Culture

Cardio health decline tied to midlife wealth

image: Andrew Sumarsono, M.D.

Image: 
UT Southwestern Medical Center

DALLAS - June 30, 2021 - A relative decline in wealth during midlife increases the likelihood of a cardiac event or heart disease after age 65 while an increase in wealth between ages 50 and 64 is associated with lower cardiovascular risk, according to a new study in JAMA Cardiology.

Although the association between socioeconomic status and cardiovascular outcomes is well established, little research has been done to determine whether longitudinal changes in wealth are associated with cardiovascular health. In the study, Andrew Sumarsono, M.D., an assistant professor of internal medicine at UT Southwestern, along with colleagues from Harvard-affiliated Brigham and Women's Hospital Heart & Vascular Center and the London School of Economics, investigated the cardiovascular toll that changes in monetary health can have in the U.S., where there is a 10- to 15-year difference in life expectancy between the population's richest 1 percent and the poorest 1 percent.

Examining a cohort of more than 5,500 adults without cardiovascular disease, they found that middle-aged participants who experienced upward wealth mobility - defined as relative increases in the total value of assets excluding primary residence - had lower cardiovascular risk after age 65 compared with peers of similar age. Conversely, participants who experienced downward wealth mobility in the latter parts of their careers had higher cardiovascular risk later in life. Cardiovascular events cited as outcomes include acute myocardial infarction, heart failure, cardiac arrhythmia, and stroke, or cardiac-related death.

"We already know that wealth relates to health, but we show that wealth trajectories also matter. This means that the cardiovascular risk associated with wealth is not permanent and can be influenced," says Sumarsono, a faculty member in the Division of Hospital Medicine.

The researchers estimate a 1 percent swing in cardiovascular risk for every $100,000 gained or lost by individuals. Notably, participants who started in the top 20 percent of wealth and experienced downward wealth mobility still had similar cardiovascular risk as those who remained fixed in the top quintile. However, those who started in the bottom fifth of wealth accumulation and experienced upward wealth mobility had lower cardiovascular risk than those fixed in the bottom quintile. The investigators suggest that this may indicate a potential legacy protection present among the wealthiest, but not the poorest. These findings linking wealth change and downstream cardiovascular events were similar across all racial or ethnic subgroups.

"We found that irrespective of one's baseline wealth, upward wealth mobility relative to peers in late-middle age was associated with lower risk of a new cardiac event or death after age 65. This suggests that upward wealth mobility may offset some of the risk associated with past economic hardship," Sumarsono says. "We also found the inverse was true - that people who experienced downward wealth mobility relative to one's peers faced a higher risk of a new cardiac event or death after 65, potentially offsetting some of the benefit associated with prior economic thriving.

"We live in a system where people can experience catastrophic losses in wealth from situations beyond their control and that opportunities to accrue wealth are not equally available across racial or socioeconomic groups," Sumarsono adds. "Policies that build resilience against large wealth losses and that address these opportunity gaps should be prioritized and may be considered a public health measure to improve overall health while also potentially narrowing racial, socioeconomic, and cardiovascular health disparities."

Credit: 
UT Southwestern Medical Center

Multitalented filaments in living cells

video: Researchers at Göttingen University have now succeeded for the first time in precisely measuring which physical effects determine the properties of the individual filaments, and which specific features only occur through the interaction of many filaments in networks. The results were published in PNAS.

Image: 
Dr Markus Osterhoff

The cells that make up our bodies are constantly exposed to a wide variety of mechanical stresses. For example, the heart and lungs have to withstand lifelong expansion and contraction, our skin has to be as resistant to tearing as possible whilst retaining its elasticity, and immune cells are very squashy so that they can move through the body. Special protein structures, known as "intermediate filaments", play an important role in these characteristics. Researchers at Göttingen University have now succeeded for the first time in precisely measuring which physical effects determine the properties of the individual filaments, and which specific features only occur through the interaction of many filaments in networks. The results were published in PNAS.

One of the most important systems that cells use to ensure their stability, elasticity and resistance to mechanical stress is the cytoskeleton: an intricate network of proteins and filaments, predominantly formed by three types of thread-like protein structures, each of which has different functions and properties. The intermediate filaments belong to this group of protein structures. These filaments form networks that can be subjected to a tremendous force without being damaged: they are the shock absorbers of the cells. At the same time, these intermediate filaments can serve as an inner tether in the case of powerful deformation and this can prevent the cell from being torn apart.

To investigate these properties, the Göttingen team created artificial networks of intermediate filaments in the laboratory and used the movement of small embedded spheres to study how the entire network behaves. In fact, there are overlapping effects in the networks: the stretching behaviour of the individual filaments; and the force and frequency with which the filaments interact at points where they cross (intersections). For this reason, the researchers investigated these aspects separately by first stretching individual filaments to determine the forces required for the stretching. They then brought two of the filaments into contact with each other in a criss-cross pattern and pulled on the point of intersection by moving one of the filaments. By arranging the filaments as if they were a "microscopic violin", they were able to determine the exact strength and frequency with which the filaments bind together. They were also able to replicate these results with computer simulations. In addition, the team observed that the networks transform over an unexpectedly long period of time and slowly "age" over the course of a week, because the filaments become longer and longer or join together to form bundles.

"All these observations increase our understanding of how our cells manage to be so incredibly robust and yet flexible," explains first author Anna Schepers from the Institute for X-ray Physics at Göttingen University. "In addition, a clearer picture of intermediate filaments helps us to understand how and why the mechanical properties of cells change, for example, during wound healing or in metastasising cancer cells," adds the research lead, Professor Sarah Köster.

Credit: 
University of Göttingen

Physicists observationally confirm Hawking's black hole theorem for the first time

There are certain rules that even the most extreme objects in the universe must obey. A central law for black holes predicts that the area of their event horizons -- the boundary beyond which nothing can ever escape -- should never shrink. This law is Hawking's area theorem, named after physicist Stephen Hawking, who derived the theorem in 1971.

Fifty years later, physicists at MIT and elsewhere have now confirmed Hawking's area theorem for the first time, using observations of gravitational waves. Their results appear in Physical Review Letters.

In the study, the researchers take a closer look at GW150914, the first gravitational wave signal detected by the Laser Interferometer Gravitational-wave Observatory (LIGO), in 2015. The signal was a product of two inspiraling black holes that generated a new black hole, along with a huge amount of energy that rippled across space-time as gravitational waves.

If Hawking's area theorem holds, then the horizon area of the new black hole should not be smaller than the total horizon area of its parent black holes. In the new study, the physicists reanalyzed the signal from GW150914 before and after the cosmic collision and found that indeed, the total event horizon area did not decrease after the merger -- a result that they report with 95 percent confidence.

Their findings mark the first direct observational confirmation of Hawking's area theorem, which has been proven mathematically but never observed in nature until now. The team plans to test future gravitational-wave signals to see if they might further confirm Hawking's theorem or be a sign of new, law-bending physics.

"It is possible that there's a zoo of different compact objects, and while some of them are the black holes that follow Einstein and Hawking's laws, others may be slightly different beasts," says lead author Maximiliano Isi, a NASA Einstein Postdoctoral Fellow in MIT's Kavli Institute for Astrophysics and Space Research. "So, it's not like you do this test once and it's over. You do this once, and it's the beginning."

Isi's co-authors on the paper are Will Farr of Stony Brook University and the Flatiron Institute's Center for Computational Astrophysics, Matthew Giesler of Cornell University, Mark Scheel of Caltech, and Saul Teukolsky of Cornell University and Caltech.

An age of insights

In 1971, Stephen Hawking proposed the area theorem, which set off a series of fundamental insights about black hole mechanics. The theorem predicts that the total area of a black hole's event horizon -- and all black holes in the universe, for that matter -- should never decrease. The statement was a curious parallel of the second law of thermodynamics, which states that the entropy, or degree of disorder within an object, should also never decrease.

The similarity between the two theories suggested that black holes could behave as thermal, heat-emitting objects -- a confounding proposition, as black holes by their very nature were thought to never let energy escape, or radiate. Hawking eventually squared the two ideas in 1974, showing that black holes could have entropy and emit radiation over very long timescales if their quantum effects were taken into account. This phenomenon was dubbed "Hawking radiation" and remains one of the most fundamental revelations about black holes.

"It all started with Hawking's realization that the total horizon area in black holes can never go down," Isi says. "The area law encapsulates a golden age in the '70s where all these insights were being produced."

Hawking and others have since shown that the area theorem works out mathematically, but there had been no way to check it against nature until LIGO's first detection of gravitational waves.

Hawking, on hearing of the result, quickly contacted LIGO co-founder Kip Thorne, the Feynman Professor of Theoretical Physics at Caltech. His question: Could the detection confirm the area theorem?

At the time, researchers did not have the ability to pick out the necessary information within the signal, before and after the merger, to determine whether the final horizon area did not decrease, as Hawking's theorem would assume. It wasn't until several years later, and the development of a technique by Isi and his colleagues, when testing the area law became feasible.

Before and after

In 2019, Isi and his colleagues developed a technique to extract the reverberations immediately following GW150914's peak -- the moment when the two parent black holes collided to form a new black hole. The team used the technique to pick out specific frequencies, or tones of the otherwise noisy aftermath, that they could use to calculate the final black hole's mass and spin.

A black hole's mass and spin are directly related to the area of its event horizon, and Thorne, recalling Hawking's query, approached them with a follow-up: Could they use the same technique to compare the signal before and after the merger, and confirm the area theorem?

The researchers took on the challenge, and again split the GW150914 signal at its peak. They developed a model to analyze the signal before the peak, corresponding to the two inspiraling black holes, and to identify the mass and spin of both black holes before they merged. From these estimates, they calculated their total horizon areas -- an estimate roughly equal to about 235,000 square kilometers, or roughly nine times the area of Massachusetts.

They then used their previous technique to extract the "ringdown," or reverberations of the newly formed black hole, from which they calculated its mass and spin, and ultimately its horizon area, which they found was equivalent to 367,000 square kilometers (approximately 13 times the Bay State's area).

"The data show with overwhelming confidence that the horizon area increased after the merger, and that the area law is satisfied with very high probability," Isi says. "It was a relief that our result does agree with the paradigm that we expect, and does confirm our understanding of these complicated black hole mergers."

The team plans to further test Hawking's area theorem, and other longstanding theories of black hole mechanics, using data from LIGO and Virgo, its counterpart in Italy.

"It's encouraging that we can think in new, creative ways about gravitational-wave data, and reach questions we thought we couldn't before," Isi says. "We can keep teasing out pieces of information that speak directly to the pillars of what we think we understand. One day, this data may reveal something we didn't expect."

Credit: 
Massachusetts Institute of Technology

Employed individuals more likely to contract the flu, study shows

image: Don Koh, University of Arkansas

Image: 
University of Arkansas

A University of Arkansas researcher and international colleagues found that employed individuals, on average, are 35.3% more likely to be infected with the flu virus.

The findings confirm a long-held assumption about one prevalent way illness spreads and could influence government policy on public health and several issues for private companies, from optimal design and management of physical work spaces to policy decisions about sick leave and remote work.

To track influenza incidence, Dongya "Don" Koh, assistant professor of economics in the Sam M. Walton College of Business, and colleagues relied on nationally representative data from the Medical Expenditure Panel Survey, which provide comprehensive health care information about families and individuals, their medical providers and U.S. employers. The survey is the most complete source of data on the cost and use of health care and health insurance coverage.

Koh and his colleagues found significant differences in flu incidence across various occupations and industries. With the former, for example, people working in sales had a 40.5% higher probability of infection than farmers. In terms of industries, for example, education, health and social services showed a 52.2% higher probability of infection than mining. The results considered individual characteristics, including vaccinations, health insurance and other circumstances.

"Cross-industry differences in flu incidence cannot be fully explained by differences within an industry-specific occupational structure," Koh said. "So we had to look at the extent of human contact and interaction at work as a potential mechanism for contagion."

To do this, the researchers constructed a measure of occupation-specific and industry-specific human exposure and interaction, based on data gleaned from O*NET OnLine, a comprehensive source for the description of jobs, occupational information and workforce development. The researchers found that higher human contact at work was positively associated with higher contagion rates.

The results were larger in years of high aggregate flu incidence and consistent with regard to firm size, number of jobs and hours worked.

"These results shouldn't surprise anyone," Koh said. "We hope they are relevant for an understanding of the spread of flu and other infectious diseases transmitted via respiratory droplets or close human contact, including SARS and COVID. The fact that contagion risk varies across occupations and industries opens the door for an assessment of nonpharmaceutical policies to combat contagion and possibly pandemics. In this sense, we think these results provide a basis for an organizational policy that both protects workers and optimizes production and efficiency."

Credit: 
University of Arkansas

Jackdaws don't console traumatized mates

video: Nest-box footage of a jackdaw pair allopreening (one bird preening another).

Image: 
Cornish Jackdaw Project

Male jackdaws don't stick around to console their mate after a traumatic experience, new research shows.

Jackdaws usually mate for life and, when breeding, females stay at the nest with eggs while males gather food.

Rival males sometimes visit the nest and attack the lone female, attempting to mate by force.

In the new study, University of Exeter researchers expected males to console their partner after these incidents by staying close and engaging in social behaviours like preening their partner's feathers.

However, males focussed on their own safety - they still brought food to the nest, but they visited less often and spent less time with the female.

"Humans often console friends or family in distress, but it's unclear whether animals do this in the wild," said Beki Hooper, of the Centre for Ecology and Conservation on Exeter's Penryn Campus in Cornwall.

"Previous studies have found consolation-like behaviour in some animals, but there is often another explanation - other than consolation - that could motivate this.

"We designed this study to rule out other explanations, so we could find out whether jackdaws, which have complex social lives and life-long partnerships, would console each other.

"We found that male jackdaws could detect their partner's distress, but did not console them.

"The decreased time males spent in the nest after an attack may be for self-preservation, where they respond to distress in their partner by avoiding the nest, a potential place of danger.

"Further work is needed to figure out why exactly males responded as they did, though."

The research team used both experimental nest "visits" of rival males - playing the sounds of an approaching male to a female alone at the nest - and recordings of males attacking nesting females in the wild.

Females became agitated after such experiences, and their returning mates clearly sensed this as their behaviour changed - decreasing "affiliative" behaviour and visiting the nest less regularly afterwards.

"Jackdaw pairs depend on each other for survival and reproduction, so based on current theory we would expect to see consolation after a traumatic event," said Dr Alex Thornton.

"The absence of consolation is striking, and it challenges common conceptions about where consolation should evolve.

"It also chimes with concerns that current theory may be influenced by anthropomorphic (attributing human characteristics to animals) expectations of how social relationships work.

"To properly understand such social behaviour among animals, we need to take account of the dangers and trade-offs they face in the wild."

Jackdaws are an extremely sociable and intelligent corvid species, with a similar number of neurons in their brains to nonhuman primates.

They show impressive levels of social intelligence, such as individual human recognition, and the ability to socially learn from group members about dangerous people.

The paper, published in the journal Royal Society Open Science, is entitled: "Wild jackdaws respond to their partner's distress, but not with consolation."

Credit: 
University of Exeter

A world first! Visualizing atomic-scale structures with the optical force

image: (a) Schematic image of photoinduced force microscopy. (b)(c) Photo-induced force microscopy images of a quantum dot measured using different wavelengths (600 nm, 520 nm). (d) Photoinduced force profiles for the images. This reflects the electronic energy structure designed for photocatalysis.

Image: 
Osaka University

Osaka, Japan - A team of scientists led by the Department of Applied Physics at Osaka University, the Department of Physics and Electronics at Osaka Prefecture University, and the Department of Materials Chemistry at Nagoya University used photoinduced force microscopy to map out the forces acting on quantum dots in three dimensions. By eliminating sources of noise, the team was able to achieve subnanometer precision for the first time ever, which may lead to new advances in photocatalysts and optical tweezers.

Force fields are not the invisible barriers of science fiction but are a set of vectors indicating the magnitude and direction of forces acting in a region of space. Nanotechnology, which involves making and manipulating tiny devices such as quantum dots, sometimes uses lasers to optically trap and move these objects. However, the ability to analyze and handle such small systems requires a better way to visualize the 3D forces acting on them.

Now, a team of researchers at Osaka University, Osaka Prefecture University, and Nagoya University has shown for the first time how photoinduced force microscopy can be used to obtain 3D force field diagrams with subnanometer resolution. "We succeeded in imaging the optical near-field of nanoparticles using a photoinduced force microscope. This measures the optical force between the sample and the probe caused by light irradiation," first author Junsuke Yamanishi says.

Laser light was directed on a quantum dot placed underneath an atomic force microscopy tip. Moving the dot relative to the tip allowed the microscope to map out the 3D photoinduced force field. The team was able to achieve such a high level of precision using a few experimental improvements. They used ultra-vacuum conditions to increase the force sensitivity, and employed heterodyne frequency modulation, which involves mixing two other frequencies, to greatly reduce the impact of thermal heating. "We reduced the photothermal effect with this unique technology and achieved a resolution of less than one nanometer for the first time ever," senior author Yasuhiro Sugawara says.

This research may represent a fundamentally new technology for the design and evaluation of functional nanomaterials. It can also help supplement the toolbox of methods available to scientists working with photocatalysts and optical functional devices to move them using lasers.

Credit: 
Osaka University

What makes vets feel good at work?

image: Uni of Adelaide vet scientists in training.

Image: 
The University of Adelaide

Receiving a simple thank you, spending time with peers and further developing their expertise, are all factors that make veterinarians feel good at work, according to a new study by researchers at the University of Adelaide.

In the study published by Vet Record, researchers investigated the positive side of veterinary work and specifically what brings vets pleasure in their job.

Lead author Madeleine Clise, a psychologist and Adjunct Lecturer at the University of Adelaide's School of Psychology says: "At a time in Australia when there are national shortages of vets, particularly in regional areas, and increased publicity about the risks and challenges in the profession, it's important to focus on what can be done to retain those in the profession and attract more people to the field.

"By focusing on what contributes to vets experiencing positive emotions, we can better understand how to improve wellbeing of those who care for our beloved pets, livestock and wildlife."

In a questionnaire completed by 273 Australian veterinarians, participants were asked to provide up to 10 responses to the prompt, 'I derive pleasure from my work as a veterinarian when...'. Over 2500 responses were grouped into themes and sub-themes and categorised using the 'Job Demands-Resources Model', which focuses on both the positive and negative aspects of a job that are indicative of employee wellbeing.

"The results highlight that there is an abundance of factors related to pleasure at work for veterinarians, above and beyond working with and helping animals," Ms Clise said.
"In fact, positive relationships between clients and vets, and vets and their colleagues, was a more frequent response than positive relationships with animals.

"Vets, just like all of us, feel good when they are shown trust and respect. And a simple 'thank you' goes a long way."

Other findings from the study suggest that having opportunities to use and develop their specialised skillsets is highly pleasurable for veterinarians in practice. A positive workplace culture, successful outcomes with patients and opportunities to collaborate with other vets were also highlighted.

Senior author Dr Michelle McArthur, Associate Professor at the University of Adelaide's School of Animal and Veterinary Sciences, says: "Managers and practice managers can use the results to enhance the work environment for employees.

"This could include introducing an informal and formal recognition system and increasing time spent with colleagues.

"Further beneficial changes could include the introduction of a peer supervision or mentoring program to support veterinary expertise and increase connectedness across the profession."

The results also showed experiencing certain positive beliefs about oneself, such as flexibility, having a positive attitude and accomplishment are associated with pleasure at work.

"So further developing personal resources, for example in the university curriculum or as ongoing professional development, could increase the overall wellbeing of veterinarians," said Dr McArthur.

The researchers hope the results will spark discussion and further focus on the positive aspects of veterinary work, which they say are often overshadowed by the negative.

"Veterinarian work is such a rewarding profession and it's important that we share the many positives with new veterinarians and those in training as reassurance, and to encourage others to join the profession," said Dr McArthur.

Credit: 
University of Adelaide

Using artificial intelligence to overcome mental health stigma

Tsukuba, Japan - Depression is a worldwide problem, with serious consequences for individual health and the economy, and rapid and effective screening tools are thus urgently needed to counteract its increasing prevalence. Now, researchers from Japan have found that artificial intelligence (AI) can be used to detect signs of depression.

In a study published this month in BMJ Open, researchers from University of Tsukuba have revealed that an AI system using machine learning could predict psychological distress among workers, which is a risk factor for depression.

Although many questionnaires exist that screen for mental health conditions, individuals may be hesitant to answer truthfully questions about subjective mood due to social stigma regarding mental health. However, a machine learning system could be used to screen depression/psychological distress without such data, something the researchers at University of Tsukuba aimed to address.

"We wanted to see if the AI system could detect psychological distress in a large population from sociodemographic, lifestyle, and sleep factors, without data about subjective states, such as mood," says lead author of the study Professor Shotaro Doki.

To investigate this, the researchers asked a group of researchers and office workers to complete an online survey about sociodemographic, lifestyle, and sleep factors. Then, they developed an AI model that predicted psychological distress according to data from 7251 participants, and compared the results obtained from the AI model with predictions made by a team of 6 psychiatrists.

"The results were surprising," explains Professor Doki. "We found that even without data about mood, the AI model and the team of psychiatrists produced similar predictions regarding moderate psychological distress."

Furthermore, for participants with severe psychological distress, the predictions made by the AI model were more accurate than the predictions of the psychiatrists.

"This newly developed model appears to easily be able to predict psychological distress among large numbers of workers, without data regarding their subjective mood," says Professor Doki. "This effectively avoids the issue of social stigma concerning mental health in the workplace, and eliminates the risk of inappropriate responses to questions asking about respondents' mood."

Thus, screening tools that do not require individuals to report their subjective mood may be more accurate, and thus better able to identify individuals who would not otherwise receive treatment. Earlier interventions to treat depression and psychological distress are likely to lessen the severity of mental illness, with important benefits for both individuals and society.

Credit: 
University of Tsukuba

Success in reversing dementia in mice sets the stage for human clinical trials

image: Neurodegenerative diseases such as Alzheimer's disease and dementia with Lewy body (DLB) are caused by the accumulation of aggregated amyloid beta and α-synucelin, respectively. The aggregated proteins impaired the proteasome activity, thereby exacerbating neuronal death. On the other hand, we developed a novel T-type calcium channel enhancer SAK3 in 2017. Since T-type calcium channel is critical for neurotransmitter release, SAK3 enhanced the acetylcholine release in the brain thereby improving learning and memory. We here found that calcium entry through T-type calcium channel activates protein kinase (CaMKII), thereby promoting Rpt-6 phosphorylation. The Rpt-6 phosphorylation promoted the degradation of aggregated amyloid beta and α-synucelin in neurons. This is the first disease modifying therapeutics in most neurodegenerative diseases such as Alzheimer's disease, dementia with Lewy body (DLB), Huntington disease (HD) and frontotemporal dementia (FTD).

Image: 
Kohji Fukunaga

Researchers have identified a new treatment candidate that appears to not only halt neurodegenerative symptoms in mouse models of dementia and Alzheimer's disease, but also reverse the effects of the disorders.

The team, based at Tohoku University, published their results on June 8 in the International Journal of Molecular Sciences. The treatment candidate has been declared safe by Japan's governing board, and the researchers plan to begin clinical trials in humans in the next year.

"There are currently no disease-modifying therapeutics for neurodegenerative disorders such as Alzheimer's disease, Lewy body dementia, Huntington disease and frontotemporal dementia in the world," said paper author Kohji Fukunaga, professor emeritus in Tohoku University's Graduate School of Pharmaceutical Sciences. "We discovered the novel, disease-modifying therapeutic candidate SAK3, which, in our studies, rescued neurons in most protein-misfolding, neurodegenerative diseases."

In a previous study, the team found that the SAK3 molecule - the base structure of which is found in the enhancement of T-type Ca2+ channel activity - appeared to help improve memory and learning in a mouse model of Alzheimer's disease.

According to previous studies, SAK3 enhances the function of a cell membrane channel thereby promoting neuronal activity in the brain. Typically, SAK3 promotes neurotransmitter releases of acetylcholine and dopamine that are significantly reduced in Alzheimer's disease and Lewy body dementia. The Ca2+ channel enhancement is thought to trigger a change from resting to active in neuronal activity. When the Ca2+ channel is dysregulated in the brain, the acetylcholine and dopamine releases are reduced. The result is a dysregulated system that a person experiences as cognitive confusion and uncoordinated motor function.

SAK3 directly binds to the subunit of this channel, resulting in the enhancement of neurotransmission thereby improving cognitive deficits. The researchers found that the same process also appeared to work in a mouse model of Lewy body dementia, which is characterized by a build-up of proteins known as Lewy bodies.

"Even after the onset of cognitive impairment, SAK3 administration significantly prevented the progression of neurodegenerative behaviors in both motor dysfunction and cognition," Fukunaga said.

In comparison, Aduhelm, the Alzheimer's drug recently approved by the U.S. Food and Drug Administration, reduces the number of amyloid plaques in the brain, but it is not yet known if the amyloid reduction actually prevents further cognitive or motor decline in patients. According to Fukunaga, SAK3 helps destroy amyloid plaque - at least in mice.

SAK3 also helps manage the destruction of misfolded alpha-synuclein. Normal alpha-synuclein helps regulate neurotransmitter transmission in the brain. The protein can misfold and aggregate, contributing to what researchers suspect may be an underlying cause of neurodegenerative symptoms. This aggregation can also lead to the loss of dopamine neurons, which help with learning and memory.

"We found that chronic administration of SAK3 significantly inhibited the accumulation of alpha-synuclein in the mice," Fukunaga said, noting that the mice received a daily oral dose of SAK3.

According to Fukunaga, SAK3 enhances the activity of the system that identifies and destroys misfolded proteins. In neurodegenerative diseases, this system is often dysfunctional, leaving misfolded proteins to muck up the cell's machinery.

"SAK3 is the first compound targeting this regulatory activity in neurodegenerative disorders," Fukunaga said. "SAK3 administration promotes the destruction of misfolded proteins, meaning the therapeutic has the potential to solve the problems of diverse protein misfolding diseases such as Parkinson's disease, Lewy body dementia and Huntington disease, in addition to Alzheimer's disease."

Credit: 
Tohoku University

Diversity of tiny bobtail squid driven by ancient biogeographic events, finds new study

image: A photo of Euprymna brenneri, the new species of bobtail squid described in the 2019 OIST study. Photo taken by Jeff Jolly, a co-author of this study.

Image: 
Jeff Jolly

Bobtail and bottletail squids are tiny marine invertebrates that are found throughout the world's oceans and are useful model animals for research

There are 68 recognized species of bobtail squid and five recognized species of bottletail squid, but the timing of their divergence from one another is still relatively unknown

Researchers at OIST, Hiroshima University and the National University of Ireland Galway, collected 32 species of bobtail and bottletail squids

They looked at the genetic variations across the entire genomes of these species to estimate their evolutionary relationships

The results showed that the divergence of these species aligned with major biogeographic events such as a global mass extinction and the division between the Indo-Pacific Sea and the Atlantic Ocean.

Bobtail and bottletail squids are small marine invertebrates that are easy to collect, reproduce quickly, and can be raised together in large numbers in laboratories, making them useful model animals for research. They're cephalopods--related to true squid, octopus, and cuttlefish, which are renowned for their intelligence and complex behaviors, but of which scientists still know little about. Now, in a new study, published in Communications Biology, researchers have used genetic techniques to show that bobtail squid and bottletail squid share a relatively recent common ancestor and that major biogeographic events might have shaped the evolution of the many different species.

"With 68 recognized species, bobtail squid are a very diverse family and split into three subfamilies. This study found that one of these subfamilies is further split into two geographic lineages." explained one of the lead authors, Dr. Gustavo Sanchez, researcher at Hiroshima University and former Visiting Research Student in the Okinawa Institute of Science and Technology Graduate University's (OIST) Molecular Genetics Unit. "In 2019, as part of my previous research at OIST, we described a new species of bobtail squid, which highlights both the diversity present and that many unknowns remain."

Bobtail and bottletail squids make up the order Sepiolida. They're small, normally between 1 and 8 cm, and live in a range of marine habitats around the globe, from shallow coastal waters to the open ocean.

For this new study, Dr. Sanchez, alongside researchers from OIST and the National University of Ireland Galway, collected 32 species of bobtail and bottletail squids from across the Indo-Pacific, the Mediterranean Sea, and the Atlantic Ocean. They use a technique called genome skimming that sequences whole genomes, albeit at low coverage. This allowed them to look at the genetic variations between these species so they could estimate their evolutionary relationships and when they diverged.

Their results revealed that bobtail and bottletail squids split into different families around 66 million years ago. This aligns with the rapid diversification of modern marine fishes, following the disappearance of more ancient groups due to a global mass-extinction (the same one that wiped out most of the dinosaurs). Bobtail squid went on to further diversify into three subfamilies--Sepiolinae and the more closely related Rossinae, and Heteroteuthinae. The researchers found that Sepiolinae, which makes up the largest of these subfamilies, can be further split into two tribes--those that are found in the Indo-Pacific Ocean and those that are found in the Mediterranean Sea and the Atlantic Ocean. This split coincided with another major biogeographic event--the closure of the Tethys Sea, around 50 million years ago, which generated the separation of these two regions and resulted in this subfamily being split in two.

A second interesting part of this study focused on the evolution of a light organ in bobtail squid that allows the production of luminescence. Producing luminescence is important for the survival of many of these animals as it allows for counter-illumination, which keeps them hidden from predators at night. The researchers found that the ancestor of the Sepiolinae subfamily likely possessed a bilobed light organ that housed luminescence-producing symbiotic bacteria. This has been retained by many of the species that exist today but was lost in two groups--one in the Indo-Pacific tribe and the other in the Mediterranean-Atlantic tribe.

"The evolutionary relationship of nearly 50% of bobtail squid still needs to be investigated but this research has provided a reliable foundation for classifying bobtail and bottletail squids," said Prof. Daniel Rokhsar, who leads the OIST Unit. "We hope that this phylogenetic work and ancestral reconstructions will be useful in future studies."

Credit: 
Okinawa Institute of Science and Technology (OIST) Graduate University

Managing attention deficit disorder by training the brain

image: Neurofeedback loop: The EEG is recorded and the participant receives an instant feedback from his/her attention level captured by the alpha rhythm through a computer game, allowing to train the brain to concentrate.

Image: 
© UNIGE

Attention Deficit Hyperactivity Disorder (ADHD) affects about 7% of children, with a two out of three chance of persisting into adulthood. This neurodevelopmental disorder is characterised by concentration difficulties, increased distractibility, impulsivity and hyperactivity. Today, ADHD is treated with pharmaceutical drugs that may have unwanted side effects. This is why scientists from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG), Switzerland, explored a new technique called 'neurofeedback', which enables ADHD patients to train their attention, based on instant feedback from the level of their brain activity. The team of neuroscientists found that not only did the training have a positive effect on patients' concentration abilities, but also that the attention improvement was closely linked to an enhanced response from the brain- the P3 wave - which is known to reflect integration of information in the brain, with higher P3 amplitudes indicating greater attention towards detected targets. The findings are open-access and have been published in the journal Clinical Neurophysiology.

Attention Deficit Hyperactivity Disorder (ADHD) develops in childhood and leads to numerous difficulties with attention, concentration and impulsiveness. It has genetic associated with environmental causes, and is characterised by a deficit in dopamine, a neurotransmitter involved in executive functions. "These disorders persist for the most part into adulthood and lead to problems in relational and socio-professional functioning, making it easier for people with this disorder to turn to alcohol or drugs", notes Marie-Pierre Deiber, a researcher in the Department of Psychiatry at UNIGE Faculty of Medicine and at the HUG Division of Psychiatric Specialties.

Today, ADHD is treated with medications that increase the concentration of dopamine, which improves the patient's attention. As the disorder is often accompanied by depression, anxiety or even bipolar disorders, treatment is generally combined with psychotherapy. "However, pharmaceutical treatments can be accompanied by significant side effects, such as nervousness, sleep disturbance, but also an increased risk of developing other psychiatric disorders or cardiovascular diseases", explains Roland Hasler, a researcher in the HUG Division of Psychiatric Specialties. "This is why we wanted to investigate a completely non-pharmacological and non-invasive treatment based on the principle of 'neurofeedback'".

Sending the brain its own signals

Neurofeedback is a type of neurocognitive intervention based on the training of "real-time" brain signals. Using an electroencephalogram (EEG) with 64 sensors, the scientists capture the electrical activity of cortical neurons and focus their analysis on the spontaneous Alpha rhythm (with frequency around 10 Hertz), coupling its amplitude fluctuation to a video game that the patients can control with the power of their attention. "The aim of neurofeedback is to make the patients aware of the moments when they are no longer attentive. With practice, brain networks then "learn" to reduce attentional lapses through neuroplasticity", explains Tomas Ros, researcher in the Department of Basic Neurosciences at UNIGE Faculty of Medicine and at the Centre for Biomedical Imaging (CIBM). To do this, the patient's EEG is connected to a computer that displays the image of a space shuttle. When the patient is in an attentive brain state (low Alpha rhythm), this makes the space shuttle move forward. But as soon as the patient is distracted or loses attention (high Alpha rhythm), this stops the space-shuttle movement instantly. Faced with the stopping of the space shuttle, the patient realizes that he/she was no longer paying attention and refocuses to restart the shuttle.

Training the brain to focus without medication?

To measure the effects of neurofeedback training, the Geneva team administered an attention test to 25 adults with ADHD, and 22 neurotypical adults. The results showed that, at baseline, ADHD patients made more mistakes and had a more variable reaction time than the control participants, in line with a signature of impaired attention. After 30 minutes of neurofeedback training, the participants took the attention test again.

"The first finding was that stimulus detection and response variability were improved, indicating attentional enhancement", says Marie-Pierre Deiber. "But what interested us most was the impact of the neurofeedback training on the P3 component, which has previously been shown to be reduced in ADHD, and directly linked to the neurocognitive processing of the stimulus." The higher the amplitude of the P3, the more efficient the processing of the stimulus is, and the more accurate the response to the attention task. "The amplitude of the P3 increased significantly after neurofeedback training, and was directly associated with a reduction in the number of errors made by the patients", reports Tomas Ros.

This study firstly shows that a single 30-minute session of neurofeedback can induce short-term plasticity in the brain and encourages attentional improvements in ADHD patients. Secondly, it supports the existence of an electro-physiological marker of attentional processing in ADHD. "Thus, the P3 could be a cerebral signature that would allow us to better understand the neurocognitive mechanisms of ADHD", continues Nader Perroud, professor in the Department of Psychiatry at UNIGE Faculty of Medicine and at the HUG Division of Psychiatric Specialties. Finally, as the effects are evident in the short term, the scientists plan to carry out a neurofeedback treatment based on multiple training sessions, in order to observe whether the brain's plasticity is strengthened over time. "The ultimate goal is to enable patients to learn to concentrate without medication and to be able to train their brain in the comfort of their home», concludes Tomas Ros.

Credit: 
Université de Genève

New findings to boost barley yields at higher temps

image: In barley the presence of a specific protein regulates the production of branches and flowers on plant stems in response to warm temperatures. A loss of function in this protein results in the formation of branch-like spikes at high temperatures.

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The University of Adelaide

An international team of researchers has identified a novel mechanism in barley plants, which could help crop growers achieve high yields as temperatures rise.

With grain production highly sensitive to changing environmental conditions, rising temperatures are known to reduce the number of seeds that can be produced on each plant. One solution is to increase the number of flowers or branches on each 'spike', which is the reproductive structure from which grain is harvested.

In a study published in Nature Plants, research led by Professor Dabing Zhang from the University of Adelaide's Waite Research Institute and Shanghai Jiao Tong University's Joint Lab for Plant Science and Breeding, explored the possibility of increasing seed production through the reproductive mechanisms in plants that respond to high temperatures.

"Cereal crops such as wheat and barley are worth over $12B to the Australian economy," said lead author Dr Gang Li with the University of Adelaide's Waite Research Institute.

"Genes that control the amount of grain produced per plant under higher temperatures are really attractive targets for breeders and researchers, particularly in the face of changing environmental conditions.

"It has long been presumed that environmental cues such as temperature are responsible for the diversity of the biological structures between cereals. However the mechanisms behind the structural changes have been largely unknown, which is why this study is important."

In the study, Professor Zhang's team found a novel mechanism by which a barley protein, known as HvMADS1, regulates the number of flowers generated on each spike, in response to high temperatures. The researchers were able to demonstrate that HvMADS1 is critical in maintaining an unbranched barley spike under high ambient temperatures.

Using a highly-efficient genome editing technique, the researchers were able to generate new plants that lack HvMADS1 function, effectively converting an unbranched barley spike into a branched structure, bearing more flowers at high ambient temperatures.

"This could ultimately result in the production of more grain per plant," said Dr Li.

Co-author Associate Professor Matthew Tucker, Deputy Director of the Waite Research Institute said: "This study reveals a new role of this protein family in responding to thermal change and directing the composition of flowers on a stem.

"With short to medium temperature rises predicted globally, plant scientists and breeders have an enormous challenge ahead of them to generate crop yields needed to feed growing populations in higher temperatures.

"By having a better understanding of the genes underpinning desirable plant traits in response to temperature scientists can offer insights into breeding climate-smart plants to sustain productivity."

The researchers say this work provides new avenues for crop breeding potential to overcome the traditional compromise between heat tolerance and high yield.

"This collaborative research demonstrates the importance of international partnerships in delivering fundamental scientific breakthroughs, and the value of gene editing strategies in crops, which are routinely used at the Waite Research Institute at the University of Adelaide," said Associate Professor Tucker.

Credit: 
University of Adelaide

The earthworm in new light

image: The atlas combines data of mass spectrometry imaging (MSI), fluorescence in situ hybridization (FISH) and microtomography (micro-CT).

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Max Planck Institute for Marine Microbiology/PNAS ref.

Earthworms experience constant chemical interactions with bacteria, fungi, plants and small invertebrates across soil ecosystems. Even within their tissues, earthworms harbor symbiotic microbes and small animal parasites that trigger internal metabolic responses such as innate immunity. To reveal the fundamental processes that enable animal-microbe symbioses to form and persist, we have to study their metabolic interactions in situ. By combining novel imaging techniques, a team of researchers around Benedikt Geier from the Max Planck Institute for Marine Microbiology (MPIMM) in Bremen, Germany, has now succeeded in imaging the exciting variety of interactions that take place inside the earthworm. This allows us to observe them in a completely new light.

The chemistry of the worm in 3D

Our understanding of the chemical interactions between small animals and the microorganisms that live inside their bodies is extremely limited. This gap of knowledge has its origin in a methodical challenge: To study the metabolic interactions in symbiosis we have to know who is producing which metabolic product where in the body. The core of this problem, however, is not only to image how molecules are distributed at the micrometer scale. Also, the chemical images are almost impossible to interpret without knowing if a tissue sample is healthy, diseased or infected with beneficial or pathogenic microbes or even animal parasites.

The new combination of high-resolution imaging techniques can offer a solution to this problem, as the research team now shows. "In our study, we introduce chemo-histo-tomography, a special three-dimensional imaging approach of the chemistry and anatomy of millimeter-sized animals and their parasites at a cellular level," says Benedikt Geier, first author of the paper. "This method offers a new strategy to visualize the most fundamental processes - metabolic interactions - in small animal symbioses. It allows us to spatially assign metabolic producs to the animal host and its microbial partners at the micrometer scale."

Chemo-histo-tomography (CHEMHIST) combines chemical imaging of metabolites based on MALDI mass spectrometry imaging with the microanatomy of the same animal that is recorded with micro-computed X-ray tomography. The latter is a non-invasive approach allowing X-ray imaging of the 3D histology, and can reach subcellular resolution. For metabolite imaging, MALDI mass spectrometry techniques have become a state-of-the-art tool to visualize micrometer-scale, natural distributions of metabolites. This enables a spatial assignment between chemical profiles and their production site and possibly to their producer.

"This advance allowed us to take an earthworm from the environment and create a 3D atlas of its chemical and physical interactions with the microorganisms naturally occurring inside its tissues," says Manuel Liebeke, leader of the Research Group Metabolic Interactions at the MPIMM and senior author of the study. "However, we were interested in more than just the biology of the earthworm. Our objective was to also make CHEMHIST applicable to animals directly sampled from their natural habitat, which can be essential for symbiosis research." The resolution of CHEMHIST outperforms existing similar methods developed for medical research in mice by up to two orders of magnitude. This may also lead into new avenues for research on insects or corals, which are key models for symbiosis research, both on land and in water.

The whole is more than the sum of the parts

Using the combination of different in situ imaging techniques through CHEMHIST, the researchers at the MPIMM in Bremen uncovered metabolites - products of the metabolism - in the earthworm that could shed light on how it chemically defends itself against parasites and how these, in turn, protect themselves against the earthworm's immune response. However, to even recognize that the chemical image data were metabolites of parasites in earthworm tissue, the 3D anatomical model was indispensable. A high-resolution micro-computer tomograph at the German Electron Synchrotron in Hamburg first made it possible to identify the parasites in the tissue.

Notably, metabolic interactions between animals and their microbes are not restricted to symbiotic tissues. Along the gut-brain axis, microbial metabolites produced in the gut can affect tissues across the host, even reaching the brain. Therefore, extending correlative chemical imaging into 3D approaches can be crucial for capturing the distribution of metabolites involved in symbiotic interactions and thus show how chemical signals from microbes possibly affect crucial processes in their host. Also, the method can be used in many ways: The research team around Liebeke and Geier is currently applying it to deep-sea mussels.

"Since I have specialized in the 3D visualization of invertebrate anatomy for years, it was particularly interesting for me to see the molecules hidden behind the morphological structures," says Bernhard Ruthensteiner, leader of the section Invertebrate Varia at the Bavarian State Collection of Zoology. The results of the study were made possible by an interdisciplinary collaboration that brought together scientists from the fields of microbiology, zoology, chemistry and physics. It quickly became clear that visualization such as the correlative 3D atlas of the worm facilitate science communication of the data.

Credit: 
Max Planck Institute for Marine Microbiology

Scientists discover new type of quasiparticle

image: The main author of the study Ilya Besedin, junior researcher at the NUST MISIS Laboratory of Superconducting Metamaterials.

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Sergey Gnuskov/NUST MISIS

Russian scientists have experimentally proved the existence of a new type of quasiparticle - previously unknown excitations of coupled pairs of photons in qubit chains. This discovery could be a step towards disorder-robust quantum metamaterials. The study was published in Physical Review B.

Superconducting qubits are a leading qubit modality today that is currently being pursued by industry and academia for quantum computing applications. However, the performance of quantum computers is largely affected by decoherence that contributes to a qubits extremely short lifespan and causes computational errors. Another major challenge is low controllability of large qubit arrays.

Metamaterial quantum simulators provide an alternative approach to quantum computing, as they do not require a large amount of control electronics. The idea behind this approach is to create artificial matter out of qubits, the physics of which will obey the same equations as for some real matter. Conversely, you can program the simulator in such a way as to embody matter with properties that have not yet been discovered in nature.

Arrays of superconducting qubits are generally described by the Bose-Hubbard model. An interesting feature of the Bose-Hubbard model is the emergence of bound boson pairs (doublons) caused by the strong quantum nonlinearity. The topological physics of doublons has been extensively explored in a series of recent theoretical works. However, the experimental investigation of topological properties of bound photon pairs is still lacking.

A group of scientists from NUST MISIS, Russian Quantum Center, ITMO University, Bauman Moscow State Technical University, Dukhov Automatics Research Institute (VNIIA) and Ioffe Institute used an array of superconducting qubits to engineer a quantum simulator. Quantum utilize entanglement and many-particle behaviors to explore and solve hard scientific, engineering, and computational problems.

"By registering the properties of qubits, we can draw conclusions about a broader class of physical systems described by the same equations. And if we can change the parameters of these equations in a controlled way, then such a device can be considered a "specialized simulator". Of course, its programmability is not the same as that of a quantum computer, but its scaling requires significantly fewer resources," explains the main author of the study Ilya Besedin, junior researcher at the NUST MISIS Laboratory of Superconducting Metamaterials.

The scientists engineered an array of superconducting transmon qubits with alternating coupling. Due to the alternation of strong and weak bonds, two zones and an edge state appear in this system. This state is classified as topological. Moreover, the experiment shows that doublons also form an edge state.

"We were able to see how doublons form these zones, and we even managed to detect how an edge doublon state appeared at the upper edge of the doublon zone as we increased the length of the array," notes Ilya Besedin.

Thus, the scientists were able to demonstrate for the first time that a new type of quasiparticles - doublon topological excitations - can arise in qubit chains.

"Research on superconducting qubits and quantum circuits is currently underway in many countries around the world, and competition in this area is growing. This study on 11 qubits shows that Russia has attained high level of scientific development in the field of superconducting quantum computing", notes Prof. Alexey Ustinov, Head of the Laboratory for Superconducting Metamaterials at NUST MISIS and Group Head at Russian Quantum Center, who co-authored the study.

Credit: 
National University of Science and Technology MISIS

How environmental factors could provide for a young brain

A stimulating environment keeps the "hippocampus" - which is the brain's memory control center - young, so to speak. Causes of this are molecular mechanisms that affect gene regulation. These current findings from studies in mice provide clues as to why an active, varied life can help preserve mental fitness in old age. Researchers from the DZNE and the Center for Regenerative Therapies Dresden (CRTD) at the Technische Universität Dresden report on this in the journal Nature Communications.

Human DNA - and this also applies to mice - contains thousands of genes. However, it is not only the genetic blueprint that is decisive for the function of a cell and whether it is healthy or not, but above all which genes can be switched on or off. Aging, living conditions and behavior are known to influence this ability to activate genes. The phenomenon, referred to as "epigenetics", was the focus of the current study. For this, researchers including Dr. Sara Zocher and Prof. Gerd Kempermann examined mice that had grown up in different environments: One group of animals experienced, from a young age, an "enriched" environment with toys and tunnel tubes. The rodents of a second group did not have such occupational opportunities.

Attachments to the DNA

When the scientists examined the genome, they found that in those mice that grew up in the stimulating environment, there was, with age, only a relatively small change in certain chemical tags of the DNA. In mice from the low-stimulus environment, these changes were much more pronounced - in comparison between young and older animals. "We registered so-called methyl groups, which stick to the DNA," explains Gerd Kempermann, speaker for the DZNE's Dresden site, DZNE research group leader and also a scientist at the CRTD. "These chemical attachments do not alter the genetic information per se. Rather, they influence whether individual genes can be activated or not."

Malleable Brains

Such "epigenetic markings" tend to diminish with age, but in the animals with stimulating living conditions, the decrease in methyl groups was comparatively small. Thus, in old mice raised in a varied environment, gene activity had, in a sense, remained young. In particular, this affected a series of genes relevant to growing new neurons and cellular connections in the hippocampus. "Epigenetically, these animals retained a younger hippocampus," Kempermann says. Therefore, the brains of these mice were more malleable - experts speak of greater "neuroplasticity" - than in conspecifics of the same age that had grown up in a low-stimulus environment.

The current study did not include behavioral experiments. However, Kempermann points out that many other studies have shown that mice raised in high-stimulus settings perform better on memory tests than those from low-stimulus environments. "It is fair to assume that this mental fitness is due to the stabilization of methylation patterns that we observed," the neuroscientist says. "Of course, the question is to what extent our findings also apply to humans. Here, the situation is likely to be more complicated. After all, it is about how living conditions influence behavior and the way humans react to external stimuli is much more complex than in mice. However, we have good reasons to believe that the basic epigenetic principles are the same in humans as in mice."

Credit: 
DZNE - German Center for Neurodegenerative Diseases