Culture

Researchers have identified a new treatment candidate that appears to not only halt neurodegenerative symptoms in mouse models of dementia and Alzheimer's disease, but also reverse the effects of the disorders.

The team, based at Tohoku University, published their results on June 8 in the International Journal of Molecular Sciences. The treatment candidate has been declared safe by Japan's governing board, and the researchers plan to begin clinical trials in humans in the next year.

"There are currently no disease-modifying therapeutics for neurodegenerative disorders such as Alzheimer's disease, Lewy body dementia, Huntington disease and frontotemporal dementia in the world," said paper author Kohji Fukunaga, professor emeritus in Tohoku University's Graduate School of Pharmaceutical Sciences. "We discovered the novel, disease-modifying therapeutic candidate SAK3, which, in our studies, rescued neurons in most protein-misfolding, neurodegenerative diseases."

In a previous study, the team found that the SAK3 molecule - the base structure of which is found in the enhancement of T-type Ca2+ channel activity - appeared to help improve memory and learning in a mouse model of Alzheimer's disease.

According to previous studies, SAK3 enhances the function of a cell membrane channel thereby promoting neuronal activity in the brain. Typically, SAK3 promotes neurotransmitter releases of acetylcholine and dopamine that are significantly reduced in Alzheimer's disease and Lewy body dementia. The Ca2+ channel enhancement is thought to trigger a change from resting to active in neuronal activity. When the Ca2+ channel is dysregulated in the brain, the acetylcholine and dopamine releases are reduced. The result is a dysregulated system that a person experiences as cognitive confusion and uncoordinated motor function.

SAK3 directly binds to the subunit of this channel, resulting in the enhancement of neurotransmission thereby improving cognitive deficits. The researchers found that the same process also appeared to work in a mouse model of Lewy body dementia, which is characterized by a build-up of proteins known as Lewy bodies.

"Even after the onset of cognitive impairment, SAK3 administration significantly prevented the progression of neurodegenerative behaviors in both motor dysfunction and cognition," Fukunaga said.

In comparison, Aduhelm, the Alzheimer's drug recently approved by the U.S. Food and Drug Administration, reduces the number of amyloid plaques in the brain, but it is not yet known if the amyloid reduction actually prevents further cognitive or motor decline in patients. According to Fukunaga, SAK3 helps destroy amyloid plaque - at least in mice.

SAK3 also helps manage the destruction of misfolded alpha-synuclein. Normal alpha-synuclein helps regulate neurotransmitter transmission in the brain. The protein can misfold and aggregate, contributing to what researchers suspect may be an underlying cause of neurodegenerative symptoms. This aggregation can also lead to the loss of dopamine neurons, which help with learning and memory.

"We found that chronic administration of SAK3 significantly inhibited the accumulation of alpha-synuclein in the mice," Fukunaga said, noting that the mice received a daily oral dose of SAK3.

According to Fukunaga, SAK3 enhances the activity of the system that identifies and destroys misfolded proteins. In neurodegenerative diseases, this system is often dysfunctional, leaving misfolded proteins to muck up the cell's machinery.

"SAK3 is the first compound targeting this regulatory activity in neurodegenerative disorders," Fukunaga said. "SAK3 administration promotes the destruction of misfolded proteins, meaning the therapeutic has the potential to solve the problems of diverse protein misfolding diseases such as Parkinson's disease, Lewy body dementia and Huntington disease, in addition to Alzheimer's disease."

Bobtail and bottletail squids are tiny marine invertebrates that are found throughout the world's oceans and are useful model animals for research

There are 68 recognized species of bobtail squid and five recognized species of bottletail squid, but the timing of their divergence from one another is still relatively unknown

Researchers at OIST, Hiroshima University and the National University of Ireland Galway, collected 32 species of bobtail and bottletail squids

They looked at the genetic variations across the entire genomes of these species to estimate their evolutionary relationships

The results showed that the divergence of these species aligned with major biogeographic events such as a global mass extinction and the division between the Indo-Pacific Sea and the Atlantic Ocean.

Bobtail and bottletail squids are small marine invertebrates that are easy to collect, reproduce quickly, and can be raised together in large numbers in laboratories, making them useful model animals for research. They're cephalopods--related to true squid, octopus, and cuttlefish, which are renowned for their intelligence and complex behaviors, but of which scientists still know little about. Now, in a new study, published in Communications Biology, researchers have used genetic techniques to show that bobtail squid and bottletail squid share a relatively recent common ancestor and that major biogeographic events might have shaped the evolution of the many different species.

"With 68 recognized species, bobtail squid are a very diverse family and split into three subfamilies. This study found that one of these subfamilies is further split into two geographic lineages." explained one of the lead authors, Dr. Gustavo Sanchez, researcher at Hiroshima University and former Visiting Research Student in the Okinawa Institute of Science and Technology Graduate University's (OIST) Molecular Genetics Unit. "In 2019, as part of my previous research at OIST, we described a new species of bobtail squid, which highlights both the diversity present and that many unknowns remain."

Bobtail and bottletail squids make up the order Sepiolida. They're small, normally between 1 and 8 cm, and live in a range of marine habitats around the globe, from shallow coastal waters to the open ocean.

For this new study, Dr. Sanchez, alongside researchers from OIST and the National University of Ireland Galway, collected 32 species of bobtail and bottletail squids from across the Indo-Pacific, the Mediterranean Sea, and the Atlantic Ocean. They use a technique called genome skimming that sequences whole genomes, albeit at low coverage. This allowed them to look at the genetic variations between these species so they could estimate their evolutionary relationships and when they diverged.

Their results revealed that bobtail and bottletail squids split into different families around 66 million years ago. This aligns with the rapid diversification of modern marine fishes, following the disappearance of more ancient groups due to a global mass-extinction (the same one that wiped out most of the dinosaurs). Bobtail squid went on to further diversify into three subfamilies--Sepiolinae and the more closely related Rossinae, and Heteroteuthinae. The researchers found that Sepiolinae, which makes up the largest of these subfamilies, can be further split into two tribes--those that are found in the Indo-Pacific Ocean and those that are found in the Mediterranean Sea and the Atlantic Ocean. This split coincided with another major biogeographic event--the closure of the Tethys Sea, around 50 million years ago, which generated the separation of these two regions and resulted in this subfamily being split in two.

A second interesting part of this study focused on the evolution of a light organ in bobtail squid that allows the production of luminescence. Producing luminescence is important for the survival of many of these animals as it allows for counter-illumination, which keeps them hidden from predators at night. The researchers found that the ancestor of the Sepiolinae subfamily likely possessed a bilobed light organ that housed luminescence-producing symbiotic bacteria. This has been retained by many of the species that exist today but was lost in two groups--one in the Indo-Pacific tribe and the other in the Mediterranean-Atlantic tribe.

"The evolutionary relationship of nearly 50% of bobtail squid still needs to be investigated but this research has provided a reliable foundation for classifying bobtail and bottletail squids," said Prof. Daniel Rokhsar, who leads the OIST Unit. "We hope that this phylogenetic work and ancestral reconstructions will be useful in future studies."

Attention Deficit Hyperactivity Disorder (ADHD) affects about 7% of children, with a two out of three chance of persisting into adulthood. This neurodevelopmental disorder is characterised by concentration difficulties, increased distractibility, impulsivity and hyperactivity. Today, ADHD is treated with pharmaceutical drugs that may have unwanted side effects. This is why scientists from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG), Switzerland, explored a new technique called 'neurofeedback', which enables ADHD patients to train their attention, based on instant feedback from the level of their brain activity. The team of neuroscientists found that not only did the training have a positive effect on patients' concentration abilities, but also that the attention improvement was closely linked to an enhanced response from the brain- the P3 wave - which is known to reflect integration of information in the brain, with higher P3 amplitudes indicating greater attention towards detected targets. The findings are open-access and have been published in the journal Clinical Neurophysiology.

Attention Deficit Hyperactivity Disorder (ADHD) develops in childhood and leads to numerous difficulties with attention, concentration and impulsiveness. It has genetic associated with environmental causes, and is characterised by a deficit in dopamine, a neurotransmitter involved in executive functions. "These disorders persist for the most part into adulthood and lead to problems in relational and socio-professional functioning, making it easier for people with this disorder to turn to alcohol or drugs", notes Marie-Pierre Deiber, a researcher in the Department of Psychiatry at UNIGE Faculty of Medicine and at the HUG Division of Psychiatric Specialties.

Today, ADHD is treated with medications that increase the concentration of dopamine, which improves the patient's attention. As the disorder is often accompanied by depression, anxiety or even bipolar disorders, treatment is generally combined with psychotherapy. "However, pharmaceutical treatments can be accompanied by significant side effects, such as nervousness, sleep disturbance, but also an increased risk of developing other psychiatric disorders or cardiovascular diseases", explains Roland Hasler, a researcher in the HUG Division of Psychiatric Specialties. "This is why we wanted to investigate a completely non-pharmacological and non-invasive treatment based on the principle of 'neurofeedback'".

Sending the brain its own signals

Neurofeedback is a type of neurocognitive intervention based on the training of "real-time" brain signals. Using an electroencephalogram (EEG) with 64 sensors, the scientists capture the electrical activity of cortical neurons and focus their analysis on the spontaneous Alpha rhythm (with frequency around 10 Hertz), coupling its amplitude fluctuation to a video game that the patients can control with the power of their attention. "The aim of neurofeedback is to make the patients aware of the moments when they are no longer attentive. With practice, brain networks then "learn" to reduce attentional lapses through neuroplasticity", explains Tomas Ros, researcher in the Department of Basic Neurosciences at UNIGE Faculty of Medicine and at the Centre for Biomedical Imaging (CIBM). To do this, the patient's EEG is connected to a computer that displays the image of a space shuttle. When the patient is in an attentive brain state (low Alpha rhythm), this makes the space shuttle move forward. But as soon as the patient is distracted or loses attention (high Alpha rhythm), this stops the space-shuttle movement instantly. Faced with the stopping of the space shuttle, the patient realizes that he/she was no longer paying attention and refocuses to restart the shuttle.

Training the brain to focus without medication?

To measure the effects of neurofeedback training, the Geneva team administered an attention test to 25 adults with ADHD, and 22 neurotypical adults. The results showed that, at baseline, ADHD patients made more mistakes and had a more variable reaction time than the control participants, in line with a signature of impaired attention. After 30 minutes of neurofeedback training, the participants took the attention test again.

"The first finding was that stimulus detection and response variability were improved, indicating attentional enhancement", says Marie-Pierre Deiber. "But what interested us most was the impact of the neurofeedback training on the P3 component, which has previously been shown to be reduced in ADHD, and directly linked to the neurocognitive processing of the stimulus." The higher the amplitude of the P3, the more efficient the processing of the stimulus is, and the more accurate the response to the attention task. "The amplitude of the P3 increased significantly after neurofeedback training, and was directly associated with a reduction in the number of errors made by the patients", reports Tomas Ros.

This study firstly shows that a single 30-minute session of neurofeedback can induce short-term plasticity in the brain and encourages attentional improvements in ADHD patients. Secondly, it supports the existence of an electro-physiological marker of attentional processing in ADHD. "Thus, the P3 could be a cerebral signature that would allow us to better understand the neurocognitive mechanisms of ADHD", continues Nader Perroud, professor in the Department of Psychiatry at UNIGE Faculty of Medicine and at the HUG Division of Psychiatric Specialties. Finally, as the effects are evident in the short term, the scientists plan to carry out a neurofeedback treatment based on multiple training sessions, in order to observe whether the brain's plasticity is strengthened over time. "The ultimate goal is to enable patients to learn to concentrate without medication and to be able to train their brain in the comfort of their home», concludes Tomas Ros.

An international team of researchers has identified a novel mechanism in barley plants, which could help crop growers achieve high yields as temperatures rise.

With grain production highly sensitive to changing environmental conditions, rising temperatures are known to reduce the number of seeds that can be produced on each plant. One solution is to increase the number of flowers or branches on each 'spike', which is the reproductive structure from which grain is harvested.

In a study published in Nature Plants, research led by Professor Dabing Zhang from the University of Adelaide's Waite Research Institute and Shanghai Jiao Tong University's Joint Lab for Plant Science and Breeding, explored the possibility of increasing seed production through the reproductive mechanisms in plants that respond to high temperatures.

"Cereal crops such as wheat and barley are worth over $12B to the Australian economy," said lead author Dr Gang Li with the University of Adelaide's Waite Research Institute.

"Genes that control the amount of grain produced per plant under higher temperatures are really attractive targets for breeders and researchers, particularly in the face of changing environmental conditions.

"It has long been presumed that environmental cues such as temperature are responsible for the diversity of the biological structures between cereals. However the mechanisms behind the structural changes have been largely unknown, which is why this study is important."

In the study, Professor Zhang's team found a novel mechanism by which a barley protein, known as HvMADS1, regulates the number of flowers generated on each spike, in response to high temperatures. The researchers were able to demonstrate that HvMADS1 is critical in maintaining an unbranched barley spike under high ambient temperatures.

Using a highly-efficient genome editing technique, the researchers were able to generate new plants that lack HvMADS1 function, effectively converting an unbranched barley spike into a branched structure, bearing more flowers at high ambient temperatures.

"This could ultimately result in the production of more grain per plant," said Dr Li.

Co-author Associate Professor Matthew Tucker, Deputy Director of the Waite Research Institute said: "This study reveals a new role of this protein family in responding to thermal change and directing the composition of flowers on a stem.

"With short to medium temperature rises predicted globally, plant scientists and breeders have an enormous challenge ahead of them to generate crop yields needed to feed growing populations in higher temperatures.

"By having a better understanding of the genes underpinning desirable plant traits in response to temperature scientists can offer insights into breeding climate-smart plants to sustain productivity."

The researchers say this work provides new avenues for crop breeding potential to overcome the traditional compromise between heat tolerance and high yield.

"This collaborative research demonstrates the importance of international partnerships in delivering fundamental scientific breakthroughs, and the value of gene editing strategies in crops, which are routinely used at the Waite Research Institute at the University of Adelaide," said Associate Professor Tucker.

Earthworms experience constant chemical interactions with bacteria, fungi, plants and small invertebrates across soil ecosystems. Even within their tissues, earthworms harbor symbiotic microbes and small animal parasites that trigger internal metabolic responses such as innate immunity. To reveal the fundamental processes that enable animal-microbe symbioses to form and persist, we have to study their metabolic interactions in situ. By combining novel imaging techniques, a team of researchers around Benedikt Geier from the Max Planck Institute for Marine Microbiology (MPIMM) in Bremen, Germany, has now succeeded in imaging the exciting variety of interactions that take place inside the earthworm. This allows us to observe them in a completely new light.

The chemistry of the worm in 3D

Our understanding of the chemical interactions between small animals and the microorganisms that live inside their bodies is extremely limited. This gap of knowledge has its origin in a methodical challenge: To study the metabolic interactions in symbiosis we have to know who is producing which metabolic product where in the body. The core of this problem, however, is not only to image how molecules are distributed at the micrometer scale. Also, the chemical images are almost impossible to interpret without knowing if a tissue sample is healthy, diseased or infected with beneficial or pathogenic microbes or even animal parasites.

The new combination of high-resolution imaging techniques can offer a solution to this problem, as the research team now shows. "In our study, we introduce chemo-histo-tomography, a special three-dimensional imaging approach of the chemistry and anatomy of millimeter-sized animals and their parasites at a cellular level," says Benedikt Geier, first author of the paper. "This method offers a new strategy to visualize the most fundamental processes - metabolic interactions - in small animal symbioses. It allows us to spatially assign metabolic producs to the animal host and its microbial partners at the micrometer scale."

Chemo-histo-tomography (CHEMHIST) combines chemical imaging of metabolites based on MALDI mass spectrometry imaging with the microanatomy of the same animal that is recorded with micro-computed X-ray tomography. The latter is a non-invasive approach allowing X-ray imaging of the 3D histology, and can reach subcellular resolution. For metabolite imaging, MALDI mass spectrometry techniques have become a state-of-the-art tool to visualize micrometer-scale, natural distributions of metabolites. This enables a spatial assignment between chemical profiles and their production site and possibly to their producer.

"This advance allowed us to take an earthworm from the environment and create a 3D atlas of its chemical and physical interactions with the microorganisms naturally occurring inside its tissues," says Manuel Liebeke, leader of the Research Group Metabolic Interactions at the MPIMM and senior author of the study. "However, we were interested in more than just the biology of the earthworm. Our objective was to also make CHEMHIST applicable to animals directly sampled from their natural habitat, which can be essential for symbiosis research." The resolution of CHEMHIST outperforms existing similar methods developed for medical research in mice by up to two orders of magnitude. This may also lead into new avenues for research on insects or corals, which are key models for symbiosis research, both on land and in water.

The whole is more than the sum of the parts

Using the combination of different in situ imaging techniques through CHEMHIST, the researchers at the MPIMM in Bremen uncovered metabolites - products of the metabolism - in the earthworm that could shed light on how it chemically defends itself against parasites and how these, in turn, protect themselves against the earthworm's immune response. However, to even recognize that the chemical image data were metabolites of parasites in earthworm tissue, the 3D anatomical model was indispensable. A high-resolution micro-computer tomograph at the German Electron Synchrotron in Hamburg first made it possible to identify the parasites in the tissue.

Notably, metabolic interactions between animals and their microbes are not restricted to symbiotic tissues. Along the gut-brain axis, microbial metabolites produced in the gut can affect tissues across the host, even reaching the brain. Therefore, extending correlative chemical imaging into 3D approaches can be crucial for capturing the distribution of metabolites involved in symbiotic interactions and thus show how chemical signals from microbes possibly affect crucial processes in their host. Also, the method can be used in many ways: The research team around Liebeke and Geier is currently applying it to deep-sea mussels.

"Since I have specialized in the 3D visualization of invertebrate anatomy for years, it was particularly interesting for me to see the molecules hidden behind the morphological structures," says Bernhard Ruthensteiner, leader of the section Invertebrate Varia at the Bavarian State Collection of Zoology. The results of the study were made possible by an interdisciplinary collaboration that brought together scientists from the fields of microbiology, zoology, chemistry and physics. It quickly became clear that visualization such as the correlative 3D atlas of the worm facilitate science communication of the data.

Russian scientists have experimentally proved the existence of a new type of quasiparticle - previously unknown excitations of coupled pairs of photons in qubit chains. This discovery could be a step towards disorder-robust quantum metamaterials. The study was published in Physical Review B.

Superconducting qubits are a leading qubit modality today that is currently being pursued by industry and academia for quantum computing applications. However, the performance of quantum computers is largely affected by decoherence that contributes to a qubits extremely short lifespan and causes computational errors. Another major challenge is low controllability of large qubit arrays.

Metamaterial quantum simulators provide an alternative approach to quantum computing, as they do not require a large amount of control electronics. The idea behind this approach is to create artificial matter out of qubits, the physics of which will obey the same equations as for some real matter. Conversely, you can program the simulator in such a way as to embody matter with properties that have not yet been discovered in nature.

Arrays of superconducting qubits are generally described by the Bose-Hubbard model. An interesting feature of the Bose-Hubbard model is the emergence of bound boson pairs (doublons) caused by the strong quantum nonlinearity. The topological physics of doublons has been extensively explored in a series of recent theoretical works. However, the experimental investigation of topological properties of bound photon pairs is still lacking.

A group of scientists from NUST MISIS, Russian Quantum Center, ITMO University, Bauman Moscow State Technical University, Dukhov Automatics Research Institute (VNIIA) and Ioffe Institute used an array of superconducting qubits to engineer a quantum simulator. Quantum utilize entanglement and many-particle behaviors to explore and solve hard scientific, engineering, and computational problems.

"By registering the properties of qubits, we can draw conclusions about a broader class of physical systems described by the same equations. And if we can change the parameters of these equations in a controlled way, then such a device can be considered a "specialized simulator". Of course, its programmability is not the same as that of a quantum computer, but its scaling requires significantly fewer resources," explains the main author of the study Ilya Besedin, junior researcher at the NUST MISIS Laboratory of Superconducting Metamaterials.

The scientists engineered an array of superconducting transmon qubits with alternating coupling. Due to the alternation of strong and weak bonds, two zones and an edge state appear in this system. This state is classified as topological. Moreover, the experiment shows that doublons also form an edge state.

"We were able to see how doublons form these zones, and we even managed to detect how an edge doublon state appeared at the upper edge of the doublon zone as we increased the length of the array," notes Ilya Besedin.

Thus, the scientists were able to demonstrate for the first time that a new type of quasiparticles - doublon topological excitations - can arise in qubit chains.

"Research on superconducting qubits and quantum circuits is currently underway in many countries around the world, and competition in this area is growing. This study on 11 qubits shows that Russia has attained high level of scientific development in the field of superconducting quantum computing", notes Prof. Alexey Ustinov, Head of the Laboratory for Superconducting Metamaterials at NUST MISIS and Group Head at Russian Quantum Center, who co-authored the study.

A stimulating environment keeps the "hippocampus" - which is the brain's memory control center - young, so to speak. Causes of this are molecular mechanisms that affect gene regulation. These current findings from studies in mice provide clues as to why an active, varied life can help preserve mental fitness in old age. Researchers from the DZNE and the Center for Regenerative Therapies Dresden (CRTD) at the Technische Universität Dresden report on this in the journal Nature Communications.

Human DNA - and this also applies to mice - contains thousands of genes. However, it is not only the genetic blueprint that is decisive for the function of a cell and whether it is healthy or not, but above all which genes can be switched on or off. Aging, living conditions and behavior are known to influence this ability to activate genes. The phenomenon, referred to as "epigenetics", was the focus of the current study. For this, researchers including Dr. Sara Zocher and Prof. Gerd Kempermann examined mice that had grown up in different environments: One group of animals experienced, from a young age, an "enriched" environment with toys and tunnel tubes. The rodents of a second group did not have such occupational opportunities.

Attachments to the DNA

When the scientists examined the genome, they found that in those mice that grew up in the stimulating environment, there was, with age, only a relatively small change in certain chemical tags of the DNA. In mice from the low-stimulus environment, these changes were much more pronounced - in comparison between young and older animals. "We registered so-called methyl groups, which stick to the DNA," explains Gerd Kempermann, speaker for the DZNE's Dresden site, DZNE research group leader and also a scientist at the CRTD. "These chemical attachments do not alter the genetic information per se. Rather, they influence whether individual genes can be activated or not."

Malleable Brains

Such "epigenetic markings" tend to diminish with age, but in the animals with stimulating living conditions, the decrease in methyl groups was comparatively small. Thus, in old mice raised in a varied environment, gene activity had, in a sense, remained young. In particular, this affected a series of genes relevant to growing new neurons and cellular connections in the hippocampus. "Epigenetically, these animals retained a younger hippocampus," Kempermann says. Therefore, the brains of these mice were more malleable - experts speak of greater "neuroplasticity" - than in conspecifics of the same age that had grown up in a low-stimulus environment.

The current study did not include behavioral experiments. However, Kempermann points out that many other studies have shown that mice raised in high-stimulus settings perform better on memory tests than those from low-stimulus environments. "It is fair to assume that this mental fitness is due to the stabilization of methylation patterns that we observed," the neuroscientist says. "Of course, the question is to what extent our findings also apply to humans. Here, the situation is likely to be more complicated. After all, it is about how living conditions influence behavior and the way humans react to external stimuli is much more complex than in mice. However, we have good reasons to believe that the basic epigenetic principles are the same in humans as in mice."

A new technique established by a team of researchers from the University of Cambridge and the University of Massachusetts reveals the fundamental physics of how a polymer such as DNA threads through holes 10,000 times smaller than the width of a human hair.

Polymers are long, chain-like molecules which are everywhere in biology. DNA and RNA are polymers formed by many consecutive copies of nucleotides coupled together. When being transported within or between cells, these biological polymers must pass through nanometre-sized holes called "nanopores".

This process also underlies a rapidly developing method for analysing and sequencing DNA called nanopore sensing.

The study, published in the journal Nature Physics, shows how the Cavendish-led team developed a new LEGO-like technique for assembling DNA molecules that have protruding bumps at specific locations along their length. By passing these DNA molecules through a nanopore and analysing simultaneous changes in the pattern of ion flow, the researchers determined with great precision how the speed of the DNA changes as it moves through.

The experimental results revealed a two-step process where the DNA speed initially slows down before accelerating close to the end of the translocation. Simulations also demonstrated this two-stage process and helped to reveal that the underlying physics of the process is determined by changing friction between the DNA and surrounding fluid.

"Our method for assembling LEGO-like molecular DNA rulers has given new insight into the process of threading polymers through incredibly small holes just a few nanometres in size," explained Senior author Dr Nicholas Bell from Cambridge's Cavendish Laboratory. "The combination of both experiments and simulations have revealed a comprehensive picture of the underlying physics of this process and will aid the development of nanopore-based biosensors. It is very exciting that we can now measure and understand these molecular processes in such minute detail."

"These results will help improve the accuracy of nanopore sensors in their various applications, for instance localising specific sequences on DNA with nanometer accuracy or detecting diseases early with target RNA detection," said lead author Kaikai Chen.

"The superior resolution in analysing molecules passing through nanopores will allow for low-error decoding of digital information stored on DNA. We are exploring and improving the utility of nanopore sensors for these applications."

Researchers at the University of Leicester have developed a new method to recycle electric vehicle batteries using a ground-breaking new approach that many will have experienced in the dentist's chair.

The Faraday Institution project on the recycling of lithium-ion batteries (ReLiB) led by Professor Andy Abbott at the University of Leicester used a new method, involving ultrasonic waves, to solve a critical challenge: how to separate out valuable materials from electrodes so that the materials can be fully recovered from batteries at the end of their life.

Current recycling methods for lithium-ion battery recycling typically feed end-of-life batteries into a shredder or high-temperature reactor. A complex set of physical and chemical processes are subsequently needed to produce useable materials. These recycling routes are energy intensive and inefficient.

If an alternate approach is taken and end-of-life batteries are disassembled rather than shredded, there is the potential to recover more material, in a purer state. The disassembly of lithium-ion batteries has been shown to recover a high yield (around 80% of the original material) in a purer state than was possible using shredded material.

The stumbling block - of how to remove and separate critical materials (such as lithium, nickel, manganese and cobalt) from used batteries in a fast, economical and environmentally-friendly way - can now be avoided thanks to the new approach which adapts technology currently in widespread use in the food preparation industry.

The ultrasonic delamination technique effectively blasts the active materials required from the electrodes leaving virgin aluminium or copper. The process proved highly effective in removing graphite and lithium nickel manganese cobalt oxides, commonly known as NMC.

The research has been published in Green Chemistry and the research team led by Professor Abbott have applied for a patent for the technique.

Professor Abbott said:

"This novel procedure is 100 times quicker and greener than conventional battery recycling techniques and leads to a higher purity of recovered materials.

"It essentially works in the same way as a dentist's ultrasonic descaler, breaking down adhesive bonds between the coating layer and the substrate.

"It is likely that the initial use of this technology will feed recycled materials straight back into the battery production line. This is a real step change moment in battery recycling."

Professor Pam Thomas, CEO, The Faraday Institution commented:

"For the full value of battery technologies to be captured for the UK, we must focus on the entire life cycle -- from the mining of critical materials to battery manufacture to recycling -- to create a circular economy that is both sustainable for the planet and profitable for industry."

Faraday Institution researchers have been focused on the life cycle of the battery - from their first production to their re-use in secondary applications to their eventual recycling, to ensure that the environmental and economic benefits from Electric Vehicle batteries are fully realised.

The research team are in initial discussions with several battery manufacturers and recycling companies to place a technology demonstrator at an industrial site in 2021, with a longer-term aim to license the technology.

The research team has further tested the technology on the four most common battery types and found that it performs with the same efficiency in each case.

Mineral resources from Chile are of great importance to Germany. According to statistics from the World Bank, thousands of tons of valuable minerals are imported from the South American country every year, including raw materials for lithium-ion batteries. But their extraction causes ecological and social problems: "The use of the limited freshwater resources in northern Chile for mining regularly fuels conflicts with the local population," says Professor Thomas Kohl from KIT's Institute of Applied Geosciences (AGW). "Northern Chile is one of the driest regions on earth, but has extensive geothermal resources. With a novel type of plant, it is not only possible to generate electricity in a climate-friendly way, but also to extract drinking water and even mineral resources at the same time." The AGW team of BrineMine, a German-Chilean research project, is developing the necessary strategies and technologies.

AGW has a long history of cooperation in the field of geothermal research in Chile. Its main partner is the Centro de Excelencia en Geotermia de Los Andes (CEGA). "BrineMine demonstrates how well the cooperation between Chilean and German institutions works," says Professor Diego Morata, director of CEGA. "Sustainable development, achieved by the combination of geothermal and green mining, can benefit Europe and the Andean region alike."

First Demonstration Plant on the Upper Rhine Graben

Part of the transdisciplinary research initiative is dedicated to the geochemical and geothermal potential of thermal wells in Chile in order to identify suitable sites. A data survey is being conducted to determine the raw materials potential with a focus on the thermal fields of the Atacama Desert. In addition, the Fraunhofer Institute for Solar Energy Systems (ISE) takes part in the BrineMine project by developing the plant technology for later industrial use. It is based on a novel process chain: First, heat from the geothermal brine is used for energy recovery. The cooled liquid, which has a relatively low concentration, is then pre-concentrated by reverse osmosis; at the same time, drinking water is obtained. The brine concentrate is then further concentrated by membrane distillation until it is saturated. "The thermal energy required for the entire process can be covered directly from the excess heat of the power plant process," explains project manager Dr. Joachim Koschikowski from ISE. "We have already set up a demonstration plant in a geothermal power plant in the Upper Rhine Graben and successfully integrated key components into ongoing power plant operations."

Optimization of Processes for Raw Material Mining

Most of the process steps are based on proven methods, but they have never been combined in this way. Detailed research is required, because, for example, both concentration and cooling increase the risk of silicate deposits. "Conventional strategies for silicate removal would greatly impair the extraction of the resources. Without water treatment, the technical plant components would be damaged," explains Valentin Goldberg from KIT's AGW. The researchers found a viable solution by changing the pH value of the brine and adding divalent cations (e.g. calcium or magnesium). "Our silicate removal method is fast and effective. Most importantly, it has no negative impact on raw material extraction," Goldberg says. The researchers describe this new approach in the Geothermics journal.

Before the first plants can be installed in Chile, further details about the process need to be clarified. In addition, specific models for economic operation are also being developed.

When positioned strategically, garment seams sewn with conductive yarn can be used to accurately track body motion, according to computer scientists at the University of Bath in the UK. Best of all, these charged seams are able to respond to subtle movements that aren't picked up by popular fitness trackers, such as watches and wristbands.

In a new study, the Bath researchers found that clothing made with conductive seams can be analysed to identify the wearer's movements.

PhD student Olivia Ruston, who presented the work at the ACM Designing Interactive Systems conference this month, said: "There are lots of potential applications for conductive yarn in any activity where you want to identify and improve the quality of a person's movement. This could be very helpful in physiotherapy, rehabilitation, and sports performance."

Groups of scientists have been creating flexible, textile sensors for garments for some time, but the Bath project is the first where researchers have experimented with the location and concentration of conductive seams. They found that where seams are placed on a garment, and the number of seams that are added, are important considerations in the design of a movement-tracking smart garment.

Ms Ruston said: "There's great potential to exploit the wearing of clothing and tech - a lot of people are experimenting with e-textiles, but we don't have a coherent understanding between technologists and fashion designers, and we need to link these groups up so we can come up with the best ideas for embedding tech into clothing."

The yarn used by Ms Ruston and her team comprises a conductive core that is a hybrid metal-polymer resistive material intended for stretch and pressure sensing. Once incorporated into a garment's seam, it is activated at low voltages. The resistance fluctuates as body movement varies the tension across the seams.

In the study, the seams were connected to a microcontroller, and then a computer, where the voltage signal was recorded.

Professor Mike Fraser, co-author and head of Computer Science, said: "Our work provides implications for sensing-driven clothing design. As opportunities for novel clothing functionality emerge, we believe intelligent seam placement will play a key role in influencing design and manufacturing processes. Ultimately, this could influence what is considered fashionable."

Mice are an important animal model of human vision due to the powerful genetic tools available in this species. However, mouse vision was thought to be different to that of humans because humans have a region of the retina specialized for fine details called the 'fovea' whereas mice do not. Researchers from the Netherlands Institute of Neuroscience (NIN) have shown that the visual cortex of mice does contain a region of enhanced visual sensitivity dubbed the 'focea', making the mouse a better model of human vision than previously expected. The findings were published in Nature Communications on the 29th June.

A specialization for high resolution vision

The fovea is a region in the human retina in which the light-sensitive cells are more closely packed together yielding higher resolution vision. It is used for reading and recognizing faces. Humans move their eyes three times per second to point the fovea at interesting parts of the world. Mice do not have this specialization and it was thought that they have no reason to move their eyes to 'scan the world' in more detail.

While studying how the retina of the mouse was mapped in cortical regions of the brain, the researchers found that the map of visual space in the cortex has a better visual resolution at a location that represents a region directly in front of and slightly above the mouse in space. They named this cortical location the 'focea' as it is reminiscent of the fovea of humans.

A better organized map of space.

To determine the source of the better resolution the researchers measured the responses from individual brain cells using electrodes. The cells at the focea did not appear to the differ from other cells. "Initially we were puzzled" explains Matthew Self, lead researcher on the project, "we were seeing a very clear focea in the map, but nothing when we measured the data from single-neurons. We realized that the focea could originate from regions of the cortex where the maps are better organized across cells".

To study this, the researchers measured maps of space across thousands of cells using a two-photon microscope. The results confirmed their hypothesis; maps of space in the focea were well-organized with neighboring cells responding to neighboring parts of space. In contrast, the maps outside the focea were more scattered. The results suggested that mice might have better vision in the focea than elsewhere.

The focea in natural behaviors

The fact that mice have a focea could mean that they also move their eyes to point their focea at interesting parts of world, analogous to the human fovea. The findings have important consequences for the use of mice as a model of human vision. Dr Self stated: "The fact that mice have a focea opens up the possibility of understanding the neural circuits underlying high-detail vision and studying the neural basis of attention and eye-movements in this species".

Lithia, Florida -- June 29, 2021 -- Surgical resident training has traditionally occurred in a master-apprentice-type relationship, with graduated responsibilities until trainees are expected to perform procedures on their own. Given recent changes in the health care system, including reduced operating room time, increased difficulty of procedures and working hour restrictions, there is less time for residents to learn using traditional methods.

Researchers from the University of Manitoba and the Pan Am Clinic recently published a paper in the journal Arthroscopy, Sports Medicine, and Rehabilitation that looked at the effectiveness of a mixed reality simulator for the training of arthroscopy novices. Following this study, the residency program has made it a requirement in the curriculum that residents in the sports rotation complete the self-learning modules.

Dr. Samuel Larrivée, one of the study's authors, stated that "sports surgeons at our institution noted anecdotally that junior residents had difficulty reaching competency in arthroscopic skills by the end of their three-month rotation, and were not as prepared when starting their senior rotation. There was a need to increase training opportunities outside of the operating room in order to prepare our residents for independent practice."

Prior to obtaining the ArthroS™ simulator from VirtaMed, the University of Manitoba Orthopedic Surgery program occasionally used simulation such as benchtop dry simulators, cadavers and an older generation simulator with active haptics. These were mostly used to complement academic teaching sessions in small groups with some success, and available for use by residents as needed. However, due to the low fidelity and difficult setup, few residents took up the opportunity.

Medical student engagement with the ArthroS simulator was different. Alisha Beaudoin, a co-author and medical student, attested to her experience using the ArthroS simulator in her early training. "I found this training to be very helpful during my surgery rotation. Many of my preceptors were impressed by my superior arthroscopic and laparoscopic skills. This training may allow students with an interest in surgery to be more prepared."

Recently, many Canadian universities have moved to competency-based curriculums where residents must demonstrate competency prior to moving to the next defined practice level. The study noted that this is similar to the training available on ArthroS and that "a user enrolled in the mentoring program is progressed through various levels of training by meeting training targets, essentially providing a proficiency-based progression."

This paper is the first in what the authors hope is a larger body of work on validating arthroscopy simulators for resident training. There are currently plans to repeat similar studies with the other modules (hip, shoulder, and ankle), with larger sample sizes, and at different levels of training.

The Study

Study participants were divided into three groups: simulator training only, mentor-based training, and a control. At the end of four weeks, surgical performance improved among both traditional and simulator-based training groups. The study concluded that "simulator training may provide enhanced skills to improve patient safety overall, as residents may become more skilled earlier in their training, leaving more time for the mentor to teach more advanced skills." Beaudoin further explains: "I believe that simulation training should be introduced into the standardized curriculum because I believe it offers a safe space to hone your skills and improve in a stress-free environment."

Based on the study results, residents are now required to complete the self-learning modules as part of training during their sports rotation. Certain modules have been identified at the junior and senior levels. Dr. Larrivée believes this will allow residents to develop their triangulation skills and memorize the steps prior to their first surgery and consolidate their knowledge.

Aerosol generated by playing woodwind and brass instruments is less than that produced when vocalising (speaking and singing) and is no different than a person breathing, new research has found. The findings, published online in the journal Aerosol Science and Technology, could be crucial to developing a roadmap for lifting COVID-19 restrictions in the performing arts, which have been significantly restricted since the start of the pandemic.

The research project, known as PERFORM (ParticulatE Respiratory Matter to InForm Guidance for the Safe Distancing of PerfOrmeRs in a COVID-19 PandeMic), was supported by Public Health England, the Department for Digital, Culture, Media and Sport (DCMS), and UKRI and was carried out by a collaborative team from Imperial College London, University of Bristol, Wexham Park Hospital, Lewisham and Greenwich NHS Trust and Royal Brompton Hospital.

The study looked at the amount of aerosols and droplets generated when playing woodwind and brass instruments compared with breathing and vocalisation (speaking and singing). The work was carried out in an environment with no background aerosol particles to complicate measurement interpretation, with nine musicians playing 13 woodwind and brass instruments.

The research team found aerosol (

Large droplets (>20 μm diameter) were not observed during instrument playing but were observed during singing and coughing. Together the findings indicate that playing woodwind and brass instruments generates less aerosol than vocalising at high volume levels.

Concentrations of aerosol emissions from the musicians during breathing and vocalising were consistent with results from a study carried out last year of a large group of professional singers. No difference was found between the aerosol concentrations generated by professional and amateur performers while breathing or vocalising, suggesting aerosol generation is consistent across amateur and professional singers regardless of vocal training.

Dr Bryan Bzdek, Lecturer in the School of Chemistry at the University of Bristol and corresponding author on the paper, said: "Our study found playing woodwind and brass instruments generates less aerosol than vocalisation, which could have important policy implications in a roadmap to lifting COVID-19 restrictions, as many performing arts activities have been, and continue to be, severely restricted."

Jonathan Reid, Director of Bristol Aerosol Research Centre and Professor of Physical Chemistry in the School of Chemistry at the University of Bristol, added: "This study confirms that the risks of transmission of SARS-CoV-2 are likely elevated during vocalisation at loud volume in poorly ventilated spaces. By comparison, playing wind instruments, like breathing, generates less particles that could carry the virus than speaking or singing."

The death of neurons specialised in the synthesis of dopamine, one of the brain's main neurotransmissors, deteriorates the motor and cognitive capacities of those with Parkinson's disease. The loss of these neurons is related to alpha-synuclein aggregation. Recent studies show that oligomers, the initial aggregates of this protein, are the most pathogenic forms of α-synuclein and are responsible for the spreading of the disease in the brain.

Therefore, one of the more promising approaches in fighting this disorder consists in neutralising these oligomers and, thus, slow down the pathological progression. However, the fact that these aggregates do not present a defined structure and that they are transitory by nature makes it extremely difficult to identify molecules that bind with enough strength as to explore any clinical application.

A scientific collaboration between researchers from the Institute for Biotechnology and Biomedicine (IBB) at the Universitat Autònoma de Barcelona (UAB) and from the Instituto de Biocomputación y Física de Sistemas Complejos (BIFI) of the Universidad de Zaragoza (UniZar) now has been able to identify a human endogenous peptide which strongly and specifically attaches to the α-synuclein oligomers, thus avoiding their aggregation and blocking their neurotoxicity, two processes closely related to the neurodegenerative decline of Parkinson's disease. The identification and study of the peptide, called LL-37, was recently published in Nature Communications.

"LL-37 interacts with the toxic alpha-synuclein oligomers in a selective manner and with a strength superior to that of any peptide previously described, equivalent to the strength exhibited by antibodies. It inhibits aggregation at very low concentrations and protects neuronal cells from being damaged", researchers point out.

They add that, "LL-37 is found naturally in the human organism, both in the brain and in the intestine, organs in which α-synuclein aggregation takes place in Parkinson's disease. This suggests that LL-37's activity might respond to a mechanism developed by the body itself as a means to naturally fight this disease."

Encouraged by this idea, researchers now want to study how its expression can be regulated and if this strategy can become a safe therapy with the potential of influencing the course of the disease. "There is a possibility that a therapy for Parkinson's disease already lies in our interior and that it only needs to be activated correctly", states Salvador Ventura, researcher at the IBB and coordinator of the study.

The identification of LL-37 was conducted under the framework of a research analysing the structure and characteristics of pathogenic oligomers with the aim of neutralising them in a specific manner. The analyses conducted demonstrate that helical peptides with a hydrophobic side and another positively charged side are ideal for this type of activity. The trials allowed researchers to identify three molecules with anti-aggregation activity: in addition to the human molecule, a second peptide present in bacteria and a third artificially made molecule were identified.

In addition to representing a possible therapeutic route for Parkinson's disease and other synuclein pathologies, the molecules identified in the study are promising tools for its diagnosis, given that they discriminate between functional and toxic α-synuclein species.

"Until now there were no molecules capable of selectively and efficiently identifying toxic α-synuclein aggregates; the peptides we present on these issues are unique and, therefore, have great potential as diagnostic and prognostic tools," says study co-coordinator Nunilo Cremades, researcher at BIFI-UniZar.

In the study, over 25,000 human peptides were computationally analysed, and single molecule spectroscopy methods, as well as protein engineering, were applied, in addition to cell cultures in vitro using toxic oligomers.

Participating in the study were researchers from the IBB-UAB and the Department of Biochemistry and Molecular Biology at the UAB Jaime Santos (first author of the article), Irantzu Pallarès and Salvador Ventura (co-coordinators of the study), members of the "Protein Folding and Conformational Diseases" group; and BIFI-UniZar researchers Pablo Gracia (second author of the article) and Nunilo Cremades (co-coordinator of the study, predoctoral researcher and lead researcher, respectively, of the "Amyloid Protein Misfolding and Aggregation" NEUROMOL group from the BIFI-Unizar.