Culture

A new study led by the University of Portsmouth has identified that one of the major factors of age-related brain deterioration is the loss of a substance called myelin.

Myelin acts like the protective and insulating plastic casing around the electrical wires of the brain - called axons. Myelin is essential for superfast communication between nerve cells that lie behind the supercomputer power of the human brain.

The loss of myelin results in cognitive decline and is central to several neurodegenerative diseases, such as Multiple Sclerosis and Alzheimer's disease. This new study found that the cells that drive myelin repair become less efficient as we age and identified a key gene that is most affected by ageing, which reduces the cells ability to replace lost myelin.

The study, published this week in the journal Ageing Cell, is part of an international collaboration led by Professor Arthur Butt at the University of Portsmouth with Dr Kasum Azim at the University of Dusseldorf in Germany, together with Italian research groups of Professor Maria Pia Abbracchio in Milan and Dr Andrea Rivera in Padua.

Professor Butt said: "Everyone is familiar with the brain's grey matter, but very few know about the white matter, which comprises of the insulated electrical wires that connect all the different parts of our brains.

"A key feature of the ageing brain is the progressive loss of white matter and myelin, but the reasons behind these processes are largely unknown. The brain cells that produce myelin - called oligodendrocytes - need to be replaced throughout life by stem cells called oligodendrocyte precursors. If this fails, then there is a loss of myelin and white matter, resulting in devastating effects on brain function and cognitive decline. An exciting new finding of our study is that we have uncovered one of the reasons that this process is slowed down in the aging brain."

Dr Rivera, lead author of the study while he was in University of Portsmouth and who is now a Fellow at the University of Padua, explained: "By comparing the genome of a young mouse brain to that of a senile mouse, we identified which processes are affected by ageing. These very sophisticated analysis allowed us to unravel the reasons why the replenishment of oligodendrocytes and the myelin they produce is reduced in the aging brain.

"We identified GPR17, the gene associated to these specific precursors, as the most affected gene in the ageing brain and that the loss of GPR17 is associated to a reduced ability of these precursors to actively work to replace the lost myelin."

The work is still very much ongoing and has paved the way for new studies on how to induce the 'rejuvenation' of oligodendrocyte precursor cells to efficiently replenish lost white matter.

Dr Azim of the University of Dusseldorf said: "This approach is promising for targeting myelin loss in the aging brain and demyelination diseases, including Multiple Sclerosis, Alzheimer's disease and neuropsychiatric disorders. Indeed, we have only touched the tip of the iceberg and future investigation from our research groups aim to bring our findings into human translational settings."

Dr Rivera performed the key experiments published in this study while at the University of Portsmouth and he has been awarded the prestigious MSCA Seal of Excellence @UniPD Fellowship to translate these findings and investigate this further in the human brain, in collaboration with Professors Raffele De Caro, Andrea Porzionato and Veronica Macchi at the Institute of Human Anatomy of the University of Padua.

The study was funded by grants from the BBSRC and MRC to Professor Butt, together with the UK and Italian MS Societies (to Professors Butt and Abbracchio, respectively), and the Swiss National Funds Fellowship and German Research Council (Dr Azim). Dr Andrea Rivera was supported by an Anatomical Society PhD Studentship (with Professor Butt), and the MSCA Seal of Excellence @UniPD (Dr Rivera).

Dr Emma Gray, Assistant Director of Research at the MS Society, said: "MS can be relentless and painful, and there are sadly still no treatments to stop disability progression. We can see a future where no one has to worry about MS getting worse but, for that to happen, we need to find ways to repair damaged myelin. This research sheds light on why cells that drive myelin repair become less efficient as we age, and we're really proud to have helped fund it. By improving our understanding of ageing brain stem cells, it gives us a new target to help slow the progression of MS, and could have important implications for future treatment."

MIAMI--In the Florida Straits at night, and under a new moon is the preference for spawning mahi-mahi, according to a new study by scientists at the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science.

These new details on the daily life of the highly sought-after migratory fish can help better manage their populations and provide scientists with new information to understand the impacts to the animal from changing environmental conditions.

To uncover these important details about the behaviors of mahi-mahi, or dolphinfish, the research team tagged captive spawning fish located at the UM Experimental Hatchery to build predictive spawning models and then used the models with data collected from mahi-mahi tagged in the wild. The study is the first to use acceleration data from remotely transmitting pop-up satellite tags to predict the spawning habitat of a wild marine fish. The UM Experimental Hatchery is the only place in the country where spawning mahi-mahi are kept in captivity.

To build the predictive models, the research team tagged five spawning mahi-mahi (Coryphaena hippurus) at the UM Hatchery and waited overnight to record the timing of when they spawned. In total, 40 individual spawning events were tracked in captivity. Then, they paired the acceleration data collected from the tags with the exact time of spawning to estimate when the animals would spawn in the wild.

To test the models' capability to estimate where and when the fish spawned in the wild, the researchers tagged 17 wild mahi-mahi off the coast of Miami and two in the Gulf of Mexico.

From an analysis of the satellite tag data, the researchers found that wild mahi-mahi spawn at night, primarily during a new moon at depths greater than they would normally be. The Florida Straits appeared to be an important spawning habitat for mahi-mahi, although the models suggest that some limited spawning takes place further north.

They found that mahi-mahi typically go deeper in the water column at night and are more surface oriented during the day. However, the phase of the moon had an effect on their nighttime depth distribution with a full moon bringing mahi-mahi closer to the surface at night.

They also found that mahi-mahi use behavioral thermoregulation to stay between a relatively narrow temperature window of about 27-28 degrees Celsius (80 - 82 degrees Fahrenheit). When surface waters are warmer, they move deeper and swim northward with the Gulf Stream to regulate their temperature, while fish tagged in cooler months stayed primarily in surface waters and migrated east and west between Florida and the Bahamas, rather than swimming north. They were also found to be the most active at cooler temperatures and in warm waters during a full moon at night.

"Mahi-mahi are highly sought after by recreational and commercial fisheries and are economically important," said Lela Schlenker, an alumna of the UM Rosenstiel school and lead author of the study. "It is critical to understand their migrations and the frequency, timing, and location of where they reproduce as well as how changing environmental conditions--like warmer oceans--might affect them to manage their populations sustainably now and in the future."

The team also found from the satellite tag data that the wild mahi-mahi travel long distances—up to 107 kilometers (66 miles) per day and dive to depths of 250 meters (820 feet).

"Together these findings suggest that as climate change continues to warm ocean waters, mahi-mahi will likely continue to shift northward and deeper throughout their migrations," said Martin Grosell," professor and chair of the Department of Marine Biology and Ecology at the UM Rosenstiel School. "This is important for recreational and commercial landings of mahi-mahi and the ecology of pelagic ecosystems. A fruitful collaboration between scientists from three departments at the Rosenstiel School, as well as colleagues from University of Massachusetts, Dartmouth and access to healthy spawning mahi-mahi in captivity revealed new information about these valuable fish," said Grosell.

CHAMPAIGN, Ill. -- A six-week training program designed to strengthen resilience against emotional distress in military veterans was associated with positive changes in brain function and increased confidence in their ability to regulate emotions, researchers report.

Published in the journal Frontiers in Psychology, the new proof-of-concept study tested two approaches for building emotional resilience in 19 veterans. The first involved weekly, 90-minute group therapy sessions focused on sharing and skills-building in 10 participants. The second trained nine veterans in the use of specific emotion-regulation strategies that previous research has shown can improve responses to emotional distress and lessen symptoms of anxiety and depression. All of the veterans in the study had been deployed in Afghanistan or Iraq in the five years prior to the study. Some reported symptoms of anxiety, depression or post-traumatic stress disorder.

"We conducted behavioral, psychometric, clinical and brain-imaging assessments before they started the training and after the training," said Florin Dolcos, a professor of psychology at the University of Illinois Urbana-Champaign who led the research with psychology professors Sanda Dolcos and doctoral student Yifan Hu. The work was conducted in the Chez Veterans Center and the Beckman Institute for Advanced Science and Technology at the U. of I.

Using resting-state functional MRI, the researchers assessed the "default" communication between brain regions while participants were awake and doing nothing. Even in a resting state, the brain is active, Sanda Dolcos said. Characteristics of a person's resting-state functional connectivity are associated with different psychological outcomes.

"Functional MRI shows how different brain regions are working together, or not," Florin Dolcos said. "For instance, in people with depression or anxiety, where the default is to ruminate on negative thoughts or memories, there is increased functional connectivity between the amygdala - a brain region involved in responding to emotional stimuli - and structures within the prefrontal cortex that regulate behavior, attention and memory."

Veterans in the group therapy intervention focused on skills such as goal-setting, problem-solving or time management. The intervention also offered psychotherapeutic approaches such as cognitive behavioral therapy. U. of I. psychology professor Howard Berenbaum and doctoral student Christian Williams designed and implemented this program. Group sizes ranged from four to eight participants.

Participants in the emotion-regulation training engaged with researchers one-on-one and learned two techniques: cognitive reappraisal, which involves finding more positive ways to think about stressful or disturbing experiences; and focused attention, in which a person directs their attention away from the most unsettling facets of an event or memory to focus instead on neutral, or even positive, details.

"We wanted to find a combination of strategies that would work both with high-intensity and low-intensity emotions, and also strategies that are less cognitively demanding," Sanda Dolcos said. Through repeated trials, some of which involved personal memories participants chose to work on in the training, the veterans gradually developed the ability to switch between strategies depending on the circumstances.

"We really wanted our participants' flexibility in using these strategies in everyday life, based on their circumstances and needs," Sanda Dolcos said.

While both groups appeared to benefit from the interventions, assessments at the end of the training revealed that participants in the emotional reappraisal and focused attention group saw greater gains in self-efficacy, the belief that one has the tools to overcome adversity.

"Higher self-efficacy is related to multiple positive outcomes because people have the confidence that they can deal with whatever life throws at them," Sanda Dolcos said. People in this group also were more likely to change their mindset about the difficult events they experienced, the researchers found.

"They developed this ability to extract meaning from the negative experiences, the traumatic experiences they went through," Hu said. "This is very, very helpful to their ability to move on and thrive."

Brain changes measured with fMRI paralleled the positive changes seen in the second group. The researchers saw a reduction in crosstalk between the amygdala and brain regions involved in self-talk, and among brain regions that control behavior, memory and attention.

Measures of depression and anxiety in participants in both groups were not significantly different at the end of the intervention than at the beginning. This may be the result of the small sample size or the brief amount of time that elapsed between the beginning and end of the intervention, researchers said. Previous studies have found that increases in a person's self-efficacy mediate a reduction in depression and anxiety, so the fact that some participants saw increases in self-efficacy may lead to further improvements with the passage of time, they said.

Further studies of emotion-regulation training should involve more participants than the current pilot study, the researchers said. But the findings offer insight into methods to help clients who have experienced traumatic events, Berenbaum said. Future interventions "are likely to bear little resemblance to traditional psychotherapy," he said. "This project demonstrated the feasibility of one potentially valuable new approach."

Imagine using stem cells from your bone marrow to grow a piece of bone tissue in the lab, after which medical doctors explore which drugs have the desired effect on your bones. In this way, a tailor-made treatment plan would be made for everyone, with the best approach being clear in advance. Personalized medicine at its best.

That vision of the future is no longer science fiction now that researchers from Eindhoven University of Technology and Radboud university medical center have actually realized the first part: growing a lifelike piece of bone tissue from human stem cells. It is the first organoid of bone, a simplified version of the original, the researchers report today in the journal Advanced Functional Materials.

Coherent picture

"With this, we present, for the first time, the full picture of early-stage bone formation," says Sandra Hofmann, associate professor in Bioengineering Bone from TU/e. And that is of great importance: how our bones are formed is still largely a mystery. Bone is a very complex material in which, on the one hand, countless cells and processes interact and, on the other hand, an ingenious matrix of collagen and mineral is built up to provide strength. Much is known about the individual components, but a coherent picture has been lacking until now.

Three types of cells play the main role in bone formation: osteoblasts (which build bone tissue), osteoclasts (which take bone away) and osteocytes (which regulate the building and breaking down of bone). "Most studies so far have focused on one of these types of cells, but that is not a good representation of the real tissue," says Hofmann. "We present here a piece of woven bone (early-stage bone) that developed from stem cells and contains two types of these cells: osteoblasts and osteocytes. We now see that we can make lifelike bone exclusively with these two cell types."

Getting wiser from molecular poking

"And perhaps more importantly, our system behaves just like early-stage bone ", says Anat Akiva, assistant professor Cell Biology at Radboudumc. "We show that both types of cells produce the proteins that they need for their functionality, and we show with the greatest detail that the matrix actually is the bone matrix we see in real tissue."

The fact that a simplified representation of the formation of bone at the molecular level is now possible offers unprecedented possibilities, according to the researchers. "A bone consists of 99% collagen and minerals, but there is also another 1% of proteins that are essential for successful bone formation," explains professor Nico Sommerdijk from Radboudumc. "So what's the role of these proteins? How do they support bone formation? Never before have we been able to look at the milestones of this process at a molecular level."

And with that, they immediately have a good entrance to investigate the cause of genetic bone diseases such as "brittle bone disease" and their possible treatments. "Remember that the origin of many diseases is at the molecular level - and so is the treatment," says Akiva. "In fact, we now have a simple system in a reliable environment in which we can poke around and see how bone cells react to the stimuli we provide."

Washington, March 9, 2021--A comprehensive meta-analysis of prior research has found, overall, that children ages 1 to 8 were less likely to understand picture books when they read the digital, versus print, version. However, when digital picture books contain the right enhancements that reinforce the story content, they outperform their print counterparts. The results were published today in Review of Educational Research, a peer-reviewed journal of the American Educational Research Association.

Authors Natalia Kucirkova at the University of Stavanger in Norway and The Open University in the United Kingdom, and May Irene Furenes and Adriana G. Bus at the University of Stavanger, analyzed the results of 39 studies that included a total 1,812 children between the ages of 1 and 8. For their analysis, the authors compared children's story comprehension and vocabulary learning when they read a book on paper versus on screen, and assessed the effects of story-related enhancements in digital books, the presence of a dictionary, and the role of adult support. The bulk of the studies were carried out between 2010 and 2019, and for the greater the part, in the last four years of that time span.

"The wide availability of digital reading options and the rich tradition of children's print books beg the question of which reading format is better suited for young readers' learning," said Kucirkova, a professor of early childhood development at the University of Stavanger and The Open University. "We found that when the print and digital versions of a book are practically the same and differ only in the voice-over or highlighted print as additional features in the digital book, then print outperforms digital."

The authors found that the digital device itself and sometimes digital enhancements that are not aligned with the story content--such as a dictionary--interfere with children's story comprehension.

When digital enhancements are designed to increase children's ability to make sense of the narrative--for instance, by prompting children's background knowledge to understand the story or providing additional explanations of story events--digital books not only outweigh the negative effects of the digital device but also outperform print books on children's story comprehension.

"Our overall findings may reflect the rather low quality of enhancements in the digital books available for young children," said Kucirkova. "Many digitized versions of picture books are inferior to the print version, yet young children widely use them."

With a few exceptions, the commercially published digital books in the studies did not include storytelling techniques that adults provide during book sharing, for example attracting children's attention to the main story elements and focusing their attention on the chain of story events.

"If we want to support all children, we need to understand the impact of digital books and make them of higher quality," said Kucirkova. "Digital books are low-cost to access and thus more readily available to students from disadvantaged backgrounds. Furthermore, we can customize digital books to a child's level of learning by including interactive features responsive to the child."

"For reasons that need to be clarified by additional research, our meta-analysis shows that children from disadvantaged socioeconomic backgrounds are more likely to be distracted from story content on digital books by their interactive features and by the reading devices themselves," said Bus, a professor at the University of Stavanger. "As a result, these children are experiencing the most difficulty comprehending digital picture books."

"Makers of children's digital books need to be careful about the enhancements they make, and educators and parents need to choose carefully which digital books young children read," said Kucirkova. "Internationally, it is important to promote the production of exemplary prototypes including text in a range of languages and provide incentives to publishers, authors, designers, and illustrators to change the status quo."

The authors found that digital books may be more effective than print books for enhancing children's vocabulary if the digital books use a dictionary that defines infrequently used words and expressions. However, digital dictionary features hinder children's ability to understand the story they are reading, indicating that focusing attention on word meanings distracts children's attention from the story content.

"This is further evidence that digital book designers need to exercise caution with seemingly small and popular additions that may be helpful for isolated outcomes such as vocabulary learning but hinder the reading session overall," Kucirkova said.

PHILADELPHIA-- Head injury in the United States is common, with over 23 million adults age 40 or older reporting a history of head injury with loss of consciousness. Many head injuries can be caused by a host of different situations - from car and motorcycle accidents to sports injuries. What's more, it has become increasingly recognized that the effects from head injuries are long-lasting. New research led by the Perelman School of Medicine at the University of Pennsylvania shows that a single head injury could lead to dementia later in life. This risk further increases as the number of head injuries sustained by an individual increases. The findings also suggest stronger associations of head injury with risk of dementia among women compared to among men and among white as compared to among Black populations.

The researchers, whose findings were published today in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, conducted the investigation using data from the Atherosclerosis Risk in Communities (ARIC) Study, which aimed to uncover associations between head injury and dementia over the span of 25 years in a diverse population in the United States. Previously, data on traumatic brain injury has been limited to select populations, such as military and medical claims databases. These are among the first findings to specifically investigate head injury and dementia risk in both Black and white populations, as well as among both males and females, in a community-based setting.

"Head injury is a significant risk factor for dementia, but it's one that can be prevented. Our findings show that the number of head injuries matter - more head injuries are associated with greater risk for dementia," said lead investigator, Andrea L.C. Schneider, MD, PhD, an assistant professor of Neurology at Penn. "The dose-dependence of this association suggests that prevention of head injury could mitigate some risk of dementia later in life. While head injury is not the only risk factor for dementia, it is one risk factor for dementia that is modifiable by behavior changes such as wearing helmets and seat belts."

The findings show that compared to participants who never experienced a head injury, a history of a single prior head injury was associated with a 1.25 times increased risk of dementia, and a history of two or more prior head injuries was associated with over 2 times increased risk of dementia compared to individuals without a history of head injury. Overall, 9.5 percent of all dementia cases in the study population could be attributed to at least one prior head injury.

To illustrate the relationship between dementia and head injuries, the authors gathered data from a diverse cohort with a mean baseline age of 54 years, comprised of 56 percent female and 27 percent Black participants from four different communities across the United States. Participants were followed for a median of 25 years through up to six in-person visits and semi-annual telephone follow-ups. Data on head injuries of participants was drawn from hospital records, as well as self-reporting from some participants.

Previous research on dementia and traumatic brain injuries suggests that women are at higher risk for dementia compared to men. Additionally, Black populations overall are at higher risk for dementia compared to people who are white. However, few prior studies have evaluated for possible differences in associations of head injury with dementia risk by sex and race.

This data from the ARIC study found evidence that females were more likely to experience dementia as a result of head injury than males. Further, the study showed that although there is increased dementia risk associated with head injury among both White and Black participants, White participants were at higher risk for dementia after head injury compared to Black participants. The authors conclude that more research is needed to better understand reasons for these observed sex and race differences in the association of head injury with dementia risk.

"Given the strong association of head injury with dementia, there is an important need for future research focused on prevention and intervention strategies aimed at reducing dementia after head injury," Schneider said. "The results of this study have already led to several ongoing research projects, including efforts to uncover the causes of head injury-related dementia as well as investigations into reasons underlying the observed sex and race differences in the risk of dementia associated with head injury."

Smart speakers, such as Amazon Echo and Google Home, have proven adept at monitoring certain health care issues at home. For example, researchers at the University of Washington have shown that these devices can detect cardiac arrests or monitor babies breathing.

But what about tracking something even smaller: the minute motion of individual heartbeats in a person sitting in front of a smart speaker?

UW researchers have developed a new skill for a smart speaker that for the first time monitors both regular and irregular heartbeats without physical contact. The system sends inaudible sounds from the speaker out into a room and, based on the way the sounds are reflected back to the speaker, it can identify and monitor individual heartbeats. Because the heartbeat is such a tiny motion on the chest surface, the team's system uses machine learning to help the smart speaker locate signals from both regular and irregular heartbeats.

When the researchers tested this system on healthy participants and hospitalized cardiac patients, the smart speaker detected heartbeats that closely matched the beats detected by standard heartbeat monitors. The team published these findings March 9 in Communications Biology.

"Regular heartbeats are easy enough to detect even if the signal is small, because you can look for a periodic pattern in the data," said co-senior author Shyam Gollakota, a UW associate professor in the Paul G. Allen School of Computer Science & Engineering. "But irregular heartbeats are really challenging because there is no such pattern. I wasn't sure that it would be possible to detect them, so I was pleasantly surprised that our algorithms could identify irregular heartbeats during tests with cardiac patients."

While many people are familiar with the concept of a heart rate, doctors are more interested in the assessment of heart rhythm. Heart rate is the average of heartbeats over time, whereas a heart rhythm describes the pattern of heartbeats.

For example, if a person has a heart rate of 60 beats per minute, they could have a regular heart rhythm -- one beat every second -- or an irregular heart rhythm -- beats are randomly scattered across that minute but they still average out to 60 beats per minute.

"Heart rhythm disorders are actually more common than some other well-known heart conditions. Cardiac arrhythmias can cause major morbidities such as strokes, but can be highly unpredictable in occurrence, and thus difficult to diagnose," said co-senior author Dr. Arun Sridhar, assistant professor of cardiology at the UW School of Medicine. "Availability of a low-cost test that can be performed frequently and at the convenience of home can be a game-changer for certain patients in terms of early diagnosis and management."

The key to assessing heart rhythm lies in identifying the individual heartbeats. For this system, the search for heartbeats begins when a person sits within 1 to 2 feet in front of the smart speaker. Then the system plays an inaudible continuous sound, which bounces off the person and then returns to the speaker. Based on how the returned sound has changed, the system can isolate movements on the person -- including the rise and fall of their chest as they breathe.

"The motion from someone's breathing is orders of magnitude larger on the chest wall than the motion from heartbeats, so that poses a pretty big challenge," said lead author Anran Wang, a doctoral student in the Allen School. "And the breathing signal is not regular so it's hard to simply filter it out. Using the fact that smart speakers have multiple microphones, we designed a new beam-forming algorithm to help the speakers find heartbeats."

The team designed what's called a self-supervised machine learning algorithm, which learns on the fly instead of from a training set. This algorithm combines signals from all of the smart speaker's multiple microphones to identify the elusive heartbeat signal.

"This is similar to how Alexa can always find my voice even if I'm playing a video or if there are multiple people talking in the room," Gollakota said. "When I say, 'Hey, Alexa,' the microphones are working together to find me in the room and listen to what I say next. That's basically what's happening here but with the heartbeat."

The heartbeat signals that the smart speaker detects don't look like the typical peaks that are commonly associated with traditional heartbeat monitors. The researchers used a second algorithm to segment the signal into individual heartbeats so that the system could extract what is known as the inter-beat interval, or the amount of time between two heartbeats.

"With this method, we are not getting the electric signal of the heart contracting. Instead we're seeing the vibrations on the skin when the heart beats," Wang said.

The researchers tested a prototype smart speaker running this system on two groups: 26 healthy participants and 24 hospitalized patients with a diversity of cardiac conditions, including atrial fibrillation and heart failure. The team compared the smart speaker's inter-beat interval with one from a standard heartbeat monitor. Of the nearly 12,300 heartbeats measured for the healthy participants, the smart speaker's median inter-beat interval was within 28 milliseconds of the standard monitor. The smart speaker performed almost as well with cardiac patients: of the more than 5,600 heartbeats measured, the median inter-beat interval was within 30 milliseconds of the standard.

Currently this system is set up for spot checks: If a person is concerned about their heart rhythm, they can sit in front of a smart speaker to get a reading. But the research team hopes that future versions could continuously monitor heartbeats while people are asleep, something that could help doctors diagnose conditions such as sleep apnea.

"If you have a device like this, you can monitor a patient on an extended basis and define patterns that are individualized for the patient. For example, we can figure out when arrhythmias are happening for each specific patient and then develop corresponding care plans that are tailored for when the patients actually need them," Sridhar said. "This is the future of cardiology. And the beauty of using these kinds of devices is that they are already in people's homes."

Charcot-Marie Tooth disease is the most common hereditary neurological disease in the world. It affects the peripheral nerves and causes progressive paralysis of the legs and hands. No treatment is currently available to fight this disease, which is due to the overexpression of a specific protein. Scientists from the CNRS, INSERM, the AP-HP and the Paris-Saclay and Paris universities have developed a therapy based on degrading the coding RNA for this protein in mice. Their work is patented and was published on 9 March 2021 in Communications Biology.

In molecular biology, transcription is when a DNA molecule is copied to make an RNA molecule. This RNA molecule is then "translated" into a protein, which can perform different functions within the body's cells. When a specific protein called PMP22 is made twice as much as normal, it causes type 1A of genetic Charcot-Marie Tooth disease to develop. This overproduction leads to gradual paralysis of the legs and hands.

The challenge then, is to standardize the expression of this protein in people with Charcot-Marie Tooth disease. French scientists1 have developed a patented2 therapy based on reducing RNA coding for the PMP22 protein. To achieve this they used other small RNA molecules capable of interfering with a specific RNA, here the one that encodes PMP22, and of degrading or reducing its translation into protein.

The difficulty in developing this therapy has been to stabilise these small RNAs, known as small interfering RNA or siRNA, which degrade very rapidly in biological environments. Researchers have coupled them with another molecule called squalene, which is typically used in cosmetology and pharmacology. Biocompatible, biodegradable and forming nanoparticles in water, squalene protects siRNA from degradation. It also controls the size of the particles formed and the amount of siRNA injected.

These scientists then showed, in mice models for this disease, that injecting these interfering RNAs completely and rapidly restored of mouse locomotor activity and strength. The siRNAs penetrate the peripheral nerves, strengthen the myelin sheath3 around those nerves, and normalize the nerve signal velocity. The effect of treatment lasts for three weeks for severe forms and more than ten weeks for milder forms of the disease.

This therapeutic strategy for hereditary peripheral neuropathies, developed entirely in France, is proof of concept for a new precision medicine based on siRNA normalization of the expression of an overexpressed gene. It will now be developed in humans with pre-clinical and clinical studies.

About 11% of women who carry to term will experience prelabor rupture of membrane--a condition where the amniotic sac breaks open early, but labor doesn't begin.

Typically, when a woman's water breaks but labor doesn't start, labor is induced. But a new University of Michigan study found that expectant management--waiting a period of time after the water breaks for labor to begin spontaneously--did not significantly increase risk to the fetus or the mother in healthy pregnancies.

Therefore, both induction and expectant management should be considered, and the decision should be made in the context of the mother's wishes and health, said study co-author Ruth Zielinski, a nurse midwife and U-M clinical professor in nursing.

The American College of Obstetricians and Gynecologists recommends induction, but in healthy pregnancies carried to term the American College of Nurse Midwives recommends expectant management be offered as an option.

During pregnancy, the fetus is surrounded by a fluid-filled membrane called the amniotic sac. At some point at the beginning of or during labor, this sac ruptures and contractions typically begin soon after. The goal of the study was to examine rates of induction, maternal infection, neonatal outcomes and time to birth in women who carried to term, and were expectantly managed at home or in the hospital.

Zielinski and colleagues looked at 2,357 women cared for by a midwestern midwifery service between January 2016 and December 2018. The amniotic sac ruptured early in 281 women (12%). Among that group, 150 (53%) opted to wait for labor onset at home; 102 (36%) were expectantly managed in the hospital; 21 (7.5%) were admitted for immediate induction of labor; and 8 (3%) were admitted for immediate cesarean birth.

Of the women who opted to wait, the majority (65%) went into labor on their own and did not need to be induced. Rates of maternal and infant infection were no different between the groups of women with prelabor rupture of membranes.

Labor is typically induced when the water breaks early because the prevailing wisdom is that as the time between the amniotic sac rupturing and the beginning of labor grows, so does the risk of infection.

"The risk of infection does increase with prolonged ruptured membranes, which is why with prelabor rupture of membranes, when the mother is a Group B strep carrier, the recommendation is a shorter duration of expectant management," Zielinski said.

Group B strep is a common bacteria that does not cause maternal infections, and providing antibiotic prophylaxis during labor is recommended to decrease the risk of transmission to the newborn.

The majority of newborns will not get sick but if they do, they get quite sick, which is why antibiotics are recommended, Zielinski said.

"Twenty-six years ago when I graduated from midwifery school, I assumed everyone wanted to avoid induction, but this is definitely not the case," she said. "Often, patients want to get things going and are fine with induction. However, with healthy, term pregnancies, waiting for a period of time for labor to start is reasonable and should be offered."

It is important for women to discuss their options with their provider, she said.

Luxembourg, 9 March 2021 - Today, Alzheimer Europe launches a new report, "Legal capacity and decision making: The ethical implications of lack of legal capacity on the lives of people with dementia", which looks at the intersection between legal rights and ethical considerations in relation to legal capacity and decision making.

The working group responsible for the report was set up by Alzheimer Europe in 2020 and was composed of experts in dementia, law, ethics, policy, research, psychology and the experience of having dementia and supporting people with dementia.

This report contains a detailed discussion and extensive recommendations on guardianship measures, treatment, care and support, communication of the diagnosis, advanced care planning, participation in research, coercive measures, restrictions of freedom during the COVID-19 pandemic, and civil and political life. The following are some of the key recommendations developed by the working group:

Guardianship legislation should be reframed as decision-making support. Substitute decision making, which would be the most extensive guardianship measure, should only be applied when all other options have been considered or tested, and have not proven sufficient to protect the rights of people with dementia.

Support should be organised in a systematic and structured manner such as in the combined supported decision-making model.

There should be greater monitoring of how legislation to involuntarily detain people with dementia is used and how this could be amended to reflect a supported decision-making approach.

Procedural safeguards should be developed to protect the rights and wellbeing of people with dementia in residential respite care and day care, and in other places where they are not free to leave but have not been lawfully detained.

Restraint should only be tolerated in extreme situations where the physical and mental integrity of the person with dementia is in serious and imminent danger and as a last resort, unless there is no time or it would be too risky to attempt another approach.

Governments should set up independent inquiries into the management of dementia care during the COVID-19 pandemic and develop guidelines to help ensure that future pandemics or similar crises are managed in a way that is both ethical and legal.

People should be allowed to confirm their desire for their advance directive to remain valid should they at some point lack the capacity to renew it or to transfer decision-making responsibility to a named person of their choice.

Every person should have access to an independent supporter to make a will and to include members of their entourage in this process if they wish.

A diagnosis of dementia or guardianship measure should never result in the automatic loss of the right to vote, marry, divorce or make a will or advance directive.

Dianne Gove, Director for Projects at Alzheimer Europe and co-author of the report, stated:

"Any loss of the right to make decisions, including both formal and informal restrictions, can have a considerable psychological, emotional and practical impact on people's lives and wellbeing. It is important to reflect on ethical issues related to legal capacity and decision making, such as the need to respect human rights, protect the dignity of all human beings, and ensure that everyone with dementia can enjoy and fully participate in civil, political, economic, social and cultural life."

Jean Georges, Executive Director of Alzheimer Europe, added:

"It is important that lawmakers, policy makers, health and social care professionals, administrative bodies, notaries and the general public all work together to remove obstacles and provide appropriate and timely support to maximise the potential for people with dementia to exercise their legal capacity. We need to create flexible and humane systems and move away from mentalities, traditions and taken-for-granted, assumptions that prevent people from making decisions and from living their lives in accordance with their own wishes and values. Appropriate support, reasonable adjustments and safeguards must be in place to maximise freedom of choice and equal opportunities for people with dementia across the whole of society."

Anxiety levels in the United States are rising sharply and have especially intensified in younger populations. According to the Anxiety and Depression Association of America, anxiety disorders affect 31.9 percent of children ages 13 to 18 years old. Because of the COVID-19 pandemic, children and adolescents have experienced unprecedented interruptions to their daily lives and it is expected that these disruptions may precipitate mental illness, including anxiety, depression, and/or stress related symptoms.

Traditional anxiety and depression treatments include cognitive behavioral therapy and psychiatric medications, which are somewhat successful in alleviating symptoms in adults. However, they have yielded some mixed results in children. Therefore, discovering appropriate means for reducing childhood anxiety and depression that are both affordable and accessible is paramount.

Using a computerized and completely remote training program, researchers from Florida Atlantic University's Charles E. Schmidt College of Science have found a way to alleviate negative emotions in preadolescent children. They examined the relationship between anxiety, inhibitory control, and resting-state electroencephalography (EEG) in a critical age-range for social and emotional development (ages 8 to 12 years old). Inhibitory control is the ability to willfully withhold or suppress a thought, action or feeling. Without it, people would act purely on impulses or on old habits of action and thought.

Results of the study published in the journal, Applied Neuropsychology: Child, reveal that computerized inhibitory training helps to mitigate negative emotions in preadolescent children. EEG results also provide evidence of frontal alpha asymmetry shifting to the left after children completed an emotional version of the training. At the baseline time point, there was further indication to support the link between inhibitory control dysfunction and anxiety/depression. Decreased inhibitory control performance predicted higher levels of anxiety and depression, signifying that inhibitory impairments could be a risk factor for the development of these conditions in children.

Prior research has focused on adults and has only used self-report measures to operationalize anxiety and depressive symptoms. This novel study expands upon research investigating cognitive and neurological mechanisms involved in childhood anxiety and depression. In addition, it includes an objective outcome measure (resting-state EEG) to enable more succinct conclusions about training efficacy.

"In the current social climate of the world, internalizing conditions like anxiety and depression are becoming increasingly common in children and adolescents. Meanwhile, the availability and accessibility of computer and tablet technology also has rapidly increased," said Nathaniel Shanok, lead author and a recent Ph.D. graduate of FAU's Department of Psychology, who received an award from the American Psychological Society in 2020 for this research. "Providing computerized cognitive training programs to children can be a highly beneficial use of this technology for improving not only academic performance, but as seen in our study, psychological and emotional functioning during a challenging time period of development."

Participants in the study were assigned to four weeks of either an emotional inhibitory control training program, a neutral inhibitory control training program, or a waitlisted control, and were tested using cognitive, emotional and EEG measures. Researchers evaluated the effects of the four-week, 16-session computerized inhibitory control training program using three tasks (go/no-go, flanker, and Stroop). The training program utilized for the study is gFocus from IQ Mindware and was created by Mark Ashton Smith, Ph.D.

Researchers found that inhibitory control accuracy was significantly and negatively related to anxiety as well as depression. Emotional and neutral training conditions led to significant reductions in anxiety, depression, and negative affect relative to the waitlist group, with the emotional training condition showing the largest reductions in anxiety and negative affect. These two conditions showed comparable improvements in inhibitory control accuracy relative to the waitlist, with greater increases observed in the neutral training condition.

"Given the predominately adverse influence of anxiety on social, psychological and cognitive functioning; early prevention, management and quality treatment plans are critical research areas to explore," said Nancy Aaron Jones, Ph.D., co-author, an associate professor, and director of the FAU WAVES Emotion Laboratory in the Department of Psychology, Charles E. Schmidt College of Science, and a member of the FAU Brain Institute. "Advancements in technology have made it possible to train certain cognitive abilities using child-friendly applications or games that can be easily accessed from a home computer. Devising computerized training programs, which target underlying cognitive characteristics related to anxiety is a promising method for attenuating symptoms and risk in children."

A critical ingredient for auroras exists much higher in space than previously thought, according to new research in the journal Scientific Reports. The dazzling light displays in the polar night skies require an electric accelerator to propel charged particles down through the atmosphere. Scientists at Nagoya University and colleagues in Japan, Taiwan and the US have found that it exists beyond 30,000 kilometres above the Earth's surface - offering insight not just about Earth, but other planets as well.

The story of aurora formation begins with supersonic plasma propelled from the Sun into space as high-speed, charged particles. When these charged particles get close to Earth, they are deflected and funnelled in streams along the planet's magnetic field lines, eventually flowing towards the poles.

"Most electrons in the magnetosphere don't reach the part of the upper atmosphere called the ionosphere, because they are repelled by the Earth's magnetic field," explains Shun Imajo of Nagoya University's Institute for Space-Earth Environmental Research, the study's first author.

But some particles receive a boost of energy, accelerating them into Earth's upper atmosphere where they collide with and excite oxygen and nitrogen atoms at an altitude of about 100 kilometres. When these atoms relax from their state of excitation, they emit the auroral lights. Still, many details about this process remain a mystery.

"We don't know all the details of how the electric field that accelerates electrons into the ionosphere is generated or even how high above Earth it is," Imajo says.

Scientists had assumed electron acceleration happened at altitudes between 1,000 and 20,000 kilometres above Earth. This new research revealed the acceleration region extends beyond 30,000 kilometres.

"Our study shows that the electric field that accelerates auroral particles can exist at any height along a magnetic field line and is not limited to the transition region between the ionosphere and magnetosphere at several thousand kilometres," says Imajo. "This suggests that unknown magnetospheric mechanisms are at play."

The team reached this finding by examining data from ground-based imagers in the US and Canada and from the electron detector on Arase, a Japanese satellite studying a radiation belt in Earth's inner magnetosphere. The data was taken from 15 September 2017 when Arase was at about 30,000 kilometres altitude and located within a thin active auroral arc for several minutes. The team was able to measure upward and downward movements of electrons and protons, ultimately finding the acceleration region of electrons began above the satellite and extended below it.

To further investigate this so-called very high-altitude acceleration region, the team next aims to analyse data from multiple aurora events, compare high-altitude and low-altitude observations, and conduct numerical simulations of electric potential.

"Understanding how this electric field forms will fill in gaps for understanding aurora emission and electron transport on Earth and other planets, including Jupiter and Saturn," Imajo says.

In the spring of 2020, the outbreak of the coronavirus pandemic appeared to coincide with the tree pollen season in the northern hemisphere. These observations prompted an international team of researchers to conduct an extensive investigation: The scientists wanted to know whether there is a demonstrable link between airborne pollen concentrations and SARS-CoV-2 infection rates.

Pollen is a significant environmental factor influencing infection rates

Under the leadership of first author Athanasios Damialis, the team at the Chair of Environmental Medicine at TUM collected data on airborne pollen concentrations, weather conditions and SARS-CoV-2 infections - taking into consideration the variation of infection rates from one day to another and the total number of positive tests. In their calculations, the team also included data on population density and the effects of lockdown measures. The 154 researchers analyzed pollen data from 130 stations in 31 countries on five continents.

The team showed that airborne pollen can account for, on average, 44 percent of the variation in infection rates, with humidity and air temperature also playing a role in some cases. During intervals without lockdown regulations, infection rates were on average 4 percent higher with every increase of 100 grains of airborne pollen per cubic meter. In some German cities, concentrations of up to 500 pollen grains per cubic meter per day were recorded during the study - which led to an overall increase in infection rates of more than 20 percent. In regions where lockdown rules were in effect, however, the infection numbers were on average only half as high at comparable pollen concentrations.

Airborne pollen weakens immune response

High pollen concentrations lead to a weaker immune response in airways to viruses that can cause coughs and colds. When a virus enters the body, infected cells usually send out messenger proteins. This is also the case with SARS-CoV-2. These proteins, known as antiviral interferons, signal nearby cells to escalate their antiviral defenses to keep the invaders at bay. Additionally, an appropriate inflammation response is activated to fight the viruses.

But if airborne pollen concentrations are high, and pollen grains are inhaled with the virus particles, fewer antiviral interferons are generated. The beneficial inflammatory response itself is also affected. Therefore, on days with a high concentration of pollen, it can lead to an increase in the number of respiratory illnesses. This also holds true for Covid-19. Whether individuals are allergic to the different pollen types is irrelevant.

"You cannot avoid exposure to airborne pollen," says Stefanie Gilles who is also first author of the study. "People in high-risk groups should, therefore, be informed that high levels of airborne pollen concentrations lead to an increased susceptibility to viral respiratory tract infections." Athanasios Damialis emphasizes: "When studying the spread of SARS-CoV-2, environmental factors such as pollen must be taken into account. Increased awareness of these effects are an important step in preventing and mitigating the impact of Covid-19."

Particle filtering masks provide protection

What can vulnerable people do to protect themselves? Claudia Traidl-Hoffmann, last author and a professor of environmental medicine, advises people at high-risk to monitor pollen forecasts over the coming months. Claudia Traidl-Hoffmann states: "Wearing a particle filtering mask when pollen concentrations are high can keep both the virus and pollen out of the airways."

Rome, Italy, March 8, 2021 - Allelica, a leading genomics software company specialising in developing polygenic risk scores (PRS) for personalised medicine, today announced publication of a study in Circulation (Vol. 143, Issue 10) showing that the effect of LDL cholesterol on a person's risk of having a heart attack depends on their genes. Using Allelica's proprietary PRS analysis software, the data showed that combining information on an individual's genetic risk of heart attack with their LDL level helps determine those at most risk from heart attack, including those potentially in need of treatment with statins or PCSK9 inhibitors. The PRS was also able to identify individuals eligible for therapeutic intervention based on current guidelines, which do not include polygenic risk, but who are in fact at low risk of heart attack based on their genes and LDL levels, so could potentially avoid treatment. A PRS is a measurement of a person's risk of disease based on their genes and is based on combining the effects of a large number of genetic variants across the genome.

By demonstrating that an individual's risk of heart attack depends on an interaction between LDL cholesterol and PRS, Allelica's research suggests that assessing LDL cholesterol on its own, as it is currently done, is at best inaccurate and at worst potentially dangerous for the more than 10% of the entire primary prevention population who have a high PRS and yet are invisible to current, non-genetic risk assessments.

"Our research shows that it's not enough to know about traditional risk factors to accurately assess someone's risk of heart attack. You need to know their genetic risk too," said Dr George Busby, CSO of Allelica. "The optimal level of LDL cholesterol needed to have normal risk of heart attack differs depending on your polygenic predisposition for heart attack."

Allelica has built digital tools for estimating an individual's PRS for Coronary Artery Disease (CAD). The PRS is based on the latest bioinformatics technology together with genetic data from around 408,000 individuals from the UK Biobank. The study published in Circulation showed that individuals with both average LDL levels (130-160 mg/dL) and high PRS have equivalent risk of suffering from a heart attack as people with hypercholesterolemia (>190mg/dL) and average PRS. People with hypercholesterolemia are usually prescribed statins, based on current clinical guidelines. The research also showed that people with high polygenic scores for CAD can reduce their risk of disease to the population average by maintaining optimal LDL levels (

"LDL cholesterol does not affect everyone's risk of heart attack in the same way. Millions of people with average LDL are likely to be in danger of a heart attack because they also have a high PRS and should probably take lipid lowering medications. At the same time, there are people who are taking drugs but potentially may not need to because their genes protect them," said Giordano Bottà, PhD, CEO of Allelica. "We were able to identify these distinct groups using our CAD PRS analysis tool, which uses a new score that we developed. Our new CAD PRS improves upon the predictive power of all those previously published."

As a next step Allelica is discussing with healthcare authorities how to incorporate its PRS for CAD into clinical routine. This will could have wide reaching implications that support the realization of the benefit of precision medicine at scale.

With the help of the European Southern Observatory's Very Large Telescope (ESO's VLT), astronomers have discovered and studied in detail the most distant source of radio emission known to date. The source is a "radio-loud" quasar -- a bright object with powerful jets emitting at radio wavelengths -- that is so far away its light has taken 13 billion years to reach us. The discovery could provide important clues to help astronomers understand the early Universe.

Quasars are very bright objects that lie at the centre of some galaxies and are powered by supermassive black holes. As the black hole consumes the surrounding gas, energy is released, allowing astronomers to spot them even when they are very far away.

The newly discovered quasar, nicknamed P172+18, is so distant that light from it has travelled for about 13 billion years to reach us: we see it as it was when the Universe was just around 780 million years old. While more distant quasars have been discovered, this is the first time astronomers have been able to identify the telltale signatures of radio jets in a quasar this early on in the history of the Universe. Only about 10% of quasars -- which astronomers classify as "radio-loud" -- have jets, which shine brightly at radio frequencies [1].

P172+18 is powered by a black hole about 300 million times more massive than our Sun that is consuming gas at a stunning rate. "The black hole is eating up matter very rapidly, growing in mass at one of the highest rates ever observed," explains astronomer Chiara Mazzucchelli, Fellow at ESO in Chile, who led the discovery together with Eduardo Bañados of the Max Planck Institute for Astronomy in Germany.

The astronomers think that there's a link between the rapid growth of supermassive black holes and the powerful radio jets spotted in quasars like P172+18. The jets are thought to be capable of disturbing the gas around the black hole, increasing the rate at which gas falls in. Therefore, studying radio-loud quasars can provide important insights into how black holes in the early Universe grew to their supermassive sizes so quickly after the Big Bang.

"I find it very exciting to discover 'new' black holes for the first time, and to provide one more building block to understand the primordial Universe, where we come from, and ultimately ourselves," says Mazzucchelli.

P172+18 was first recognised as a far-away quasar, after having been previously identified as a radio source, at the Magellan Telescope at Las Campanas Observatory in Chile by Bañados and Mazzucchelli. "As soon as we got the data, we inspected it by eye, and we knew immediately that we had discovered the most distant radio-loud quasar known so far," says Bañados.

However, owing to a short observation time, the team did not have enough data to study the object in detail. A flurry of observations with other telescopes followed, including with the X-shooter instrument on ESO's VLT, which allowed them to dig deeper into the characteristics of this quasar, including determining key properties such as the mass of the black hole and how fast it's eating up matter from its surroundings. Other telescopes that contributed to the study include the National Radio Astronomy Observatory's Very Large Array and the Keck Telescope in the US.

While the team are excited about their discovery, to appear in The Astrophysical Journal, they believe this radio-loud quasar could be the first of many to be found, perhaps at even larger cosmological distances. "This discovery makes me optimistic and I believe -- and hope -- that the distance record will be broken soon," says Bañados.

Observations with facilities such as ALMA, in which ESO is a partner, and with ESO's upcoming Extremely Large Telescope (ELT) could help uncover and study more of these early-Universe objects in detail.