Culture

ITHACA, N.Y. - Cornell University astronomers have created five models representing key points from our planet's evolution, like chemical snapshots through Earth's own geologic epochs.

The models will be spectral templates for astronomers to use in the approaching new era of powerful telescopes, and in the hunt for Earth-like planets in distant solar systems.

"These new generation of space- and ground-based telescopes coupled with our models will allow us to identify planets like our Earth out to about 50 to 100 light-years away," said Lisa Kaltenegger, associate professor of astronomy and director of the Carl Sagan Institute.

For the research and model development, Kaltenegger, doctoral student Jack Madden and Zifan Lin authored "High-Resolution Transmission Spectra of Earth through Geological Time," published in Astrophysical Journal Letters.

"Using our own Earth as the key, we modeled five distinct Earth epochs to provide a template for how we can characterize a potential exo-Earth - from a young, prebiotic Earth to our modern world," she said. "The models also allow us to explore at what point in Earth's evolution a distant observer could identify life on the universe's 'pale blue dots' and other worlds like them."

Kaltenegger and her team created atmospheric models that match the Earth of 3.9 billion years ago, a prebiotic Earth, when carbon dioxide densely cloaked the young planet. A second throwback model chemically depicts a planet free of oxygen, an anoxic Earth, going back 3.5 billion years. Three other models reveal the rise of oxygen in the atmosphere from a 0.2% concentration to modern-day levels of 21%.

"Our Earth and the air we breathe have changed drastically since Earth formed 4.5 billions years ago," Kaltenegger said, "and for the first time, this paper addresses how astronomers trying to find worlds like ours, could spot young to modern Earth-like planets in transit, using our own Earth's history as a template."

In Earth's history, the timeline of the rise of oxygen and its abundancy is not clear, Kaltenegger said. But, if astronomers can find exoplanets with nearly 1% of Earth's current oxygen levels, those scientists will begin to find emerging biology, ozone and methane - and can match it to ages of the Earth templates.

"Our transmission spectra show atmospheric features, which would show a remote observer that Earth had a biosphere as early as about 2 billion years ago," Kaltenegger said.

Using forthcoming telescopes like NASA's James Webb Space Telescope, scheduled to launch in March 2021, or the Extremely Large Telescope in Antofagasta, Chile, scheduled for first light in 2025, astronomers could watch as an exoplanet transits in front of its host star, revealing the planet's atmosphere.

"Once the exoplanet transits and blocks out part of its host star, we can decipher its atmospheric spectral signatures," Kaltenegger said. "Using Earth's geologic history as a key, we can more easily spot the chemical signs of life on the distant exoplanets."

The cerebral cortex is the relatively thin, folded, outer "gray matter" layer of the brain crucial for thinking, information processing, memory, and attention. Not much has been revealed about the genetic underpinnings that influence the size of the cortex's surface area and its thickness, both of which have previously been linked to various psychiatric traits, including schizophrenia, bipolar disorder, depression, attention deficit hyperactivity disorder (ADHD), and autism.

Now, for the first time, more 360 scientists from 184 different institutions - including UNC-Chapel Hill - have contributed to a global effort to find more than 200 regions of the genome and more than 300 specific genetic variations that affect the structure of the cerebral cortex and likely play important roles in psychiatric and neurological conditions.

The study, published in Science, was led by co-senior authors Jason Stein, PhD, assistant professor in the Department of Genetics at the UNC School of Medicine; Sarah Medland, PhD, senior research fellow at the QIMR Berghofer Medical Research Institute in Australia; and Paul Thompson, PhD, associate director of the Mark and Mary Stevens Neuroimaging and Informatics Institute at the University of Southern California. Ten years ago, these scientists cofounded the ENIGMA Consortium, an international research network that has brought together hundreds of imaging genomics researchers to understand brain structure, function, and disease based on brain imaging and genetic data.

"This study was only possible due to a huge scientific collaboration of more than 60 sites involved in MRI scanning and genotyping participants," Stein said. "This study is the crown jewel of the ENIGMA Consortium, so far."

The researchers studied MRI scans and DNA from more than 50,000 people to identify 306 genetic variants that influence brain structure in order to shed light on how genetics contribute to differences in the cerebral cortex of individuals. Genetic variants or variations are simply the slight genetic differences that make us unique. Generally speaking, some variants contribute to differences such as hair color or blood type. Some are involved in diseases. Most of the millions of genetic variants, though, have no known significance. This is why pinpointing genetic variants associated with cortex size and structure is a big deal. Stein and colleagues consider their new genetic roadmap of the brain a sort of "Rosetta stone" that will help translate how some genes impact physical brain structure and neurological consequences for individuals.

Among the findings of the research published in Science:

Some genetic variants are associated with cortical folding, measured as surface area, while other genetic variants are associated with the thickness of the cortex.

Genes that determine surface area are related to very early development in the fetal cortex, while thickness appears to be driven by genes active in the adult cortex.

People at genetic risk for depression or insomnia are genetically inclined toward having lower surface area, while people with a genetic risk for Parkinson's disease tend to have higher surface area.

The vast scale of the project allowed the discovery of specific genes that drive brain development and aging in people worldwide.

"Most of our previous understanding of genes affecting the brain are from model systems, like mice," Stein said. "With mice, we can find genes, knock out genes, or over express genes to see how they influence the structure or function of the brain. But there are a couple of problems with this."

One problem is, quite simply, a mouse is not a human. There are many human-specific features that scientists can only study in the human brain.

"The genetic basis for a mouse is very different than the genetic basis for humans," Stein said, "especially in in the noncoding regions of the genome."

Genes contain DNA, the basic human code that, when translated into action, creates proteins that "do" things, such as help your finger muscles type or your heart beat or your liver process toxins. But only about 3 percent of the human genome codes for proteins. The vast majority of the human genome is called the noncoding genome. Much of this region is not shared between mice and humans. This noncoding genome consists of tiny molecular switches that can modulate the expression of other genes. These switches don't directly alter the function of a protein, but they can affect the amounts of a protein that is expressed. Turns out, most genetic variants associated with psychiatric disorders are found in the noncoding region of the genome.

These findings can now be a resource for scientists to help answer important questions about the genetic influences on the brain and how they relate to numerous conditions.

AURORA, Colo. (March 26, 2020) - Assessing adverse childhood experiences and current anxiety and depression symptoms may help ease cognitive distress in women who have undergone a surgical menopause for cancer risk-reduction, or RRSO, according to a new study published in Menopause.

Researchers, including Dr. Neill Epperson of the University of Colorado Anschutz Medical Campus, remotely collected extensive cognitive data from women across the nation. 552 women who are BRCA1 and BRCA2 mutation carriers and have undergone RRSO completed the assessments, which measured executive function (a cognitive process that allows individuals to manage information in a planful versus reactive manner), exposure to early life stress, and mood symptoms.

Results show that adverse childhood experiences (ACE) were associated with more severe symptoms of executive dysfunction and worse performances on cognitive tasks post-surgical menopause. Changes in mood, such as anxiety and depressive symptoms, partially mediated ACE associations on subjective and objective measures of executive function. These findings indicate that assessing history of childhood adversity and current anxiety and depression symptoms may help to identify women who will experience executive cognitive complaints after surgical menopause.

This research emphasizes the importance of considering psychological state during other medical procedures. "We can't change the past for women who have experienced serious childhood adversities such as abuse, neglect, divorce, parental substance abuse, or exposure to domestic violence, but we can identify a patient population that is easily assessed for these ACEs as well as current negative mood symptoms," said Epperson, study lead investigator and professor and Chair of psychiatry at the University of Colorado School of Medicine. "Our hope is that assessment of childhood adversity and history of depression and anxiety would become part of the pre-surgical risk-benefit discussion between patients and their doctors."

"Many women have told me over the years that their doctor did not warn them about the potential brain effects of undergoing a surgical menopause. While these women may have made the same decision regarding surgery given its life preserving benefits, they indicated that they wish they had been informed about the potential cognitive and mood effects so that they could be prepared and seek treatment sooner", says Epperson.

Highly focused, intense doses of radiation called stereotactic ablative radiation (SABR) may slow progression of disease in a subset of men with hormone-sensitive prostate cancers that have spread to a few separate sites in the body, according to results of a phase II clinical trial of the therapy.

The trial, called ORIOLE (Primary outcomes of a Phase II randomized trial of observation versus stereotactic ablative radiation for oligometastatic prostate cancer), and led by Johns Hopkins Kimmel Cancer Center researchers since 2016, compared the effectiveness of SABR versus "wait and watch" observation in recurrent cases of oligometastatic prostate cancer.

"It has been a longstanding question, especially important now in the era of immunotherapy, whether any type of radiation, and SABR specifically, can stimulate the immune system," Tran said. "Our trial offers the best data to date to suggest that SABR can cause a systemic immune response."

Oligometastatic cancers are those that have spread from a primary tumor to one to three sites within the body. Of the estimated 1.3 million men worldwide newly diagnosed with prostate cancer each year, some 20% have metastatic disease, although it's unclear what percentage of those overall have oligometastatic cancers. Prostate cancer is the third most common cancer and the most common cancer among men in the United States, resulting in about 30,000 deaths annually. Metastatic prostate cancer is incurable, and men with recurrent hormone-sensitive cancers may prefer to delay one of the standard treatments, an antihormone therapy called androgen deprivation therapy. It often causes unpleasant side effects, including erectile disfunction, loss of bone density leading to fractures, loss of muscle mass and physical strength, fatigue, weight gain and growth of breast tissue among other things.

A report on the study is published March 26 in the journal JAMA Oncology.

Among the 54 men enrolled in the trial, the disease progressed within six months in seven out of 36 (19%) of participants treated with SABR, compared to 11 out of 18 participants (61%) undergoing observation alone. The risk of new cancers at six months was also lower, occurring in 16% of those receiving SABR compared to 63% of those under observation.

There were no significant differences in clinically meaningful side effects or in reports of pain related to the treatment between the two groups, the study found. The average age of the men on the ORIOLE trial were 68-years old, and most participants were Caucasian.

Analysis of immune system white cells in blood drawn from the patients indicated that SABR treatment was associated with an expanded population of T cells, suggesting that the treatment stimulated a full-body immune system response to their cancers, according to the study leader Phuoc Tran, M.D., Ph.D., professor of radiation oncology and molecular radiation sciences at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Kimmel Cancer Center. Tran co-directs the Kimmel Cancer Center's Cancer Invasion and Metastasis program with Andrew Ewald, Ph.D., and Ashani Weeraratna, Ph.D., aimed at studying the process by which cancers spread, to expand and develop better treatments for patients with advanced cancers.

The findings suggest SABR might be usefully paired with other immunotherapies to treat recurrent oligometastatic prostate cancers, but Tran cautioned that any potential benefits of such combined therapy will need to be tested in future clinical trials.

The research team also detected a set of tumor mutations in genes known to be important for suppressing cancer development in some patients that correlated with a higher risk of cancer progression even among those undergoing SABR. "This may be a molecular signature which is indicative of the underlying biology of the patient's cancer," said Tran.

The biomarker could help clinicians know "which patients are going to benefit the most from a metastasis-directed therapy like SABR" compared to a systemic treatment such as chemotherapy, Tran explained.

The ORIOLE results also suggest that SABR treatment may remove or affect signals that promote the development of micrometastases in recurrent oligometastatic prostate cancer, rather than just "resetting" the clock on the disease until metastases grow large again, said Tran.

Tran and team will continue with phase II studies to determine if they can increase the number of participants with slower disease progression. In the ORIOLE trial, patients with metastatic lesions in the bone were most likely to have their cancers recur in a new bone site. To target these new metastatic bone lesions, Tran and colleagues have another clinical trial called RAVENS that combines SABR with a drug called radium-223 (Xofigo®) that targets metastatic cancer in the bones.

MADISON, Wis. -- Removing a gene from the cells that produce insulin prevents mice from developing Type 1 diabetes by sparing the cells an attack from their own immune system, a new UW-Madison study shows.

The cellular sleight-of-hand may suggest ways to prevent Type 1 diabetes in high-risk individuals, as well as other diseases in which the immune system targets the body's own cells.

People with Type 1 diabetes -- once called juvenile diabetes -- make little or no insulin, a hormone necessary to make energy from the sugar in their blood. At an early stage in the disease, their immune system's frontline soldiers, called T cells, incorrectly identify insulin-producing beta cells as a threat and kill them, leading to complete insulin deficiency.

The resulting chaos must be managed for the rest of a patient's life with diet, blood sugar measurement and insulin shots. Type 1 diabetes afflicts as many as 20 million people around the world, contributing to glaucoma, nerve damage, high blood pressure and stroke. In the U.S., it shortens life expectancy by more than a decade.

"The thing is, individuals who are at high risk can be identified," says Feyza Engin, a biomolecular chemistry professor at the University of Wisconsin-Madison and lead author of a new study published today in the journal Cell Metabolism. "They have autoantibodies in their blood serum, meaning we can actually tell who is going to develop Type 1 diabetes within a couple of years. But there's not much for clinicians to do but send them home, because there's no cure for Type 1 diabetes."

Engin's lab altered a line of mice genetically destined to develop Type 1 diabetes. Right before the immune attack usually begins, they removed from the beta cells alone a gene called IRE1-alpha, involved in the mouse cells' response to stress.

Engin expected removing this gene in insulin-producing cells would lead to accelerated diabetes. But the gene removal made a striking and unexpected difference in the mice.

"We expected the beta cells would die soon," Engin said. "Instead, my students told me that the blood glucose levels of the mice were becoming normal following an initial increase lasting a couple of weeks. I couldn't believe it. I said, 'What? No. Just measure it one more time.'"

The beta cells were indeed becoming normal insulin producers. But first they were taking a step backward into immaturity.

"Once we remove this gene, it's almost like the beta cells are undergoing a disguise," says Engin, who was joined by first author Hugo Lee, a graduate student, in publishing the results. "They lose their mature identity. They de-differentiate and exhibit features of progenitor cells, and express hormones of other cell types in addition to insulin."

If that de-differentiation happens before an auto-immune response puts the beta cells in danger, the T cells they meet respond differently.

"When they de-differentiate, they don't act like typical beta cells anymore. They reduce the expression of many genes that signal to immune cells, 'Come and eat me!'" Engin says. "Those signals go down, and that actually is altering the diabetogenic activity of T cells. They don't really recognize the beta cells as a problem anymore. They don't attack."

And then, just as importantly, the immature, de-differentiated beta cells re-differentiate into functional, mature beta cells.

"The mice experienced a little transient hyperglycemia. They have relatively high blood sugar, which isn't dangerous, for a few weeks," says Engin, whose lab is supported by the National Institutes of Health and the Juvenile Diabetes Research Foundation. "But then the beta cells get back to work, and make insulin like they're supposed to."

The T cells alter their activity and stick with the change, leaving the beta cells alone for as long as the lab has followed the mice so far.

"That's the beauty of it," Engin says. "Even after the beta cells come back, the T cells leave them alone. They still have no diabetogenic activity one year later, which is like 40 or 50 years in a human life."

Two drugs being tested in clinical trials for Type 1 diabetes target the stress response of beta cells -- including a drug whose efficacy Engin discovered in mice while working at Harvard University. Her lab's new findings could help guide the way candidate diabetes drugs in clinical trials are used, or help create new therapies. And they may have a similar effect in other auto-immune disorders -- like arthritis, lupus and multiple sclerosis -- in which a particular cell type's activity draws dysfunctional immune attention.

"We've found a very important time point where de-differentiation helps greatly reduce the immune cells' diabetogenic activity," Engin says. "If you can determine an appropriate cell targeted by auto-immune response, and make those victim cells less functional, less mature in the beginning, maybe they can avoid their role in the progress of other diseases, too."

What The Study Did: Head congestion is one of the most common symptoms experienced by astronauts during spaceflight. This observational study examined preflight and postflight head magnetic resonance images (MRIs) of 35 astronauts who participated in either a short-duration (30 days or less) Space Shuttle mission or a long-duration (greater than 30 days) International Space Station mission. Researchers  investigated whether there were differences in the development of certain physiological changes of the paranasal sinuses and mastoid air cells associated with symptoms of head congestion.

Authors: Donna R. Roberts, M.D., of the Medical University of South Carolina in Charleston, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaoto.2020.0228)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

How the novel coronavirus that causes COVID-19 made the leap from animals to humans is a puzzle that scientists are trying to solve as humanity comes to grip with the deadly pandemic sweeping the globe.

At the frontline of this scientific work is Professor Edward Holmes, an evolutionary virologist who holds a joint position with the School of Life and Environmental Sciences and the School of Medical Sciences at the University of Sydney.

He has been working closely with scientists in China and around the world to unlock the genetic code of SARS-CoV-2, which is the virus that causes COVID-19, to understand its origins and assist in the race other scientists are engaged in to find an effective vaccine.

Their work will also help in the monitoring and prevention of other viruses that could potentially transfer from wildlife into humans, causing what are known as zoonotic diseases.

Already this year, Professor Holmes has co-authored four papers on the novel coronavirus, including two of the earliest descriptions of the virus (published in Nature and The Lancet).

This week he publishes two more.

Brought forward for early publication on Thursday by Nature after peer review, the first paper identifies a similar coronavirus to the one now infecting humans in the Malayan pangolin population of southern China. Professor Holmes, a co-author, is the only non-China based academic on the paper.

Understanding the evolutionary pathway by which this novel coronavirus has transferred to humans will help us not only combat the current pandemic but assist in identifying future threats from other coronaviruses in other species.

This paper is an important part of solving that puzzle.

Professor Holmes said: "The role that pangolins play in the emergence of SARS-CoV-2 (the cause of COVID-19) is still unclear. However, it is striking is that the pangolin viruses contain some genomic regions that are very closely related to the human virus. The most important of these is the receptor binding domain that dictates how the virus is able to attach and infect human cells."

The paper identifies pangolins as possible intermediate hosts for the novel human virus that has emerged. The authors call for these animals and others to be removed from wet markets in order to prevent zoonotic transmission to humans.

Professor Holmes said: "It is clear that wildlife contains many coronaviruses that could potentially emerge in humans in the future. A crucial lesson from this pandemic to help prevent the next one is that humans must reduce their exposure to wildlife, for example by banning 'wet markets' and the trade in wildlife."

Just last week Nature Medicine published research co-authored by Professor Holmes with scientists from Scripps Research Institute in La Jolla California, the University of Edinburgh, Columbia University in New York and Tulane University, New Orleans.

That paper has dispelled the fanciful idea that the novel coronavirus was a manufactured biological agent.

Using comparative analysis of genomic data, the scientists show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.

Professor Holmes said: "There is simply no evidence that SARS-CoV-2 - the cause of COVID-19 - came out of a lab. In reality, this is the sort of natural disease emergence event that researchers in the field like myself have been warning about for many years."

That paper has quickly become the highest ranked academic study of all time as measured by Altmetric, a company that monitors media coverage of research papers.

"The high Altmetric is a strong indication of the remarkable global interest in this topic," Professor Holmes said.

And today, Professor Holmes publishes a commentary in the journal Cell with his colleague Professor Yong-Zhen Zhang from the Shanghai Public Health Clinical Centre and the School of Life Science at Fudan University, Shanghai.

In that article they outline our current knowledge of what the genomic data reveals about the emergence of SARS-CoV-2 virus and discuss the gaps in our knowledge.

This includes taking samples from the Wuhan wet market where it is believed the virus originated. The paper says that "genome sequences of 'environmental samples' - likely surfaces - from the market have now been obtained and phylogenetic analysis reveals that they are very closely related to viruses sampled from the earliest Wuhan patients".

However, Professor Holmes and Professor Zhang are quick to point out that as "not all of the early [COVID-19] cases were market associated, it is possible that the emergence story is more complicated than first suspected".

The paper says that the SARS-CoV-2 virus is likely to become the fifth endemic coronavirus in the human population. It concludes that "coronaviruses clearly have the capacity to jump species boundaries and adapt to new hosts, making it straightforward to predict that more will emerge in the future".

How we respond to that will require more research to assist develop public health policy.

They point to policy and other measures to help prevent other coronaviruses becoming a health danger to humans. These include:

- Surveillance of animal coronaviruses in a variety of mammalian species. It is known that bats carry many coronaviruses, we know little about what other species carry these viruses and which has the potential to emerge in humans.

- Increase action against the illegal wildlife trade of exotic animals

- Removal of mammalian and perhaps avian wildlife from wet markets

BOSTON - It's now accepted that gut-barrier dysfunction and gut-derived chronic inflammation play a role in human aging, but how that process is regulated is still largely a mystery. A team led by Richard Hodin, MD, chief of the Division of General and Gastrointestinal Surgery at Massachusetts General Hospital (MGH) has uncovered an important piece of the puzzle which is described in the journal JCI Insight.

Studying mice and fruitflies, researchers found that the enzyme intestinal alkaline phosphotase (IAP) helped prevent intestinal permeability and gut-derived systemic inflammation, resulting in less frailty and extended life span. "Oral IAP supplementation in older mice significantly preserved gut barrier function and was associated with preserving the homeostasis of the gut microbiota during aging," said Hodin. "In other words, the enzyme maintained the composition of the gut bacteria and controlled the low-grade chronic inflammation that can happen with aging."

Because the scientists were using animal models, they were able to test blood from the portal venous system, which goes from the GI tract into the liver and then on through the rest of the body. "This gave us a more direct measure of what's passing across the gut barrier than blood from a human arm would," said Hodin, who began studying the function of IAP over a decade ago after connecting the dots in a couple of obscure papers suggesting the enzyme blocks an endotoxin called LPS. "I was studying IAP for other reasons, not knowing anything about its function," he said. "No one really did."

Because IAP is a naturally occurring enzyme that almost entirely remains in the gut rather than traveling throughout the system, Hodin believes it should prove nontoxic to humans, and those who are found have low levels, especially as they age, will simply be able to supplement. "Because IAP confers anti-inflammatory properties systemically," Hodin said, "it could have implications not only for inflammatory bowel diseases like Crohn's and ulcerative colitis, but also for other human conditions that we now know are linked to the gut and inflammation, such as obesity and diabetes." The team is already at work on the next steps toward getting FDA approval for a supplement.

What The Study Did: This study examined the medical records of 33 newborns born to women with COVID-19.

Author: Wenhao Zhou, M.D., of the National Children's Medical Center, Children's Hospital of Fudan University in Shanghai, China, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamapediatrics.2020.0878)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Ependymoma is a rare form of brain cancer that implicates children and is often tricky to diagnose. Since effective treatment options can be initiated only after a well-formed diagnosis, there is a dire need among the medical community to identify markers for ependymoma, which in turn, will help oncologists tailor therapy better. Richard Wong's and Mitsutoshi Nakada's team at Kanazawa University has now shown how one gene closely linked to ependymoma can help with not just diagnosis, but also treatment options for the condition.

A gene known as TPR shows an elevated presence in 38% of ependymoma cases. Thus, the team first sought out to investigate how an increase in the TPR gene correlated to the development of cancer cells. Each gene present in a cell contains a code for the creation of a specific protein. The TPR gene contains the code for an eponymous protein. Therefore, cancer samples from patients were assessed for the levels of TPR protein. As expected, levels of TPR were abnormally high in these tumor tissues.

The researchers then moved on to investigate whether these abnormal TPR levels could lead to cancer progression. For this purpose, mice were implanted with human ependymoma cancer tissue into their brains. The TPR gene was then deleted in these tissues so that the mice were unable to create the TPR protein. When the tumor tissues were subsequently analyzed, a reduction of cancer growth was seen. The TPR gene was thus vital for the growth of ependymoma tumors.

Deletion of the TPR protein is known to induce a process called autophagy within cells. Autophagy is initiated when a cell is under undue stress and results in the death of damaged cells. The patient tumor samples, with their high levels of TPR protein, showed little or no presence of autophagy. However, autophagy was remarkably high in the mice with TPR depletion. Ependymoma cells were thus spared of autophagic death due to the increased presence of TPR. These damaged cells continued to grow by circumventing the biological systems set up to keep them in check. The high TPR levels were also accompanied by an increase in HSF-1 and MTOR, molecules which are responsible for cell growth and survival.

Finally, the possibility of lowering TPR levels therapeutically to control the cancer was assessed. The mice were given a drug called rapamycin, which inhibits MTOR. The treatment not only led to decreased TPR levels, but also shrank the tumor tissues within their brains.

"Thus, TPR can serve as a potential biomarker, and MTOR inhibition could be an effective therapeutic approach for ependymoma patients", conclude the researchers. While looking out for increased levels of TPR in patients can help oncologists achieve a more comprehensive diagnosis, reducing TPR levels with the help of drugs can help keep the tumors in check.

People say life gets better with age. Now research suggests this may be because older people have the wisdom and time to use mindfulness as a means to improve wellbeing.

Healthy ageing researchers at Flinders University say certain characteristics of mindfulness seem more strongly evident in older people compared to younger people - and suggest ways for all ages to benefit.

"This suggests that mindfulness may naturally develop with time and life experience," says behavioural scientist Associate Professor Tim Windsor, who co-authored a recent study based on an online community survey of 623 participants aged between 18 and 86?years.

"The significance of mindfulness for wellbeing may also increase as we get older, in particular the ability to focus on the present moment and to approach experiences in a non-judgmental way.

"These characteristics are helpful in adapting to age-related challenges and in generating positive emotions."

Mindfulness refers to the natural human ability to be aware of one's experiences and to pay attention to the present moment in a purposeful, receptive, and non-judgmental way. Using mindful techniques can be instrumental in reducing stress and promoting positive psychological outcomes.

From middle age to old age, the Flinders University survey highlights the tendency to focus on the present-moment and adopt a non-judgmental orientation may become especially important for well-being with advancing age.

In one of the first age-related studies of its kind, the researchers assessed participants' mindful qualities such as present-moment attention, acceptance, non-attachment and examined the relationships of these qualities with wellbeing more generally.

"The ability to appreciate the temporary nature of personal experiences may be particularly important for the way people manage their day-to-day goals across the second half of life," says study lead author Leeann Mahlo, who is investigating mindfulness in older adulthood as part of her PhD research.

"We found that positive relationships between aspects of mindfulness and wellbeing became stronger from middle age onwards," she says.

"Our findings suggest that if mindfulness has particular benefits in later life, this could be translated into tailored training approaches to enhanced wellbeing in older populations."

Mindfulness skills can help build wellbeing at any age, adds clinical psychology PhD candidate Ms Mahlo.

Tips to develop mindful techniques include:

Becoming aware of our thoughts and surroundings and paying attention to the present moment in an open and nonjudgmental way. This can prevent us from focusing on the past or worrying about the future in unhelpful ways.

Understanding that our thoughts, feelings and situations exist in the moment and will not last. This can help us to respond in flexible, more optimistic ways to challenging circumstances, including those that we are facing with concerns related to the COVID-19 disease.

Finding out more about mindfulness via app-based programs such as Calm, Headspace, Insight Timer, Smiling Mind, and Stop, Breathe & Think. These are available for use on computers or smartphones and offer flexible ways of learning and practising mindfulness - including for people now spending more time at home.

Although the overall prevalence of overweight and obesity in children and adolescents has fallen slightly over the past decade, the rates of both conditions have increased in the most disadvantaged neighbourhoods. This is the conclusion of a new study based on data from more than one million children in Catalonia, which was carried out by the Barcelona Institute for Global Health (ISGlobal) --a centre supported by "la Caixa"-- and the IDIAPJGol Institute.

Levels of childhood overweight and obesity have plateaued in many middle- and high-income countries over the past decade, but prevalence rates remain high. In Spain, around 41% of children aged 6 to 9 years were overweight and/or obese in 2015--the second-highest prevalence rate in Europe. In the Catalonia region, childhood overweight and obesity rates are similar to those of Spain as a whole.

The new study, published in Jama Network Open, was based on data from 1.1 million children and adolescents in Catalonia aged 2 to 17 years with at least one height and weight record in the Information System for Research in Primary Care (SIDIAP) between 2006 and 2016. The children were divided into three age groups: 2-5 years, 6-11 years and 12-17 years. Prevalence rates and time trends for overweight and obesity were calculated and stratified by socio-demographic characteristics: age, sex, urban/rural residence, nationality, and the socioeconomic deprivation score of the family's census tract, as calculated using the MEDEA index.

In general, the findings showed that the prevalence of overweight and obesity decreased slightly in both sexes and all age groups. During the ten-year study period, rates of overweight and obesity fell from 40% to 38% in girls aged 6 to 11 years and from 42% to 40% in boys of the same age group. However, prevalence rates rose in the most deprived urban areas and in children of non-Spanish nationalities.

In areas with lower socio-economic levels, rates of overweight and/or obesity increased slightly, whereas wealthier areas saw a significant decrease, leading to a wider inequality gap. For example, between 2006 and 2016, the obesity rate in girls aged 6 to 11 years fell by 15.8% in neighbourhoods with the highest socio-economic level but increased by 7.3% in the most disadvantaged areas.

Jeroen de Bont, researcher at ISGlobal and IDIAPJGol and lead author of the study, commented: "The data can be extrapolated to Spain as a whole and they may reflect the impact of the 2008 economic crisis, which exacerbated inequality within urban areas and increased the number of vulnerable families, who may be more likely to follow unhealthy nutritional habits."

Children from North, Central and South America?--the vast majority of whom were Latin American?--had the highest rates of overweight and/or obesity. Specifically, 56% of boys and 50% of girls of these nationalities between the ages of 6 and 11 years were overweight and/or obese. Children of African and Asian nationalities saw the largest increase in overweight or obesity during the study period.

"With the exception of Latin America, children of non-Spanish nationalities were less overweight and/or obese at the start of the study, but their prevalence rates increased over the years until they reached the levels of overweight and/or obesity in Spanish children. This trend was especially pronounced in African and Asian children," commented de Bont. The children's "gradual adoption of the Western lifestyle and eating habits" could explain these findings, he added.

Talita Duarte-Salles, researcher at IDIAPJGol and co-coordinator of the study, commented: "These prevalence rates are alarming, since obesity in childhood and adolescence is associated with health consequences later in life, including cardiovascular, musculoskeletal and endocrine diseases."

The study also found that children between 6 and 7 years of age were the most vulnerable to developing overweight and/or obesity. "These findings demonstrate the importance of public health promotion programmes at early ages where primary healthcare professionals can play a key role in identifying overweight children during routine visits," commented Duarte-Salles.

"Specific health initiatives focused on the most vulnerable groups are urgently needed to address the high prevalence of childhood overweight and obesity in Spain and worldwide," concluded ISGlobal researcher Martine Vrijheid, co-coordinator of the study.

Our body's ability to detect disease, foreign material, and the location of food sources and toxins is all determined by a cocktail of chemicals that surround our cells, as well as our cells' ability to 'read' these chemicals. Cells are highly sensitive. In fact, our immune system can be triggered by the presence of just one foreign molecule or ion. Yet researchers don't know how cells achieve this level of sensitivity.

Now, scientists at the Biological Physics Theory Unit at Okinawa Institute of Science and Technology Graduate University (OIST) and collaborators at City University of New York have created a simple model that is providing some answers. They have used this model to determine which techniques a cell might employ to increase its sensitivity in different circumstances, shedding light on how the biochemical networks in our bodies operate.

"This model takes a complex biological system and abstracts it into a simple, understandable mathematical framework," said Dr. Vudtiwat Ngampruetikorn, former postdoctoral researcher at OIST and the first author of the research paper, which was published in Nature Communications. "We can use it to tease apart how cells might choose to spend their energy budget, depending on the world around them and other cells they might be talking to."

By bringing a quantitative toolkit to this biological question, the scientists found that they had a different perspective to the biologists. "The two disciplines are complimentary to one another," said Professor Greg Stephens, who runs the unit. "Biologists tend to focus on one area and delve deeply into the details, whereas physicists simplify and look for patterns across entire systems. It's important that we work closely together to make sure that our quantitative models aren't too abstract and include the important details."

On their computers, the scientists created the model that represented a cell. The cell had two sensors (or information processing units), which responded to the environment outside the cell. The sensors could either be bound to a molecule or ion from the outside, or unbound. When the number of molecules or ions in chemical cocktail outside the cell changed, the sensors would respond and, depending on these changes, either bind to a new molecule or ion, or unbind. This allowed the cell to gain information about the outside world and thus allowed the scientists to measure what could impact its sensitivity.

"Once we had the model, we could test all sorts of questions," said Dr. Ngampruetikorn, "For example, is the cell more sensitive if we allow it to consume more energy? Or if we allow the two sensors to cooperate? How does the cell's prior experiences influence its sensitivity?"

The scientists looked at whether allowing the cell to consume energy and allowing the two sensors to interact helped the cell achieve a higher level of sensitivity. They also decided to vary two other components to see if this had an impact--the level of noise, which refers to the amount of uncertainty or unnecessary information in the chemical cocktail, and the signal prior, which refers to the cell's acquired knowledge, gained from past experiences.

Previous research had found that energy consumption and sensor interactions were important for cell sensitivity, but this research found that that was not always true. In some situations--such as if the chemical cocktail had a low level of noise and the correlations between different chemicals are high--the scientists found that allowing the cell to consume energy and the sensors to interact did help it achieve a higher level of sensitivity. However, in other situations--such as if there was a higher level of noise--this was not the case.

"It's like tuning into a radio," explained Professor Stephens. "If there's too much static (or noise), it doesn't do any good to turn up the radio (or, in this case, amplify the signal with energy and interactions)."

Despite this, Dr. Ngampruetikorn explained, energy consumption and sensor interactions do remain important mechanisms in many situations. "It would be interesting to continue to use this model to determine exactly how energy consumption can influence a cell's sensitivity," he said. "And in what situations it's most valuable."

Although the scientists decided to look specifically at how cells respond to their surroundings, they stressed that the general framework of their model could be used to shed light on sensing strategies across the biological world. Professor Stephens explained that whilst there's a huge amount of effort going in to characterizing isolated, individual systems, there's considerably less work looking for common principles. "If we can find these principles, then it could renew our understanding of how living systems function, from cell communication and the brain, to animal behavior and social interactions."

In 2013, the German Stiftung Warentest found harmful benzene in drinks with cherry flavor. But how did the substance get into the drinks? Was the source benzaldehyde, an essential component of the cherry flavoring? And if so, how could the problem be solved? A new study by the Leibniz-Institute for Food Systems Biology and the Technical University of Munich (TUM) is now able to answer these questions.

According to the German Federal Institute for Risk Assessment (Bundesinstitut für Risikobewertung, BfR), benzene is mainly absorbed by our bodies via the air we breathe. Non-smokers take in an average of 200 micrograms of benzene per day. Smokers take in around ten times as much. But our food can also contain traces of this harmful substance and thus contribute to the exposure.

When the Stiftung Warentest examined soft drinks in 2013, they came across small quantities of benzene. One drink contained just under 4.6 micrograms of benzene per liter. For comparison: In Germany, one liter of drinking water is allowed to contain only 1 microgram of the substance. At that time, experts at the Stiftung Warentest supposed that the odorant benzaldehyde was the cause of the benzene contaminations observed.

"As our research is specialized on odorants, we followed up on this supposition in the interest of consumer protection and at the suggestion of the German Association of the Flavor Industry (Deutscher Verband der Aromenindustrie, DVAI)," says lead author Stephanie Frank from the Leibniz-Institute for Food Systems Biology at the Technical University of Munich.

To do this, the team of scientists first established a reliable, highly sensitive quantitation method of benzene. Then, they carried out experiments with various model solutions which contained benzene-free benzaldehyde. The team also examined cherry juice produced under laboratory conditions, to which they also added the pure odorant.

Light is the crucial factor

"Our findings confirm the assumption of the Stiftung Warentest and also explain how the formation of benzene occurs. An important requirement in solving the problem in the long term," reports food chemist Stephanie Frank.

As the study proves, the longer the odorant is exposed to light, the more benzaldehyde is converted into benzene. But the light intensity is also decisive. In contrast, the pH value, the oxygen content, the presence of metal ions or the temperature did not affect the benzene production in the model solutions.

To the surprise of the researchers, no benzene was formed in the cherry juice produced under laboratory conditions during light exposure. Frank reasons that it is possible that the dark red color of the drink acts as a light protection filter and prevents the formation of benzene. The benzene found in a few soft drinks sold commercially is probably the result of added cherry flavoring which has already been contaminated with benzene.

"This is why we must be sure to protect flavorings containing benzaldehyde from light, from when the substance is produced to when the product is sold, for example, by storing them in amber glass vials," recommends Peter Schieberle, Professor for Food Chemistry at the Technical University of Munich.

Researchers at UCL have developed a new way to make blood stem cells present in the umbilical cord 'more transplantable', a finding in mice which could improve the treatment of a wide range of blood diseases in children and adults.

Blood stem cells, also known as haematopoietic stem cells (HSCs), generate every type of cell in the blood (red cells, white cells and platelets), and are responsible for maintaining blood production throughout life.

When treating certain cancers and inherited blood disorders, it is sometimes necessary to replace the bone marrow by allogeneic stem cell transplantation - which involves using stem cells from a healthy donor.

The umbilical cord is a useful source of blood stem cells, and cord blood transplants lead to fewer long-term immune complications than bone marrow transplants. Although umbilical cord transplants have been used in young children for the last 30 years, most cord blood units* contain insufficient HSCs to be suitable for older children and adults and 30% of all units contain too few even for the youngest children, and go to waste.

The study, published in the journal Cell Stem Cell, highlights how a protein called NOV/CCN3, which is normally found at low levels in the blood, can be used to rapidly increase the number HSCs in single umbilical cord blood units that are capable of transplantation. This finding potentially opens the door to units that would otherwise be discarded being made available for patients of all ages.

"Trying to increase the actual number of hematopoietic stem cells in umbilical cord blood is both expensive and challenging. It is known that not all HSCs present in a cord blood unit can or will transplant, indicating that cord blood units have untapped transplantation potential," explained Dr Rajeev Gupta, Clinical Associate Professor at UCL Cancer Institute and first author of the study.

"We explored an alternative approach to harness this potential by increasing the functionality - rather than the number - of HSCs, and so enhance the ability of umbilical cord blood units to transplant.

"We'd previously discovered that a regulatory protein known as NOV is essential for the normal function of human HSCs, and so we asked whether highly purified NOV might be used to manipulate cord blood HSCs to make them more transplantable."

Using cell cultures and mouse models in the lab, the research team at UCL Cancer Institute found that umbilical cord blood units exposed to NOV showed significantly more transplantation potential than regular samples. In fact, the frequency of functional HSCs in the sample increased six-fold. Strikingly, these effects were achieved with only an eight-hour exposure.

"Using NOV, we've shown that we can rapidly manipulate blood stem cells to alter their state - changing non-functioning HSCs to functioning HSCs - which enhances cord blood engraftment potential. This finding offers a new strategy for improving blood transplants. The next stage will be to take our research into a clinical setting to explore how this can benefit patients with blood cancers and other blood disorders," said Dr Gupta.

Commenting on the study, Professor Alejandro Madrigal, Scientific Director of the Anthony Nolan Institute, and a world-leading scientist in the field of stem cell transplantation, said: "Cord blood transplantation has been shown to improve engraftment and provide a better outcome for many people. However, unfortunately, stem cells numbers in many cord blood units might be inadequate for optimal transplantation.

"This research is extremely encouraging, since with the simple addition of NOV/CCN3, there is an increase in the functionality of existing stem cells.

"This practical solution could enable many more cord blood units, which have a limited number of stem cells, to be made available for transplantation and could make a huge difference to the many patients."