Culture

FOR IMMEDIATE RELEASE

STUDY SUGGESTS THAT SMOOTHER SILICONE BREAST IMPLANTS REDUCE SEVERITY OF IMMUNE SYSTEM REACTIONS

According to researchers at Johns Hopkins Medicine, the Massachusetts Institute of Technology (MIT) and Rice University in Houston, silicone breast implants with a smoother surface design have less risk of producing inflammation and other immune system reactions than those with more roughly textured coatings. Results of the experiments using mice, rabbits and samples of human breast tissue advance knowledge of how the body responds to such implants, providing new information to physicians and affirming the benefits of certain smoother surfaces, the researchers say.

A summary of the experiments, funded by an implant manufacturer, are published June 21 in Nature Biomedical Engineering.

Breast implants, surgically inserted following mastectomies or to augment breast size, can be filled with either saline or silicone, but both types have a silicone outer shell. Previous studies showed that most of the 400,000 women each year in the U.S. who receive silicone implants will need to have them replaced within 10 years because of pain and shape shifting of the implant caused by immune system cells that contribute to scarring and fibrous tissue.

"Our aim is to provide patients with as much information as possible so they can make informed decisions to guide their own personal health," says Joshua Doloff, Ph.D., assistant professor of biomedical engineering at The Johns Hopkins University and a first author of the research, which began during his postdoctoral training at MIT.

Doloff, whose research overall focuses on the interface between implantable devices and the human body, says scientists have long known that the immune system biologically walls off foreign objects in the body by creating inflammation and scarring that can be disfiguring and painful.

For the past decade, scientists have been examining how to design implant surfaces in ways that reduce such effects.

Previous studies found that implants with absolutely smooth coatings produce strong immune rejection responses over time, and according to Doloff, they may also more easily "flip" inside the body and contribute to a higher rate of replacement. So, manufacturers also marketed implants with textured surfaces to try to address immune system rejection and to "stick" like Velcro to human tissue, enabling better and more stable positioning in the body. More than 90% of breast implants used in the U.S. are characterized as smooth, according to the researchers, whereas most implants used outside of the U.S. .

An implant with the highest degree of textured surface was taken off the U.S. market in 2019 because of its links to higher rates of a type of cancer called breast implant-associated anaplastic large cell lymphoma among patients with these "macrotextured" implants.

In the current study, the researchers analyzed outcomes of placing in mice tiny versions of implants with five different surface designs. The implants included one with a completely smooth surface, one slightly contoured at the level of an individual human cell, as well as others with different surfaces. Of note, they also implanted one with the 90-micron macrotextured surface like the implants taken off the market.

Establishment Labs helped manufacture the mini-implants, using similar manufacturing methods used in the market. Two of the full scale commercial implants, including one with a surface design that includes a roughness of approximately 4 microns on average as well as other characteristics including skewness and the number, distribution and size of contact points, are also manufactured by Establishment Labs, which funded the research.

Among human-scale size implants used in rabbits, the implant with design features that include a 4 micron surface roughness resulted in the least fibrous tissue surrounding it -- about 10 times less -- at three weeks and six months post-implantation when compared with the 90 micron implant.

Tissue surrounding implants in mice and rabbits with the specific design that includes a 4 micron roughness had the highest activity of the gene FOXP3, suggesting the production of more immune cells called Tregs, which act as traffic police to reduce the amount of inflammation and fibrous tissue created by immune system cells.

The research team also sequenced genetic expression levels from specific cell types in the tissue surrounding implants in mice to find that genes associated with pro-inflammatory responses, including STAT1 and CXCL10, increase about fivefold to tenfold with more highly textured implants.

Among tissue collected from implants removed from 15 healthy patients at the University of Texas MD Anderson Cancer Center in Houston and the Costa Rican Institute for Research and Teaching on Nutrition and Health Foundation, patients with implants with design features that include a 4 micron surface roughness had the most significantly reduced fibrous tissue formation surrounding the implants compared to the more heavily textured devices or to completely smooth ones.

Doloff says other areas of active research for implantable devices include development of biosensors that can detect rupture, leakage or inflammation of surrounding tissue. He says the surface design that includes roughness of 4 microns may be worth studying in biomaterials other than breast implants. He also plans to study the amount of immune response, inflammation and fibrous tissue among implants in women following cancer diagnosis and treatment.

"Engineers should know how something works, not just that it works, so we can improve on existing technologies, says Doloff.

PHILADELPHIA - Researchers have been investigating the potential health-promoting qualities of extra virgin olive oil (EVOO) for decades, including its possible medicinal value for preventing cancer, Alzheimer's, and cardiovascular disease, as part of the well-known Mediterranean diet. However, consumers in the U.S. have been slow to embrace it as a staple in their diet. This reluctance, say scientists, might be in part due to EVOO's bitter taste and pungency, which is caused by the presence of substances known as phenolic compounds, the very ones believed to contribute to EVOO health benefits. In 2005, researchers from the Monell Chemical Senses Center identified one of these compounds as an anti-inflammatory that they named oleocanthal and is mostly responsible for the oil's strong, pungent sensation localized to the throat.

Now, another team from Monell has shown that the presence of certain food proteins, such as those in egg yolk, suppresses EVOO's purported less desirable sensory qualities. The team published their findings in Scientific Reports.

"Knowing that the oil can be consumed without bitterness or stinging sensation might increase the popularity of this healthy food," said first author Catherine Peyrot des Gachons, PhD, a Monell senior research associate. "Our findings show that, in many cases, people are not going to perceive the bitterness and pungency once mixed in food."

While experimenting in the laboratory, investigators put the EVOO into a mayonnaise-like material that would be easier for sensory study participants to assess, rather than drinking unadulterated EVOO from a drinking glass, as is commonly done for EVOO tasting. They discovered that after several hours the oil-mayo mixture was much less pungent and bitter. Even a small amount of egg yolk in the mixture was sufficient to cause this reduction.

"This was a big surprise to us," said coauthor Gary Beauchamp, PhD, Distinguished Member of Monell. "But it probably would not be a surprise to people from the Mediterranean area who are much more familiar with consuming extra virgin olive oil in foods and even neat."

The team showed that proteins in the egg yolk were responsible for eliminating EVOO pungency and bitterness. Others such as whey protein yielded similar sensory suppression. The researchers hypothesize that eliminating bitterness and pungency in EVOO happens when proteins interact with oleocanthal and the bitter-tasting phenolic compounds.

The possibility that oleocanthal could be bound by food protein raises a significant conundrum for scientists. For example, the authors ask, could this binding reduce oleocanthal's medicinal effects in the human body? Or, to the contrary, might it make oleocanthal more available in the human body compared to oleocanthal alone? "We don't know the answer to those questions, but it certainly raises some interesting and important issues of bioavailability of this compound," said Beauchamp.

Knowing definitively that EVOO can be comfortably consumed when mixed with other foods might encourage people to consume more, say the researchers, thereby gaining from its medicinal and culinary benefits. However, consumers need to know that only high quality EVOOs contain enough oleocanthal to impart putative health advantages. Olive oil is more expensive than other forms of fat, but there may be a major payoff - the potential for health benefits that other cooking oils do not possess, say the study's authors.

CHAMPAIGN, Ill. -- Researchers report that they have developed a method to combine three brain-imaging techniques to more precisely capture the timing and location of brain responses to a stimulus. Their study is the first to combine the three widely used technologies for simultaneous imaging of brain activity. The work is reported in the journal Human Brain Mapping.

The new "trimodal" approach combines functional MRI, electroencephalography and a third technique, called EROS, that tracks the activity of neurons near the surface of the brain using near-infrared light.

"We know that fMRI is very good at telling us where in the brain things are happening, but the signal is quite slow," said postdoctoral researcher Matthew Moore, the first author of the study, which was conducted at the University of Illinois Urbana-Champaign's Beckman Institute for Advanced Science and Technology. "And when we measure electrical activity through EEG, it is very good at telling us when things happen in the brain - but it's less precise about where."

The third method, called event-related optical signal, provides a measure of spatial information that is similar to fMRI but, like EEG, can more accurately assess the timing of brain responses. This helps researchers fill in the blanks left by the other two technologies, Moore said. The result is a clearer picture of how different parts of the brain are activated and communicate with one another when an individual engages in a cognitive task and is distracted - in this case, by emotionally challenging information.

Functional MRI captures a signal from the flow of oxygenated blood in the brain when a person sees or responds to a stimulus. This signal is very useful for determining which brain structures are being activated, Moore said.

"Changes in blood oxygenation levels occur over a period of seconds, but the brain actually responds within hundreds of milliseconds," he said. This lag between brain activity and oxygenation signals means fMRI is unable to detect changes occurring faster than seconds.

"On the other hand, EEG is very good at telling us when things happen," Moore said. "But we're collecting from sensors placed on the scalp, and we're getting a summation of activity, so really, we're blurring across centimeters of the scalp."

The third technique, EROS, was developed by two co-authors of the new report, U. of I. psychology professors Monica Fabiani and Gabriele Gratton. This method shines near-infrared light into the brain and measures changes in how the light scatters, a reflection of neural activity. EROS provides precise information about where and when the brain responds, but it can only penetrate a few centimeters below the scalp, so it cannot detect events occurring deeper in the brain, as fMRI can, the researchers said.

Combining the three techniques was no easy task. There is limited space available on the scalp for various electrodes and sensors, and the EEG and EROS equipment had to fit within an fMRI coil and could not contain any magnetic metals, the researchers said. Over a period of years, the researchers found a way to include EROS patches that could share space with EEG electrodes on the scalp. They tested different combinations of the three techniques to determine how to intertwine them and how to interpret the information coming through the different channels.

To study how the brain behaves when an individual tries to focus on a task but is distracted by emotional information, the researchers gave study participants a goal of quickly picking out circles from a series of squares and other images that had either emotionally neutral or negative content.

The imaging results revealed that various brain regions responded rapidly to the stimuli. The signals cycled back and forth between locations over parts of the prefrontal and parietal cortices, brain areas that work together to maintain attention and process distractions. This switching occurred on a time scale of hundreds of milliseconds, the researchers found.

The ability to switch attention from a distraction and get back on task is highly relevant to normal cognitive function, said study leader Florin Dolcos, a professor of psychology at Illinois who studies emotional regulation and cognition.

"Sometimes people with depression or anxiety are not able to switch away from emotional distractions and focus," he said. "Better imaging studies will make it easier to test individuals who have been trained in specific emotion-regulation strategies to see if those strategies are working to improve their cognition. And now we can image this with precision in real time, at the mind's speed," he said.

The trimodal approach will provide better answers to other questions about how the brain operates, the researchers said.

"In previous work, these three technologies were applied on the same individuals at different times," Gratton said. "But we gain a lot from measuring these things together."

"This new approach could have a profound effect on neuroscience theory in general, on human neuroscience," Fabiani said. "Because now we don't have to guess about how these different signals align."

Rare-earth elements are in many everyday products, such as smart phones, LED lights and batteries. However, only a few locations have large enough deposits worth mining, resulting in global supply chain tensions. So, there's a push toward recycling them from non-traditional sources, such as waste from burning coal -- fly ash. Now, researchers in ACS' Environmental Science & Technology report a simple method for recovering these elements from coal fly ash using an ionic liquid.

While rare-earth elements aren't as scarce as their name implies, major reserves are either in politically sensitive locations, or they are widely dispersed, which makes mining them challenging. So, to ensure their supply, some people have turned to processing other enriched resources. For instance, the ash byproduct from coal-fired power plants has similar elemental concentrations to raw ores. Yet, current methods to extract these precious materials from coal fly ash are hazardous and require several purification steps to get a usable product. A potential solution could be ionic liquids, which are considered to be environmentally benign and are reusable. One in particular, betainium bis(trifluoromethylsulfonyl)imide or [Hbet][Tf2N], selectively dissolves rare-earth oxides over other metal oxides. This ionic liquid also uniquely dissolves into water when heated and then separates into two phases when cooled. So, Ching-Hua Huang, Laura Stoy and colleagues at Georgia Tech wanted to see if it would efficiently and preferentially pull the desired elements out of coal fly ash and whether it could be effectively cleaned, creating a process that is safe and generates little waste.

The researchers pretreated coal fly with an alkaline solution and dried it. Then, they heated ash suspended in water with [Hbet][Tf2N], creating a single phase. When cooled, the solutions separated. The ionic liquid extracted more than 77% of the rare-earth elements from fresh material, and it extracted an even higher percentage (97%) from weathered ash that had spent years in a storage pond. Finally, rare-earth elements were stripped from the ionic liquid with dilute acid. The researchers found that adding betaine during the leaching step increased the amounts of rare-earth elements extracted. The team tested the ionic liquid's reusability by rinsing it with cold water to remove excess acid, finding no change in its extraction efficiency through three leaching-cleaning cycles. The researchers say that this low-waste approach produces a solution rich in rare-earth elements, with limited impurities, and could be used to recycle precious materials from the abundance of coal fly ash held in storage ponds.

Results of the MOSAiC expedition show: the expected recovery of the ozone layer may fail to happen anytime soon, if global warming is not slowed down

In spring 2020, the MOSAiC expedition documented an unparalleled loss of ozone in the Arctic stratosphere. As an evaluation of meteorological data and model-based simulations by the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) now indicates, ozone depletion in the Arctic polar vortex could intensify by the end of the century unless global greenhouse gases are rapidly and systematically reduced. In the future, this could also mean more UV radiation exposure in Europe, North America and Asia when parts of the polar vortex drift south. With their new findings, the experts call into question the commonly held assumption that, thanks to the ban on the production of chlorofluorocarbons (-CFCs), ozone loss would grind to a halt in just a few decades. The AWI study was jointly conducted with the University of Maryland and the Finnish Meteorological Institute, and has now been published online in the science magazine Nature Communications.

On 12 October 2020, when Polarstern returned to Bremerhaven from MOSAiC - the largest Arctic expedition in history - she brought with her troubling news: broad expanses of open water to the north of Greenland, and sea ice riddled with meltwater pools at the North Pole, bore witness to the dramatic effects of global warming that could already be seen in the Arctic. But the rapid melting wasn't the only thing that worried Expedition Leader Markus Rex: "Readings taken during the expedition showed that the chemical loss of ozone over the Arctic in the spring of 2020 was worse than ever before. A comprehensive analysis has now determined that this was also due to climate change. Unfortunately, our work indicates that, if climate change continues unchecked, loss of ozone over the Arctic will likely continue to worsen through the end of the 21st century, despite the global ban on ozone-destroying substances." During MOSAiC, at the altitude range of maximum ozone concentration, approx. 95% of the ozone had been destroyed. As a result, the thickness of the ozone layer was reduced by more than half, even though the concentration of ozone-destroying substances has declined since the turn of the millennium - a success of the international efforts to protect the ozone layer.

Does that mean the ozone layer - a protective barrier against harmful UV radiation - over the Arctic is increasingly at risk?

To find the answer, a team led by the AWI experts Peter von der Gathen and Markus Rex, and by Ross Salawitch from the University of Maryland, compared the data from 53 computer models created in the context of the international "Coupled Model Intercomparison Project Phases 5 and 6" (CMIP5, CMIP6). Working from this basis, the researchers then projected the ozone depletion in the Arctic polar vortex up to the year 2100. The vortex, a relatively self-contained low-pressure system in the stratosphere at an altitude of 15 to 50 kilometres, forms over the Arctic every autumn and stays for varying durations throughout winter and spring. "For ozone to be depleted in the Arctic, the stratosphere must cool down considerably at the altitude where the ozone layer is," says Peter von der Gathen, first author of the study. "Chlorine, which is normally bound in harmless substances, is released at low temperatures. Subsequently, chlorine together with bromine destroy ozone when exposed to sunlight. However, this only takes place when temperatures sink low enough during winter. Accordingly, in our study we estimated the ozone loss in the next few decades on the basis of the long-term temperature trend in the polar vortex and the expected decline in chlorine and bromine compounds."

Despite the production ban issued in the 1987 Montreal Protocol, substances like chlorofluorocarbons (CFCs) and halons, which contain ozone-destroying chlorine and bromine atoms, are still abundant in the atmosphere, because they break down only very slowly. "The concentrations of these substances in the polar vortex continued to rise until the year 2000," says Peter von der Gathen. "Since then, they've been on decline and are currently at roughly 90 percent of the maximum. Only by the end of the century they will have fallen below 50 percent, according to an assessment of the World Meteorological Organization. Since the pattern of warm and cold stratospheric winters in the polar vortex is very irregular, the degree of ozone depletion varies accordingly. Superimposed on this, however, our analysis of meteorological data from the past 56 years shows a significant trend toward lower temperatures in the cold stratospheric winters and associated increases in ozone losses. In addition, the analysis of the climate models clearly shows that this trend is part of climate change and therefore the product of global greenhouse-gas emissions."

The complex underlying mechanism is at least partly understood: the same gases that result in global warming at the Earth's surface (like CO2) also promote cooling of higher atmospheric layers in the stratosphere, where the ozone layer is located. "In addition, due to climate change we notice changes in the prevailing wind systems. We suppose that these changes also contribute to lower temperatures in the polar vortex. Up to now, the trend towards colder winters in the Arctic stratosphere was debated among researchers. Even when assuming such a trend it was believed that climate change would, in the worst case, prolong the recurring ozone depletion over the Arctic by a few years," Peter von der Gathen explains. "By then at the latest - that's what we assumed, too - the falling concentrations of CFCs would become such a dominating factor that the ozone loss would continually fade. But, according to our new calculations, things could also turn out very differently in the Arctic."

The team's analysis shows that the future chemical loss of ozone in the Arctic will greatly depend on the amount of greenhouse gases emitted by the end of the century. If emissions are substantially reduced in the coming decades, the study actually predicts an early and then steady decline in the degree of ozone loss; but for less optimistic scenarios characterised by rising greenhouse-gas emissions, the opposite could happen. "If we don't reduce our greenhouse-gas emissions rapidly and decisively, loss of ozone in the Arctic stratosphere could, despite the great success of the Montreal Protocol, continue to worsen through the end of this century, instead of following the generally expected path towards a full recovery of the ozone layer" explains Markus Rex. "This represents a fundamental paradigm shift in our assessment of the future of the Arctic ozone layer. And the future of the Arctic ozone layer is relevant for life in Europe, North America and Asia: the Arctic polar vortex occasionally drifts south, which can lead to a few days with a reduced ozone layer over populated areas in spring, increasing levels of UV radiation and ultimately a greater risk of sunburn and acquiring skin cancer during these periods."

For Markus Rex, the message from the Arctic is clear: "There are plenty of good reasons to quickly and comprehensively reduce greenhouse-gas emissions. Now we can add the risk of intensified ozone depletion over the Arctic to the list."

Researchers at Karolinska Institutet in Sweden have developed a technology for cost-effective surveillance of the global spread of new SARS-CoV-2 variants. The technique is presented in the scientific journal Nature Communications.

Since the onset of the pandemic, thousands of viral genomes have been sequenced to reconstruct the evolution and global spread of the coronavirus. This is important for the identification of particularly concerning variants that are more contagious, pathogenic, or resistant to the existing vaccines.

For global surveillance of the SARS-CoV-2 genome, it is crucial to sequence and analyse many samples in a cost-effective way. Therefore, researchers in the Bienko-Crosetto laboratory at Karolinska Institutet and Science for Life Laboratory (SciLifeLab) in Sweden have developed a new method, named COVseq, that can be used for surveillance of the viral genome on a massive scale at a low cost.

First, many copies of the viral genome are created using so-called multiplex PCR (polymerase chain reaction). The samples are then labelled and pooled together in the same sequencing library, using a previous method developed in the Bienko-Crosetto laboratory and now adapted for SARS-CoV-2 analysis.

"By performing reactions in very small volumes and pooling together hundreds of samples into the same sequencing library, we can sequence potentially thousands of viral genomes per week at a cost of less than 15 dollars per sample," says Ning Zhang, postdoctoral researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet and co-first author together with PhD students Michele Simonetti and Luuk Harbers at the same department.

Comparative analyses of 29 SARS-CoV-2 positive samples revealed that COVseq had a similar ability as the standard method to identify small changes in the genome. Analyses of 245 additional samples showed that COVseq also had a high ability to detect emergent coronavirus variants of potential concern. The key advantage of COVseq over existing methods is cost-effectiveness.

"Our inexpensive method could immediately be used for SARS-CoV-2 genomic surveillance by public health agencies and could also be easily adapted to other RNA viruses, such as influenza and dengue viruses," says Nicola Crosetto, senior researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, and last author of the paper.

The origins of seven types of kidney cancer, including several rare subtypes, have been identified by researchers at the Wellcome Sanger Institute, Great Ormond Street Hospital (GOSH), the Princess Máxima Center for Pediatric Oncology and Oncode Institute. The findings confirm that these cancers have their origin in specific forms of developmental cells present in the maturing fetus.

The study, published today (23 June) in Nature Communications, used computational methods to analyse existing datasets and pinpoint the 'cellular signals' given off by different cancers as they emerge. This method holds promise as a tool for diagnosing patients with rare cancers - in the study, one patient's cryptic kidney cancer was identified as a Wilms-like tumour by looking at its cellular signals.

All cancers are derived from normal cells that have started to multiply uncontrollably. By comparing patterns of gene expression in cancer and normal cells, it is possible to learn about aspects of each tumour's origin and behaviour. This type of analysis has been made possible by the advent of single-cell mRNA sequencing, a high-resolution technology that can identify different cell types present in a tissue according to the genes expressed by individual cells.

Previous studies have used these techniques to compare normal and diseased tissue in some of the most common kidney cancers, but to conduct single-cell sequencing on many hundreds of tumours would not be achievable.

In this study, researchers at the Wellcome Sanger Institute and their collaborators turned to computational techniques to mine Human Cell Atlas (HCA) reference data* and databases of tumour gene expression. They assessed mRNA signals in 1,300 childhood and adult renal tumours, spanning seven different tumour types, in order to investigate the origins of these cancers**.

The results confirmed that these childhood cancers are developmental in origin, occurring after errors in a particular developmental cell type's journey to maturity. In contrast, adult kidney cancers emerged from mature cell types and do not revert to a developmental pattern of gene expression in the vast majority of cases.

Each cancer type was also found to exhibit unique 'cellular signals', or patterns of gene expression, that could be used to classify them in future.

Dr Matthew Young, first author of the study from the Wellcome Sanger Institute, said: "It has long been assumed that childhood tumours have 'fetal' origins. Now we can replace that loose definition with a precise, quantitative measurement of the cellular signals that different tumour types exhibit. Our analysis also refutes the theory that adult tumours revert to a developmental state, unless they are a highly lethal subtype of adult kidney cancer."

The study sheds light on the behaviour and origins of some kidney tumour subtypes whose rarity would have made it difficult to examine otherwise. These were congenital mesoblastic nephroma, clear cell sarcoma of the kidney, malignant rhabdoid tumour of the kidney, and chromophobe renal cell carcinoma.

The method pioneered in the study also helped to classify one patient's tumour, which clinicians had been unable to diagnose fully.

Dr Karin Straathof, a senior author of the study from Great Ormond Street Hospital, said: "Sometimes it is not possible to fully diagnose childhood kidney cancers via the usual methods, which can impact our ability to adopt the best course of treatment. One of the samples used in this study was from a child with one of these undiagnosed tumours. But by analysing the genes expressed by the tumour cells, we were able to recognise it as Wilms' tumour. My hope is that this approach can be used in such cases in future."

In recent studies, researchers have identified the origins of individual childhood cancers, such as neuroblastoma, using mRNA single-cell sequencing on small numbers of tumours. Here, computational analysis of existing data has been used to determine the origin of a larger groups of childhood cancers.

Dr Sam Behjati, a senior author of the study from the Wellcome Sanger Institute, said: "Not only does this computational approach using existing datasets validate previous results on the origins of childhood kidney cancers, it provides a new way of expanding this research to much larger numbers of tumours and rare cancer types. I believe that the success of this approach could act as a blueprint for investigating the behaviour and origins of the entire spectrum of human cancer."

Chronic psychosocial stress--which involves a pathway called the hypothalamic-pituitary-adrenal axis (HPA axis)--may contribute to the development of Alzheimer's disease. A new review published in Biological Reviews describes how environmental and genetic factors can impact individuals' HPA axis, and ultimately their risk of Alzheimer's disease.

The review also proposes a mechanism by which genetic factors that influence the HPA axis may also affect inflammation, a key driver of neurodegeneration.

"What we know is that chronic stress does affect many biological pathways within our body. There is an intimate interplay between exposure to chronic stress and pathways influencing the body's reaction to such stress," said senior author David Groth, PhD, of Curtin University, in Australia. "Genetic variations within these pathways can influence the way the brain's immune system behaves leading to a dysfunctional response. In the brain, this leads to a chronic disruption of normal brain processes, increasing the risk of subsequent neurodegeneration and ultimately dementia."

June is Alzheimer's & Brain Awareness Month.

In a study published in the Journal of Bone and Mineral Research, investigators developed and validated a genetic risk score for predicting the onset and severity of the most common type of scoliosis in adolescents--called adolescent idiopathic scoliosis (AIS). AIS causes spinal deformities in as many as 3% of youth, and because its heritability is high, genetic data could help improve detection.

Use of the score may help clinicians identify children at risk of developing AIS who could benefit from preventive therapies.

"We found that a risk score based on genome-wide association study data could predict not only susceptibility to AIS, but also its severity. We hope our findings will be useful for personalized medicine," said senior author Chikashi Terao, MD, PhD, of the RIKEN Center for Integrative Medical Sciences, in Japan.

June is Scoliosis Awareness Month.

Viral mutations during the COVID-19 pandemic could cause the SARS-CoV-2 virus to become more dangerous. A new study published in Genetic Epidemiology has examined the genetic code of SARS-CoV-2 viruses that have infected patients, looking for links between different mutations and patient deaths.

For the study, investigators analyzed 7,548 SARS-CoV-2 genomes of COVID-19 patients worldwide and looked for an association between genomic variants and mortality. In total, 29,891 locations in the viral genome were assessed.

One location was significantly linked with patient mortality. Mutations at this location cause changes in part of the SARS-CoV-2 spike protein, which plays a key role in viral entry into host cells.

"When, in the fall of 2020, we applied methodology from genome-wide association studies to COVID-19 genomes, we noticed one locus in the COVID-19 genomes from Brazil that was associated with mortality and that later became part of the definition of the P.1 strain from Brazil," said co-lead author Georg Hahn, PhD, of Harvard University. The P1. strain was behind a deadly COVID-19 surge in the Latin American country. It's more contagious and more resistant to antibodies than the original strain.

New research published in the Journal of Cellular and Molecular Medicine indicates that SARS-CoV-2, the virus that causes COVID-19, produces microRNAs that can have impacts on infected cells. MicroRNAs are genetic molecules that prevent the production of particular proteins by binding to and destroying messenger RNAs that code for those proteins.

Investigators found that the virus' microRNAs affect individuals' respiratory system, immune response, and vitamin D pathways. Understanding these impacts could provide new insights related to SARS-CoV-2 infection, pathogenesis, and treatment.

"Our finding highlighted genes' involvement in three crucial molecular pathways and may help develop new therapeutic targets related to SARS-CoV-2," the authors wrote.

An article published in the Journal of School Health stresses that food literacy--understanding the impact of food choices on our health, environment, and economy--should be a priority for K-12 schools during the COVID-19 pandemic and beyond.

The authors note that it is essential for a person to be food literate to achieve healthy eating. They stress that the COVID-19 pandemic has exacerbated and highlighted pre-existing health inequalities that are largely driven by socioeconomic and environmental factors. Also, addressing the learning gap between children from lower-income and higher-income families, which has been widened by COVID-19, must include efforts to enhance health and food literacy in schools. The researchers offer a model that can serve as a reference for schools as they strive to advance their health and food literacy agendas.

"Similar to health literacy, food literacy involves many skills and is connected to other literacies that help us make health decisions and take actions," said lead author Sandra D. Vamos, EdD, EdS, MSc, of Western Michigan University. "Our conceptual model as a visual tool draws connections between relevant theories and constructs, which can help guide school-wide thinking and inter-related health and food literacy efforts, whether it be through practice opportunities, research, policy, or interventions."

Boston, MA - Using genome-wide association studies (GWAS) methodology to analyze whole-genome sequencing data of SARS-CoV-2 mutations and COVID-19 mortality data can identify highly pathogenic variants of the virus that should be flagged for containment, according to Harvard T.H. Chan School of Public Health and MIT researchers.

Using this biostatistical methodology, the researchers pinpointed a mutation in the variant known as P.1, or Gamma, as being linked to increased mortality and, potentially, greater transmissibility, higher infection rates, and increased pathogenicity before the P.1 variant had been identified.

The team's methodology is described online on June 23, 2021 in the journal Genetic Epidemiology.

"Based on our experience, GWAS methodology might provide suitable tools that could be used to analyze potential links between mutations at specific locations in viral genomes and disease outcome," said Christoph Lange, professor of biostatistics at Harvard Chan School and senior author of the paper. "This could enable better real-time detection of novel, deleterious variants/new viral strains in pandemics."

The first patients in Brazil with the P.1 variant were documented in January 2021 and within a few weeks the variant caused a spike in cases in Manaus, Brazil. The city had already been hard hit by the pandemic in May 2020, and researchers thought that the city's residents had achieved population immunity because so many people in the area had developed antibodies for the virus during that initial wave. Instead, P.1, which has several mutations in the spike protein the virus uses to attach to and invade a host cell, caused a second wave of infections and seemed to have higher transmissibility and be more likely to cause death than the earlier variants seen in the area.

In September 2020, several months before the first P.1 patient was documented, the Harvard Chan School and MIT team repurposed methodology used in GWAS, which are widely used to link certain genetic variations with specific diseases, to tease apart the relative pathogenicity of various SARS-CoV-2 mutations. The team looked for links between each mutation of the SARS-CoV-2 virus's single-stranded RNA and mortality in 7,548 COVID-19 patients. Data for the study came from the global initiative on sharing avian influenza data (GISAID) database, which contains the genetic sequence and related clinical and epidemiological data associated with SARS-CoV-2 and influenza viruses.

The researchers found one mutation--at locus 25,088bp in the virus's genome--that alters the spike protein and was linked to a significant increase in mortality in COVID-19 patients. The team flagged the variant with this mutation, which was later identified as part of P.1.

The team's biostatistical methodology should have broader applications beyond the P.1 variant and SARS-CoV-2, according to the researchers.

"We expect that this approach would work in similar scenarios involving other diseases, provided the quality of the data collected in public databases is sufficiently high," said Georg Hahn, research associate and instructor of biostatistics at Harvard Chan School and co-first author of the paper.

A new United Nations report calls for an urgent change in the way the world's oceans are managed.

The report from the International Resource Panel, hosted by the UN Environment Programme, raises concerns that if changes are not made quickly, the consequences will be dire.

The Governing Coastal Resources Report was launched today at an event addressed by Ambassador Peter Thomson, UN Secretary-General's Special Envoy for the Ocean. It outlines the effect land-based human activities have on the marine environment.

Put into context - 80 per cent of marine and coastal pollution originates on land, but there are very few, if any, truly effective governance mechanisms that manage land-ocean interactions. The report provides policy makers with options to help reduce the effect of land-based activities on coastal resources and support a transition to a sustainable ocean-based economy.

"The report draws together an evidence base that demonstrates beyond question the need for enhanced governance coordination between terrestrial activities and marine resources," said Izabella Teixeira and Janez Potočnik, Co-Chairs of the International Resource Panel.

Lead author of the report - Steve Fletcher, Professor of Ocean Policy and Economy and Director of the Sustainability and the Environment research theme at the University of Portsmouth, said: "There is no doubt that the future of our oceans are at risk, and so is the critical role they play in supporting life on Earth and human wellbeing, as well as regulating the climate. This is a global issue in which isolated interventions will have minimal impact. Systemic change is the key to success by bringing together countries, governments, business and communities to take collective action."

Professor Fletcher, who is also Director of the University's Revolution Plastics initiative, added: "We've got to stop looking at the problem in a fragmented way - land-based activities in one country may contribute to degradation of coastal resources in another region. This should now be a global priority where the most impactful land-based activities are prioritised for urgent action and so generating the most benefit most quickly."

The report sends five key messages to world policy makers:

Living coastal resources are most threatened by land-based activities. Agriculture, ports and harbours and aquaculture are particularly impactful activities.

All parts of the blue economy are vulnerable to changes in coastal resources arising from land-based activities, particularly fishing, aquaculture and tourism.

Existing land-sea governance approaches cannot cope with the impacts on coastal resources created by land-based activities.

Land-sea governance urgently needs to be strengthened to protect coastal resources from the impacts of land-based activities and to support the transition to a sustainable blue economy.

Tackling the impacts of land-based activities on coastal resources is a global priority.

The report also provides policy makers with five options for strengthening existing land-sea governance structures:

Ecosystem-based management should be a guiding principle of coastal resource governance as it provides a holistic approach to the consideration of all influences on coastal resources.

Existing area-based management tools, with enhancement and adaptation, should be used to counteract the impacts of land-based activities on coastal resources.

Improved coordinating mechanisms are needed to overcome fragmented governance between sectors and between terrestrial and marine governance arrangements.

Implementation-focused capacity development programmes should be formulated and disseminated to target land-sea governance practitioners.

Filling evidence gaps, particularly related to the impacts of land-based activities on abiotic coastal resources, should be prioritised and their implications for effective governance determined.

Using data for more than 500 young stars observed with the Atacama Large Millimeter/Submillimeter Array (ALMA), scientists have uncovered a direct link between protoplanetary disk structures--the planet-forming disks that surround stars--and planet demographics. The survey proves that higher mass stars are more likely to be surrounded by disks with "gaps" in them and that these gaps directly correlate to the high occurrence of observed giant exoplanets around such stars. These results provide scientists with a window back through time, allowing them to predict what exoplanetary systems looked like through each stage of their formation.

"We found a strong correlation between gaps in protoplanetary disks and stellar mass, which can be linked to the presence of large, gaseous exoplanets," said Nienke van der Marel, a Banting fellow in the Department of Physics and Astronomy at the University of Victoria in British Columbia, and the primary author on the research. "Higher mass stars have relatively more disks with gaps than lower mass stars, consistent with the already known correlations in exoplanets, where higher mass stars more often host gas-giant exoplanets. These correlations directly tell us that gaps in planet-forming disks are most likely caused by giant planets of Neptune mass and above."

Gaps in protoplanetary disks have long been considered as overall evidence of planet formation. However, there has been some skepticism due to the observed orbital distance between exoplanets and their stars. "One of the primary reasons that scientists have been skeptical about the link between gaps and planets before is that exoplanets at wide orbits of tens of astronomical units are rare. However, exoplanets at smaller orbits, between one and ten astronomical units, are much more common," said Gijs Mulders, assistant professor of astronomy at Universidad Adolfo Ibáñez in Santiago, Chile, and co-author on the research. "We believe that planets that clear the gaps will migrate inwards later on."

The new study is the first to show that the number of gapped disks in these regions matches the number of giant exoplanets in a star system. "Previous studies indicated that there were many more gapped disks than detected giant exoplanets," said Mulders. "Our study shows that there are enough exoplanets to explain the observed frequency of the gapped disks at different stellar masses."

The correlation also applies to star systems with low-mass stars, where scientists are more likely to find massive rocky exoplanets, also known as Super-Earths. Van der Marel, who will become an assistant professor at Leiden University in the Netherlands beginning September 2021 said, "Lower mass stars have more rocky Super-Earths--between an Earth mass and a Neptune mass. Disks without gaps, which are more compact, lead to the formation of Super-Earths."

 This link between stellar mass and planetary demographics could help scientists identify which stars to target in the search for rocky planets throughout the Milky Way. "This new understanding of stellar mass dependencies will help to guide the search for small, rocky planets like Earth in the solar neighborhood," said Mulders, who is also a part of the NASA-funded Alien Earths team. "We can use the stellar mass to connect the planet-forming disks around young stars to exoplanets around mature stars. When an exoplanet is detected, the planet-forming material is usually gone. So the stellar mass is a 'tag' that tells us what the planet-forming environment might have looked like for these exoplanets."

And what it all comes down to is dust. "An important element of planet formation is the influence of dust evolution," said van der Marel. "Without giant planets, dust will always drift inwards, creating the optimal conditions for the formation of smaller, rocky planets close to the star."

The current research was conducted using data for more than 500 objects observed in prior studies using ALMA's high-resolution Band 6 and Band 7 antennas. At present, ALMA is the only telescope that can image the distribution of millimeter-dust at high enough angular resolution to resolve the dust disks and reveal its substructure, or lack thereof. "Over the past five years, ALMA has produced many snapshot surveys of nearby star-forming regions resulting in hundreds of measurements of disk dust mass, size, and morphology," said van der Marel. "The large number of observed disk properties has allowed us to make a statistical comparison of protoplanetary disks to the thousands of discovered exoplanets. This is the first time that a stellar mass dependency of gapped disks and compact disks has been successfully demonstrated using the ALMA telescope."

"Our new findings link the beautiful gap structures in disks observed with ALMA directly to the properties of the thousands of exoplanets detected by the NASA Kepler mission and other exoplanet surveys," said Mulders. "Exoplanets and their formation help us place the origins of the Earth and the Solar System in the context of what we see happening around other stars."