They got more than me! The brain circuit for socially subjective reward valuation

Researchers from the National Institute for Physiological Sciences (NIPS) identify an important brain circuit for determining the value of your own reward in relation to others' rewards.

Although you might never have consciously considered it, it's very likely that when you receive a reward, part of the value that you place on it depends on what other people have received as similar rewards. In a recent study published in Nature Communications, Japanese researchers have identified an important brain circuit for this specific process. Although researchers have identified the brain regions that are important for deciding the value of a reward in relation to those of others (a process the authors termed 'socially subjective reward valuation'), the connections between these regions have never been tested experimentally. The research team from the National Institute for Physiological Sciences (NIPS) decided to create a temporary disconnect between the medial prefrontal cortex, which is part of the social brain network, and the lateral hypothalamus, which is involved in social reward valuation. "We used a relatively new technique that is commonly known as DREADD, or 'designer receptor exclusively activated by designer drug', in macaque monkeys," says senior author of the study Masaki Isoda. "This method allowed us to temporarily block most of the connections from the brain's medial prefrontal cortex to the lateral hypothalamus."

To test the effects of functionally disconnecting two regions of the monkeys' brains responsible for socially subjective reward valuation, the researchers used an existing experimental setup. Two monkeys were sat together and shown pictures on a screen. After seeing each picture, only one of the monkeys (or sometimes neither of the monkeys) received water as a reward. By varying the probability of reward for each monkey over a series of tests, the researchers were able to see what happened when the monkeys expected a reward for themselves (they made many licking motions with their tongues) versus a reward for the other monkey (they made fewer licking motions).

"Using this test, we were able to see the effects of disconnecting the medial prefrontal cortex from the lateral hypothalamus on the monkeys' expectations of rewards," says Isoda. "We were excited to see that, with this disconnect, the monkeys were much less susceptible to the prospect of others receiving rewards, but that their own expectations of a reward did not change, suggesting that this pathway is a key circuit in socially subjective reward valuation only."

Together with recent research suggesting that the medial prefrontal cortex/lateral hypothalamus circuit is crucial for social rank information in mice, these results indicate that this circuit underlies many important social behaviors. A better understanding of this pathway will aid in the clinical diagnosis and treatment of injuries or alterations to the medial prefrontal cortex and lateral hypothalamus.

Source: ScienceDaily

Modified virtual reality tech can measure brain activity

 Researchers have modified a commercial virtual reality headset, giving it the ability to measure brain activity and examine how we react to hints, stressors and other outside forces.

The research team at The University of Texas at Austin created a noninvasive electroencephalogram (EEG) sensor that they installed in a Meta VR headset that can be worn comfortably for long periods. The EEG measures the brain's electrical activity during the immersive VR interactions.

The device could be used in many ways, from helping people with anxiety, to measuring the attention or mental stress of aviators using a flight simulator, to giving a human the chance to see through the eyes of a robot.

"Virtual reality is so much more immersive than just doing something on a big screen," said Nanshu Lu, a professor in the Cockrell School of Engineering's Department of Aerospace Engineering and Engineering Mechanics who led the research. "It gives the user a more realistic experience, and our technology enables us to get better measurements of how the brain is reacting to that environment."

The research is published in Soft Science.

The pairing of VR and EEG sensors has made its way into the commercial sphere already. However, the devices that exist today are costly, and the researchers say their electrodes are more comfortable for the user, extending the potential wearing time and opening up additional applications.

The best EEG devices today consist of a cap covered in electrodes, but that does not work well with the VR headset. And individual electrodes struggle to get a strong reading because our hair blocks them from connecting with the scalp. The most popular electrodes are rigid and comb-shaped, inserting through the hairs to connect with the skin, an uncomfortable experience for the user.

"All of these mainstream options have significant flaws that we tried to overcome with our system," said Hongbian Li, a research associate in Lu's lab.

For this project, the researchers created a spongy electrode made of soft, conductive materials that overcome those issues, an effort led by Li. The modified headset features electrodes across the top strap and forehead pad, a flexible circuit with conductive traces similar to Lu's electronic tattoos, and an EEG recording device attached to the back of the headset.

This technology will play into another major research project at UT Austin: A new robot delivery network that will also serve as the largest study to date on human-robot interactions.

Lu is a part of that project, and the VR headsets will be used by people either traveling with robots or in a remote "observatory." They will be able to watch along from the robot's perspective, and the device will also measure the mental load of this observation for long periods.

"If you can see through the eyes of the robot, it paints a clearer picture of how people are reacting to it and lets operators monitor their safety in case of potential accidents," said Luis Sentis, a professor in the Department of Aerospace Engineering and Engineering Mechanics who is co-leading the robot delivery project and is a co-author on the VR EEG paper.

To test the viability of the VR EEG headset, the researchers created a game. They worked with José del R. Millán, a faculty member in the Chandra Family Department of Electrical and Computer Engineering and the Dell Medical School and an expert in brain-machine interfaces, to develop a driving simulation that has the user press a button to react to turn commands.

The EEG measures the brain activity of the users as they make driving decisions. In this case, it shows how closely the subjects are paying attention.

The researchers have filed preliminary patent paperwork for the EEG, and they're open to partner with VR companies to create a built-in version of the technology.

Source: ScienceDaily

Astronomers shed new light on formation of mysterious fast radio bursts

 More than 15 years after the discovery of fast radio bursts (FRBs) -- millisecond-long, deep-space cosmic explosions of electromagnetic radiation -- astronomers worldwide have been combing the universe to uncover clues about how and why they form.

Nearly all FRBs identified have originated in deep space outside our Milky Way galaxy. That is until April 2020, when the first Galactic FRB, named FRB 20200428, was detected. This FRB was produced by a magnetar (SGR J1935+2154), a dense, city-sized neutron star with an incredibly powerful magnetic field.

This groundbreaking discovery led some to believe that FRBs identified at cosmological distances outside our galaxy may also be produced by magnetars. However, the smoking gun for such a scenario, a rotation period due to the spin of the magnetar, has so far escaped detection. New research into SGR J1935+2154 sheds light on this curious discrepancy.

In the July 28 issue of the journal Science Advances, an international team of scientists, including UNLV astrophysicist Bing Zhang, report on continued monitoring of SGR J1935+2154 following the April 2020 FRB, and the discovery of another cosmological phenomenon known as a radio pulsar phase five months later.

Unraveling a Cosmological Conundrum

To aid them in their quest for answers, astronomers rely in part on powerful radio telescopes like the massive Five-hundred-meter Aperture Spherical radio Telescope (FAST) in China to track FRBs and other deep-space activity. Using FAST, astronomers observed that FRB 20200428 and the later pulsar phase originated from different regions within the scope of the magnetar, which hints towards different origins.

"FAST detected 795 pulses in 16.5 hours over 13 days from the source," said Weiwei Zhu, lead author of the paper from National Astronomical Observatory of China (NAOC). "These pulses show different observational properties from the bursts observed from the source."

This dichotomy in emission modes from the region of a magnetosphere helps astronomers understand how -- and where -- FRBs and related phenomena occur within our galaxy and perhaps also those at further cosmological distances.

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Tau-regulating protein identified as a promising target for developing Alzheimer's disease treatment

 A gene encoding a protein linked to tau production -- tripartite motif protein 11 (TRIM11) -- was found to suppress deterioration in small animal models of neurodegenerative diseases similar to Alzheimer's disease (AD), while improving cognitive and motor abilities, according to new research from the Perelman School of Medicine at the University of Pennsylvania. Additionally, TRIM11 was identified as playing a key role in removing the protein tangles that cause neurodegenerative diseases, like AD. The findings are published today in Science.

AD is the most common cause of dementia in older adults, with an estimated 6 million Americans currently living with the disease. It is a progressive brain disorder that slowly destroys memory and thinking skills. Foundational research at Penn Medicine led by Virginia M.Y. Lee, PhD, the John H. Ware III Professor in Alzheimer's Research in Pathology and Laboratory Medicine, and the late John Q. Trojanowski, MD, PhD, a former professor of Geriatric Medicine and Gerontology in Pathology and Laboratory Medicine, reveals that one of the underlying causes of neurodegenerative diseases is neurofibrillary tangles (NFTs) of tau proteins, which cause the death of neurons, leading to the symptoms of AD, like loss of memory.

In addition to AD, aggregation of tau proteins into NFTs is associated with over 20 other dementias and movement disorders including progressive supranuclear palsy, Pick's disease, and chronic traumatic encephalopathy, collectively known as tauopathies. Nevertheless, how and why tau proteins clump together and form the fibrillar aggregates that make up NFTs in patients with these diseases remains unclear. This major gap in knowledge has made the development of effective therapies challenging for researchers.

"Most organisms have protein quality control systems that remove defective proteins, and prevent the mis-folding and accumulation of tangles -- like the ones we see with tau proteins in the brain of those with taupathies -- but until now we didn't know how this works in humans, or why it malfunctions in some individuals and not others," said senior author, Xiaolu Yang, PhD, a professor of Cancer Biology at Penn. "For the first time, we have identified the gene that oversees tau function, and have a promising target for developing treatments to prevent and slow the progression of Alzheimer's disease and other related disorders."

Yang and his team, including first author Zi-Yang Zhang, PhD, a postdoctoral researcher in Yang's lab, previously found that TRIM proteins play an important role in protein quality control in animal cells. After examining over 70 human TRIMs, they found that TRIM11 has a major role in suppressing tau aggregation. TRIM11 possesses three main functions related to the quality control of tau proteins. First, it binds to tau proteins, especially the mutant variants that cause disease, and helps eliminate them. Second, it acts as a "chaperone" for tau, preventing the proteins from mis-folding. Finally, TRIM11 dissolves pre-existing tau aggregates.

Using postmortem brain tissues of 23 individuals with AD and 14 health controls from the Center for Neurodegenerative Disease Research tissue bank -- created and maintained by Lee and Trojanowski -- researchers validated these findings, and found that levels of TRIM11 protein are substantially reduced in the brains of individuals with AD, compared to healthy control individuals.

To determine the potential utility of TRIM11 as a therapeutic agent, researchers used adeno-associated viral vector (AAV), a tool commonly used in gene therapy, to deliver the TRIM11 gene into the brain of multiple mouse models. Researchers found that mice with tau pathologies receiving the TRIM11 gene exhibited a marked decrease in the development and accumulation of NFTs, and had much improved cognitive and motor abilities.

"Not only do these findings tell us that TRIM11 could play an important role in protecting people from Alzheimer's and similar diseases, but we also see that we might be able to develop future therapies that replenish TRIM11 in individuals with lower levels," said Yang. "We are eager to work with our colleagues to explore the possibility of developing gene therapies that halt the progression of neurodegenerative disease."

This study was supported by the National Institutes of Health (R01CA243520, UL1TR000003) and funding received by Penn under a sponsored research agreement with Wealth Strategy Holding Limited.

Note:Yang is an inventor on patents and patent applications owned by the University of Pennsylvania related to TRIM proteins, and is a co-founder and equity holder of Evergreen Therapeutics LLC, which received investments from Wealth Strategy Holding Limited. Penn and Yang have either received, or may receive in the future, financial consideration related to the licensing of certain Penn intellectual property to Evergreen Therapeutics LLC.

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Researchers successfully train a machine learning model in outer space for the first time

 For the first time, a project led by the University of Oxford has trained a machine learning model in outer space, on board a satellite. This achievement could revolutionise the capabilities of remote-sensing satellites by enabling real-time monitoring and decision making for a range of applications.

Data collected by remote-sensing satellites is fundamental for many key activities, including aerial mapping, weather prediction, and monitoring deforestation. Currently, most satellites can only passively collect data, since they are not equipped to make decisions or detect changes. Instead, data has to be relayed to Earth to be processed, which typically takes several hours or even days. This limits the ability to identify and respond to rapidly emerging events, such as a natural disaster.

To overcome these restrictions, a group of researchers led by DPhil student Vít Růžička (Department of Computer Science, University of Oxford), took on the challenge of training the first machine learning program in outer space. During 2022, the team successfully pitched their idea to the Dashing through the Stars mission, which had issued an open call for project proposals to be carried out on board the ION SCV004 satellite, launched in January 2022. During the autumn of 2022, the team uplinked the code for the program to the satellite already in orbit.

The researchers trained a simple model to detect changes in cloud cover from aerial images directly onboard the satellite, in contrast to training on the ground. The model was based on an approach called few-shot learning, which enables a model to learn the most important features to look for when it has only a few samples to train from. A key advantage is that the data can be compressed into smaller representations, making the model faster and more efficient.

Vít Růžička explained: 'The model we developed, called RaVAEn, first compresses the large image files into vectors of 128 numbers. During the training phase, the model learns to keep only the informative values in this vector; the ones that relate to the change it is trying to detect (in this case, whether there is a cloud present or not). This results in extremely fast training due to having only a very small classification model to train.'

Whilst the first part of the model, to compress the newly-seen images, was trained on the ground, the second part (which decided whether the image contained clouds or not) was trained directly on the satellite.

Normally, developing a machine learning model would require several rounds of training, using the power of a cluster of linked computers. In contrast, the team's tiny model completed the training phase (using over 1300 images) in around one and a half seconds.

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New RNA-based therapy combats melanoma in mouse models

 Investigators at the Icahn School of Medicine at Mount Sinai have designed an innovative RNA-based strategy to activate dendritic cells -- which play a key role in immune response -- that eradicated tumors and prevented their recurrence in mouse models of melanoma.

The findings, which suggest that the approach has the potential to be effective against tumors that have already spread to other parts of the body and against different cancer types, were reported in the July 27 issue of Nature Nanotechnology.

Cancer cells employ strategies to switch off various stages of the cancer-immunity cycle, the process by which dendritic cells educate T cells to kill cancer cells. This immunosuppressive environment that impedes activation of cancer-killing T cells allows tumors to grow, say the researchers.

"Most approaches to boost this critical role of dendritic cells -- or adoptive cell therapies -- aim to increase the activation signals provided to dendritic cells when specific molecules on their surface bind to tumor cells. However, these have not been as successful in clinical trials as hoped. This is because tumors have a tendency to evolve in different ways to switch off each stage of the cancer-immunity cycle," says Yizhou Dong, PhD, corresponding author of the study, Professor of Oncological Sciences, and a member of the Icahn Genomics Institute and the Marc and Jennifer Lipschultz Precision Immunology Institute at Icahn Mount Sinai.

The researchers named their approach CATCH. As part of the regimen, the researchers used new types of lipid nanoparticles to deliver two mRNA therapeutics -- a process similar to that used successfully for COVID-19 vaccines -- to ensure the dendritic cells were sufficiently activated to enhance the cancer-immunity cycle in established tumors.

Using multiple bioassays to gain insights on the effects of the CATCH regimen on different types of immune cells, the researchers showed that their strategy not only reactivated the cycle but also removed obstacles at other stages. This caused a change in the tumor's microenvironment, shifting it from having cell types that weaken T cells' ability to fight cancer to having cell types that actually support and enhance their ability to fight tumors.

Beyond the positive findings in mouse models of melanoma, the researchers conducted further tests to evaluate the effectiveness of the CATCH regimen in restarting the cancer immunity cycle more broadly. Their investigations revealed encouraging results, as the regimen reduced tumors in mouse models of B cell lymphoma by 83 percent. They also tested it in mouse models of breast cancer, where approximately half of the mice favorably responded.

Next, the researchers plan feasibility and safety testing for using the CATCH regimen in early-phase clinical trials for patients.

"Dendritic cells have been a key focus for the development of new cancer therapies as these cells organize the cancer-immunity cycle. In theory, the CATCH regimen using this particular RNA-based technology has the potential to provide a much more effective approach for using dendritic cells for cancer immunotherapy to treat a wide range of solid tumors," says Brian Brown, PhD, Director of the Icahn Genomics Institute and Associate Director of the Marc and Jennifer Lipschultz Precision Immunology Institute at Icahn Mount Sinai.

The study was funded in part by National Cancer Institute grant P30 CA016058 and National Institute of General Medical Sciences grant R35GM144117.

sources-science daily

What these scientists learned from offering genetic screening to 13,000 Oregonians for free

 Early genetic testing can improve cancer outcomes, but individuals often don't undergo this screening if they lack a family history or can't afford a test. A clinical laboratory team at Oregon Health & Science University is hoping to change that for residents of their state by providing free genetic screening for inherited cancer and familial hypercholesteremia to all adults with an Oregon address. After screening over 13,000 Oregonians since 2018, the team presents their methods, findings, and lessons learned on July 27 in The American Journal of Human Genetics.

"We're hoping that this can really be used as a model for other states that want to do low-cost population screening," says first author Timothy O'Brien, a staff scientist at Knight Diagnostic Laboratories. "We've provided a kind of roadmap where up-and-coming screening programs can look at us and see both what worked and what could be improved upon."

The team recruited participants through social media ads and tabling at events like farmers markets. They even set up vending machines where individuals could retrieve and return testing kits that collected a mouthwash saliva sample. After the onset of the COVID-19 pandemic, individuals could request a testing kit through the mail. Once participants gave their consent through a HIPAA-compliant app, samples were processed at a clinical laboratory to screen for disease-causing variants in 31 genes related to inherited cancer and 1 gene related to familial hypercholesteremia.

"We wanted to report on any disease-causing variant that was deemed to be actionable, which means there's something you can do about it," says senior author Sue Richards, a Professor Emeritus of Molecular & Medical Genetics at Oregon Health & Science University. "It could be something like changing your screening habits, taking a prophylactic surgery or medication, or consulting with your clinician."

710 out of over 13,000 participants screened positive for a disease-causing variant. All participants with confirmed positive results received a call from a genetic counselor to explain their results, how the results impact their disease risk, and recommendations for medical management. "Genetic counseling is critical to this program," says Richards. "It's not easy for the public to understand these genetic testing reports because they're fairly technical, and it's important to understand that just because they carry a disease-causing variant may not mean that they will develop that type of cancer. The counselor also talks to them not only about their own health and family history but also how they pass that information along to other family members, since they are at risk of having the variant as well."

When the laboratory team first started this project, they had to scale up the lab's genetic testing workflow to about ten times its original capacity by focusing on a select group of disease-causing variants and employing the help of robots, which performed more tedious tasks. This allowed the group to process up to 1,000 samples per month with one lab technologist at the estimated cost of $50 per participant. To reduce the possibility of a laboratory mix-up resulting in a false positive, all participants with positive results were asked to undergo secondary screening using a different genetic sequencing method. Even so, the researchers report zero clinically relevant sample mix-ups out of the 20,000 specimens that they sequenced.

From their sequencing results, the researchers have also assembled a large repository of data that can be used to analyze the genetic risk factors of Oregon's population and conduct additional research studies. Approximately 5% of participants screened positive for a disease-causing inherited cancer variant, which was higher than several prior population-screening studies have reported and may be because people with a personal or family history of cancer were more likely to seek testing.

This higher-than-expected prevalence could also be because prior studies screened for a different set of genes. The American College of Medical Genetics and Genomics (ACMG) details a minimum set of genes not related to the individual's condition but recommended to analyze in those undergoing clinical testing. However, if the researchers had only examined genes from this list, they would have missed 59% of disease-causing variants in their study population. In addition, the most common disease-causing variants detected in the study were not on ACMG's list. This highlights how expanding the range of genes being tested can have a significant impact on how many people receive positive results in large screening studies.

The team plans on continuing their screening program in the future and increasing efforts to reach a more diverse population of participants. Currently, 76% of study participants are female, so the study is looking at how to recruit more male participants. In addition, by translating their consent app into Spanish, the researchers plan on reaching more of Oregon's Spanish-speaking population.

"The overall goal of this project was really to help Oregonians and empower them with this health information," says O'Brien. "We feel like we've been able to accomplish that and hope that this continues to be a strong proponent of health for Oregonians in the future."

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