Earth

Greater sports participation among Aboriginal and Torres Strait Islander children is linked with better academic performance, according to new research from the University of South Australia.

Conducted in partnership with the University of Sydney and the University of Technology Sydney, the world-first study found that Aboriginal and Torres Strait Islander children who played organised sports every year over four years, had numeracy skills which were advanced by seven months, compared to children who did less sport.

The study used data from four successive waves of Australia's Longitudinal Study of Indigenous Children, following 303 students (with a baseline age of five to six years old) to assess cumulative sports participation against academic performance in standardised NAPLAN and PAT outcomes.

Sports participation has been linked with better cognitive function and memory in many child populations, but this is the first study to confirm the beneficial association between ongoing involvement in sport and academic performance among Aboriginal and Torres Strait Islander children.

Lead researcher, UniSA's Dr Dot Dumuid, says the study highlights the importance of sports as a strategy to help close the gap* for Australia's first nations peoples.

"Playing sport has always had strong cultural importance to Aboriginal and Torres Strait Islanders, so understanding how sports can boost numeracy among Indigenous children is a valuable step towards improving health and reducing disadvantage," Dr Dumuid says.

"When children play sport, they're learning the social structures of a team, how to work within rules, how to focus their attention, and key strategies for success.

"Interestingly, when children play sport, they're not only activating parts of the brain that are involved in learning, but they're also inadvertently practising mathematical computations such as 'how much time is left in the game?' and 'how many points do we need to win?', and it's this that may well be contributing to improved numeracy."

Aboriginal and Torres Strait Islanders comprise a relatively large proportion of athletes in Australia's leading sports teams. While only representing about three percent of the population, they make up nine percent of AFL players, and 22 per cent of State of Origin players.

Encouraging sports in Aboriginal and Torres Strait Islander communities could have many other benefits for health and wellbeing, says co-researcher and Professor of Indigenous Health Education at UTS, John Evans.

"Playing sport creates a sense of belonging, and builds self-esteem, coherence and purpose," Professor Evans says.

"This is especially important for people living in rural and remote areas where opportunities for social interaction and structured activities can be limited.

"If we can find ways to encourage greater participation among Aboriginal and Torres Strain Islander communities, while removing key barriers - such as financial costs and lack of transport - we could promote healthier living, more cohesive societies while also and boosting academic performance among Indigenous children."

A new paper from UC Santa Cruz researchers, published in Proceedings of the National Academy of Sciences, shows that fear of humans causes mountain lions to increase their energy expenditures as they move through the landscape, and this can ultimately limit the size of the home ranges they're able to maintain.

"Mountain lions fear us, and that fear has all kinds of impacts on their behavior and ecology, and ultimately, potentially even their populations and conservation," said professor Chris Wilmers, the senior author on the paper.

Wilmers is principal investigator for the Santa Cruz Puma Project, through which he and colleagues have been studying local mountain lion populations for over a decade. Barry Nickel, director of UC Santa Cruz's Center for Integrated Spatial Research, led the most recent study, which relied on data from five adult female pumas and eight adult males that were outfitted with tracking collars as they roamed their natural habitats.

Throughout the two-month study period, the tracking collars recorded high-resolution GPS and accelerometer data, which Wilmers said worked "essentially like a Fitbit" to help the team estimate how many calories a mountain lion burned based on where, how far, and how fast the cat was moving. The ultimate goal was to integrate the energy cost of navigating physical terrain with the cost of avoiding humans to see how both factors affect use of habitats.

To assess the impacts of physical terrain, researchers compared topography with trends in the cats' movement data. This showed that less rugged terrain requires less energy for pumas to navigate, which may help to explain why mountain lions prefer habitats with easy-to-traverse valleys or ridges. And to get a sense for how fear of humans affected the cats, researchers also compared housing densities with collar tracking data.

This analysis showed that, in areas with higher housing densities, pumas were engaging in more energetically demanding movements, like stopping less and moving more quickly. Their movements were also much less efficient: instead of taking the shortest path to their destination, they took longer, meandering paths to navigate around perceived risks.

"Humans, as a risk factor, are actually increasing the energy an animal needs to traverse this landscape," Nickel explained. "And this is primarily through changes in their behavior as a means to avoid humans."

The constant vigilance that cats used as they moved through human-dominated landscapes is incredibly energy intensive. Nickel and the research team estimate that, in otherwise identical terrain, pumas expend 13 percent more calories per five-minute period in habitats close to people than they would in remote wildland habitats.

As a result, researchers found that fear of humans had a greater impact than variations in terrain on the amount of energy it takes for mountain lions to move about their habitats. In fact, the effect of increasing housing density on energetic costs of movement was four to 10 times greater than the effect of increasing slope and ruggedness of the terrain.

That's a problem because pumas might compensate for increased energy costs in navigating their habitats by reducing the total size of their territories. And this trend showed up very clearly in the tracking data.

Both males and females reduced the size of their home ranges in response to overall increased energy costs of navigating the landscape, but males, in particular, were especially affected by housing density. Male pumas in habitats most dominated by humans had 78.8 percent smaller home ranges compared to those with the most remote habitats.

Human-induced risk has actually become the primary driver of male patterns of space use among pumas. Females didn't show this same trend, but the research team suspects males may be more vulnerable to human impacts because they typically have to establish larger home ranges to improve their odds of finding a mate.

Overall, researchers are concerned that pressure to avoid humans may harm the health of local mountain lion populations.

"It constrains their space use, which could then affect other aspects of their ecology, like finding mates, finding food, competing with other males, or other natural interactions," Nickel said.

Skeletal muscle is the largest tissue in the human body and is responsible not only for locomotion but for energy metabolism and heat production. Age-related muscle atrophy reduces motor function and contributes to the need for nursing care. In addition, muscle atrophy associated with various chronic diseases is known to be a risk factor for life expectancy. Myoblasts, the progenitor cells of muscle, play an important role in maintaining muscle homeostasis. However, it has been reported that the differentiation ability of myoblasts decreases with age and disease, and this is thought to be one of the causes of muscle atrophy. In order to prevent or treat muscle atrophy, a research team led by Assistant Professor Tomohide Takaya of Shinshu University, Faculty of Agriculture studied molecules that promote myoblast differentiation.

The research group focused on oligo-DNA (short single-stranded DNA), which exhibits diverse activities in vivo. As a result of searching for sequences that promote myoblast differentiation among 50 types of oligo-DNA derived from the genome sequence of lactobacilli, they found that an 18-base oligo-DNA with telomere sequence has an extremely strong inducing effect on myoblast differentiation. This "myogenetic oligo-DNA" (myoDN) acts as an aptamer that binds to protein nucleolin in myoblasts by forming a characteristic three-dimensional structure. As a result, myoDN was found to promote myoblast differentiation by inhibiting nucleolin function and ultimately activating the p53 signaling pathway.

The number of people with muscle atrophy is increasing in our hyper-aged society. The deterioration of people's motor function, QOL, and life expectancy due to muscle atrophy is now a major social problem. One possible solution to this problem is the activation of muscle stem cells, and the research team searched for molecules that promote the differentiation of muscle stem cells or muscle formation.

Usually, in such research screenings, scientists look for molecules that act on a predetermined target. However, the group of researchers wanted to find a new molecule that had never been found before, so a target was not set, and instead the group searched for a molecule that would act on a predetermined target. Prof. Takaya constructed an experimental system to reliably determine only whether the final indicator, muscle formation was achieved or not. As a result, the group was fortunate enough to find a unique molecule, myoDN. Oligo-DNA derived from the genome sequence of lactic acid bacteria was identified to differentiate myoblasts. This myoDN is expected to be applied as a nucleic acid medicine as a useful molecule for the prevention and treatment of muscle diseases including muscle atrophy.

myoDN was designed by the co-author of the study, Dr. Takeshi Shimosato, also of the Faculty of Agriculture, Shinshu University. myoDN was originally designed as an immunomodulatory molecule, but unfortunately, it did not have that function and was stored as a rejected molecule in the Shimosato lab. Nobody understood how myoDN worked when it was first found. However, the relationship between the three-dimensional structure and molecular function of myoDN was completely consistent with predictions of computer simulations performed by Dr. Koji Umezawa of the Faculty of Agriculture, Shinshu University and the actual experimental results.

The fate of stem cells can be controlled by oligo-DNA derived from microbial genomes but not contain genetic information. The ultimate goal is to develop myoDN-based drugs for the treatment of muscle atrophy and muscle diseases in humans so that people will be able to continue to live a vigorous life even as they age. As the world's first oligo-DNA that promotes muscle differentiation, myoDN is expected to be developed for application as a preventive and therapeutic agent for muscle atrophy.

To predict when earthquakes are likely to occur, seismologists often use statistics to monitor how clusters of seismic activity evolve over time. However, this approach often fails to anticipate the time and magnitude of large-scale earthquakes, leading to dangerous oversights in current early-warning systems. For decades, studies outside the seismology field have proposed that these major, potentially devastating seismic events are connected to a range of non-seismic phenomena - which can be observed days or even weeks before these large earthquakes occur. So far, however, this idea hasn't caught on in the wider scientific community. In this special issue, EPJ Special Topics proposes the Global Earthquake Forecasting System (GEFS): the first collaborative initiative between multi-disciplinary researchers devoted to studying a diverse array of non-seismic earthquake precursors.

By promoting the integration of these ideas with existing theories in seismology, GEFS could lead to significant improvements of earthquake early warning systems; potentially saving lives and protecting critical infrastructures when future disasters hit. The initiative is rationalised via a subtle atomic-level defect-based mechanism for explaining a variety of earthquake precursors, building on decades of laboratory experiments in physical chemistry and solid-state physics. The theory suggests that, as stresses build up in tectonic plates prior to seismic activity, electron-hole pairs are generated in the Earth's crust. The electrons are confined to the stressed rocks, but the positively charged holes flow out into the surrounding, less stressed rocks, producing electrical currents that can travel over large distances. These currents in turn can trigger wide-ranging secondary effects ranging from unusual low to ultralow electromagnetic radiation, to emissions of spectroscopically distinct thermal infrared from the Earth's surface, to changes in the atmosphere and ionosphere.

This special issue documents the findings of researchers around the world, who have used both ground- and space-based observations to link these non-seismic patterns to the occurrence of subsequent large earthquakes. The work creates a strong rationale for global efforts to continually monitor the Earth for key signs of these precursors, which are often intermittent and weak. If its aims are realised, GEFS could be the first step towards a widespread collaboration between different scientific communities, each with the shared goal of improving our ability to forecast large earthquakes in the future.

G3BP proteins inhibit the metabolic driver MTOR - a signaling protein that plays a central role in tumor diseases and developmental disorders of the brain. This is reported in this week´s issue of the renowned journal Cell. The study was led by scientists from the University of Innsbruck and the German Cancer Research Center (DKFZ) in collaboration with the Medical University of Innsbruck and a Europe-wide research network.

The signaling protein MTOR (Mechanistic Target of Rapamycin) is a sensor for nutrients such as amino acids and sugars. When sufficient nutrients are available, MTOR boosts metabolism and ensures that sufficient energy and building blocks are available for the growth and function of all cells in the human body. "Because MTOR is such a central switch for metabolism, errors in its activation lead to serious diseases. These include cancers associated with excessive metabolic activity, cell growth and proliferation. Dysregulated MTOR also causes malformations of the nervous system, disturbing stimulus processing and eliciting behavioral disorders and epilepsy." explains Kathrin Thedieck, Professor of Biochemistry at the University of Innsbruck.

To prevent errors in MTOR-based signal processing, the cell controls its activity very precisely. This is achieved through so-called suppressors, molecules that inhibit a protein and help to regulate its activity. The TSC complex is such a suppressor for MTOR. It is named after the disease that is caused by its absence - tuberous sclerosis complex (TSC) disease. Together with MTOR, the TSC complex localizes to small cellular structures, the lysosomes, where it keeps MTOR in check. If the TSC complex - for example due to changes (mutations) in one of its components - no longer remains at the lysosome, this can lead to excessive MTOR activity with severe consequences for human health.

A molecular TSC anchor at lysosomes

The teams led by Kathrin Thedieck at the University of Innsbruck and Christiane Opitz at DKFZ therefore investigated how the TSC complex binds to lysosomes. They discovered that the G3BP (Ras GTPase-activating protein-binding protein) proteins localize to lysosomes, together with the TSC complex. There, the G3BP proteins form an anchor that ensures that the TSC complex can bind to the lysosomes. This anchor function plays a crucial role in breast cancer. If the amount of G3BP decreases, not only MTOR activity but also cell motility is increased in cancer cell cultures. MTOR inhibitors suppress this hypermotility. In breast cancer patients, low G3BP correlates with a worse prognosis. "G3BP proteins could therefore be valuable markers to personalize therapies and improve the efficacy of drugs that inhibit MTOR." says Christiane Opitz.

G3BP proteins also inhibit MTOR in the brain. In zebrafish, an important animal model for pharmaceutical research, the scientists observed disturbances in brain development when G3BP was missing. Loss of G3BP also resulted in neuronal hyperactivity and ensuing behavioral abnormalities reminiscent of epilepsy in humans. Compounds that target MTOR suppressed the neuronal hyperactivity. "We therefore anticipate that patients with neurological disorders and G3BP malfunction could benefit from MTOR inhibitors and we look forward to further exploring this together with our scientific network," says Kathrin Thedieck. Also Lukas A. Huber, Director of Cell Biology at the Medical University of Innsbruck, is pleased with the joint success: "Through this successful collaboration a strong research focus on MTOR and lysosomes is emerging at the two Innsbruck universities, and I am excited to embark on our next projects." states Lukas A. Huber.

Scientists have identified that the evolutionary development of human and primate brains may have been similar for communication and memory.

Although speech and language are unique to humans, experts have found that the brain's pathway is similarly wired in monkeys which could signify an evolutionary process dating back at least 25 million years.

In a study, published in the journal Neuron, teams led by Newcastle University and the University of Iowa, compared auditory cortex information from humans and primates and found strong links.

Professor Chris Petkov, from Newcastle University's Faculty of Medical Sciences, UK, said: "Our language abilities help us to crystallise memories and make them vivid, such as 'the singer sounded like a nightingale'.

"Therefore, it's often thought that the human language and memory brain systems went through a substantial transformation during our recent evolutionary history, distinguishing us from every other living animal.

"We were astounded to see such striking similarity with other primates, and this discovery has substantial importance for science and neurological disorders."

Stimulating auditory cortex

Scientists used information from neurosurgery patients being monitored for treatment. With humans, stimulation of a specific part of the brain can be visualized if brain imaging is used at the same time.

The experts also compared the results from stimulating auditory cortex and visualising areas important for language and memory in monkeys.

The brain stimulation highlighted a previously unseen ancestral brain highway system that is deeply shared by humans and monkeys, one that is likely to have been present in ancestral primates to both species.

The finding is important because brain stimulation is a common treatment for neurological and psychiatric disorders. However, how brain stimulation works is not well understood and requires work that cannot be conducted with humans. Work with non-human primates has paved the way for current brain treatments, including Parkinson's disease.

Inspiring new research

The study has generated unique new brain scanning information that can now be globally shared to inspire further discovery by the international scientific community.

Professor Matthew Howard III, chief neurosurgeon at the University of Iowa Carver Medical Center, USA, co-author of the study, said: "This discovery has tremendous potential for understanding how brain stimulation could help patients, which requires studies with animal models not possible to conduct with humans."

Professor Timothy Griffiths, consultant neurologist at Newcastle University, also co-author of the study, added: "This discovery has already inspired new research underway with neurology and neurosurgery patients."

Research from North Carolina State University shows that extreme weather events, such as hurricanes and increased precipitation, affect both the amount and the composition of picophytoplankton in the Neuse River Estuary. The work is a first step in determining how a wetter climate may affect the estuarine ecosystem.

Picophytoplankton are defined as any phytoplankton measuring less than three micrometers in size. Although well studied as part of the oceanic ecosystem and food web, picophytoplankton are understudied in estuarine systems, even though they occur in significant numbers within these environments.

"Picophytoplankton are important primary producers in aquatic ecosystems," says Ryan Paerl, assistant professor of marine, earth and atmospheric sciences and lead author of the research. "They provide food for larger microorganisms, play a role in carbon fixation and cycling, and are sentinels of good ecosystem health. So understanding the effect of moderate to extreme precipitation events on these tiniest members of the ecosystem gives us a more complete sense of impacts of storms on estuaries and the life within them."

Paerl and his team conducted a study of picophytoplankton numbers and composition in the Neuse River Estuary - a major component of the second largest estuary in the lower U.S. - from July 2017 to December 2018, taking monthly or bimonthly samples at 11 sites along the estuary and using flow cytometry to identify the amount and composition of picophytoplankton.

During "stable" conditions - warm, sunny weather - picophytoplankton were found in concentrations of 1 million cells per milliliter. However, increased precipitation overall and the arrival of Hurricane Florence in September 2018 had huge impacts on the picophytoplankton in the estuary, bringing numbers down at least a thousand-fold, to 1,000 cells per milliliter or fewer.

The composition of picophytoplankton changed following these extreme weather events as well, from primarily cyanobacteria to primarily picoeukaryotic phytoplankton (PEUK).

"We saw that precipitation and resulting increased river flow acts like a hose on these picophytoplankton, flushing them out of the estuary," Paerl says. "Then the PEUKs have mini-blooms after the flushing events. They do really well and grow very quickly after disturbances. The good news for the food web is that PEUKs often can produce excellent nutrients, like fatty acids, and PEUKs are desirable prey so their growth and consumption could be giving the food web a quick shot in the arm after these events."

As recent climate reports predict wetter weather in the southeastern U.S., the researchers think that the PEUKs may become more important players in estuarine ecosystems than they are currently.

"Picophytoplankton make up an average of 40% of all phytoplankton biomass in the Neuse River estuary, and that number can be over 70% during stable warm summer months," Paerl says. "And these picophytoplankton are really impacted by storms - even those that aren't hurricane strength. The result is a shift in concentration and population that could have long-term effects on food webs and biochemistry in the estuary."

The work appears in Scientific Reports and was performed in partnership with the UNC-Chapel Hill Institute of Marine Sciences (UNC-IMS) Neuse River Estuary Modeling and Monitoring Project (ModMon), which is led by Hans Paerl and supported by the North Carolina Department of Environmental Quality, as well as the Lower Neuse Basin Association. Former NC State graduate student Rebecca Venezia and current Ph.D. student Joel Sanchez also contributed to the work.

Air pollution is linked to a heightened risk of progressive and irreversible sight loss, known as age related macular degeneration (AMD), reveals a large long term study led by UCL researchers.

They found that people in the most polluted areas were at least 8% more likely to report having AMD, according to the findings published in the British Journal of Ophthalmology.

Lead author Professor Paul Foster (UCL Institute of Ophthalmology) said: "Here we have identified yet another health risk posed by air pollution, strengthening the evidence that improving the air we breathe should be a key public health priority. Our findings suggest that living in an area with polluted air, particularly fine particulate matter or combustion-related particles that come from road traffic, could contribute to eye disease.

"Even relatively low exposure to air pollution appears to impact the risk of AMD, suggesting that air pollution is an important modifiable risk factor affecting risk of eye disease for a very large number of people."

AMD is the leading cause of irreversible blindness among people over 50 in high-income countries, with the numbers of those affected projected to reach 300 million by 2040. Known risk factors include older age, smoking, and genetic make-up.

Air pollution has been implicated in brain conditions such as Alzheimer's disease, Parkinson's disease and stroke, while a 2019 study by the same research team found that air pollution was linked to elevated glaucoma risk. Particulate matter exposure is one of the strongest predictors of mortality among air pollutants.

To see if air pollution might also be implicated in AMD risk, the researchers drew on data from 115,954 UK Biobank study participants aged 40-69 with no eye problems at the start of this study in 2006.

Participants were asked to report any formal diagnosis of AMD by a doctor. And structural changes in the thickness and/or numbers of light receptors in the retina - indicative of AMD - were assessed in 52,602 of the participants, for whom complete data were available in 2009 and 2012, using retinal imaging (non-invasive optical coherence tomography or OCT).

Measures of ambient air pollution included those for particulate matter (PM2.5), nitrogen dioxide (NO2), and nitrogen oxides (NOx). The estimates for these were provided by the Small Area Health Statistics Unit as part of the BioSHaRE-EU Environmental Determinants of Health Project. Official information on traffic, land use, and topography was used to calculate the annual average air pollution levels at participants' home addresses.

The research team found that people in areas with higher levels of fine particulate matter pollution were more likely to report having AMD (specifically, they found an 8% difference in AMD risk between people living in the 25th and 75th percentiles of pollution levels), after accounting for potentially influential factors such as underlying health conditions and lifestyle. All pollutants, except coarse particulate matter, were associated with changes in retinal structure.

The researchers caution that this observational study cannot confirm cause, but their findings align with evidence from elsewhere in the world.

While they cannot yet confirm a mechanism, they suggest that ambient air pollution could plausibly be associated with AMD through oxidative stress or inflammation.

Dr Sharon Chua (UCL Institute of Ophthalmology), the paper's first author, adds: "Higher exposure to air pollution was also associated with structural features of AMD. This may indicate that higher levels of air pollution may cause the cells to be more vulnerable to adverse changes and increase the risk of AMD."

A team led by plant biologists at the Universities of Freiburg and Göttingen in Germany has shown for the first time that mosses have a mechanism to protect them against cold that was previously known only in flowering plants. Professor Ralf Reski at the Cluster of Excellence Centre for Integrative Biological Signalling Studies (CIBSS) at the University of Freiburg and Professor Ivo Feussner at the Center for Molecular Biosciences (GZMB) at the University of Göttingen have also demonstrated that this mechanism has an evolutionarily independent origin - mosses and flowering plants use a similar mechanism that hinges on distantly related genes. Moreover, it protects the organisms against pathogens as well as cold. The moss Physcomitrella and the flowering plant Arabidopsis served as model organisms. The team has published its study in the journal Nature Plants.

More than 500 million years ago plants began to leave the water and colonize the land. Mosses and flowering plants diverged evolutionarily from a common ancestral plant. However, both had to find ways to protect themselves from low temperatures on land. For example, it is vital for all plants to maintain the fluidity of their cell membranes. Only sufficiently fluid membranes enable transport processes across the barrier that surrounds a plant cell as a protective envelope. When the temperature drops, the membrane hardens and becomes less permeable, which impairs cell functions. Plants can counteract this as their cell membranes contain lipids, which contain fatty acids. The more unsaturated fatty acids these lipids contain, the lower the temperature at which the membrane solidifies.

The research team from Freiburg and Göttingen has identified a new protein that plays an essential role in the regulation of fluidity in mosses. It influences the degree of saturation of fatty acids in a group of membrane lipids known as sphingolipids. When the researchers deleted the gene responsible for the formation of this protein, they found that the plants were more sensitive to cold. At the same time, they were more susceptible to oomycetes - filamentous organisms related to algae that include pathogens of plant diseases such as downy mildew and potato blight.

"Sphingolipids are important building blocks of cell recognition and signal transduction in humans, animals and plants. We have discovered a previously unknown regulator of these sphingolipids in moss and shown that it also functions in a flowering plant. This opens up completely new possibilities in synthetic biology," Reski explains.

Feussner adds "Our work shows that mosses and flowering plants have followed different pathways during evolution to adjust membrane fluidity in cold conditions in a similar way. This is an impressive example of convergence in plant evolution at the molecular level."

How mosses acquired this particular gene is unclear. The team found it also in the genome data of fungi, choanoflagellates, diatoms and a small group of unicellular algae that have been little studied so far.

Hitting a pothole on the road in just the wrong way might create a bulge on the tire, a weakened spot that will almost certainly lead to an eventual flat tire. But what if that tire could immediately begin reknitting its rubber, reinforcing the bulge and preventing it from bursting?

That's exactly what blood vessels can do after an aneurysm forms, according to new research led by the University of Pittsburgh's Swanson School of Engineering and in partnership with the Mayo Clinic. Aneurysms are abnormal bulges in artery walls that can form in brain arteries. Ruptured brain aneurysms are fatal in almost 50% of cases.

The research, recently published in Experimental Mechanics, is the first to show that there are two phases of wall restructuring after an aneurysm forms, the first beginning right away to reinforce the weakened points.

"Imagine stretching a rubber tube in a single direction so that it only needs to be reinforced for loads in that direction. However, in an aneurysm, the forces change to be more like those in a spherical balloon, with forces pulling in multiple directions, making it more vulnerable to bursting," explained Anne Robertson, professor of mechanical engineering and materials science at Pitt, whose lab led the research. "Our study found that blood vessels are capable of adapting after an aneurysm forms. They can restructure their collagen fibers in multiple directions instead of just one, making it better able to handle the new loads without rupturing."

Researchers have known that blood vessels have the ability to change and restructure over time, but this study represents the first observation of a new, primary phase of restructuring that begins immediately.

The researchers used a rabbit model developed by David Kallmes of the Mayo Clinic to observe this restructuring in the brain tissue over time. To see this process up close, the researchers partnered with Simon Watkins at Pitt's Center for Biologic Imaging, taking advantage of the center's state-of-the-art multiphoton microscopes to image the architecture of the fibers inside the aneurysm wall.

"We found that the first phase of restructuring involves laying down an entirely new layer of collagen fibers in two directions to better handle the new load, while the second phase involves remodeling existing layers so their fibers lie in two directions," explained Chao Sang, who was a primary investigator on this research as part of his doctoral dissertation in Pitt's Department of Mechanical Engineering and Materials Science

"The long-term restructuring is akin to a scar forming after a cut has healed, while this first phase that we observed can be thought of as having a role similar to clotting immediately after the cut--the body's first response to protect itself," added Robertson, who has a secondary appointment in the Swanson School's Department of Bioengineering. "Now that we know about this first phase, we can begin to investigate how to promote it in patients with aneurysms, and how factors like age and preexisting conditions affect this ability and may place a patient at higher risk for aneurysm rupture."

For many years, clinicians have been hesitant to diagnose adolescents with Borderline Personality Disorder (BPD), believing it was a mental health "death sentence" for a patient because there was no clear treatment. Carla Sharp, professor of psychology and director of the Developmental Psychopathology Lab at the University of Houston, begs to differ.

And her new research, published in Journal of Abnormal Child Psychology backs her up.

"Like adult BPD, adolescent BPD appears to be not as intractable and treatment resistant as previously thought," reports Sharp. "That means we should not shy away from identifying BPD in adolescents and we shouldn't shy away from treating it."

Borderline Personality Disorder is marked by patterns of varying moods, self-image and behavior, and it results in impulsive actions, problems in relationships and a tendency to think in purely black and white. People with BPD may experience intense episodes of anger, depression and anxiety that can last from a few hours to days.

Sharp said Borderline Personality Disorder is treatable, therapy helps, and early intervention for adolescents is of critical importance.

"We ignore Borderline Personality Disorder at our peril, because compared with other mental disorders, BPD is among the leading causes of suicidal behaviors and self-harm in young people," she said. Up to 10% of BPD patients will die by suicide.

Sharp's research is the first study to show that adolescent borderline pathology follows a similar downward course after discharge from inpatient treatment previously demonstrated for adults. Her conclusions come after examining data collected from 500 adolescent inpatients and following them every six months over an 18-month follow-up period to measure their symptoms of BPD.

The results showed a significant downward trend of BPD features across all time points and across both parent-and adolescent self-reporting which mirrors the reduction in BPD symptomology reported for adults with BPD. Interestingly, the teens Sharp studied were not undergoing specialized treatment for BPD and yet they still improved.

"It sends a message to clinicians: 'Don't put your head in the sand!' If the pathology is there, diagnose it and treat it with your best evidence-based treatment," said Sharp emphatically. The standard therapies for BPD in adults and adolescents currently are dialectical behavior therapy and mentalization-based therapy. But even if clinicians are not trained in those specialized treatments, it would be ethically appropriate to make use of best available scientific evidence to inform practice, consistent with practice-based evidence recommendations from the American Psychological Association, she said.

"Our work contributes to the growing consensus that the discrimination and stigmatization of BPD are not justified. Instead, a clinical course very similar to adult BPD is described which highlights the potential therapeutic rewards of diagnosing and treating adolescent patients with BPD," said Sharp.

Irvine, Calif., Jan. 25, 2021 -- Scientists at the University of California, Irvine and NASA's Jet Propulsion Laboratory have for the first time quantified how warming coastal waters are impacting individual glaciers in Greenland's fjords. Their work is the subject of a study published recently in Science Advances.

Working under the auspices of the Oceans Melting Greenland mission for the past five years, the researchers used ships and aircraft to survey 226 glaciers in all sectors of one of Earth's largest islands. They found that 74 glaciers situated in deep, steep-walled valleys accounted for nearly half of Greenland's total ice loss between 1992 and 2017.

Such fjord-bound glaciers were discovered to be the most subject to undercutting, a process by which warm, salty water at the bottom of the canyons melts the ice from below, causing the masses to break apart more quickly than usual. In contrast, the team found that 51 glaciers positioned in shallower gullies experienced less undercutting and contributed only about 15 percent of the total ice loss.

"I was surprised by how lopsided it was. The biggest and deepest glaciers are undercut much faster than the smaller glaciers in shallow fjords," said lead author Michael Wood, a post-doctorate researcher at NASA's Jet Propulsion Laboratory in Southern California, who began this research as a doctoral student at UCI. "In other words, the biggest glaciers are the most sensitive to the warming waters and those are the ones really driving Greenland's ice loss."

The study highlighted the dynamic whereby deeper fjords allow the intrusion of warmer ocean water than shallow ones, hastening the process of undercutting with some of Greenland's largest glaciers.

Greenland is home to one of Earth's only two ice sheets, the largest being Antarctica's. The ice in Greenland is more than two miles (three kilometers) thick in places. At the edges of the land mass, the vast glaciers extending from the ice sheet travel slowly down valleys like icy conveyor belts, which inch into the fjords and then melt or break off as icebergs. The ice is replenished by snowfall that is compressed over time into the ice pack.

If the ice sheet were in balance, the amount of snow accumulating on the top would roughly equal the ice lost from melt, evaporation and calving - chunks breaking free from anchored masses and floating off into the ocean.

But the ice sheet has been out of balance since the 1990s. Melt has accelerated and calving has increased, causing glaciers that extend into the sea to retreat back toward land. Together, these are resulting the ice sheet shrinkage.

According to the research team, the build-up of warm salty water at the bottom of fjords has been accelerated by increasing temperatures in the summer months, which heat the surfaces of glaciers, creating pools of meltwater. This liquid leaks through cracks in the ice to form subsurface freshwater rivers which flows into the sea where it interacts with salty water beneath fjords.

Glacier meltwater is free of salt, so it is lighter than seawater and rises to the surface as a plume, dragging up warm water and putting it in contact with the bottoms of glaciers. Fjord depth is a fairly immutable factor, but other factors such as seawater temperature and the amount of meltwater from glaciers surfaces are greatly impacted by climate warming. All three factors combine to cause accelerated deterioration of Greenland's ice sheet, the researchers said.

As the water temperature around Greenland's coastline is predicted to continue to increase in the future, these findings suggest that some climate models may underestimate glacial ice loss by at least a factor of two if they do not account for undercutting by a warm ocean.

The study also lends insight into why many of Greenland's glaciers never recovered after an abrupt ocean warming between 1998 and 2007, which caused an increase in ocean temperature by nearly 2 degrees Celsius. Although ocean warming paused between 2008 and 2017, the glaciers had already experienced such extreme undercutting in the previous decade that they continued to retreat at an accelerated rate.

"We have known for well over a decade that the warmer ocean plays a major role in the evolution of Greenland glaciers," said OMG deputy principal investigator Eric Rignot, also of JPL and UCI. "But for the first time, we have been able to quantify the undercutting effect and demonstrate its dominant impact on the glacier retreat over the past 20 years."

Epilepsy, a neurological disease that causes recurring seizures with a wide array of effects, impacts approximately 50 million people across the world. This condition has been recognized for a long time -- written records of epileptic symptoms date all the way back to 4000 B.C.E. But despite this long history of knowledge and treatment, the exact processes that occur in the brain during a seizure remain elusive.

Scientists have observed distinctive patterns in the electrical activity of neuron groups in healthy brains. Networks of neurons move through states of similar behavior (synchronization) and dissimilar behavior (desynchronization) in a process that is associated with memory and attention. But in a brain with a neurological disorder like epilepsy, synchronization can grow to a dangerous extent when a collection of brain cells begins to emit excess electricity. "Synchronization is thought to be important for information processing," Jennifer Creaser of the University of Exeter said. "But too much synchronization--such as what occurs in epileptic seizures or Parkinson's disease--is associated with disease states and can impair brain function."

Measurements of epileptic seizures have revealed that desynchronization in brain networks often occurs before or during the early stages of a seizure. As the seizure progresses, networks become increasingly more synchronized as additional regions of the brain get involved, leading to high levels of synchronization towards the seizure's end. Understanding the interactions between the increased electrical activity during a seizure and changes in synchronization is an important step towards improving the diagnosis and treatment of epilepsy.

Jennifer Creaser, Peter Ashwin (University of Exeter), and Krasimira Tsaneva-Atanasova (University of Exeter, Technical University of Munich, and Bulgarian Academy of Sciences) explored the mechanisms of synchronization that accompany seizure onset in a paper that published in December in the SIAM Journal on Applied Dynamical Systems. In their study--which took place at the Engineering and Physical Science Research Council's Centre for Predictive Modelling in Healthcare at the University of Exeter and University of Birmingham--the researchers used mathematical modeling to explore the interplay between groups of neurons in the brain that leads to transitions in synchronization changes during seizure onset. "Although this is a theoretical study of an idealized model, it is inspired by challenges posed by understanding transitions between healthy and pathological activity in the brain," Ashwin said.

The authors utilize an extended version of an existing mathematical model that represents the brain as a network connecting multiple nodes of neuron groups. The model network consists of bistable nodes, meaning that each node is able to switch between two stable states: resting (a quiescent state) and seizure (an active and oscillatory state). These nodes remain in their current state until they receive a stimulus that gives them a sufficient kick to escape to the other state. In the model, this stimulus comes from other connected nodes or appears in the form of "noise" -- outside sources of neural activity, such as endocrine responses that are associated with an emotional state or physiological changes due to disease.

The influence between neighboring nodes is governed by a coupling function that represents the way in which the nodes in the network communicate with each other. The first of the two possible types of coupling is amplitude coupling, which is governed by the "loudness" of the neighboring nodes. The second is phase coupling, which is related to the speed at which the neighbors are firing. Although the researchers needed to utilize a simple formulation on a small network to even make their analysis possible--a more complex and realistic system would be too computationally taxing--they expected their model to exhibit the same types of behaviors that clinical recordings of real brain activity have revealed.

The nodes in the modeled system all begin in the healthy resting state. In previous research, the authors found that adding a small amount of noise to the system caused each node to transition to the active state -- but the system's geometry was such that returning to the resting state took much longer than leaving. Because of this, these escapes can spread sequentially as a "domino effect" when a number of nodes are connected. This leads to a cascade of escapes to the active state--much like a falling line of dominos--that spreads activity across the network.

Creaser, Ashwin, and Tsaneva-Atanasova's new paper builds upon this previous research on the domino effect to explore the transitions into and out of synchrony that occur during cascades of escapes. The team used their model to identify the circumstances that bring about these changes in synchrony and investigate how the type of coupling in a network affects its behavior.

When the model incorporated only amplitude coupling, it exhibited a new phenomenon in which the domino effect could accelerate or decelerate. However, this effect had no bearing on synchronization changes in the network; all of the nodes started and remained synchronized. But when the model incorporated more general amplitude and phase coupling, the authors found that the nodes' synchrony could change between consecutive escapes during the domino effect. They then determined which conditions would cause changes in synchrony under phase-amplitude coupling. This change in synchrony throughout the sequence of escapes was the study's most novel result.

The results of this work could facilitate further studies on seizures and their management. "The mathematical modeling of seizure initiation and propagation can not only help to uncover seizures' complex underlying mechanisms, but also provide a means for enabling in silico experiments to predict the outcome of manipulating the neural system," Tsaneva-Atanasova said. Understanding the interplay between synchronized and desynchronized dynamics in brain networks could help identify clinically-relevant measures for seizure treatment. For example, Creaser and Tsaneva-Atanasova recently served as the lead and senior author, respectively, on a paper that utilized a simpler version of the model to classify patterns of seizure onset that were recorded in a clinical setting. In the future, these kinds of modeling studies may lead to the personalization of seizure identification and treatment for individuals with epilepsy.

Astrocytes are the most abundant type of cells within the central nervous system (CNS), but they remain poorly characterized. Researchers have long assumed that astrocytes' primary function is to provide nutrients and support for the brain's more closely scrutinized nerve cells; over the years, however, increasing evidence has shown that astrocytes can also actively promote neurodegeneration, inflammation, and neurological diseases. Now, a team led by researchers from Brigham and Women's Hospital, has shown that a specific astrocyte sub-population can do the opposite, instead serving a protective, anti-inflammatory function within the brain based on signals regulated by the bacteria that reside in the gut. Findings on the new anti-inflammation pathway are published in Nature.

"Over the years, many labs, including mine, have identified important roles for astrocytes in promoting neurological diseases," said corresponding author Francisco Quintana, PhD, of the Ann Romney Center for Neurologic Diseases at the Brigham. "This is the first case in which we're showing that at least a subset of these cells (astrocytes) can prevent inflammation. The reason we haven't seen this before was because we were studying these cells as if they were uniform, or one single cell type. But now we have the resolution to see the differences between these cells."

The researchers used refined gene- and protein-analysis tools to identify the novel astrocyte subset. The astrocyte population resides close to the meninges (the membrane enclosing the brain) and expresses a protein called LAMP1, along with a protein called TRAIL, which can induce the death of other cells. These features help the LAMP1+TRAIL+ astrocytes limit CNS inflammation by inducing cell death in T-cells that promote inflammation.

To determine what mechanism controls LAMP1+TRAIL+ astrocytes in the brain, the researchers performed a series of tests using the gene-editing tool CRISPR-Cas9. They found that a particular signaling molecule, called interferon-gamma, regulates TRAIL expression. Moreover, they found that the gut microbiome induces the expression of interferon-gamma in cells that circulate through the body and ultimately reach the meninges, where they can promote astrocyte anti-inflammatory activities.

Understanding the mechanisms driving the anti-inflammatory functions of LAMP1+TRAIL+ astrocytes could enable researchers to develop therapeutic approaches to combat neurological diseases, like multiple sclerosis. For example, they are exploring probiotic candidates that can be used to regulate the astrocytes' anti-inflammatory activity. Additionally, the research team's more recent data indicates that certain brain tumors exploit this pathway to evade the body's immune response. The investigators are therefore developing cancer immunotherapies to retaliate against the tumors' attacks.

"Finding microbiome-controlled anti-inflammatory subsets of astrocytes is an important advance in our understanding of CNS inflammation and its regulation," Quintana said. "This is a very novel mechanism by which the gut controls inflammation in the brain. It guides new therapies for neurological diseases, and we believe that this mechanism could contribute to the pathogenesis of brain tumors."

Quintana's lab identified the only other subset of astrocyte known to be regulated by the gut microbiome in 2016, but the investigators believe that there are likely others. "It's becoming clear that the gut flora are important in many diseases," he said. "We're lucky that we've been leading the charge to identify different subsets of astrocytes and the mechanisms that control them. We have a list of other populations of astrocytes, and we're working to see how the gut flora may control them."

COLUMBUS, Ohio - There could be an intervention on the horizon to help prevent heart damage caused by the common chemotherapy drug doxorubicin, new research suggests.

Scientists found that this chemo drug, used to treat many types of solid tumors and blood cancers, is able to enter heart cells by hitchhiking on a specific type of protein that functions as a transporter to move a drug from the blood into heart cells.

By introducing another anti-cancer drug in advance of the chemo, the researchers were able to block the transporter protein, effectively stopping the delivery of doxorubicin to those cardiac cells. This added drug, nilotinib, has been previously found to inhibit activation of other, related transport proteins.

The current findings are based on lab experiments in cell cultures and mice. The researchers are continuing studies with hopes to start designing human trials of the drug intervention later in 2021.

"The proposed intervention strategy that we'd like to use in the clinic would be giving nilotinib before a chemotherapy treatment to restrict doxorubicin from accessing the heart," said first author Kevin Huang, who graduated in December from The Ohio State University with a PhD in pharmaceutical sciences. "We have pretty solid preclinical evidence that this intervention strategy might work."

The study is published today (Jan. 25, 2021) in Proceedings of the National Academy of Sciences.

Doxorubicin has long been known for its potential to increase patients' risk for serious heart problems, with symptoms sometimes surfacing decades after chemo, but the mechanisms have been a mystery. The risk is dose-dependent - the more doses a patient receives, the higher the risk for cardiac dysfunction later in life that includes arrhythmia and a reduction in blood pumped with each contraction, a hallmark symptom of congestive heart failure.

Huang worked in the lab of senior study authors Shuiying Hu and Alex Sparreboom, faculty members in pharmaceutics and pharmacology and members of the Ohio State Comprehensive Cancer Center's Translational Therapeutics program. This research and other studies targeting different transport proteins to prevent chemo-related nerve pain were also part of Huang's dissertation.

"Our lab works on the belief that drugs don't naturally or spontaneously diffuse into any cell they would like to. We hypothesize that there are specialized protein channels found on specific cells that will facilitate movement of internal or external compounds into the cell," Huang said.

For this work, the team focused on cardiomyocytes, cells composing the muscle behind the heart contractions that pump blood to the rest of the body. The researchers examined cardiomyocytes that were reprogrammed from skin cells donated by two groups of cancer patients who had been treated with doxorubicin - some who suffered cardiac dysfunction after chemo, and others who did not.

The scientists found that the gene responsible for production of the transport protein in question, called OCT3, was highly expressed in the cells derived from cancer patients who had experienced heart problems after treatment with doxorubicin.

"We used mouse models and engineered cell models to demonstrate doxorubicin does transport through this protein channel, OCT3," Huang said. "We then looked prospectively into what this means from a therapy perspective."

Blocking OCT3 became the goal once researchers found that genetically modified mice lacking the OCT3 gene were protected from heart damage after receiving doxorubicin. Further studies showed that inhibiting OCT3 did not interfere with doxorubicin's effectiveness against cancer.

Hu and Sparreboom have specialized in a class of drugs called tyrosine kinase inhibitors, which block specific enzymes related to many cell functions. Nilotinib, a chronic myeloid leukemia drug, is a tyrosine kinase inhibitor that is also known to act on OCT3.

Additional experiments showed that cardiac function was preserved in mice that were pretreated with nilotinib before receiving doxorubicin - and the pretreatment did not interfere with doxorubicin's ability to kill cancer cells.

The researchers plan to gather additional supporting evidence before pursuing a Phase 1 clinical trial testing the safety of two components of the proposed drug intervention in humans: blocking the function of the OCT3 transporter protein and demonstrating that inhibiting OCT3 in patients treated with doxorubicin protects those patients' hearts from chemo-induced injury.