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Holographic acoustic device precisely targets diseased neurons in brain

Researchers at Washington University in St. Louis have developed a noninvasive technology to treat human brain diseases, such as Parkinson’s disease, that simultaneously involve damage in various regions of the brain. The holographic acoustic device, combined with genetic engineering, precisely targets affected neurons in selected cell types at multiple diseased brain regions.

Hong Chen, associate professor of biomedical engineering in the McKelvey School of Engineering and of neurosurgery in the School of Medicine, and her team created the noninvasive “AhSonogenetic” device to alter genetically selected neurons in the brains of mice. The results of the study were published June 17 in the journal Proceedings of the National Academy of Sciences

Multiple technologies

AhSonogenetics combines several of Chen’s group’s recent advances. In 2021, she and her team launched Sonogenetics, a method that uses focused ultrasound to deliver a viral construct containing ultrasound-sensitive ion channels to genetically selected neurons in the brain. They use non-invasive low-intensity focused ultrasound to deliver a small burst of warmth, which opens ion channels and activates the neurons. Chen’s team was the first to show that sonogenetics could modulate the behavior of freely moving mice.

In 2022, the team designed and 3D-printed a flexible and versatile tool known as an Airy beam-enabled binary acoustic metasurface, which allowed them to manipulate ultrasound beams. She is currently developing Sonogenetics 2.0, which combines the advantage of ultrasound and genetic engineering to modulate defined neurons noninvasively and precisely in the brains of humans and animals. AhSonogenetics brings them together as a potential method to intervene in neurodegenerative diseases.

Sonogenetics gives researchers a way to precisely control brains, while airy-beam technology allows researchers to bend or steer the sound waves to generate arbitrary beam patterns inside the brain at high spatial resolution.

Treating Parkinson’s disease

Chen’s team tested the technique on a mouse model of Parkinson’s disease. With AhSonogenetics, they were able to stimulate two brain regions simultaneously in a single mouse, eliminating the need for multiple implants or interventions. This stimulation alleviated Parkinson’s-related motor deficits in the mouse model, including slow movements, difficulty walking and freezing behaviors.

The device, which costs roughly $50 to make, can be tailored in size to fit various brain sizes, expanding its potential applications. The design file for the Airy-beam holographic transducer is available on GitHub: https://github.com/ChenUltrasoundLabWUSTL/AiryBeam_Lens_Design. Funding was provided by the National Institutes of Health.

Citation: CitHu Z, Yang Y, Gong Y, Chukwu C, Ye D, Yue Y, Yuan J, Kravitz AV, Chen H. Airy-beam holographic sonogenetics for advancing neuromodulation precision and flexibility. Proceedings of the National Academy of Sciences June 17, 2024. DOI. 10.1073/pnas.2402200121 (open access)

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Amber-like polymer allows for long-term storage of DNA and digital files

MIT researchers have developed a glassy, amber-like polymer that can be used for long-term storage of DNA, including entire human genomes or digital files such as photos. 

“The rapid decline in DNA sequencing costs has fueled the demand for nucleic acid collection to unravel genomic information, develop treatments for genetic diseases, and track emerging biological threats,” the researchers say.

Most current methods for storing DNA require expensive freezing temperatures and are not feasible in many parts of the world. The new polymer can store DNA at room temperature while protecting the molecules from damage caused by heat or water. 

“Freezing DNA is the number one way to preserve it, but it’s very expensive, and it’s not scalable,” says James Banal, a former MIT postdoc. “I think our new preservation method is going to be a technology that may drive the future of storing digital information on DNA.”

The researchers showed that they could use this polymer to store DNA sequences and that the DNA can be easily removed from the polymer without damaging it.

Banal and Jeremiah Johnson, the A. Thomas Geurtin Professor of Chemistry at MIT, are the senior authors of the study, published in the Journal of the American Chemical Society.

Capturing DNA

DNA offers a way to store this digital information at very high density: a coffee mug full of DNA could store all of the world’s data. DNA is also very stable and relatively easy to synthesize and sequence.

The researchers decided to make a thermoset polymer from styrene and a cross-linker, which form an amber-like thermoset called “cross-linked polystyrene.” This thermoset is also very hydrophobic, so it can prevent moisture from getting in and damaging the DNA.

“Inspired by the millennia-long preservation of fossilized biological specimens in calcified minerals or glassy amber, we present Thermoset-REinforced Xeropreservation (T-REX): a method for storing DNA in deconstructable glassy polymer networks,” say the researchers.

Storing information

Using these polymers, the researchers showed that they could encapsulate DNA of varying length, from tens of nucleotides up to an entire human genome (more than 50,000 base pairs). After storing the DNA and then removing it, the researchers sequenced it and found that no errors had been introduced, which is a critical feature of any digital data storage system.

The researchers also showed that the thermoset polymer can protect DNA from temperatures up to 75 degrees Celsius (167 degrees Fahrenheit). They are now working on ways to streamline the process of making the polymers and forming them into capsules for long-term storage.

Storing genomes

The earliest application they envision is storing genomes for personalized medicine, and they also anticipate that these stored genomes could undergo further analysis as better technology is developed in the future. 

The research was funded by the National Science Foundation.

Citation: Elisabeth Prince, Ho Fung Cheng, James L. Banal, and Jeremiah A. Johnson. Reversible Nucleic Acid Storage in Deconstructable Glassy Polymer Networks, Journal of the American Chemical Society. 10.1021/jacs.4c01925

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AI-powered exoskeleton helps restore mobility immediately

Researchers have used AI and computer simulations to train robotic exoskeletons, which can help users save energy while walking, running, and climbing stairs.

As described in the journal Nature, the novel method customizes exoskeleton controllers to assist locomotion for elderly or stroke survivors without relying on lengthy human-involved experiments in a clinic.

“It can also apply to knee or ankle exoskeletons or other multi-joint exoskeletons,” said Xianlian Zhou, associate professor and director at New Jersey Institute of Technology’s BioDynamics Lab, in a statement. “It can be used in above-the-knee or below-the-knee prostheses, providing immediate benefits for millions of able-bodied and mobility-impaired individuals.”

No user training

Previously, patients had to spend hours “training” an exoskeleton so the technology knew how much force was needed (and where and when to apply it). The new method allows someone to use the exoskeleton immediately. The closed-loop simulation incorporates exoskeleton controller and physics models of musculoskeletal dynamics, human-robot interaction, and muscle reactions.

This research was supported by the National Science Foundation, the National Institutes of Health, and the National Institute on Disability, Independent Living, and Rehabilitation Research.

Citation: Luo, S., Jiang, M., Zhang, S., Zhu, J., Yu, S., Dominguez Silva, I., Wang, T., Rouse, E., Zhou, B., Yuk, H., Zhou, X., & Su, H. (2024). Experiment-free exoskeleton assistance via learning in simulation. Nature, 630(8016), 353-359. 10.1038/s41586-024-07382-4

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How to create ‘wired miniature brains’

Researchers at the University of California San Diego have created highly realistic brain cortical organoids—miniature artificial brains with functioning neural networks.

The new technique, published in Nature Protocols, will enable scientists to perform more advanced research, according to Alysson Muotri, senior author and director of the UC San Diego Sanford Stem Cell Institute (SSCI) Integrated Space Stem Cell Orbital Research Center, in a statement.

Neurological disorders

The new research ranges from autism to schizophrenia (and other neurological disorders in which electrical activity is altered), testing potentially therapeutic drugs and gene therapies before patient use and screening for efficacy and side effects.

Previous methods of creating brain organoids have not enabled researchers to study the brain’s electrical activity, says Muotri. The new method enables researchers to study neural networks created from the stem cells of patients with various neurodevelopmental conditions. These new tiny replicas of the human brain are so realistic they rival “the complexity of the fetal brain’s neural network,” he said.

Organoids in space

Muotri and researchers at the Federal University of Amazonas in Manaus, Amazonas, Brazil, are also teaming up to record and investigate Amazonian tribal remedies for Alzheimer’s disease.

In March, Muotri—in partnership with NASA—sent brain organoids to space. The organoids were made from the stem cells of patients with Alzheimer’s disease and ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease). The payload was returned in May 2024 for testing.

Microgravity

Using microgravity (experienced by astronauts in space) the researchers plan to mimic an accelerated version of Earth-based aging, allowing the researchers to witness the effects of several years of disease progression while studying the month-long mission’s payload, including potential changes in protein production, signaling pathways, oxidative stress and epigenetics. Other research possibilities for the brain organoids include disease modeling and understanding human consciousness, says Muotri.

This work was supported by the National Institutes of Health, California Institute for Regenerative Medicine (CIRM), a grant from the Department of Defense, and a “Humans in Space” grant by Boryung in Korea.

Citation: Fitzgerald, M. Q., Chu, T., Puppo, F., Blanch, R., Chillón, M., Subramaniam, S., & Muotri, A. R. (2024). Generation of “semi-guided” cortical organoids with complex neural oscillations. Nature Protocols, 1-27. https://doi.org/10.1038/s41596-024-00994-0

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Good global-warming news

A new study published in the journal Nature Climate Change has revealed “significant progress” in reducing levels in the atmosphere of chemicals that destroy Earth’s protective ozone layer.

Decline of harmful hydrochlorofluorocarbons (HCFCs)

The findings show, for the first time, a notable decline in the atmospheric levels of potent “ozone-depleting substances” (ODS) called hydrochlorofluorocarbons (HCFCs). These are harmful greenhouse gases, so a reduction should also lessen global warming.

The Montreal Protocol introduced controls on the production and usage of ODS, which were once widely used in manufacturing hundreds of products, including refrigerators, aerosol sprays, foams and packaging. HCFCs were developed as replacements for chlorofluorocarbons (CFCs) and CFC production has been banned globally since 2010.

Replacement with non-ozone-depleting compounds

According to lead author Luke Western, Marie Curie Research Fellow at the University of Bristol’s School of Chemistry, “production of HCFCs is currently being phased out globally, with a completion date slated for 2040. These are being replaced by non-ozone-depleting hydrofluorocarbons (HFCs) and other compounds. By enforcing strict controls and promoting the adoption of ozone-friendly alternatives, the protocol has successfully curbed the release and levels of HCFCs into the atmosphere.”

The results rely on high-precision measurements at globally distributed atmospheric observatories, using data from the Advanced Global Atmospheric Gases Experiment (AGAGE) and the National Atmospheric and Oceanic Administration (NOAA).

Two forms of ozone

The good: In the atmosphere, good O3 (ozone) protects us from the sun’s harmful UV rays. The famous hole in the ozone layer was created by the use of CFCs. These are now banned, so the hole is shrinking.

The bad: At ground level in urban environments, bad O3 (in the form of photochemical smog) is created by the reaction of urban pollution and sunlight. It becomes a powerful urban pollutant with negative health effects, as noted in What’s Worse Than Global Warming?

Citation: Western, L. M., Daniel, J. S., Vollmer, M. K., Clingan, S., Crotwell, M., Fraser, P. J., Ganesan, A. L., Hall, B., Harth, C. M., Krummel, P. B., Mühle, J., Salameh, P. K., Stanley, K. M., Reimann, S., Vimont, I., Young, D., Rigby, M., Weiss, R. F., Prinn, R. G., . . . Montzka, S. A. (2024). A decrease in radiative forcing and equivalent effective chlorine from hydrochlorofluorocarbons. Nature Climate Change, 1-3. https://doi.org/10.1038/s41558-024-02038-7

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Sugar substitute xylitol linked to increased risk of heart attack and stroke

Cleveland Clinic researchers have found higher amounts of the sugar alcohol xylitol are associated with an increased risk of cardiovascular events like heart attack and stroke.  

The team, led by Stanley Hazen, M.D., Ph.D., found an association in a large-scale patient analysis, preclinical research models and a clinical intervention study. Findings were published in the European Heart Journal.   

Xylitol is a common sugar substitute used in sugar-free candy, gums, baked goods and oral products like toothpaste. Over the past decade, the use of sugar substitutes has increased significantly in processed foods that are promoted as healthy alternatives, said Hazen in a statement.

Investigating sugar alcohols and artificial sweeteners

“This study again shows the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combatting conditions like obesity or diabetes,” said Dr. Hazen, Chair of Cardiovascular and Metabolic Sciences at Cleveland Clinic’s Lerner Research Institute and Co-Section Head of Preventive Cardiology in the Heart, Vascular & Thoracic Institute.

Xylitol is a sugar substitute commonly used in sugar-free candy, gums, baked goods, and oral products like toothpaste. The use of sugar substitutes has increased significantly in processed foods as these products have been promoted as healthier alternatives to sugar.

Research limitation: association, not causation

The authors note that further studies assessing the long-term cardiovascular safety of xylitol are warranted. The research had several limitations, including the fact that the studies demonstrate association and not causation. They recommend talking to your doctor or a certified dietitian to learn more about healthy food choices and for personalized recommendations.   

The study was partly supported by the National Institutes of Health and the Office of Dietary Supplements.

Citation: Marco Witkowski, Ina Nemet, Xinmin S Li, Jennifer Wilcox, Marc Ferrell, Hassan Alamri, Nilaksh Gupta, Zeneng Wang, Wai Hong Wilson Tang, Stanley L Hazen, Xylitol is prothrombotic and associated with cardiovascular risk, European Heart Journal, 2024, ehae244, https://doi.org/10.1093/eurheartj/ehae244

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AI-powered tool lets scientists rapidly analyze complex biological images

Scientists at Chan Zuckerberg Biohub San Francisco (CZ Biohub SF) have developed Omega, an open-source software tool that significantly advances the bioimage analysis field, according to the scientists.

Omega is integrated into large language models (LLMs), such as OpenAI’s ChatGPT, enabling scientists to process and analyze biological images using natural language conversations, rather than issuing formal commands or writing code.

Omega was created by Loïc A. Royer and his team, and documented in a paper published June 10, 2024 in Nature Methods.

A plug-in for napari, Omega is an open-source image viewer used worldwide in diverse scientific fields, especially in biomedical research. “Omega allows users to quickly generate and edit code to solve complex image processing tasks,” explained Royer, a senior group leader and director of imaging AI at CZ Biohub SF.

In this example, the user asks Omega to z-project 3D images.

Omega’s collaborative features include:

  • Interactive image analysis: Users can instruct Omega to perform specific tasks, such as segmenting cell nuclei, counting objects, and generating detailed reports, all through simple conversational prompts.
  • On-demand widget creation: Omega can create custom widgets tailored to user-defined tasks, facilitating specialized image filtering, transformations, and visualizations.
  • An AI-augmented code editor: Omega includes an intelligent code editor that enhances code management with automatic commenting, error detection, and correction features.
  • Multimodal capabilities: Beyond text, Omega can interpret visual data, integrating multiple data types to provide comprehensive

Scientific community members are already using Omega, which has been available for download from a GitHub repository since May 2023. Royer said regular updates have been posted since then.

Omega source code: GitHub repository.

Citation: Royer, L. A. (2024). Omega—Harnessing the power of large language models for bioimage analysis. Nature Methods, 1-3. https://doi.org/10.1038/s41592-024-02310-w

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Are you ready for embodiment with a bionic tool?

To explore this idea, researchers used virtual reality to test whether humans can feel embodiment in prosthetic “hands” resembling a pair of tweezers.

In the journal iScience, they report that participants felt an equal degree of embodiment with tweezer hands. They were also faster and more accurate in completing motor tasks in virtual reality than when they were equipped with a virtual human hand.

Merging with tools

“For our biology to merge seamlessly with tools, we need to feel that the tools are part of our body,” says first author and cognitive neuroscientist Ottavia Maddaluno in a statement.

“Our findings demonstrate that humans can experience a grafted tool as an integral part of their own body.” Maddaluno and a team conducted the work at the Sapienza University of Rome and the Santa Lucia Foundation IRCCS.

Tweezers vs. native hand

To investigate this possibility, the researchers conducted a series of experiments in VR with healthy participants. They had either a human-like hand or a “bionic tool” resembling a large pair of tweezers grafted onto the end of their wrist.

For example, participants were asked to pop bubbles of a specific color by pinching them with either their tweezers or between their index finger and thumb. Result: participants were faster and more accurate at popping virtual bubbles when they had tweezer-hands.

Next, the team used a “cross-modal congruency task” to compare implicit or unconscious embodiment for the virtual hand and bionic tool. During this test, the researchers applied small vibrations to the participants’ fingertips and asked them to identify their stimulated fingers.

At the same time, a flickering light was displayed on the virtual reality screen, either on the same finger as the tactile stimulus or on a different finger.

By comparing the participants’ accuracy and reaction times during trials with matched and mismatched stimuli, the researchers could assess how distracted they were by the visual stimulus.

Simplicity rules

There was a bigger difference between matched and mismatched trials when participants had tweezers rather than human hands, indicating that the non-anthropomorphic prosthesis resulted in an even greater sense of embodiment.

The researchers speculate that this is due to the tweezer-hands’ relative simplicity compared to a human-like hand, which might make it easy for the brain to compute and accept.

The researchers also note that this could relate to the “uncanny valley” hypothesis since the virtual human hands might have been too eerily similar yet distinct for perfect embodiment.

Robotics and prosthetic limbs

The researchers say that this study could inform robotics and prosthetic limb design. “The next step is to study if these bionic tools could be embodied in patients that have lost limbs,” says Maddaluno. “And we also want to investigate the plastic changes that this kind of bionic tool can induce in the brains of both healthy participants and amputees.”

This research was supported by the European Research Council.

Citation: Matteo Marucci et al. June 6, 2024. Rewiring the evolution of the human hand: How the embodiment of a virtual bionic tool improves behavior. iScience https://doi.org/10.1016/j.isci.2024.109937 (open access)

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What’s worse than global warming?

That’s the conclusion of a new study that finds climate change will likely generate upward spikes of ozone at ground level by 2050.

That could result in many parts of the United States (for example) falling out of compliance with air quality standards. That means increasing risks to public health, according to a statement by James East, first author of a paper on the study and a researcher at Harvard University. “Warmer temperatures are correlated with increases to ozone in polluted areas,” East said.

Higher air pollution

Ozone can naturally occur at ground level, but it’s often formed by volatile organic compounds (VOCs) interacting with nitrogen oxides (NOx)—both are air pollutants.

“That means areas that already have higher levels of air pollution of VOCs and NOx will likely see increases in ozone as average temperatures go up,” says East.

“That’s important because ground-level ozone can cause a wide array of health problems, including decreased lung function and inflammation of airways, contributing to hundreds of thousands of deaths each year.

“Even in the best-case scenario, we found that more variability in ozone levels is projected for 2050, meaning that we’d still expect to see an increase in the number of days where there is an exceptionally high increase in ozone, violating the air quality standard,” East said.

Worst-case scenario

In the worst-case scenario, the climate is highly sensitive to carbon dioxide. In that case, the study says the high end of ozone measurements would increase by more than 2.3 ppb (parts per billion). This would mean that many parts of the country would see a significant increase in the number of days when ozone levels exceed air quality standards.

“Our study finds that between 5 million and 13 million additional people will be exposed to dangerously high levels of ozone in 2050,” East says.

The paper, “Projecting Changes in the Frequency and Magnitude of Ozone Pollution Events Under Uncertain Climate Sensitivity,” is published in the open-access journal Earth’s Future.

The work was supported by the Natural Sciences and Engineering Research Council of Canada.

Citation: East, J. D., Monier, E., Saari, R. K., & Garcia-Menendez, F. (2024). Projecting Changes in the Frequency and Magnitude of Ozone Pollution Events Under Uncertain Climate Sensitivity. Earth’s Future, 12(6), e2023EF003941. https://doi.org/10.1029/2023EF003941 (open access)

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Using AI to decode dog vocalizations

Have you ever wanted to understand what your (or someone else’s) dog is trying to say to you?

University of Michigan researchers are exploring the possibilities of using AI to do just that. They are developing tools to identify whether a dog’s bark conveys playfulness or aggression. The same models can also glean other information from animal vocalizations, such as the animal’s age, breed and sex.

Models trained on human speech

The study, which was conducted in collaboration with Mexico’s National Institute of Astrophysics, Optics and Electronics (INAOE) Institute in Puebla, found that AI models originally trained on human speech can be used as a starting point to train new systems that target animal communication. 

This approach enabled the researchers to tap into robust models that form the backbone of the various voice-enabled technologies we use today, including voice-to-text and language translation.

These new models are trained to distinguish nuances in human speech, like tone, pitch and accent. They convert this information into a format that a computer can use to identify what words are being said, recognize the individual speaking, and more.

The researchers used a dataset of dog vocalizations (recorded from 74 dogs of varying breeds, ages and sex in various contexts) to modify a machine-learning and speech representation model called Wav2Vec2, which was originally trained on human speech data.

Animal welfare

According to the researchers, this study also has important implications for animal welfare. Understanding the nuances of dog vocalizations could greatly improve how humans interpret and respond to dogs’ emotional and physical needs, enhancing their care and preventing potentially dangerous situations.

Citation: Abzaliev, A., Espinosa, H. P., & Mihalcea, R. (2024). Towards Dog Bark Decoding: Leveraging Human Speech Processing for Automated Bark Classification. ArXiv. /abs/2404.18739, https://arxiv.org/abs/2404.18739 (open-access)

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