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New tool activates deep brain neurons by combining ultrasound, genetics: It is the first work to show that sonothermogenetics can control behavior by stimulating a specific target deep in the brain

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New tool activates deep brain neurons by combining ultrasound, genetics: It is the first work to show that sonothermogenetics can control behavior by stimulating a specific target deep in the brain

Neurological disorders such as Parkinson’s disease and epilepsy have had some treatment success with deep brain stimulation, but those require surgical device implantation. A multidisciplinary team at Washington University in St. Louis has developed a new brain stimulation technique using focused ultrasound that is able to turn specific types of neurons in the brain on and off and precisely control motor activity without surgical device implantation.

The team, led by Hong Chen, assistant professor of biomedical engineering in the McKelvey School of Engineering and of radiation oncology at the School of Medicine, is the first to provide direct evidence showing noninvasive, cell-type-specific activation of neurons in the brain of mammal by combining ultrasound-induced heating effect and genetics, which they have named sonothermogenetics. It is also the first work to show that the ultrasound- genetics combination can robustly control behavior by stimulating a specific target deep in the brain.

Results of the three years of research, which was funded in part by the National Institutes of Health’s BRAIN Initiative, were published online in Brain Stimulation May 11, 2021.

The senior research team included experts from both the McKelvey School of Engineering and the School of Medicine, including Jianmin Cui, professor of biomedical engineering; Joseph P. Culver, professor of radiology, of physics and of biomedical engineering; Mark J. Miller, associate professor of medicine in the Division of Infectious Diseases in the Department of Medicine; and Michael Bruchas, formerly of Washington University, now professor of anesthesiology and pharmacology at the University of Washington.

“Our work provided evidence that sonothermogenetics evokes behavioral responses in freely moving mice while targeting a deep brain site,” Chen said. “Sonothermogenetics has the potential to transform our approaches for neuroscience research and uncover new methods to understand and treat human brain disorders.”

Using a mouse model, Chen and the team delivered a viral construct containing TRPV1 ion channels to genetically-selected neurons. Then, they delivered small burst of heat via low-intensity focused ultrasound to the select neurons in the brain via a wearable device. The heat, only a few degrees warmer than body temperature, activated the TRPV1 ion channel, which acted as a switch to turn the neurons on or off.

“We can move the ultrasound device worn on the head of free-moving mice around to target different locations in the whole brain,” said Yaoheng Yang, first author of the paper and a graduate student in biomedical engineering. “Because it is noninvasive, this technique has the potential to be scaled up to large animals and potentially humans in the future.”

The work builds on research conducted in Cui’s lab that was published in Scientific Reports in 2016. Cui and his team found for the first time that ultrasound alone can influence ion channel activity and could lead to new and noninvasive ways to control the activity of specific cells. In their work, they found that focused ultrasound modulated the currents flowing through the ion channels on average by up to 23%, depending on channel and stimulus intensity. Following this work, researchers found close to 10 ion channels with this capability, but all of them are mechanosensitive, not thermosensitive.

The work also builds on the concept of optogenetics, the combination of the targeted expression of light-sensitive ion channels and the precise delivery of light to stimulate neurons deep in the brain. While optogenetics has increased discovery of new neural circuits, it is limited in penetration depth due to light scattering and requires surgical implantation of optical fibers.

Sonothermogenetics has the promise to target any location in the mouse brain with millimeter-scale resolution without causing any damage to the brain, Chen said. She and the team continue to optimize the technique and further validate their findings.

Story Source:
Materials provided by Washington University in St. Louis. Original written by Beth Miller. Note: Content may be edited for style and length.

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How 3D printers can give robots a soft touch

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New tool activates deep brain neurons by combining ultrasound, genetics: It is the first work to show that sonothermogenetics can control behavior by stimulating a specific target deep in the brain


Soft skin coverings and touch sensors have emerged as a promising feature for robots that are both safer and more intuitive for human interaction, but they are expensive and difficult to make. A recent study demonstrates that soft skin pads doubling as sensors made from thermoplastic urethane can be efficiently manufactured using 3D printers.

“Robotic hardware can involve large forces and torques, so it needs to be made quite safe if it’s going to either directly interact with humans or be used in human environments,” said project lead Joohyung Kim, a professor of electrical & computer engineering at the University of Illinois Urbana-Champaign. “It’s expected that soft skin will play an important role in this regard since it can be used for both mechanical safety compliance and tactile sensing.

As reported in the journal IEEE Transactions on Robotics, the 3D-printed pads function as both soft skin for a robotic arm and pressure-based mechanical sensors. The pads have airtight seals and connect to pressure sensors. Like a squeezed balloon, the pad deforms when it touches something, and the displaced air activates the pressure sensor.

Kim explained, “Tactile robotic sensors usually contain very complicated arrays of electronics and are quite expensive, but we have shown that functional, durable alternatives can be made very cheaply. Moreover, since it’s just a question of reprogramming a 3D printer, the same technique can be easily customized to different robotic systems.”

The researchers demonstrated that this functionality can be naturally used for safety: if the pads detect anything near a dangerous area such as a joint, the arm automatically stops. They can also be used for operational functionality with the robot interpreting touches and taps as instructions.

Since 3D-printed parts are comparatively simple and inexpensive to manufacture, they can be easily adapted to new robotic systems and replaced. Kim noted that this feature is desirable in applications where cleaning and maintaining parts is expensive or infeasible.

“Imagine you want to use soft-skinned robots to assist in a hospital setting,” he said. “They would need to be regularly sanitized, or the skin would need to be regularly replaced. Either way,there’s a huge cost. However, 3D printing is a very scalable process, so interchangeable parts can be inexpensively made and easily snapped on and off the robot body.”

Tactile inputs like the kind provided by the new pads are a relatively unexplored facet of robotic sensing and control. Kim hopes that the ease of this new manufacturing technique will inspire more interest.

“Right now, computer vision and language models are the two major ways that humans can interact with robotic systems, but there is a need for more data on physical interactions, or ‘force-level’ data,” he said. “From the robot’s point of view, this information is the most direct interaction with its environment, but there are very few users — mostly researchers — who think about this. Collecting this force-level data is a target task for me and my group.



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Honey bees experience multiple health stressors out-in-the-field

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New tool activates deep brain neurons by combining ultrasound, genetics: It is the first work to show that sonothermogenetics can control behavior by stimulating a specific target deep in the brain


It’s not a single pesticide or virus stressing honey bees, and affecting their health, but exposure to a complex web of multiple interacting stressors encountered while at work pollinating crops, found new research out of York University.

Scientists have been unable to explain increasing colony mortality, even after decades of research examining the role of specific pesticides, parasitic mites, viruses or genetics. This led the research team to wonder if previous studies were missing something by focussing on one stressor at a time.

“Our study is the first to apply systems level or network analyses to honey bee stressors at a massive scale. I think this represents a paradigm shift in the field because we have been so focussed on finding the one big thing, the smoking gun,” says corresponding author of the new paper York Faculty of Science Professor Amro Zayed, York Research Chair in Genomics. “But we are finding that bees are exposed to a very complicated network of stressors that change quickly over time and space. It’s a level of complexity that we haven’t thought about before. To me, that’s the big surprise of this study.”

The paper, Honey bee stressor networks are complex and dependent on crop and region, published today in Current Biology, takes a much broader look at the interplay of stressors and their effects. The study team also included researchers from the University of British Columbia, Agriculture and Agri-Food Canada, the University of Victoria, the University of Lethbridge, the University of Manitoba, l’Université Laval, the University of Guelph, and the Ontario Beekeepers’ Association.

Not all stressors are the same, however. Some stressors are more influential than others — what researchers call the social media influencers of the bee world — having an outsized impact on the architecture of a highly complex network and their co-stressors. They also found that most of these influencer stressors are viruses and pesticides that regularly show up in combination with specific other stressors, compounding the negative effects through their interactions.

“Understanding which stressors co-occur and are likely to interact is profoundly important to unravelling how they are impacting the health and mortality of honey bee colonies,” says lead author, York Postdoctoral Fellow Sarah French of the Faculty of Science.

“There have been a lot of studies about major pesticides, but in this research, we also saw a lot of minor pesticides that we don’t usually think about or study. We also found a lot of viruses that beekeepers don’t typically test for or manage. Seeing the influencer stressors interact with all these other stressors, whether it be mites, other pesticides or viruses, was not only interesting, but surprising.”

French says the way influencer stressors co-occur with other stressors is similar to the way humans experience co-morbidities, such as when someone is diagnosed with heart disease. They are more likely to also have diabetes or high blood pressure or both, and each one impacts the other. “That’s similar to the way we examine bee colonies. We look at everything that’s going on in the colony and then compare or amalgamate all the colonies together to look at the broader patterns of what is happening and how everything is related. Two or multiple stressors can really synergize off each other leading to a much greater effect on bee health.”

From Québec to British Columbia, honey bee colonies were given the job of pollinating some of Canada’s most valuable crops — apples, canola oil and seed, highbush and lowbush blueberry, soybean, cranberry and corn. The study covered multiple time scales, providing numerous snapshots, rather than the usual single snapshot in time. The research team found that honey bees were exposed to an average of 23 stressors at once that combined to create 307 interactions.

Honey bees are a billion dollar industry. In 2021, honey bees contributed some $7 billion in economic value by pollinating orchards, vegetables, berries and oil seeds like canola, and produced 75 to 90 million pounds of honey. Figuring which stressors would provide the most benefit if managed would go a long way toward developing the right tools to tackle them, something beekeepers are often lacking.

The research is part of the BEECSI: ‘OMIC tools for assessing bee health project funded to the tune of $10 million by Genome Canada in 2018 to use genomic tools to develop a new health assessment and diagnosis platform powered by stressor-specific markers.

More research is needed to unravel how the stressors are interacting and impacting honey bee mortality and colony health going forward, says French. “It’s really teasing apart which of these compounds might have that relationship and how can we build off this to study those specific relationships.”

It can’t come soon enough, honey bees are currently facing poor health, colony loss, parasites, pathogens and heightened stressors worldwide. Some beekeepers in this country and the United States face a loss over winter of up to 60 per cent of their colonies.

“Our study suggests some combinations are occurring very frequently,” adds Zayed, “and that is relevant because we see them again and again, but we don’t know how these combinations affect bee health. It helps to prioritize which experiments we can now take back to the lab and establish how these interactions affect bees.”



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First evidence of human occupation in lava tube cave in Saudi Arabia

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New tool activates deep brain neurons by combining ultrasound, genetics: It is the first work to show that sonothermogenetics can control behavior by stimulating a specific target deep in the brain


Recent strides in interdisciplinary archaeological research in Arabia have unveiled new insights into the evolution and historical development of regional human populations, as well as the dynamic patterns of cultural change, migration, and adaptation to environmental fluctuations.

Despite the challenges posed by limited preservation of archaeological assemblages and organic remains in arid environments, these discoveries are reshaping our understanding of the region’s rich cultural heritage.

One such breakthrough led by Griffith University’s Australian Research Centre for Human Evolution (ARCHE), in collaboration with international partners, comes from the exploration of underground settings, including caves and lava tubes, which have remained largely untapped reservoirs of archaeological abundance in Arabia.

Through meticulous excavation and analysis, researchers have uncovered a wealth of evidence at Umm Jirsan, spanning from the Neolithic to the Chalcolithic/Bronze Age periods (~10,000-3,500 years ago).

“Our findings at Umm Jirsan provide a rare glimpse into the lives of ancient peoples in Arabia, revealing repeated phases of human occupation and shedding light on the pastoralist activities that once thrived in this landscape,” said Dr Mathew Stewart, the lead researcher and a Research Fellow at ARCHE.

“This site likely served as a crucial waypoint along pastoral routes, linking key oases and facilitating cultural exchange and trade.”

Rock art and faunal records attest to the pastoralist use of the lava tube and surrounding areas, painting a vivid picture of ancient lifeways.

Depictions of cattle, sheep, goat and dogs corroborate the prehistoric livestock practices and herd composition of the region.

Isotopic analysis of animal remains indicates that livestock primarily grazed on wild grasses and shrubs, while humans maintained a diet rich in protein, with a notable increase in the consumption of C3 plants over time, suggesting the emergence of oasis agriculture.

“While underground localities are globally significant in archaeology and Quaternary science, our research represents the first comprehensive study of its kind in Saudi Arabia,” added Professor Michael Petraglia, Director of ARCHE.

“These findings underscore the immense potential for interdisciplinary investigations in caves and lava tubes, offering a unique window into Arabia’s ancient past.”

The research at Umm Jirsan underscores the importance of collaborative, multidisciplinary approaches to archaeological inquiry and highlights the significance of Arabia’s archaeological heritage on the global stage.

Researchers involved in this study work in close partnership with the Heritage Commission, Saudi Ministry of Culture, and the Saudi Geological Survey. Additional partners include King Saud University and key institutions in the UK, the USA, and Germany.



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