used pig lungs from a butcher, and adding synthetic CF mucus. They then introduced the S. aureus and found that it tended to aggregate in the mucus, rather than invading the lung tissue as would happen with an abscess.

Due to the lack of knowledge of how S. aureus affects the lungs of children with Cystic Fibrosis they tend to be treated with antibiotics, although this often does not alleviate symptoms of lung disease and there has been a debate into if antibiotics are the best treatment. This research led by the University of Warwick paves the way for new treatments for S. aureus in CF to be explored.

Dr Esther Sweeney, from the School of Life Sciences at the University of Warwick comments:

"The model we have used with pig lung has shown that S.aureus preferentially grows within mucus. We think this potentially represents the clinical situation for people with CF better than historical research models and our model could be used to further investigate the best ways of treating MRSA infection associated with cystic fibrosis. In future this may help to reduce inappropriate use of antibiotics."

Dr Freya Harrison, from the School of Life Sciences at the University of Warwick adds:

"Knowing how exactly how the lungs are affected by different bacteria is key to treating infection efficiently. We need to know which bacteria do the most damage, and how best to target them to get rid of them. We decided to make a new model using a pig lung, rather than mice, because pig lungs are more similar to human lungs, and we can combine them with artificial CF mucus. We think this makes bacteria behave more like they would in the lungs of a person with CF."

CAMBRIDGE, MA -- When someone struggles to open a lock with a key that doesn't quite seem to work, sometimes jiggling the key a bit will help. Now, new research from MIT suggests that coronaviruses, including the one that causes Covid-19, may use a similar method to trick cells into letting the viruses inside. The findings could be useful for determining how dangerous different strains or mutations of coronaviruses may be, and might point to a new approach for developing treatments.

Studies of how spike proteins, which give coronaviruses their distinct crown-like appearance, interact with human cells typically involve biochemical mechanisms, but for this study the researchers took a different approach. Using atomistic simulations, they looked at the mechanical aspects of how the spike proteins move, change shape, and vibrate. The results indicate that these vibrational motions could account for a strategy that coronaviruses use, which can trick a locking mechanism on the cell's surface into letting the virus through the cell wall so it can hijack the cell's reproductive mechanisms.

The team found a strong direct relationship between the rate and intensity of the spikes' vibrations and how readily the virus could penetrate the cell. They also found an opposite relationship with the fatality rate of a given coronavirus. Because this method is based on understanding the detailed molecular structure of these proteins, the researchers say it could be used to screen emerging coronaviruses or new mutations of Covid-19, to quickly assess their potential risk.

The findings, by MIT professor of civil and environmental engineering Markus Buehler and graduate student Yiwen Hu, are being published today in the print edition of the journal Matter after being posted online on October 30.

All the images we see of the SARS-CoV-2 virus are a bit misleading, according to Buehler.

"The virus doesn't look like that," he says, because in reality all matter down at the nanometer scale of atoms, molecules, and viruses "is continuously moving and vibrating. They don't really look like those images in a chemistry book or a website."

Buehler's lab specializes in atom-by-atom simulation of biological molecules and their behavior. As soon as Covid-19 appeared and information about the virus' protein composition became available, Buehler and Hu, a doctoral student in mechanical engineering, swung into action to see if the mechanical properties of the proteins played a role in their interaction with the human body.

The tiny nanoscale vibrations and shape changes of these protein molecules are extremely difficult to observe experimentally, so atomistic simulations are useful in understanding what is taking place. The researchers applied this technique to look at a crucial step in infection, when a virus particle with its protein spikes attaches to a human cell receptor called the ACE2 receptor. Once these spikes bind with the receptor, that unlocks a channel that allows the virus to penetrate the cell.

That binding mechanism between the proteins and the receptors works something like a lock and key, and that's why the vibrations matter, according to Buehler. "If it's static, it just either fits or it doesn't fit," he says. But the protein spikes are not static; "they're vibrating and continuously changing their shape slightly, and that's important. Keys are static, they don't change shape, but what if you had a key that's continuously changing its shape -- it's vibrating, it's moving, it's morphing slightly? They're going to fit differently depending on how they look at the moment when we put the key in the lock."

The more the "key" can change, the researchers reason, the likelier it is to find a fit.

Buehler and Hu modeled the vibrational characteristics of these protein molecules and their interactions, using analytical tools such as "normal mode analysis." This method is used to study the way vibrations develop and propagate, by modeling the atoms as point masses connected to each other by springs that represent the various forces acting between them.

They found that differences in vibrational characteristics correlate strongly with the different rates of infectivity and lethality of different kinds of coronaviruses, taken from a global database of confirmed case numbers and case fatality rates. The viruses studied included SARS-CoV, MERS-CoV, SATS-CoV-2, and of one known mutation of the SARS-CoV-2 virus that is becoming increasingly prevalent around the world. This makes this method a promising tool for predicting the potential risks from new coronaviruses that emerge, as they likely will, Buehler says.

In all the cases they have studied, Hu says, a crucial part of the process is fluctuations in an upward swing of one branch of the protein molecule, which helps make it accessible to bind to the receptor. "That movement is of significant functional importance," she says. Another key indicator has to do with the ratio between two different vibrational motions in the molecule. "We find that these two factors show a direct relationship to the epidemiological data, the virus infectivity and also the virus lethality," she says.

The correlations they found mean that when new viruses or new mutations of existing ones appear, "you could screen them from a purely mechanical side," Hu says. "You can just look at the fluctuations of these spike proteins and find out how they may act on the epidemiological side, like how infectious and how serious would the disease be."

Potentially, these findings could also provide a new avenue for research on possible treatments for Covid-19 and other coronavirus diseases, Buehler says, speculating that it might be possible to find a molecule that would bind to the spike proteins in a way that would stiffen them and limit their vibrations. Another approach might be to induce opposite vibrations to cancel out the natural ones in the spikes, similarly to the way noise-canceling headphones suppress unwanted sounds.

As biologists learn more about the various kinds of mutations taking place in coronaviruses, and identify which areas of the genomes are most subject to change, this methodology could also be used predictively, Buehler says. The most likely kinds of mutations to emerge could all be simulated, and those that have the most dangerous potential could be flagged so that the world could be alerted to watch for any signs of the actual emergence of those particular strains. Buehler adds, "The G614 mutation, for instance, that is currently dominating the Covid-19 spread around the world, is predicted to be slightly more infectious, according to our findings, and slightly less lethal."

SALT LAKE CITY - Utah scientists have discovered new functions of a key cellular machine that regulates gene packaging and is mutated in 20% of human cancers. The study was published in print today in the journal Molecular Cell.

Genes are segments of cellular DNA, and gene packaging is called chromatin. Genes are tightly packaged when they are not activated and then unpackaged by chromatin remodeling machines when genes need to be turned on. Mutations in chromatin regulating machines are a significant driver of cancer and other human diseases, as the mutant chromatin regulators improperly unpackage and express genes, which disrupts normal cell growth, identity, and development.

Chromatin remodeling machines have been a longstanding focus of Brad Cairns, PhD, study lead author, who discovered the first chromatin remodeling machine in 1996. Cairns is a scientist at Huntsman Cancer Institute (HCI) and professor and chair of oncological sciences at the University of Utah (U of U). The Cairns Lab works to understand how chromatin impacts gene expression in humans and other organisms and provides instructions for cell growth, identity, and development. An important aspect of this work is better understanding the role of chromatin in cancer and other diseases.

The major component of chromatin is nucleosomes, which are similar to beads upon which DNA is wrapped like a string, explaining why chromosomes look like beads on a string under a powerful microscope. Cairns and colleagues wanted to know how these beads are moved along or removed from the DNA to unpackage and expose genes. Previous work showed that chromatin remodeling machines have a motor-like component that drives the machine along the DNA, disrupting the nucleosome beads. The fuel for the cellular motor is called ATP, a chemical produced in cells. When properly regulated, the motor ensures that the right genes are properly unpackaged. However, when the motor is misregulated, the wrong genes are unpackaged--and cancer or improper development results.

Cairns's team wanted to understand how the motor of the machine is regulated. "These really are machines: they contain a 'gas pedal' and a 'clutch' that together control whether and how the motor moves the machine along the DNA. This new paper shows the gas pedal and clutch sit right on the motor, and the cancer-causing mutations localize to the clutch and gas pedal itself, making the motor hyperactive and unpackaging genes when it should not." The work reveals how factors in the cell can activate the machine to do its work at the right place and time.

Cairns and his colleagues used data on mutations in human tumors from the COSMIC cancer database, the largest cancer genomics database in the world, in order to study the human chromatin remodeling machine called BAF/PBAF. BAF/PBAF is mutated in 20% of all human tumors, including pancreatic cancer, gastric cancer, and melanoma. They studied these human mutations using yeast as a model system. This analysis revealed a structural hub that tells the motor when to engage (the clutch) and how fast to run along the DNA (the gas pedal), move nucleosomes, and open up genes for their activation. Notably, the team found a series of cancer mutations in an area of the hub that regulates the motor activity and thus ensures proper movement or removal of nucleosomes and proper gene expression. These mutations in the regulatory hub of the motor created a hyperactive and dysregulated motor that improperly opens up chromatin. The team's findings shed light on a key regulatory behavior of healthy cells and explain how a set of cancer-causing mutations promote cancer.

BINGHAMTON, NY -- Emergencies, by their very nature, are hard to predict. When and where the next crime, fire or vehicle accident will happen is often a matter of random chance.

What can be measured, however, is how long it takes for emergency services personnel to consider a particular incident to be resolved -- for instance, suspects apprehended, flames extinguished or damaged cars removed from the street.

New York City is among the large urban areas that maintain those kinds of statistics, and a team of researchers at Binghamton University, State University of New York has used deep-learning techniques to analyze the numbers and suggest improved public safety through re-allocation of resources.

Arti Ramesh and Anand Seetharam -- both assistant professors in the Department of Computer Science at the Thomas J. Watson College of Engineering and Applied Science -- worked with PhD students Gissella Bejarano, MS '17, and Adita Kulkarni, MS '17 (who earned her doctorate earlier this year), and master's student Xianzhi Luo to develop DeepER, an encoder-decoder sequence-to-sequence model that uses Recurrent Neural Networks (RNNs) as the neural network architecture.

The research utilized 10 years of publicly available data from New York City's five boroughs, broken down by categories and subcategories reflecting the types of emergencies as well as the time between when the incident was reported and when it "closed."

"Multiple events can occur at the same time, and we would expect the timetable to resolve those incidents to be longer because the personnel, resources and equipment are going to be shared across the incident sites," Seetharam said. "That is reflected in the resolution times. Then we use that to predict what's going to happen in the future."

This latest study builds on previous research looking at similar data for non-emergency events -- essentially all of the 311 calls throughout New York City.

"The differences between the two sets of data are that emergency incidents are fewer in number, and non-emergency incidents are a little more predictable," Seetharam said.

"Emergency incidents are harder to predict, such as when a fire is going to start or the nature of that fire. The resolution time would depend on how big the fire is. Non-emergency incidents are more predictable. A streetlight is not working, a repair technician is sent, and it gets fixed."

The research team believes that DeepER could be tweaked for other large cities such as Los Angeles and Chicago, or possibly a cluster of smaller cities with similar characteristics that would provide enough data to make predictions.

"You need to understand the characteristics of that particular city," Seetharam said. "For instance, Los Angeles may have fewer incidents related to structural problems during winter because they do not see snow. That could be a different set of incidents.

"The only practical difficulty would be how they collect their data and how they label their data. If similar incidents are labeled in the same way, we can train the model on these other numbers."

Ethereal, swaying pillars of brown kelp along California's coasts grow up through the water column, culminating in a dense surface canopy of thick fronds that provide homes and refuge for numerous marine creatures. There's speculation that these giant algae may protect coastal ecosystems by helping alleviate acidification caused by too much atmospheric carbon being absorbed by the seas.

A new on-site, interdisciplinary analysis of giant kelp in Monterey Bay off the coast of California sought to further investigate kelp's acidification mitigation potential. "We talk about kelp forests protecting the coastal environment from ocean acidification, but under what circumstances is that true and to what extent?" said study team member Heidi Hirsh, a PhD student at Stanford's School of Earth, Energy & Environmental Sciences (Stanford Earth). "These kinds of questions are important to investigate before trying to implement this as an ocean acidification mitigation strategy."

The team's findings, published on Oct. 22 in the journal JGR Oceans, show that near the ocean's surface, the water's pH was slightly higher, or less acidic, suggesting the kelp canopy does reduce acidity. However, those effects did not extend to the ocean floor, where sensitive cold-water corals, urchins and shellfish dwell and the most acidification has occurred.

"One of the main takeaways for me is the limitation of the potential benefits from kelp productivity," said Hirsh, the lead author on the study.

Why kelp?

Kelp is an ecologically and economically important foundation species in California, where forests line nutrient-rich, rocky bottom coasts. One of the detrimental impacts of increased carbon in the atmosphere is its subsequent absorption by the planet's oceans, which causes acidification - a chemical imbalance that can negatively impact the overall health of marine ecosystems, including animals people depend on for food.

Kelp has been targeted as a potentially ameliorating species in part because of its speedy growth - up to 5 inches per day - during which it undergoes a large amount of photosynthesis that produces oxygen and removes carbon dioxide from the water. In Monterey Bay, the effects of giant kelp are also influenced by seasonal upwelling, when deep, nutrient-rich, highly acidic water from the Pacific is pulled toward the surface of the bay.

"It's this very complicated story of disentangling where the benefit is coming from - if there is a benefit - and assessing it on a site-by-site basis, because the conditions that we observe in southern Monterey Bay may not apply to other kelp forests," Hirsh said.

The researchers set up operations at Stanford's Hopkins Marine Station, a marine laboratory in Pacific Grove, California, and collected data offshore from the facility in a 300-foot-wide kelp forest. Co-author Yuichiro Takeshita of the Monterey Bay Aquarium Research Institute (MBARI) provided pH sensors that were distributed throughout the area to understand chemical and physical changes in conjunction with water sampling.

"We are moving beyond just collecting more chemistry data and actually getting at what's behind the patterns in that data," said co-principal investigator Kerry Nickols, an assistant professor at California State University, Northridge. "If we didn't look at the water properties in terms of how they're changing and the differences between the top and the bottom of the kelp forests, we really wouldn't understand what's going on."

With the new high-resolution, vertical measurements of pH, dissolved oxygen, salinity and temperature, the researchers were able to distinguish patterns in the seawater chemistry around the kelp forest. At night, when they expected to see more acidic water, the water was actually less acidic relative to daytime measurements - a result they hypothesize was caused by the upwelling of acidic, low oxygen water during the day.

"It was wild to see the pH climb during the night when we were expecting increased acidity as a function of kelp respiration," Hirsh said. "That was an early indicator of how important the physical environment was for driving the local biogeochemical signal."

Designing a nature-based solution

While this project looked at kelp's potential to change the local environment on a short-term basis, it also opens the doors to understanding long-term impacts, like the ability to cultivate "blue carbon," the underwater sequestration of carbon dioxide.

"One of the reasons for doing this is to enable the design of kelp forests that might be considered as a blue carbon option," said co-author Stephen Monismith, the Obayashi Professor in the School of Engineering. "Understanding exactly how kelp works mechanistically and quantitatively is really important."

Although the kelp forests' mitigation potential in the canopy didn't reach the sensitive organisms on the sea floor, the researchers did find an overall less acidic environment within the kelp forest compared to outside of it. The organisms that live in the canopy or could move into it are most likely to benefit from kelp's local acidification relief, they write.

A model for future study

The research also serves as a model for future investigation about the ocean as a three-dimensional, fluid habitat, according to the co-authors.

"The current knowledge set is pretty large, but it tends to be disciplinary - it's pretty rare bringing all these elements together to study a complex coastal system," said co-PI Rob Dunbar, the W.M. Keck Professor at Stanford Earth. "In a way, our project was kind of a model for how a synthetic study pulling together many different fields could be done."

Monismith is also a member of Bio-X and an affiliate of the Stanford Woods Institute for the Environment. Dunbar is also a member of Bio-X and a senior fellow with Stanford Woods Institute for the Environment. Co-authors on the study include Sarah Traiger from California State University, Northridge and David Mucciarone from Stanford's Department of Earth System Science.