Brain

The study led by Imperial College London found that flexibility, as well as density, in the bone nanostructure is an important factor in assessing how likely someone is to suffer fractures.

The findings, published today in Scientific Reports, suggest that doctors should look not only at bone density, but also bone flexibility, when deciding how to prevent bone breakages.

Clinicians use DEXA scans, which look at how porous or dense bones are, to assess the likelihood of fractures. DEXA scans detect bone weakness in osteoporosis, a condition that causes weakened bones, and to inform treatments, like prescribing the medicine bisphosphonate, to help prevent fractures in these people.

However, some people whose bones seem healthy on DEXA scans are more likely than others to suffer fractures. To find out why, the researchers looked to the building blocks of bone: stiff minerals surrounding flexible collagen fibrils, which are responsible for our bones' resistance to fracture during trips and falls.

They used high energy intense beams of X-rays generated by Diamond Light Source, the UK's national synchrotron, to examine bone flexibility at the nanoscale. They were able to assess how the collagen and minerals within bone flex and then break apart under load in the nanostructure of hip bone samples.

They compared the behaviour of the bone tissue samples under load between three groups of donors: those who had not suffered a hip fracture, or any other fracture; those without a bisphosphonate treatment history who had suffered a fractured hip; and those with a bisphosphonate treatment history who had suffered a fractured hip.

The team found that donors without fractures were more likely to have flexible collagen and mineral nanostructure than those with who had suffered fractures.

Irrespective of bisphosphonate treatment, the collagen and minerals were less flexible under load in patients with fractures, meaning the mineral broke away from the collagen at much lower forces.

The researchers say the bones may have fractured because the tissue was too inflexible and could not deform to absorb energy during a bump or fall - and that this highlights the importance of flexibility in the collagen and minerals of bone.

Therefore, flexibility at the nanoscale could be important in predicting future bone fractures and a target for new treatments - a finding that could inform future preventative treatment of bone fractures.

Study co-author Dr Ulrich Hansen, of Imperial's Department of Mechanical Engineering, said: "We tend to think of our bones as solid, hard support structures, but flexibility appears to be extremely important in bone health. If bones are too hard, they are less able to absorb impact and more likely to break. Our study suggests that flexibility could be just as important as density in preventing fractures."

Osteoporosis link

One of the main risk factors for age-related hip fractures is osteoporosis, a disease where bone density is lost leaving patients prone to fractures. Usually, old bone tissue is broken down and replaced with new tissue. Osteoporosis occurs when the breaking down of bone outpaces its replacement.

Three million people in the UK and 200 million worldwide live with osteoporosis. Patients are often given bisphosphonate, which addresses this imbalance by binding to the surface of bones and blocking bone removal.

In this study the researchers found that donors with hip fractures who had received bisphosphonates for between one and 13 years had lower tissue strength and nanoscale flexibility than the untreated fracture donors and a control group.

Bisphosphonates are clinically proven to reduce the risk of fractures by increasing bone mass and mineral density as well as filling pits created by overactive bone cells. The researchers say their results could be because in some bisphosphonate users, the drug might bind itself to and harden the mineral crystals that surround the collagen fibers within bone. The hardening could make bone less flexible and therefore less able to absorb impact.

However, the findings could also be a result of the patients' bones being more osteoporotic in the first place, and these results could be because the researchers couldn't control for additional factors like initial disease severity.

Co-author Dr Richard Abel from the Department of Surgery and Cancer said: "We were surprised to see that bisphosphonate users seemed to have less flexible bone nanostructures. Perhaps after a long period of treatment in some patients, there is a loss of flexibility at the nanoscale that offsets some of the strength benefits from increases in bone density. More research is needed to determine exactly why this is and how this could affect clinical practice in long-term users.

"Perhaps we need to build on the existing treatment framework to add new diagnostics, therapies and follow ups that address nanoscale bone health - and address the collagen, not just the mineral. That way we can treat everyone in the best way possible."

Lead author Dr Shaocheng Ma from the Department of Mechanical Engineering said: "It's possible that the amount of mineral strain is key in setting off the fracture process. However, in patients who have taken bisphosphonates for a long time the mineral could become too stiff, causing it to break away from the collagen. This releases the collagen and allows it to stretch uncontrollably, which then results in a fracture."

The researchers say that people who are taking bisphosphonates should continue to follow the advice of their doctors and seek a review of treatment after five and ten years as per clinical guidelines.

Currently, the diagnosis, treatment and follow up for fragility focuses on the mineral in bone, but this study highlights the role of other factors like collagen, and the interaction between mineral and collagen at the nanoscale.

A new scientific study has revealed unique life strategies of two major groups of microbes that live below Earth’s surface. A publication in Frontiers in Microbiology reports that these groups, originally thought to rely on symbiotic relationships with other organisms, may also live independently and use an ancient mode of energy production.

“These microbes, which belong to the groups Patescibacteria and DPANN, are really special, really exciting examples of the early evolution of life,” said Ramunas Stepanauskas, a senior research scientist at Bigelow Laboratory for Ocean Sciences and an author of the paper. “They may be remnants of ancient forms of life that had been hiding and thriving in the Earth’s subsurface for billions of years.”

Stepanauskas led a research team that used advanced molecular techniques and bioinformatics to analyze thousands of microbial genomes and learn about their evolutionary history. Reading their genetic code revealed that these two groups of abundant microbes lack the capability to breathe in order to synthesize ATP, the common energy currency of life.

The team found that these microbes, which live in a variety of environments in Earth’s interior, appear to gain energy only through the process of fermentation. Many organisms are capable of fermentation, including humans when their muscles run out of oxygen during intense exercise – but they use it only as a supplementary source of energy.

“Our findings indicate that Patescibacteria and DPANN are ancient forms of life that may have never learned how to breathe,” Stepanauskas said. “These two major branches of the evolutionary tree of life constitute a large portion of the total microbial diversity on the planet – and yet they lack some capabilities that are typically expected in every form of life.”

The researchers found that the most recent common ancestors of these two lineages lacked the ability to breathe, just as their modern descendants do. For the first two billion years of Earth’s existence, there was no oxygen in the atmosphere. Today, oxygen is a key component of Earth’s atmosphere and essential to the life it can support – but just a few hundred feet underground, conditions have not changed, and this recent discovery suggests that some subsurface life hasn’t, either.

Scientists had previously speculated that because Patescibacteria and DPANN have very simple genetic features and metabolism, they must live symbiotically and depend upon host organisms to survive. In the new study, the research team found no evidence that Patescibacteria and DPANN are dominated by symbionts – most of them seem to live as free cells and rely on the primitive pathway of fermentation to supply themselves with energy.

“Dependence on other organisms is a feature of life,” said Jacob Beam, a former postdoctoral researcher at Bigelow Laboratory and the lead author of this study. “There are no absolutes in biology, and our research shows that microbes can vary along the spectrum of interdependencies.”

Scientists analyzed microbes from diverse environments around the globe, including a mud volcano at the bottom of the Mediterranean Sea, hydrothermal vents in the Pacific, and the world’s deepest gold mines in South Africa. Bigelow Laboratory Bioinformatics Scientist Julie Brown, Research Scientist Nicole Poulton, former Postdoctoral Research Scientists Eric Becraft and Oliver Bezuidt, and Research Experience for Undergraduates intern Kayla Clark worked on this project, alongside with an international team of scientists who contributed to fieldwork, laboratory, and computational analyses.

In addition to revealing the inner workings of Earth’s subsurface and the evolution of life, these findings can provide a model system of what life on other planets may look like. Environments on Mars and other bodies in the solar system likely resemble Earth’s subsurface, and Patescibacteria and DPANN represent examples of life that appear to require very little energy to survive, which scientists expect would be a requirement for life on other planets.

“This project would not have been possible without the collaboration of this diverse group of scientists collecting samples around the world and uniting their expertise,” Beam said. “Through the collaboration of a global group of scientists working together, we know more about the inner workings of these microbes that form a major fraction of the total biodiversity on our planet.”

This work was funded by the National Science Foundation, the United States Department of Energy, the Simons Foundation, the Russian Science Foundation, and the National Aeronautics and Space Administration.

Journal

Frontiers in Microbiology

DOI

10.3389/fmicb.2020.01848

During the SARS-CoV-2 pandemic, social media platforms have played a major role in conveying information from health care leaders and government officials to communities about how to help stop the spread of COVID-19. Yet as quickly as new and accurate information on the virus becomes available, so, too do counterfeit health products, such as illegal or unapproved testing kits, untested treatments and purported cures.

In a new study published in the Journal of Medical Internet Research Public Health and Surveillance on August 25, 2020, researchers at University of California San Diego School of Medicine found thousands of social media posts on two popular platforms -- Twitter and Instagram -- tied to financial scams and possible counterfeit goods specific to COVID-19 products and unapproved treatments

"We started this work with the opioid crisis and have been performing research like this for many years in order to detect illicit drug dealers," said Timothy Mackey, PhD, associate adjunct professor at UC San Diego School of Medicine and lead author of the study. "We are now using some of those same techniques in this study to identify fake COVID-19 products for sale. From March to May 2020, we have identified nearly 2,000 fraudulent postings likely tied to fake COVID-19 health products, financial scams, and other consumer risk."

According to Mackey, the fraudulent posts came in two waves focused on unproven marketing claims for prevention or cures and fake testing kits. He said a third wave of fake pharmaceutical treatments is now materializing and will worsen when public health officials announce development of an effective vaccine or other therapeutic treatments.

The researchers identified suspected posts through a combination of Natural Language Processing and machine learning. Topic model clusters were transferred into a deep learning algorithm to detect fraudulent posts. The findings were customized to a data dashboard in order to enable public health intelligence and provide reports to authorities, including the World Health Organization and U.S. Food & Drug Administration (FDA).

"We're in a post-digital era and as this boom of digital adoption continues, we will see more of these fraudulent postings targeting consumers as criminals seek to take advantage of those in need during times of a crisis," said Mackey.

Mackey provided three key tips to help identify a fraudulent post or scam:

If it's too good to be true, it probably is. Look out for mentions of bulk or rapid sales, cheap pricing and questionable claims such as FDA approval or specific certifications.
Importing products from another country. If you're a United States consumer, it is likely illegal to import products such as COVID-19 tests from another country. Such purchases should be considered risky.
Illegitimate contact methods. If the seller is conducting business or a transaction through social media direct messages or another non-traditional communications application, including Skype or WhatsApp, it probably isn't legitimate.

"We recommend that anyone concerned of contracting COVID-19 or hoping to be tested first work with their personal health care provider or local public health agency to ensure safe access to testing or treatment, and report any suspicious activity to federal authorities," said Mackey.

"Our hope is that the results from this study will better inform social media users so they can better decipher between fraudulent and legitimate posts. We conducted this research with the goal that eventually it will lead to improved tools and policy changes so that social media can be used as a force for good."

The first few weeks of a tree seedling's life can be the most precarious.

As it pushes thin new roots into the ground it's also reaching up with tiny new leaves. Water and energy are precious. Most seedlings never make it past their first month on the ground.

But while much is known about the growing process, there remains a layer of mystery around the mechanisms within these small plants. Now, a new study by a University of Georgia researcher sheds some light on the microscopic tissues that help tree seedlings grow. The results could change how researchers and growers view the first weeks of a tree's life.

"I've been working on newly germinated seedlings for 20 years, and I feel this is one of the first breakthroughs for me about how different they are, even from a 20-week-old seedling," said Dan Johnson, an assistant professor of tree physiology and forest ecology at the UGA Warnell School of Forestry and Natural Resources. "It's these first few weeks of life that seem to be fundamentally different."

Johnson and a team of researchers used a high-powered X-ray called a synchrotron to take extremely detailed cross-section images of ponderosa pine seedlings at various stages of hydration. Located at the University of California-Berkeley, the synchrotron accelerates electrons to nearly the speed of light, and while they will instantly kill a human cell, plants, it turns out, can withstand the intense power for a short period of time.

So, Johnson and his collaborators X-rayed the intact stem of the pine seedlings over several days, taking images of what was going on inside the plant. The pictures show extremely detailed black-and-white images that detail pockets of hydrated cells in gray. As the images progress and the seedlings dry out, black pockets of air can be seen on the images, almost as if the stems are being eaten from the outside in.

He and other researchers thought the plant's xylem--a central nervous system of the plant, in a sense--would quickly dry up if it went without water. Turns out, they were wrong--and the resulting images offer never-before-seen insights into the first few weeks of a tree seedling's life.

"The way we thought these seedlings were going to fail, hydraulically, as they dried out, was not at all how they failed," he said. "We thought the vascular tissue--the xylem--was going to be filled with air. We call it embolism in humans. But what we found was, it wasn't the xylem that dried out, it was all the tissue surrounding it. Even in some of the seedlings that looked like they were ripped apart (for lack of water), the xylem is fully hydrated."

All plants have xylem tissue; it transports water throughout the plant. And in older plants, the xylem often does dry out as a plant faces drought. But the images that Johnson captured show that seedlings' plumbing is completely different from their older cousins.

The findings were published in the August issue of the American Journal of Botany. The study was supported by two grants from the National Science Foundation.

"To me, this is the most vulnerable life stage. If a seedling is going to die, it's going to die in the first few weeks of life," said Johnson. "In the field, we see 99% of natural regeneration seedlings die--you'll come back to the field one day and thousands have died. And they die in places where it just dries out too quickly."

Johnson said his findings point to how sensitive tissues outside the xylem are to water loss in the first few weeks of a seedling's life. When a wild-sewn seedling survives, it's often because that particular site had more favorable conditions, such as more moisture or the seed landed in a depression where it was more protected from the elements.

In addition to the detailed black-and-white images, the team also made corresponding color images of the seedling stems with a laser, using a process called confocal microscopy. Different cells reflect in different colors, creating a rainbow of circles that researchers can use to better identify parts of the stem.

But while the yellows, reds and blues are striking on the laser-produced images, the real eye-opener for Johnson was the black-and-white reality of the decimated, dried out stems and their central core, which was the last to give up.

"I was completely shocked. It was not what any of us on the paper expected," said Johnson, pointing to one image of a withered stem that looks almost chewed up. "That's at a desiccation level that would kill that plant. So, to have that xylem so full when it's so dead is counter-intuitive."

While the discovery may bring more questions than answers, Johnson notes that the survival of the xylem may change how plants' first few weeks are understood. It's almost as if, he said, the first leaves to emerge from a seedling are connected to a completely different set of tissues. "The xylem might not be the plumbing to the first few leaves of the plant, which is bizarre because that's what we learned in plant physiology," he added.

All plants and animals respire, releasing energy from food. At the cellular level, this process occurs in the mitochondria. But there are differences at the molecular level between how plants and animals extract energy from food sources. Discovering those differences could help revolutionize agriculture.

"Plant respiration is a crucial process biologically for growth, for biomass accumulation," said Maria Maldonado, a postdoctoral researcher in the lab of James Letts, assistant professor in the Department of Molecular and Cellular Biology, College of Biological Sciences. "If you're thinking of crops, the extent to which they grow is related to biomass accumulation and the interplay between photosynthesis and respiration."

In a study appearing in eLife, Maldonado, Letts and colleagues provide the first-ever, atomic-level, 3D structure of the largest protein complex (complex I) involved in the plant mitochondrial electron transport chain.

"For mammals or yeast, we have higher resolution structures of the entire electron transport chain and even supercomplexes, which are complexes of complexes, but for plants, it's been an entire black box," said Maldonado. "Until today."

Figuring out the structure and functionality of these plant protein complexes could help researchers improve agriculture and even design better pesticides.

"Lots of pesticides actually target the mitochondrial electron transport chain complexes of the pest," said Letts. "So by understanding the structures of the plant's complexes, we can also design better-targeted pesticides or fungicides that will kill the fungus but not the plant and not the human who eats the plant."

Growing mung beans in the dark

To make their food, plants utilize chloroplasts to conduct photosynthesis. But chloroplasts can pose a problem to scientists studying the molecular minutiae of the mitochondrial electron transport chain.

"Plants have mitochondria and they also have chloroplasts, which make the plant green, but the organelles are very similar in size and have very similar physical properties," said Maldonado.

These similarities make it difficult to isolate mitochondria from chloroplasts in a lab setting. To get around this, the researchers used "etiolated" mung beans (Vigna radiata), meaning they grew the plants in the dark, which prevented chloroplasts from developing and caused the plants to appear bleached.

"Mung beans are an oilseed such that they store energy in the form of seed oils and then the sprouts start burning those oils like its fuel," said Letts. Without chloroplasts the plants are unable to photosynthesize, limiting their energy streams.

By separating mitochondria from chloroplasts, the researchers gained a clearer structural image of complex I and its subcomplexes.

"We used single-particle cryoelectron microscopy to solve the structure of the complexes after purifying them from mitochondrial samples," said Letts.

With these structures, scientists can see, at the atomic level, how the building block proteins of complex I are assembled and how those structures and their assembly differs compared to the complexes present in the cells of mammals, yeast and bacteria.

"Our structure shows us for the first time the details of a complex I module that is unique to plants," said the researchers. "Our experiments also gave us hints that this assembly intermediate may not just be a step towards the fully assembled complex I, but may have a separate function of its own."

The researchers speculated that complex I's unique modular structure may give plants the flexibility to thrive as sessile organisms.

"Unlike us, plants are stuck in the ground, so they have to be adaptable," said Letts. "If something changes, they can't just get up and walk away like we can, so they've evolved to be extremely flexible in their metabolism."

With the structure of complex I now in hand, the researchers plan to conduct functional experiments. Further understanding complex I's functionality could open the doorway to making crop plants more energy efficient.

A recently published study led by The University of Texas at Arlington says that student debt may hurt students' chances of securing full-time employment due to added pressure in their job search.

Ariane Froidevaux, assistant professor of management in the College of Business, is first author of "Is Student Loan Debt Good or Bad for Full-Time Employment Upon Graduation From College?" in the Journal of Applied Psychology.

In 2020, student loan debt in the United States hit a record high of $1.56 trillion, according to the Institute for College Access & Success, with the average student loan debt at about $30,000. Previous studies have found significant long-term consequences of student loan debt, such as reduced wealth accumulation and homeownership.

"Student debt mainly had more negative effects on college students' likelihood of securing a full-time job than beneficial ones," Froidevaux said. "You can do certain things like getting a job during the summer that may help you get a full-time job upon graduation. But in the end, student debt leaves students with a lot of stress, and it is long-lasting."

Mo Wang of the University of Florida, Jaclyn Koopmann of Auburn University and Peter Bamberger of Tel Aviv University co-authored the article. The researchers say that having student loan debt is a financial stressor to students that leads to additional stress during their job search, which in turn can harm their chances of securing a full-time job.

"Student loan debt creates an anticipated loss of financial resources, which brings higher levels of stress to student job-seekers," said Froidevaux, who is a fellow of the Eunice and James L. West Distinguished Professorship. Her research interests include career transitions, retirement and aging in the workplace, and identity negotiation.

The more financially strained individuals are, the less likely they are to have sufficient energy and motivation to invest in their search for a successful job placement, she said. Results from the study also suggest that students who are more stressed about their student loans were likelier to work more hours in part-time jobs. This stress in searching for a job reduced the likelihood of securing full-time employment upon graduation from college. The research team used data from 1,248 graduating seniors from four different American universities.

The researchers suggest students can ease the strain of debt by recognizing that it will occur and taking steps to reduce that stress. Froidevaux said that if students reappraise debt as an investment in future earnings, they sometimes can better deal with it.

The research team suggests that students aren't the only ones who can take steps to ease the burden of loan debt. University career development offices should consider adopting job search interventions aimed at improving stress management and financial planning. Businesses, too, can support their new employees by implementing human resource policies such as student loan repayment assistance.

"Student loan debt is a fact of life for most college graduates," said George Benson, professor and chair of the Management Department in the College of Business. "This research shows that the impact goes beyond the debt itself. I like that the research gives recommendations for ways to reduce stress. It also has suggestions for those businesses that hire our graduates to help those stress levels."

Finnish children have a very positive attitude towards early childhood education and care (ECEC), according to new research from the University of Eastern Finland. Published in Early Child Development and Care this August, the study explored children's negative experiences of early childhood education and care. The researchers have published an article on children's positive experiences already earlier.

"Studying children's experiences of, and their participation in, early childhood education and care is very topical in Finland right now, since the country's new ECEC legislation from 2018 places increasing emphasis on children's interests and participation," Postdoctoral Researcher Kaisa Pihlainen from the University of Eastern Finland says.

Furthermore, the UN's Convention on the Rights of the Child stipulates that the child shall be given the opportunity to be heard matters affecting him or her, and the importance of taking the child's opinions into consideration in the related decision-making is also emphasised.

The study involved 2,500 children aged between 2 and 6 years. Most of the negative experiences of ECEC reported by children were related to their interaction with peers, i.e. they reported getting pushed around or hit, or being yelled at or called names.

Other themes children highlighted as negative were associated with play, discomfort, rules and restrictions, guided activities, ECEC professionals and their activities, and environmental factors. Children's gender and age had a statistically significant effect on negative experiences connected with interaction and guided activities. Having to take a nap in the middle of the day in particular was highlighted as a negative thing, because it was seen to take time away from playing. Many of the negative experiences reported by children were also linked to play, since play is a key activity in ECEC. Children felt that their peers disturbed their play, or that they were left out completely.

"We know that being excluded is one of the most stressful events in childhood, and some children may experience rejection more strongly than others," Postdoctoral Researcher Pihlainen points out.

The newly published study focused on children's negative experiences of ECEC, and the researchers have published a study on children's positive experiences already earlier. According to Postdoctoral Researcher Pihlainen, children's positive experiences of ECEC were associated with their own and guided activities, such as play and excursions. Children in family day care settings also highlighted more positive things than others relating to human relationships and everyday situations. The youngest children in day care centres were able to name more persons by their names than others, and six-year-old children mentioned special days and trips as the most important source of positive experiences.

The objective of quality evaluation in ECEC is to identify strengths and targets for development. Children's experiences haven't been taken into consideration in quality evaluation on a large scale before and, according to Postdoctoral Researcher Pihlainen, the new findings now provide an opportunity to support children's resilience and sense of belonging, both of which are important elements in ECEC quality.

"Our findings suggest that quality evaluation performed by children is a promising method that can supplement multi-methodological quality evaluation in ECEC. The findings can be used to improve ECEC practices by paying specific attention to children's participation and to the things they experience as positive or negative."

The study is based on data collected by means of children's interviews conducted by their parents. Parents used a rigorous interview protocol with open-ended and closed questions. The researchers point out that the involvement of parents in data collection strengthens collaboration and builds trust between families and ECEC. At the same time, however, it is important to acknowledge that parents' participation in collecting children's views involves some challenges.

A team led by the Department of Energy's Oak Ridge National Laboratory developed a novel, integrated approach to track energy-transporting ions within an ultra-thin material, which could unlock its energy storage potential leading toward faster charging, longer lasting devices.

Scientists have for a decade studied the energy-storing possibilities of an emerging class of two-dimensional materials - those constructed in layers that are only a few atoms thick - called MXenes, pronounced "max-eens."

The ORNL-led team integrated theoretical data from computational modeling of experimental data to pinpoint potential locations of a variety of charged ions in titanium carbide, the most studied MXene phase. Through this holistic approach, they could track and analyze the ions' motion and behavior from the single-atom to the device scale.

"By comparing all the methods we employed, we were able to form links between theory and different types of materials characterization, ranging from very simple to very complex over a wide range of length and time scales," said Nina Balke, ORNL co-author of the published study that was conducted within the Fluid Interface Reactions, Structures and Transport, or FIRST, Center. FIRST is a DOE-funded Energy Frontier Research Center located at ORNL.

"We pulled all those links together to understand how ion storage works in layered MXene electrodes," she added. The study's results allowed the team to predict the material's capacitance, or its ability to store energy. "And, in the end, after much discussion, we were able to unify all these techniques into one cohesive picture, which was really cool."

Layered materials can enhance energy stored and power delivered because the gaps between the layers allow charged particles, or ions, to move freely and quickly. However, ions can be difficult to detect and characterize, especially in a confined environment with multiple processes at play. A better understanding of these processes can advance the energy storage potential of lithium-ion batteries and supercapacitors.

As a FIRST center project, the team focused on the development of supercapacitors - devices that charge quickly for short-term, high-power energy needs. In contrast, lithium-ion batteries have a higher energy capacity and provide electrical power longer, but the rates of discharge, and therefore their power levels, are lower.

MXenes have the potential to bridge the benefits of these two concepts, Balke said, which is the overarching goal of fast-charging devices with greater, more efficient energy storage capacity. This would benefit a range of applications from electronics to electric vehicle batteries.

Using computational modeling, the team simulated the conditions of five different charged ions within the layers confined in an aqueous solution, or "water shell." The theoretical model is simple, but combined with experimental data, it created a baseline that provided evidence of where the ions within the MXene layers went and how they behaved in a complex environment.

"One surprising outcome was we could see, within the simulation limits, different behavior for the different ions," said ORNL theorist and co-author Paul Kent.

The team hopes their integrated approach can guide scientists toward future MXene studies. "What we developed is a joint model. If we have a little bit of data from an experiment using a certain MXene, and if we knew the capacitance for one ion, we can predict it for the other ones, which is something that we weren't able to do before," Kent said.

"Eventually, we'll be able to trace those behaviors to more real-world, observable changes in the material's properties," he added.

Scientists at the University of Sussex have collaborated with an Oxford company, M-SOLV, and a team of scientists from across Europe to develop a highly sensitive and accurate Nitrogen Dioxide (NO2) sensor, which has life-saving potential applications in domestic, public and industrial settings. A major air pollutant that originates from combustion engines and industrial processes, long-term exposure to NO2 can cause respiratory issues, which can be particularly severe and even life-threatening for babies and asthma sufferers.

The gas sensor could, for the first time, provide accurate readings of the NO2 levels in the local environment in an affordable and portable Internet-of-Things device, which could sync with smartphones and applications.

European Union regulations allow a threshold of 20 parts-per-billion (ppb) of NO2 in the air to be overcome not more than 18 times in a year. However, in London alone, the monthly average is regularly above this. Monitoring of air quality to prevent such exposure at ppb levels is currently only possible with unwieldy, expensive equipment and is therefore scarcely implemented.

The challenge the scientists faced, therefore, was to create a device that was sensitive and accurate enough to detect below 20 parts-per-billion of NO2 in the air, but which would also operate in real-world situations and that would be convenient and affordable enough to have the potential for widespread use.

Their breakthrough came when they developed an NO2 sensing layer based on a laser deposited carbon aerogel (LDCA), which they found to have exceptional selectivity towards NO2 over other common air pollutants, making it unique amongst carbon nanomaterials.

Using a scalable and cheap one-step-laser process, the thin, porous and well-adhered film of LDCA is then deposited on to electrodes, which can then be housed in a range of device structures for continuous air monitoring. The sensor is so sensitive that it can detect close to 10 parts-per-billion of NO2 in under 15 minutes and, crucially, can operate at room temperature - even performing well in humid conditions, a problematic environment for many other sensors.

Professor Alan Dalton, who heads up the Materials Physics group at the University of Sussex says: "Like condensation on a windowpane, nanomaterials such as the carbon that we have used in this development, nearly always have surface water. Normally this is a really bad thing as it interferes with the technology, but in this case, we've been able to use this layer of water to our advantage to selectively dissolve NO2 instead of other volatiles normally found in ambient conditions.

"As a physicist this is really exciting as this is what gives our sensor such a high rate of sensitivity to NO2 in real-world conditions, ensuring that we avoid false positive readings. As a father, one of the things that has motivated me to pursue this development was hearing about the influence of dangerous levels of NO2 in the air - something which we're seeing regularly in our big cities - on infant morbidity. It's not news that urban environments are seeing high levels of pollution, but without widespread and accurate air quality monitoring most of us are in the dark about how harmful the air in our local area might really be for ourselves and our children."

Potential applications for the sensor could include: as a safety device to monitor the air quality in a baby's bedroom; to help inform the best walking or cycling routes and times of day to avoid high pollution levels; and even by estate agents to provide prospective house buyers with information on the Nitrogen Dioxide levels in a home and area. The scientists hope that the technology will be utilised by councils to track pollution levels in urban environments and industry.

Peter Lynch, a postdoctoral researcher at the University of Sussex who played a key role on the sensor development, says: "As a team of scientists from across Europe, one of our shared goals was to develop a sensor that would not only perform fantastically outside of the lab, but that would also be affordable enough to be available to your average household, ensuring that more of us have access to information on air quality in our local area and on an hour-by-hour basis.

"As well as helping individuals make informed choices, our hope is that this data could also feed into a national - even world-wide - pollution monitoring database, in order to effect positive action on air quality."

Adam Brunton, Director of Business Development at M-SOLV, who are manufacturing the NO2 sensing device, said: "One nice thing about this sensor is that it is made using familiar equipment and materials that we already have in our Large Area Electronics Manufacturing Clean room here in Oxford. This means that it is compatible with standard smartphone manufacturing techniques and can be easily integrated with processing electronics, wireless communications, mobile networks, etc. Getting remote access to data from an individual device or a huge network of these sensors is therefore quite a straightforward process"

COLUMBUS, Ohio - Inserting genetic material into the body to treat diseases caused by gene mutations can work, scientists say - but getting those materials to the right place safely is tricky.

Scientists report today (Aug. 21) in the journal Science Advances that the lipid-based nanoparticles they engineered, carrying two sets of protein-making instructions, showed in animal studies that they have the potential to function as therapies for two genetic disorders.

In one experiment, the payload-containing nanoparticles prompted the production of the missing clotting protein in mice that are models for hemophilia. In another test, the nanoparticles' cargo reduced the activation level of a gene that, when overactive, interferes with clearance of cholesterol from the bloodstream.

Each nanoparticle contained an applicable messenger RNA - molecules that translate genetic information into functional proteins.

"We demonstrated two applications for lipid-like nanomaterials that effectively deliver their cargo, appropriately biodegrade and are well-tolerated," said Yizhou Dong, senior author of the study and associate professor of pharmaceutics and pharmacology at The Ohio State University.

"With this work, we have lowered potential side effects and toxicity, and have broadened the therapeutic window. This gives us confidence to pursue studies in larger animal models and future clinical trials."

This work builds upon a collection of lipid-like spherical compounds that Dong and colleagues had previously developed to deliver messenger RNA. This line of particles was designed to target disorders involving genes that are expressed in the liver.

The team experimented with various structural changes to those particles, effectively adding "tails" of different types of molecules to them, before landing on the structure that made the materials the most stable. The tiny compounds have a big job to do: embarking on a journey through the bloodstream, carrying molecules to the target location, releasing the ideal concentration of messenger RNA cargo at precisely the right time and safely degrading.

The tests in mice suggested these particles could do just that.

The researchers injected nanoparticles containing messenger RNA holding the instructions to produce a protein called human factor VIII into the bloodstream of normal mice and mouse models for hemophilia. A deficiency of this protein, which enables blood to clot, causes the bleeding disorder. Within 12 hours, the deficient mice produced enough human factor VIII to reach 90 percent of normal activity. A check of the organs of both protein-deficient mice and normal mice showed that the treatment caused no organ damage.

"It can be helpful to think of this as a protein-replacement therapy," Dong said.

In the second experiment, nanomaterials were loaded with two types of instructions: messenger RNA carrying the genetic code for a DNA base editor, and a guide RNA to make sure the edits occurred in a specific gene in the liver called PCSK9. Dozens of mutations that increase this gene's activity are known to cause high cholesterol by reducing clearance of cholesterol from the bloodstream.

Analyses showed that the treatment resulted in the intended mutation of about 60 percent of the target base pairs in the PCSK9 gene, and determined that only a low dose was needed to produce high editing effect.

Dong credited academic and industry partners for helping advance this work. Co-corresponding authors include Denise Sabatino of Children's Hospital of Philadelphia and Delai Chen from Boston-based Beam Therapeutics, who provided expertise in hemophilia and DNA base editing, respectively.

Dong and first author Xinfu Zhang are inventors on patent applications filed by Ohio State related to the lipid-like nanoparticles. This technology has been licensed for further clinical development.

Once only associated with colder climate conditions of the last glacial period, a new study finds that rapid, pulse-like increases in atmospheric carbon dioxide (CO2) also occurred during earlier, warmer interglacial periods. Using a new record of atmospheric CO2 concentrations retrieved from the EPICA Dome C Antarctic ice core, Christoph Nehrbass-Ahles and colleagues show that these abrupt CO2 releases are a pervasive phenomenon of Earth’s coupled climate-carbon system, perhaps linked to changes in the strength of the Atlantic Meridional Overturning Circulation (AMOC). The results suggest that similar jumps in atmospheric carbon could also occur in the future should global warming similarly impact circulation in the Atlantic Ocean.  Abrupt bursts of CO2 released to the atmosphere on centennial time scales are known to have occurred during the colder periods of the last glacial cycle. While these carbon dioxide jumps are thought to have been absent during the warmer climate conditions of previous interglacial periods, submillenial-scale records of atmospheric CO2 variability needed to evaluate this only exist for roughly the last 60,000 years, and not beyond the last glacial. Previously locked in ancient Antarctic ice, Nehrbass-Ahles et al. present a high-resolution CO2 record from 330,000 to 450,000 years ago, which reveals pronounced CO2 releases under both cold and warm climate periods. Based on the findings, the authors suggest these events are a pervasive feature of the natural carbon cycle that may go undetected in CO2 records of insufficient temporal resolution and precision, and also that the pulse-like release events relate to disruptions in the AMOC caused by melting ice sheets. Future rapid increases in atmospheric CO2 could occur if similar human climate change-driven ice melt disrupts the AMOC, they say.

Personalized cancer treatments are no longer just options of the future. In the past few years, researchers have made significant progress in 'teaching' the body's immune T cells to recognize and kill specific cancer cells, and human clinical trials have shown that this approach can successfully eliminate tumors.

Cancer patients today can be a part of the following clinical scenario: a patient comes to the hospital where physicians and scientists analyze his or her tumor to identify cancer-specific markers that would serve as targets for the novel therapy. Blood is drawn from the patient and sent to Baylor College of Medicine's Center for Cell and Gene Therapy where the immune T cells are transformed into cells with a mission to identify and kill cells with the tumor-specific tags. The final cells are infused back into the patient to complete their job.

"At the Center, we genetically engineer the patient's T cells to arm them with the tools they need to identify the patient's tumor-specific markers and eliminate the cancer," said Dr. Maksim Mamonkin, assistant professor of pathology & immunology and member of the Center for Cell and Gene Therapy at Baylor.

Although this treatment can effectively eliminate tumors, the 'training' of the T cells is complex and expensive. "Sometimes, the trained T cells are not highly potent because the patient already received a number of treatments that weakened the immune cells we work with," Mamonkin said.

In addition, the process to manufacture the therapeutic T cells is time consuming. "Sometimes it takes weeks to get the T cells ready, and in this time the patient may take a turn for the worse," Mamonkin said.

The next step: off-the-shelf therapies

"Now that we know that this type of cell immunotherapy has a lot of promise, the next step is to streamline it, make it more accessible and make sure that the resulting T cells have the highest potency," said Mamonkin, who also is a member of the Dan L Duncan Comprehensive Cancer Center.

Researchers are developing ready-to-use, off-the-shelf therapeutic T cells. These are genetically engineered T cells that are manufactured from normal, healthy donors. The cells are expanded and well characterized, and have shown to be effective at killing cancer cells. The cells are cryo-preserved - stored frozen in liquid nitrogen - until it's time to use them.
In this scenario, a cancer patient comes to the hospital and the tumor markers are identified. Then, with the identity of the tumor-specific tags in hand, the physician goes to a room filled with large below-zero freezers searching for the one that holds little containers with healthy immune T cells that have been genetically engineered to recognize and destroy cells with the patient's cancer-specific markers. These 'off-the-shelf,' ready-made cells are thawed, prepared and infused into the patient several days later.

"This approach solves two limitations of the original approach: it avoids the time-consuming, elaborate steps of training and expanding the patient's cells and results in therapeutic T cells of higher potency," Mamonkin said. "However, the novel approach presents a new set of limitations."

Dealing with rejection

One of the limitations of the off-the-shelf approach emerges when the therapeutic T cells enter the patient's body. The patient's own immune system recognizes the cells as foreign, such as it happens with organ transplants, and may reject the therapeutic cells.

"This is a major problem because rejection not only would reduce the duration of the T cells activity against the tumor, but also would preclude giving subsequent doses of cells. The immune system would reject subsequent doses of the cells right way," said first author, Feiyan Mo, graduate student in Mamonkin's lab. "To solve this problem we thought that the best defense was a good offense."
The researchers gave the therapeutic T cells a tool that would enable them to fight back the attack of the patient's immune cells against them. They genetically engineered the therapeutic T cells to express a receptor called alloimmune defense receptor, or ADR. ADR recognizes a specific molecule, called 4-1BB, that is only expressed on the patient's activated T cells and natural killer (NK) cells that would attack them. 4-1BB is not expressed on resting T and NK cells that do not turn against the therapeutic T cells.

"Both experiments in the lab and animal models with blood cancers or solid tumors showed that ADR protected off-the-shelf therapeutic T cells from being rejected," Mo said. "Not only did they resist rejection, but they also expanded more and persisted longer than therapeutic T cells without ADR."
The researchers are optimistic that this approach may also work in patients. They plan to conduct clinical trials on 2021.

Beyond cancer applications

"If successful, this approach can be extended to targeting other disease-causing T-cells, such as those rejecting transplanted organs, mediating graft-versus-host disease or perpetuating autoimmunity," said Mamonkin. "We are very excited to develop this concept for several applications beyond cancer therapy."
This technology has been licensed to Fate Therapeutics, a clinical-stage biopharmaceutical company that plans on integrating ADR into their clinical products.

"The BCM Ventures team is very pleased to partner with Fate Therapeutics in a licensing relationship to support their implementation of the ADR technology developed in the Mamonkin laboratory here at BCM. This approach promises to enhance the effectiveness of off-the-shelf cell therapies, and it will now be used more extensively in the clinical setting which stands to benefit patients," said Michael Dilling, director of Baylor Licensing Group. "BCM has been an innovator in the development of cell therapies and the commercial sector increasingly looks to BCM as a source for new innovations."

Feiyan Mo, who took the lead on this work, has received an NIH NCI F99/F00 Predoctoral-to-postdoctoral Fellowship Award to help facilitate the translation of ADR to the clinic and continue postdoctoral studies in cancer biology. She is a Baylor graduate student and is co-mentored by Drs. Mamonkin, Malcolm Brenner and Helen Heslop.
Are you interested in learning all the details of this work? Find them in the journal Nature Biotechnology.

A new measurement technology developed at the University of Bern provides unique insights into the climate of the past. Previous CO2 concentrations in the atmosphere could be reconstructed more accurately than ever before, thanks to high-resolution measurements made on an Antarctic ice core. The study, which analyzed the Earth's atmospheric composition between 330,000 and 450,000 years ago, was made possible by the commitment of experts, and their decades of experience, at the University of Bern. The results of the study have been published in Science.

Melting ice masses disturbed the ocean circulation

In 2008, the Bern ice core specialists were able to show that the CO2 concentration in the atmosphere during the last 800,000 years was consistently much lower than today. Since then, the ice core experts have built upon those findings enabling a much more detailed reconstruction of the 330,000 to 450,000 year time window. Until now, the maximum speed and frequency of naturally occurring centennial scale jumps in the CO2 concentration remained unknown. This study shows that abrupt CO2 rises are a pervasive feature of our climate system and that they can even occur during interglacial periods. "Until now, it had been assumed that the climate was very stable during previous interglacial periods and that there were no abrupt changes in the atmospheric CO2 concentration," explains Christoph Nehrbass-Ahles, lead author of the study, who earned a doctorate from the University of Bern and is now based at the University of Cambridge. According to Nehrbass-Ahles, the abrupt rises were always evident when melting ice masses in Greenland or Antarctica considerably disturbed the ocean circulation. If the CO2 in the atmosphere rose quickly, simultaneous changes in the Atlantic Ocean's circulation could also be detected.

CO2 increase was ten times slower than today

The fact that rapid CO2 jumps could be detected not only during glacial periods but also during two previous interglacial periods surprised the researchers. "We measured these events in the ice several times and always came to the same conclusion," explains Nehrbass-Ahles. Why the CO2 concentration in the atmosphere suddenly rose during previous interglacial periods cannot be conclusively explained by the researchers. "We do not know why this happened yet," explains Bernese climate researcher Thomas Stocker, co-author of the study: "This raises new research questions." However, the CO2 jumps in previous interglacial periods are far exceeded by the current development: "These natural jumps in the CO2 concentration in the atmosphere happened almost ten times slower than the human-driven increase over the last decade," Nehrbass-Ahles emphasizes.

The largest jump in the past corresponds to the current CO2 emissions over only six years

The researchers compared the CO2 jumps of the past with the ongoing human-driven rise of CO2 concentration in the atmosphere. According to Stocker, the largest centennial CO2 jump in the past was around 15 ppm (parts per million is the unit for atmospheric CO2 concentration), which is approximately equivalent to the increase caused by humankind over the last of six years. "This may not seem significant at first glance," says Stocker, "but in light of the quantities of CO2 that we are still allowed to emit in order to achieve the 1.5°C climate target agreed in Paris, such increases are definitely relevant." The findings of this study put us under even greater pressure to protect the climate.

WASHINGTON--Girls with anorexia nervosa can have stunted growth and may not reach their full height potential, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Anorexia nervosa is a condition in which a person loses an unhealthy amount of weight on purpose by dieting, sometimes along with excessive exercise, binge eating, and/or purging behaviors. People with anorexia nervosa have an intense fear of gaining weight and a disturbed body image (such as thinking they are fat even when they are very underweight).

"Our findings emphasize the importance of early and intensive intervention aiming at normalization of body weight, which may result in improved growth and allow patients to reach their full height potential," said the study's corresponding author, Dalit Modan-Moses, M.D., of The Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, in Tel Hashomer, Israel. "We suggest that the height impairment is a marker for other complications of anorexia nervosa affecting the person's overall health in several aspects: bone health, cognitive function, and problems with pregnancy and childbirth later in life. Early diagnosis and treatment could prevent, or at least reduce, the risk of these complications."

The researchers studied 255 girls around 15 years old who were hospitalized for anorexia nervosa. They measured their height at the time of admission, discharge and at adult height and found it was lower than expected. Adult height was significantly shorter than expected when compared to the genetic potential according to average of the patient's mother and father's heights.

"This study may have implications for the management of malnutrition in adolescents with other chronic diseases in order to achieve optimal adult height and bone health," Modan-Moses said.

Operators beyond the confines of conventional emergency healthcare are willing and able to assist in a crisis, a University of Gothenburg study shows. Hotels, schools, and veterinary clinics are among those ready for inclusion in a crisis preparedness system, to enable emergency healthcare to be scaled up with the utmost speed.

The purpose of the study was to investigate the prospects of creating a system in which units outside emergency healthcare serve as alternative care facilities when patient numbers surge. This may happen, for example, owing to terrorist acts, major accidents, or large-scale disease outbreaks.

The fact that the study was partially conducted while the current pandemic was under way is due to chance. Nevertheless, interest in the results -- now published in Sustainability, the scientific journal -- is naturally increasing.

The lead author is Viktor Glantz, whose research has been within the framework of a master's degree program at Sahlgrenska Academy, University of Gothenburg. His clinical work is as a nurse in surgical emergency and trauma care at Sahlgrenska University Hospital, and in coordinating emergency preparedness throughout the Hospital.

In the study, 100 actors within the civil society in Sweden -- hotels, sports facilities, schools, dental clinics, veterinary clinics, and healthcare centers -- were questioned about their capacity and willingness to join a regional preparedness system for upscaling emergency care: what is known as the community's 'flexible surge capacity' (FSC).

At just over 40 percent, the rate of response to this questionnaire survey roughly corresponded to expectations. Almost all the respondents wanted to be involved, including in the preparatory work, jointly with the healthcare services.

"There are huge numbers of people in civil society who feel they're unnecessarily helpless in an emergency situation. Everyone can see that there ought to be preparedness, but no one's taken on the task of actually developing it," Glantz says.

"In the spring, for example, a great number of veterinarians have been there in empty clinics because of reduced demand due to the corona pandemic. They could absolutely have received uncomplicated somatic patients if there'd been preparedness, contracts, and support from the healthcare sector. But you can't shoot from the hip: there has to be a plan for training and practice sessions -- who does what, which patients go where, and who pays."

Besides the questionnaires, 12 qualitative interviews were conducted with representatives of various units that were not designated emergency care facilities. The questions related to existing capacity and skills, access to premises and materials, the categories of patients they could receive, and shortcomings in terms of further preparedness and more advanced care, such as small-scale surgical operations.

The interviewees were open to receiving patients with minor injuries from, for example, accident sites. Some units could conceive of providing care for people with somewhat more severe injuries as well. In general, Glantz sensed in the operators a strong drive to cooperate in the preparedness system, and even to participate in its actual development.

"The will to help the emergency care services at times of crisis and disaster definitely exists in civil society. Now it's our turn to capture, respond to and channel that willingness to help out in the best possible way," Glantz says.

"We've got to start using all available resources, regardless of whether they belong to the military, ambulance and paramedical services, or primary care. Everything has to be available when we need it, at once -- but for that we have to be prepared for crises and disasters before they happen," Glantz concludes.