Culture

The discovery of a Roman road submerged in the Venice Lagoon is reported in Scientific Reports this week. The findings suggest that extensive settlements may have been present in the Venice Lagoon centuries before the founding of Venice began in the fifth century.

During the Roman era, large areas of the Venice Lagoon which are now submerged were accessible by land. Roman artefacts have been found in lagoon islands and waterways, but the extent of human occupation of the lagoon during Roman times has been unclear.

Mapping the lagoon floor using sonar, Fantina Madricardo and colleagues discovered 12 archaeological structures aligned in a northeasterly direction for 1,140 metres, in an area of the lagoon known as the Treporti Channel. The structures were up to 2.7 metres tall and 52.7 metres long. Previous surveys of the Treporti Channel uncovered stones similar to paving stones used by Romans during road construction, indicating that the structures may be aligned along a Roman road. The researchers also discovered an additional four structures in the Treporti Channel that were up to four metres tall and 134.8 metres long. Based on its dimensions and similarity to structures discovered in other areas, the largest of these structures is thought to be a potential harbour structure, such as a dock. Previously collected geological and modelling data indicates that the road is located on a sandy ridge that was above sea level during the Roman era but is now submerged in the lagoon.

The findings suggest that a permanent settlement may have been present in the Treporti Channel during the Roman era. The authors propose that the road may have been linked to a wider network of Roman roads in the Italian Veneto Region and may have been used by travellers and sailors to journey between what is now the city of Chioggia and the Northern Venice Lagoon.

Newly-hatched pterosaurs may have been able to fly but their flying abilities may have been different from adult pterosaurs, according to a study published in Scientific Reports.

Pterosaurs were a group of flying reptiles that lived during the Triassic, Jurassic and Cretaceous Periods (228 to 66 million years ago). Due to the rarity of fossilised pterosaur eggs and embryos, and difficulties distinguishing between hatchlings and small adults, it has been unclear whether newly-hatched pterosaurs were able to fly.

Darren Naish and colleagues modelled hatchling flying abilities using previously obtained wing measurements from four established hatchling and embryo fossils from two pterosaur species, Pterodaustro guinazui and Sinopterus dongi. The authors also compared these wing measurements with those of adults from the same species and compared the strength of the humerus bone, which forms part of the wing, of three hatchlings with those of 22 adult pterosaurs.

The researchers found that hatchling humerus bones were stronger than those of many adult pterosaurs, indicating that they would have been strong enough for flight. The authors also found that while hatchlings had long, narrow wings suited to long-distance flight, their wings were shorter and broader than those of adult pterosaurs, with a larger wing area relative to hatchling mass and body size. These wing dimensions may have may have made hatchlings less efficient than adult pterosaurs at long-distance travel, but may have resulted in them being more agile fliers, enabling them to suddenly change direction and speed.

The authors speculate that the agile flying style of hatchling pterosaurs may have enabled them to rapidly escape predators and made them better suited to chasing nimbler prey and flying amongst dense vegetation than adult pterosaurs. This could indicate that pterosaurs occupied dense habitats as hatchlings and open environments as adults, according to the authors.

Geneticists from Trinity College Dublin have discovered how a specific genetic mutation called H3K27M causes a devastating, incurable childhood cancer, known as diffuse midline glioma (DMG), and - in lab studies working with model cell types - successfully reverse its effects to slow cancer cell growth with a targeted drug.

Their landmark work - just published in leading international journal, Nature Genetics and supported by Worldwide Cancer Research and The Brain Tumour Charity - translates crucial new understanding of the genetics of DMG progression into a highly promising, targeted therapeutic approach and offers significant hope of improved treatments in the future.

The scientists now call for clinical trials to begin imminently, in which an already approved class of drugs called "EZH2 inhibitors" can be assessed. These drugs target the same key biological pathway involved in DMG as they do successfully in lymphomas and sarcomas -- two cancers common in adults.

Key findings and implications

The scientists behind this important work discovered:

How a specific genetic mutation called H3K27M causes DMG

How to target this cancer-causing gene with a drug that slows cancer cell growth

They have also established a specific model cell line for evaluating further targeted DMG approaches

Adrian Bracken, Professor in Trinity's School of Genetics and Microbiology, led the exciting research.

He said: "We've taken a huge step forward in our study of DMG tumours and hope that the insights will help us design and implement precision oncology-based treatment approaches in DMG patients in the future. Crucially, 'EZH2 inhibitor' drugs have already received approval from the United States Food and Drug Administration for the treatment of two types of adult cancer. We propose these drugs could be impactful for children with DMG and, as a result, call for clinical trials to begin next.

"Ultimately, we hope that our work - together with that of others focused in this area - will lead to curative clinical approaches for what is a truly terrible disease that can devastate families and for which there are currently no therapeutic options."

Paediatric gliomas - harrowing, devastating cancers

Paediatric gliomas like DMG are among the most devastating of childhood cancers. Tumours typically arise in the brain and are very challenging to treat, with prognosis extremely poor. As such, effective therapeutic options are urgently needed.

Dr Jane Pears, paediatric consultant oncologist at Our Lady's Children's Hospital, Crumlin, who treats children with this disease said: "Despite combined best efforts, these tumours remain a devastating diagnosis for children and their families. The best treatment we can currently offer may extend survival for a few months but is not curative. We are now entering an exciting era of expansion of our knowledge of this disease at a molecular level, which in turn will lead us towards more targeted treatments. Thanks to collaborative translational efforts between scientists, such as Prof. Bracken and his team working in the laboratory, and doctors in the clinical setting, this will hopefully lead to the improved outcomes that we all so dearly wish to see."

Speaking to the importance of the work, Maeve Lowery, Professor of Translational Cancer Medicine at Trinity, and Academic Director of the Trinity St James's Cancer Institute (TSJCI) said: "These findings have the potential to transform the treatment landscape of DMG tumours and improve outcomes for children with this challenging disease. Importantly, this pivotal work illustrates the success of a precision oncology approach - where understanding how cancers develop on a genomic level can accelerate the development of more effective treatments with less side effects. The Precision Oncology Research Program at TSJCI, led by Prof Bracken, will build on this success to continue to develop new and innovative treatment strategies for adult and childhood cancers."

Dr Becky Birch, Head of Research at The Brain Tumour Charity, which helped fund the study, said: "This is a really promising discovery that we hope will now pave the way for new and targeted treatments to be developed for children with diffuse midline gliomas (DMGs). With average survival still heartbreakingly short at less than 12 months, we urgently need to find new options to help slow the growth of this rare and often-inoperable cancer and give children diagnosed more time to live. It's really exciting that we now better understand how a specific genetic mutation may be driving the disease, and even more so that drugs that may inhibit this process have already been tested in other cancers. If further research can now design EZH2 inhibitors to more effectively target DMG cells, we hope these drugs can be quickly advanced into clinical trials for children diagnosed with this devastating disease."

Developing cancer treatments - why this research is different

Ordinarily, developing effective cancer treatments can take decades; indeed, it can take years before scientists are able to develop model systems in relevant cell types that afford them the chance to "look under the genetic bonnet".

Such investigations can first help us understand how cancers function. That information then provides the all-important clues as to how we can fight them. Further lab-based studies can hone these approaches, ultimately opening the doors to clinical trials and, if we're lucky, improved treatments.

The scientists behind this study have therefore taken great strides in the battle against DMG, having discovered key aspects of this disease at a genetic level; proposed an available strategy to target it; and created a model of the disease that can be used in continued work to advance further improved treatment strategies.

NOTICE: This summary has been updated to correct misspellings of the last names of both Perspective authors. The Perspective authors are Sanne Cottaar and Paula Koelemeijer. We apologize for our error.

The first direct seismic observations from NASA’s InSight lander, presented in three studies in this issue, provide clues to the composition of Mars. Researchers across these studies report preliminary findings from the Insight mission and begin to map – for the first time – the interior of a planet apart from Earth. “These three studies provide important constraints on the present-day structure of Mars and are also key for improving our understanding of how the planet formed billions of years ago and evolved through time,” write Sanne Cottaar and Paula Koelemeijer in a related Perspective. Studying a planet’s interior layers – its crust, mantle and core – can reveal key insights into its formation and evolution, as well as uncovering any geomagnetic and tectonic activity it hosts. Such deep interior regions can be probed by measuring the waves that travel through the planet’s body following seismic events like a quake. Such methods have been instrumental in surveying the internal characteristics of Earth.

In early 2019, NASA’s Martian lander InSight (Interior Exploration using Seismic Investigations, Geodesy and Heat Transport) began to detect and record marsquakes from its position on the surface of Mars, including several subcrustal quakes that resemble tectonic events on Earth. Brigitte Knapmeyer-Endrun and colleagues used marsquakes and ambient seismic noise to image the structure of the Martian crust below the InSight landing site, finding evidence for a multi-layered crust with either two or three interfaces. Extrapolating this data to the entire planet, Knapmeyer-Endrun et al. show how the average thickness of Mars’ crust lies between 24 and 72 kilometers (km). Amir Khan et al. used direct and surface reflected seismic waves from eight low-frequency marsquakes to probe deeper and reveal the structure of Mars’ mantle to a depth of nearly 800 km. Their findings suggest that a thick lithosphere lies close to 500 km below the surface and, like the Earth, likely has a low-velocity layer beneath it. According to Khan et al., Mars’ crustal layer is likely highly enriched in heat-producing radioactive elements, which heats this region at the expense of the planet’s interior. Deeper still, Simon Stähler and colleagues used the faint seismic signals reflected off the Martian core-mantle boundary to investigate the Martian core. They found that Mars’ relatively large liquid metal core has a radius of nearly 1,830 kilometers and begins roughly halfway between the surface and the center of the planet, suggesting that the planet’s mantle consists of only one rocky layer, rather than two, like in Earth. According to Stähler et al., the findings indicate that the iron-nickel core is less dense than previously thought and enriched in lighter elements. “Direct seismic observations on Mars represent a major leap forward in planetary seismology,” write Cottaar and Koelemeijer. “Over the coming years, as more marsquakes are measured, scientists will refine these models of the red planet and reveal more of Mars’ enigmatic mysteries.”

Journal

Science

DOI

10.1126/science.abf2966

Of the nearly 100 SARS-CoV-2 vaccines currently undergoing clinical trials, only seven are delivered intranasally - despite this vaccine type's long success in providing protection from influenza. In a Perspective, Frances Lund and Troy Randall argue that intranasal vaccines could be beneficial in the continued fight against COVID-19, especially considering respiratory viruses like SARS-CoV-2 predominantly enter the nasal passage first. Currently authorized COVID-19 vaccines are delivered via intramuscular injection, where they elicit systemic immune responses and central immune memory. While several versions are currently being administered worldwide, many more are in development. However, according to the authors, given the respiratory propensity of the virus, it is surprising that so few intranasal vaccines, which deliver their antigens directly to the site of infection, are being considered. Here, Lund and Randal discuss the potential of intranasal COVID-19 vaccines, highlighting their advantages, drawbacks and rationale for use over intramuscular options. In addition to being needle-free, intranasal vaccines provide two additional layers of protection compared to intramuscular vaccines. Intranasal vaccine-elicited immunoglobulin A (IgA) and resident memory B and T cells in the nasal passages and upper airways provide a barrier to infection, impede viral replication and reduce viral shedding. Lund and Randall note that effective vaccination strategies need not be restricted to a single delivery system and suggest that an ideal vaccination strategy may consist of an intramuscular vaccine combined with an intranasal booster.

Like dreaming of walking through a world they've not yet experienced, the retinas of neonatal mice practice for what mature eyes must later process by generating spontaneous patterns of activity that mimic the perception of directional movement through space, according to a new study. Essential functions in the mammalian visual system, including the ability to locate objects and detect motion, are present even at the first onset of vision. Optic flow, the perceived relative motion of objects and surfaces that seemingly stream by a field of vision during movement, is one of these functions. However, how the visual system organizes its functional characteristics before visual sensory experience is even possible remains unclear. And, while previous studies have revealed spontaneous retinal activity prior to functional vision, the role of this spontaneous activity in visual system development is unknown. Xinxin Ge and colleagues examined the spontaneous activity of ganglion cells in mice at multiple ages throughout development in vivo and discovered an intrinsic mechanism in the developing retina that prepares the downstream visual system for motion detection before the newborn mice can see. According to Ge et al., spontaneous waves of retinal activity during this transient window flow in the same pattern as would be produced if the mouse was physically moving through the environment. This patterned, spontaneous activity effectively trains the visual system and the associated brain circuits to process directional information and to interpret movement through space at eye opening.

Advances in microscopy have enabled researchers to picture loops of DNA strands for the first time. The images reveal how the human genome organises itself in three-dimensional space at much higher resolution than previously possible.

The findings, published in a new study in the journal Molecular Cell, also reveal that the process of DNA being copied into RNA - transcription - indirectly shapes the architecture of the genome. An international team led by Pia Cosma at the Centre for Genomic Regulation (CRG) in Barcelona and Melike Lakadamyali at the Perelman School of Medicine at the University of Pennsylvania in the United States found that transcription generates a force that moves across DNA strands like ripples through water.

Known as supercoiling, the force causes structural proteins known as cohesins to 'surf' across DNA strands, changing the scaffold's architecture and morphing the overall shape of the genome. While it is known that genome organization regulates gene transcription, it is the first-time researchers have found transcription to impact genome organization the other way round through supercoiling.

According to the researchers, the discovery of this new force may have future implications for the understanding of genetic diseases such as Cornelia de Lange syndrome, which is caused by mutations in genes encoding for cohesin or cohesin regulators. The findings may also be relevant for developmental disorders linked to how chromatin folds, as well as opening new avenues of research in genome fragility and cancer development.

The researchers studied the biological mechanisms that enable two metres of DNA to be squeezed into a tight space in each human cell. In this condensed state, the DNA, also known as chromatin, contains many loops that bring together different regions of the genome that would normally be far apart. The resulting physical proximity is important for transcribing DNA into RNA which then makes proteins, making chromatin looping a fundamental biological mechanism for human health and disease.

According to Vicky Neguembor, Staff Scientist at the CRG and first author of the paper, "Chromatin looping is what allows individual cells to switch different information on and off, which is why for example a neuron or a muscle cell with the same genomic information can still behave so differently. Loops are also one of the ways the genome gets compacted to fit into the nucleus."

"What we have found is important because it shows the biological process of transcription plays an additional role beyond its fundamental task of creating RNA that eventually turn into proteins. Transcription indirectly compacts the genome in an efficient manner and helps different regions of the genome talk to each other."

Previous techniques used to study this process could predict where loops were located but not their actual shape or how they look like within the cells. To improve image resolution, the researchers used a special type of microscopy that use high-power lasers under specific chemical conditions to track the blinking of fluorescent molecules. The technique provides ten times higher resolution than conventional microscopy, and combined with advanced imaging analysis techniques the researchers were able to identify chromatin loops, and the cohesins that hold the structure together like paper clips, within intact cells.

Manipulating RNA can allow plants to yield dramatically more crops, as well as increasing drought tolerance, announced a group of scientists from the University of Chicago, Peking University and Guizhou University.

In initial tests, adding a gene encoding for a protein called FTO to both rice and potato plants increased their yield by 50% in field tests. The plants grew significantly larger, produced longer root systems and were better able to tolerate drought stress. Analysis also showed that the plants had increased their rate of photosynthesis.

"The change really is dramatic," said University of Chicago Prof. Chuan He, who together with Prof. Guifang Jia at Peking University, led the research. "What's more, it worked with almost every type of plant we tried it with so far, and it's a very simple modification to make."

The researchers are hopeful about the potential of this breakthrough, especially in the face of climate change and other pressures on crop systems worldwide.

"This really provides the possibility of engineering plants to potentially improve the ecosystem as global warming proceeds," said He, who is the John T. Wilson Distinguished Service Professor of Chemistry, Biochemistry and Molecular Biology. "We rely on plants for many, many things--everything from wood, food, and medicine, to flowers and oil--and this potentially offers a way to increase the stock material we can get from most plants."

Rice nudged along

For decades, scientists have been working to boost crop production in the face of an increasingly unstable climate and a growing global population. But such processes are usually complicated, and often result only in incremental changes.

The way this discovery came about was quite different.

Many of us remember RNA from high school biology, where we were taught that the RNA molecule reads DNA, then makes proteins to carry out tasks. But in 2011, He's lab opened an entire new field of research by discovering the keys to a different way that genes are expressed in mammals. It turns out that RNA doesn't simply read the DNA blueprint and carry it out blindly; the cell itself can also regulate which parts of the blueprint get expressed. It does so by placing chemical markers onto RNA to modulate which proteins are made and how many.

He and his colleagues immediately realized that this had major implications for biology. Since then, his team and others around the world have been trying to flesh out our understanding of the process and what it affects in animals, plants and different human diseases; for example, He is a co-founder of a biotech company now developing new anti-cancer medicines based on targeting RNA modification proteins.

He and Guifang Jia, a former UChicago postdoctoral researcher who is now an associate professor at Peking University, began to wonder how it affected plant biology.

They focused on a protein called FTO, the first known protein that erases chemical marks on RNA, which Jia found as a postdoctoral researcher in He's group at UChicago. The scientists knew it worked on RNA to affect cell growth in humans and other animals, so they tried inserting the gene for it into rice plants--and then watched in amazement as the plants took off.

"I think right then was when all of us realized we were doing something special," He said.

The rice plants grew three times more rice under laboratory conditions. When they tried it out in real field tests, the plants grew 50% more mass and yielded 50% more rice. They grew longer roots, photosynthesized more efficiently, and could better withstand stress from drought.

The scientists repeated the experiments with potato plants, which are part of a completely different family. The results were the same.

"That suggested a degree of universality that was extremely exciting," He said.

It took the scientists longer to begin to understand how this was happening. Further experiments showed that FTO started working early in the plant's development, boosting the total amount of biomass it produced.

The scientists think that FTO controls a process known as m6A, which is a key modification of RNA. In this scenario, FTO works by erasing m6A RNA to muffle some of the signals that tell plants to slow down and reduce growth. Imagine a road with lots of stoplights; if scientists cover up the red lights and leave the green, more and more cars can move along the road.

Overall, the modified plants produced significantly more RNA than control plants.

Modifying the process

The process described in this paper involves using an animal FTO gene in a plant. But once scientists fully understand this growth mechanism, He thinks there could be alternate ways to get the same effect.

"It seems that plants already have this layer of regulation, and all we did is tap into it," He said. "So the next step would be to discover how to do it using the plant's existing genetics."

He can imagine all sorts of uses down the road--and he's working with the university and the Polsky Center for Entrepreneurship and Innovation to explore the possibilities.

"Even beyond food, there are other consequences of climate change," said He. "Perhaps we could engineer grasses in threatened areas that can withstand drought. Perhaps we could teach a tree in the Midwest to grow longer roots, so that it's less likely to be toppled during strong storms. There are so many potential applications."

A new study showed that a wearable computer vision device can reduce collisions for both people who are blind or those who are visually impaired and using a long cane and/or guide dog by 37 percent, compared to using other mobility aids alone.

People who have visual impairments are at a significantly higher risk for collisions and falls. Commonly used mobility aids like long canes and guide dogs can offer benefits, but come with limitations in effectiveness and costs, respectively. While some electronic devices are marketed direct-to-consumer claiming to warn wearers of surrounding objects, there has been little evidence of their effectiveness in actual daily mobility settings. This is one of the first randomized-controlled trials to look at the potential benefit of the devices at home and outside of a controlled lab environment. The new study led by vision rehabilitation researchers at Mass Eye and Ear, a member of Mass General Brigham was published July 22 in JAMA Ophthalmology.

"Independent travel is an essential part of daily life for many people who are visually impaired, but they face a greater risk of bumping into obstacles when they walk on their own," said Gang Luo, PhD, an associate scientist at the Schepens Eye Research Institute of Mass Eye and Ear, and an associate professor of ophthalmology at Harvard Medical School. "Although many blind individuals use long canes to detect obstacles, collision risks are not completely eliminated. We sought to develop and test a device that can augment these everyday mobility aids, further improving their safety."

Vibrating wearable device prototype put to test

The experimental device used in the trial was created by Dr. Luo and colleagues in his vision rehabilitation lab, including the lead author Shrinivas Pundlik, PhD, who designed the computer vision algorithm. The device and data recording unit were enclosed in a sling backpack with a chest-mounted, wide-angle camera on the strap, and two Bluetooth-connected wristbands worn by the user. The camera is connected to a processing unit that captures images and analyzes collision risk based on the relative movement of incoming and surrounding objects in the camera's field of view. If an imminent collision is detected on the left or right side, the corresponding wristband will vibrate; a head-on collision will cause both wristbands to vibrate. Unlike other devices that simply warn of nearby objects whether or not a user is moving toward the objects, this device analyzes relative motion, warning only of approaching obstacles that pose a collision risk, and ignoring objects not on a collision course.

The new study included 31 blind and visually impaired adults who use either a long cane or guide dog (or both) to aid their daily mobility. After being trained to use the device, they used it for about a month at home in conjunction with their typical mobility device (mostly a long cane). The device was randomized to switch between active mode, in which the users could receive vibrating alerts for imminent collisions, and silent mode, in which the device still processed and recorded images, but did not give users any warning even if potential collisions were detected. The silent mode is equivalent to the placebo condition in many clinical trials testing drugs. The wearers and researchers would not know when the device modes changed during the testing and analysis. Collisions were analyzed by researchers from the recorded videos. The effectiveness of the device was evaluated by comparing collision incidents that occurred during active and silent modes. The study found that the collision frequency in active mode was 37 percent less than that in silent mode.

Providing a new option for the visually impaired

Long canes are one of the most effective and affordable mobility tools for a person who is blind or visually impaired, but they have limitations. Canes primarily detect hazards on the ground that are within reach; however, hazards above ground level are often missed. Additionally, the range of long cane sweeping can be restricted in busy environments, such as cities, in order avoid hitting nearby pedestrians. Guide dogs are highly effective, but hard to come by and cost-prohibitive for many, as training a guide dog typically costs $45,000-$60,000. A chest-mounted, collision-warning device could provide an option to help people avoid overhanging or moving obstacles that pose challenges to long cane users, Dr. Luo explained.

Alex Bowers, PhD, a clinical researcher and one of the co-authors of the paper, added that the video recording from the study also provides rich data about daily life mobility of people with visual impairments. This can, in turn help researchers better understand the challenges of collision detection in this population.

"Long canes are still very helpful and cost-effective tools that work well in many situations, but we hope a wearable device like this can fill in the gaps that the cane might miss, providing a more affordable, easier to obtain option than a guide dog," Dr. Bowers said. "The insights provided by our data can be valuable for improving mobility aid training."

Next, Dr. Luo and his team seek to leverage ongoing improvements in mobile processing power and cameras to make the device smaller and more cosmetically appealing. With additional funding, the team hopes that such a device could be submitted to the U.S. Food and Drug Administration for approval so that it could be commercially available for people with low vision.

"Dr. Luo and his team are making great contributions to supporting and ensuring travel independence in our low-vision community," said Joan W. Miller, MD, Chief of Ophthalmology at Mass Eye and Ear, Massachusetts General Hospital, and Brigham and Women's Hospital, and Chair of Ophthalmology and David Glendenning Cogan Professor of Ophthalmology at Harvard Medical School.

New European Union regulations on batteries could offer a huge boost to the global decarbonisation mission - but only if it leverages its political and economic weight to ensure a fairer global marketplace.

According to a team of scientists and researchers writing in Science, the new regulations, due to come into force from January 2022, have the potential to unify policy on approaches such as recycling, use of recycled raw materials, and creating a circular economy.

Contributing to the study were experts at Newcastle University, the University of Birmingham, Circular Energy Storage Research and Consulting, University of California, Davis and the National Institute of Clean and Low Carbon Energy (NICE) America Research.

The European Union is a significant market for Electric Vehicles globally, and the effects of its regulation will be felt by battery supply chains in many other countries, including the United Kingdom, even though it has left the European Union.

Although these rules are both necessary and welcome, whilst well-intentioned, the researchers argue, their effects are hard to predict and could result in a competitive disadvantage for European companies. This is because the EU must operate in the global marketplace where there is an imbalance between new and mature markets and uncertainty caused by the rapid rate of growth and innovation in the lithium-ion battery (LIB) market.

China, for example, has a well-developed LIB market, with relatively strict regulations around recycling and decarbonising the supply chain. In the US, in contrast, although electrification of transport has been declared a priority, legislation to promote a circular economy in the sector is lagging behind both China and the EU.

Dr Oliver Heidrich, of Newcastle University, led the study. He says: "Balancing the challenges of climate change, sustainability and competitiveness is a difficult task. Formal assessments along the supply and value chain from raw material extraction, achieving carbon reductions targets to final disposal are needed to ensure social, environmental and economic aspects are addressed successfully".

Companies that are able to comply with more stringent regulations have a big competitive advantage in these markets. This is particularly true in China where there are well-established, tougher domestic requirements. Companies in markets where there is ready access to both virgin and recycled materials - such as China and South Korea - are also likely to have an advantage over EU companies, where supply chains are less well-developed and may still rely on imported materials.

The US shares the EU's situation with a less developed supply chain, however battery makers will retain a higher degree of freedom to operate which can be crucial for innovation in both battery technology and electric mobility.

"While it is critical to ensure a high degree of sustainability in the battery supply chain we must not forget that the end game is a decarbonised and less polluting transportation sector," says Hans Eric Melin, of Circular Energy Storage Research and Consulting. "By raising the bar to a higher level than for almost any other product there is a significant risk that the European battery industry, which is well behind global leaders, will struggle to keep up with the required pace. This could limit automotive makers' ability to produce electric vehicles at the scale required by 2030 and might also cause distortion of innovation and a slow down of investments."

Global standards, argue the researchers, are the only way to make this essential supply chain both predictable and powerful. The new, advanced standards set out by the EU, together with its significant share of the EV market, could give it leverage to lead the way in setting such standards.

"The EU Battery Regulation has admirable intentions, but unintended consequences could be felt by manufacturers, recyclers and other actors across the world. Whilst difficult to achieve, and politically challenging, a co-ordinated, global approach would ensure a more rapid and effective transition to electric transport," says Dr Gavin Harper, of the University of Birmingham

The European market can provide significant leverage to set standards across the globe in order to stimulate innovation in the areas of cascaded use and recycling and serve as a steppingstone to more formal global standards. Policies and legislations that address environmental or social issues are very much needed and do need to consider the unintended consequences as much as the in-tended consequences

Newly-hatched pterosaurs may have been able to fly but their flying abilities may have been different from adult pterosaurs, according to a new study.

Pterosaurs were a group of flying reptiles that lived during the Triassic, Jurassic and Cretaceous Periods (228 to 66 million years ago). Due to the rarity of fossilised pterosaur eggs and embryos, and difficulties distinguishing between hatchlings and small adults, it has been unclear whether newly-hatched pterosaurs were able to fly.

Researchers from the Universities of Portsmouth and Bristol, along with palaeontologist Darren Naish, found that hatchling humerus bones were stronger than those of many adult pterosaurs, indicating that they would have been strong enough for flight.

In the study, published in Scientific Reports, the researchers modelled the flying abilities of hatchlings using previously obtained wing measurements from four established hatchling and embryo fossils from two pterosaur species, Pterodaustro guinazui and Sinopterus dongi. They also compared these wing measurements with those of adults from the same species and compared the strength of the humerus bone, which forms part of the wing, of three hatchlings with those of 22 adult pterosaurs.

Study co-author Dr Mark Witton from the University of Portsmouth said: "Although we've known about pterosaurs for over two centuries, we've only had fossils of their embryos and hatchlings since 2004. We're still trying to understand the early stages of life in these animals. One discussion has centred around whether pterosaurs could fly as hatchlings or, like the vast majority of birds and bats, they had to grow a little before they could take wing.

"We found that these tiny animals - with 25 cm wingspans and bodies that could neatly fit in your hand - were very strong, capable fliers. Their bones were strong enough to sustain flapping and take-off, and their wings were ideally shaped for powered (as opposed to gliding) flight. However, they would not have flown exactly like their parents simply because they were so much smaller: flight capabilities are strongly influenced by size and mass, and so pterosaur hatchlings, being hundreds of times smaller than their parents, were likely slower, more agile fliers than the wide-ranging, but less manoeuvrable adults."

Dr Liz Martin-Silverstone from the University of Bristol’s School of Earth Sciences said: “There have been several debates about whether juvenile pterosaurs could fly, but this is the first time it’s been studied through a more biomechanical point of view. It’s exciting to discover that even though their wings may have been small, they were built in a way that made them strong enough to fly.”

The researchers found that while hatchlings had long, narrow wings suited to long-distance flight, their wings were shorter and broader than those of adult pterosaurs, with a larger wing area relative to hatchling mass and body size. These wing dimensions may have made hatchlings less efficient than adult pterosaurs at long-distance travel, but may have resulted in them being more agile fliers, enabling them to suddenly change direction and speed.

The authors speculate that the agile flying style of hatchling pterosaurs may have enabled them to rapidly escape predators and made them better suited to chasing nimbler prey and flying amongst dense vegetation than adult pterosaurs.

Dr Witton said: "That gives us a lot to think about with regard to flying reptile ecology. How independent were the hatchlings from their parents? Did flight style influence habitat choices, and did these change as pterosaurs grew? There's still a lot to learn about the life histories of these animals, but we're confident that, whatever they were doing as they grew up, they were capable of flying from the moment they hatched."

A research team led by Wim Annaert (VIB-KU Leuven) uncovered the early assembly of gamma-secretase, a protein complex linked to numerous cellular processes including the development of Alzheimer's disease. In a first step, two dimeric subcomplexes are formed, which independently exit the ER and only afterwards assemble into a four-subunit complex. This 'buckle up' mechanism is thought to prevent premature assembly and activity. The new insights are very relevant, as gamma-secretase is an important potential therapeutic target for Alzheimer's and other conditions.

An enzyme complex involved in plaque production

Gamma-secretase is best known as the enzyme that cleaves the amyloid precursor protein, generating a small peptide called amyloid beta, the main constituent of the plaques found in the brains of people affected by Alzheimer's disease. Ever since the discovery of its implication in disease, gamma-secretase has been studied and tested as a potential therapeutic target, but its role in the body is much broader than producing amyloid.

We now know that gamma-secretase is a complex made up of four components, two of which have multiple homologues, resulting in variety of complexes with distinct subcellular distributions, providing a basis for substrate selectivity. All four gamma-secretase components are transmembrane proteins that are co-translationally inserted into the endoplasmic reticulum (ER). But how these four subunits get assembled in such stable enzyme complexes remained unknown until now.

Dissecting the assembly line

The Annaert lab at the VIB-KU Leuven Center for Brain & Disease Research is specialized in membrane trafficking and has a long track record of studying the gamma-secretase complex. By combining biochemistry and high-resolution imaging, they have now uncovered the early steps of the gamma-secretase assembly process.

"To dissect the assembly steps, we used a method developed by Randy Schekman of UC Berkeley (who won the Noble Prize in Medicine in 2013), and with whom we collaborated on this endeavor. This approach unveiled that in fact dimers of two out of the four subunits are formed in the ER, in this way preventing the premature breakdown of individual subunits," says Wim Annaert. "These dimers only get fully assembled into gamma-secretase complexes shortly thereafter, between ER-exit and their transition to the Golgi complex."

Only fully assembled complexes are transported through the Golgi onto their final destination in different cellular compartments.

Interestingly, the dimer assembly signature remains visible in the high-resolution structure of gamma-secretase, suggesting a 'buckle up model' for dimer assembly: one side of the dimers act as 'buckles', while the other side functions as the belt through interactions keeping the full complex in place.

"This 'buckle up' mechanism could prevent the untimely processing of substrates," says Annaert. "Given the broad range of substrates and pathways controlled by gamma-secretase -from developmental processes to cancer and Alzheimer, the precise tuning of this assembly process allows for further spatiotemporal regulation of gamma-secretase activity."

The insights are extremely relevant, as problems during complex assembly may also have a significant impact on the many physiological and pathological processes regulated by gamma-secretase.

In a new study, published recently in the journal Circulation Research, scientists discover how the production of protective molecules known as specialised pro-resolving mediators (SPM) is altered in patients with COVID-19.

The results suggest that treatments which increase SPM production, such as dexamethasone or SPM based drugs, could play a key role in limiting inflammation in these patients.

Currently there is little understanding around the mechanisms that lead to uncontrolled inflammation in patients with COVID-19.

The study found a link between decreased SPM blood levels and disrupted white blood cell responses in patients with a higher disease burden. The findings also revealed that dexamethasone, the first drug approved for treatment of patients with COVID-19, increased the levels of these protective molecules in these patients. Furthermore, treatment of white blood cells with SPM improved their function and reduced the expression of molecules linked to the spread of inflammation. Understanding these mechanisms will help provide new leads into the development of treatments to limit disease severity in patients with COVID-19.

This study offers a new insight into the disrupted biological processes that contribute to increased disease severity in COVID-19 patients. Results suggest that treatments which increase SPM production, such as dexamethasone or SPM based drugs, could play a key role in limiting inflammation in this patient group.

Jesmond Dalli, Professor in Molecular Pharmacology and Lipid Mediator Unit Director at Queen Mary University of London said: "The observation that dexamethasone increased the production of SPM was a surprising finding. This finding suggests that SPM may serve as biomarkers to determine the efficacy of this drug in limiting inflammation in patients with COVID-19. Another surprising finding was that blood levels of these molecules remained altered several weeks after resolution of clinical symptoms."

"Our results are the first to relate the impact that COVID-19 infections on immune responses and to explore the utility of using SPM to rectify white blood cell behaviour. Given the extensive body of literature demonstrating the protective role of these molecules in limiting inflammation in both viral and bacterial infections these results suggest that SPM and SPM-based therapeutics may be useful in the treatment of infections to limit inflammation without compromising the ability of the immune system to deal with the invading pathogen".

Mauro Perretti (Dean for Research, School of Medicine and Dentistry) said: "This study is a perfect example of a productive partnership between Barts and the London School of Medicine at Queen Mary and Barts NHS Trust, a partnership established in difficult circumstances yet successful thanks to the will and commitment of our scientists and clinicians. The paper presents world class data on how resolution pathways impact on COVID infection, opening opportunities for new therapies and new markers to predict patient outcome".

Alexandria, Va., USA - Jiachen Lin, Harvard School of Dental Medicine, Boston, Mass., USA., presented the poster "Burden of Oral Diseases in Emerging Countries: A Prediction Model" at the virtual 99th General Session & Exhibition of the International Association for Dental Research (IADR), held in conjunction with the 50th Annual Meeting of the American Association for Dental Research (AADR) and the 45th Annual Meeting of the Canadian Association for Dental Research (CADR), on July 21-24, 2021.

The goal of this study was to investigate the burden of oral diseases and predict trends by 2025 in the U.S. and emerging countries. Global Burden of Disease data from 1990-2017 was used to analyze the prevalence and disability-adjusted life years of oral diseases across the U.S., Brazil, Russia, India, China, Mexico, Indonesia, Nigeria and Turkey by gender and age groups (

In the prediction model, females and older adults had a higher burden of oral diseases. Notably, Nigeria was expected to continue with the lowest estimated oral diseases burden compared to the other countries. Although the U.S. had a relatively lower oral diseases burden than emerging countries, forecasts suggest a large increase of disability-adjusted life years attributed to oral diseases across all age groups.

These results provide insightful information for policymakers to identify effective oral health strategies and allocation of resources to decrease the burden of oral diseases among populations with purported higher and increasing burden of oral diseases in the next five years.

View this poster presentation in the IADR General Session Virtual Experience Platform.

View a PDF of this press release.

International Association for Dental Research

The International Association for Dental Research (IADR) is a nonprofit organization with over 10,000 individual members worldwide, with a mission to drive dental, oral and craniofacial research for health and well-being worldwide. To learn more, visit http://www.iadr.org.

Since early 2019, researchers have been recording and analysing marsquakes as part of the InSight mission. This relies on a seismometer whose data acquisition and control electronics were developed at ETH Zurich. Using this data, the researchers have now measured the red planet's crust, mantle and core - data that will help determine the formation and evolution of Mars and, by extension, the entire solar system.

Mars once completely molten

We know that Earth is made up of shells: a thin crust of light, solid rock surrounds a thick mantle of heavy, viscous rock, which in turn envelopes a core consisting mainly of iron and nickel. Terrestrial planets, including Mars, have been assumed to have a similar structure. "Now seismic data has confirmed that Mars presumably was once completely molten before dividing into the crust, mantle and core we see today, but that these are different from Earth's," says Amir Khan, a scientist at the Institute of Geophysics at ETH Zurich and at the Physics Institute at the University of Zurich. Together with his ETH colleague Simon Stähler, he analysed data from NASA's InSight mission, in which ETH Zurich is participating under the leadership of Professor Domenico Giardini.

No plate tectonics on Mars

The researchers have discovered that the Martian crust under the probe's landing site near the Martian equator is between 15 and 47 kilometres thick. Such a thin crust must contain a relatively high proportion of radioactive elements, which calls into question previous models of the chemical composition of the entire crust.

Beneath the crust comes the mantle with the lithosphere of more solid rock reaching 400-600 kilometres down - twice as deep as on Earth. This could be because there is now only one continental plate on Mars, in contrast to Earth with its seven large mobile plates. "The thick lithosphere fits well with the model of Mars as a 'one-plate planet'," Khan concludes.

The measurements also show that the Martian mantle is mineralogically similar to Earth's upper mantle. "In that sense, the Martian mantle is a simpler version of Earth's mantle." But the seismology also reveals differences in chemical composition. The Martian mantle, for example, contains more iron than Earth's. However, theories as to the complexity of the layering of the Martian mantle also depend on the size of the underlying core - and here, too, the researchers have come to new conclusions.

The core is liquid and larger than expected

The Martian core has a radius of about 1,840 kilometres, making it a good 200 kilometres larger than had been assumed 15 years ago, when the InSight mission was planned. The researchers were now able to recalculate the size of the core using seismic waves. "Having determined the radius of the core, we can now calculate its density," Stähler says.

"If the core radius is large, the density of the core must be relatively low," he explains: "That means the core must contain a large proportion of lighter elements in addition to iron and nickel." These include sulphur, oxygen, carbon and hydrogen, and make up an unexpectedly large proportion. The researchers conclude that the composition of the entire planet is not yet fully understood. Nonetheless, the current investigations confirm that the core is liquid - as suspected - even if Mars no longer has a magnetic field.

Reaching the goal with different waveforms

The researchers obtained the new results by analysing various seismic waves generated by marsquakes. "We could already see different waves in the InSight data, so we knew how far away from the lander these quake epicentres were on Mars," Giardini says. To be able to say something about a planet's inner structure calls for quake waves that are reflected at or below the surface or at the core. Now, for the first time, researchers have succeeded in observing and analysing such waves on Mars.

"The InSight mission was a unique opportunity to capture this data," Giardini says. The data stream will end in a year when the lander's solar cells are no longer able to produce enough power. "But we're far from finished analysing all the data - Mars still presents us with many mysteries, most notably whether it formed at the same time and from the same material as our Earth." It is especially important to understand how the internal dynamics of Mars led it to lose its active magnetic field and all surface water. "This will give us an idea of whether and how these processes might be occurring on our planet," Giardini explains. "That's our reason why we are on Mars, to study its anatomy."