Daily Archives: 1 Apr 2021

Engineering

A Robot That Senses Hidden Objects (Engineering)

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System uses penetrative radio frequency to pinpoint items, even when they’re hidden from view.

In recent years, robots have gained artificial vision, touch, and even smell. “Researchers have been giving robots human-like perception,” says MIT Associate Professor Fadel Adib. In a new paper, Adib’s team is pushing the technology a step further. “We’re trying to give robots superhuman perception,” he says.

The researchers have developed a robot that uses radio waves, which can pass through walls, to sense occluded objects. The robot, called RF-Grasp, combines this powerful sensing with more traditional computer vision to locate and grasp items that might otherwise be blocked from view. The advance could one day streamline e-commerce fulfillment in warehouses or help a machine pluck a screwdriver from a jumbled toolkit.

The research will be presented in May at the IEEE International Conference on Robotics and Automation. The paper’s lead author is Tara Boroushaki, a research assistant in the Signal Kinetics Group at the MIT Media Lab. Her MIT co-authors include Adib, who is the director of the Signal Kinetics Group; and Alberto Rodriguez, the Class of 1957 Associate Professor in the Department of Mechanical Engineering. Other co-authors include Junshan Leng, a research engineer at Harvard University, and Ian Clester, a PhD student at Georgia Tech.

As e-commerce continues to grow, warehouse work is still usually the domain of humans, not robots, despite sometimes-dangerous working conditions. That’s in part because robots struggle to locate and grasp objects in such a crowded environment. “Perception and picking are two roadblocks in the industry today,” says Rodriguez. Using optical vision alone, robots can’t perceive the presence of an item packed away in a box or hidden behind another object on the shelf — visible light waves, of course, don’t pass through walls.

But radio waves can.

For decades, radio frequency (RF) identification has been used to track everything from library books to pets. RF identification systems have two main components: a reader and a tag. The tag is a tiny computer chip that gets attached to — or, in the case of pets, implanted in — the item to be tracked. The reader then emits an RF signal, which gets modulated by the tag and reflected back to the reader.

The reflected signal provides information about the location and identity of the tagged item. The technology has gained popularity in retail supply chains — Japan aims to use RF tracking for nearly all retail purchases in a matter of years. The researchers realized this profusion of RF could be a boon for robots, giving them another mode of perception.

“RF is such a different sensing modality than vision,” says Rodriguez. “It would be a mistake not to explore what RF can do.”

RF Grasp uses both a camera and an RF reader to find and grab tagged objects, even when they’re fully blocked from the camera’s view. It consists of a robotic arm attached to a grasping hand. The camera sits on the robot’s wrist. The RF reader stands independent of the robot and relays tracking information to the robot’s control algorithm. So, the robot is constantly collecting both RF tracking data and a visual picture of its surroundings. Integrating these two data streams into the robot’s decision making was one of the biggest challenges the researchers faced.

“The robot has to decide, at each point in time, which of these streams is more important to think about,” says Boroushaki. “It’s not just eye-hand coordination, it’s RF-eye-hand coordination. So, the problem gets very complicated.”

The robot initiates the seek-and-pluck process by pinging the target object’s RF tag for a sense of its whereabouts. “It starts by using RF to focus the attention of vision,” says Adib. “Then you use vision to navigate fine maneuvers.” The sequence is akin to hearing a siren from behind, then turning to look and get a clearer picture of the siren’s source.

With its two complementary senses, RF Grasp zeroes in on the target object. As it gets closer and even starts manipulating the item, vision, which provides much finer detail than RF, dominates the robot’s decision making.

RF Grasp proved its efficiency in a battery of tests. Compared to a similar robot equipped with only a camera, RF Grasp was able to pinpoint and grab its target object with about half as much total movement. Plus, RF Grasp displayed the unique ability to “declutter” its environment — removing packing materials and other obstacles in its way in order to access the target. Rodriguez says this demonstrates RF Grasp’s “unfair advantage” over robots without penetrative RF sensing. “It has this guidance that other systems simply don’t have.”

RF Grasp could one day perform fulfilment in packed e-commerce warehouses. Its RF sensing could even instantly verify an item’s identity without the need to manipulate the item, expose its barcode, then scan it. “RF has the potential to improve some of those limitations in industry, especially in perception and localization,” says Rodriguez.

Adib also envisions potential home applications for the robot, like locating the right Allen wrench to assemble your Ikea chair. “Or you could imagine the robot finding lost items. It’s like a super-Roomba that goes and retrieves my keys, wherever the heck I put them.”

The research is sponsored by the National Science Foundation, NTT DATA, Toppan, Toppan Forms, and the Abdul Latif Jameel Water and Food Systems Lab (J-WAFS).

Featured image: MIT researchers developed a picking robot that combines vision with radio frequency (RF) sensing to find and grasps objects, even if they’re hidden from view. The technology could aid fulfilment in e-commerce warehouses. Credits: Courtesy of the researchers

Reference: Tara Boroushaki et al., “Robotic Grasping of Fully-Occluded Objects using RF Perception”, ArXiv, 2020. Link to paper

Provided by MIT

Medicine

Diet + Exercise + Chemo = Increased Survival in Youth With Leukemia (Medicine)

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Children’s Hospital Los Angeles study finds risk of detectable cancer cells decreased by 70% after one month of treatment in patients with ALL

Overweight children and adolescents receiving chemotherapy for treatment of leukemia are less successful battling the disease compared to their lean peers. Now, research conducted at the Cancer and Blood Disease Institute at Children’s Hospital Los Angeles indicates that modest changes in diet and exercise can greatly increase survival in youth treated for acute lymphoblastic leukemia (ALL), the most common childhood cancer.

“To our knowledge, this is the first study to show that by limiting calories and increasing exercise we can make chemotherapy more effective in eliminating leukemia cells within the first month of therapy, decreasing the chances of disease relapse in children and adolescents,” says Principal Investigator Etan Orgel, MD, MS, Director of the Medical Supportive Care Service in the Cancer and Blood Disease Institute at Children’s Hospital Los Angeles. The study is published in the American Society of Hematology’s journal Blood Advances.

Youth who are obese when they begin chemotherapy are more than twice as likely to have remaining cancer cells after one month of treatment–and an increased chance of disease relapse–compared to their lean counterparts. To address this, the investigators worked with registered dietitians and physical therapists who created personalized diet and exercise plans for 40 patients between the ages of 10 and 21 with newly diagnosed leukemia.

The investigators found that patients who reduced their caloric intake by at least 10% and began a modest exercise regimen beginning at diagnosis were, on average, 70% less likely to have remaining leukemia cells in their bone marrow one month after beginning chemotherapy, compared to previously treated patients who did not participate in the diet and exercise intervention. Remaining leukemia cells, called minimal residual disease, is one of the strongest predictors of poor survival outcomes.

“This is proof of concept that it is possible to increase the effectiveness of chemotherapy without adding other medications and their potential side effects,” says Dr. Orgel, who is also an associate professor of clinical pediatrics at the Keck School of Medicine of USC. “This short-term intervention is inexpensive and easily available to providers and families everywhere.”

The investigators found that by limiting fat, patients also had decreased insulin resistance as well as increased levels of adiponectin, a metabolic hormone associated with glucose regulation. Identification of these potential biomarkers paves the way to using this intervention to impact other types of cancer.

“Changing diet and exercise made the chemotherapy work better– that’s the big news of this study. But we also need to figure out how,” says Steven Mittelman, MD, PhD, Chief of Pediatric Endocrinology at UCLA Mattel Children’s Hospital and member of UCLA’s Jonsson Comprehensive Cancer Center. “Understanding the biological changes responsible for this effect will help us make these interventions even better.” Dr. Mittelman co-led the study and was senior author on the paper.

This clinical trial, called Improving Diet and Exercise in ALL (IDEAL-1), builds on basic and preclinical research conducted for more than a decade at Children’s Hospital Los Angeles. This “bench-to-bedside and back” approach provides new insights for treating devastating diseases, like cancer. Physicians observe an unmet clinical need in their patients, collaborate with colleagues in the lab and can then deliver an intervention to the clinic to test its effectiveness.

A randomized trial is planned for later this year. Called IDEAL-2, the study will be conducted by Dr. Orgel and Dr. Mittelman through the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) consortium, headquartered at Children’s Hospital Los Angeles under the medical leadership of Alan Wayne, MD, and Deepa Bhojwani, MD.

Additional study authors include: Celia Framson, Rubi Buxton, Jonathan Tucci and David Freyer of CHLA; Jiyoon Kim and Gang Li of UCLA; Weili Sun of Janssen Pharmaceuticals; Matthew Oberley of Caris Life Sciences; and Christina Dieli-Conwright of the Dana-Farber Cancer Institute. The study was funded, in part, by the Gabrielle Angel Foundation for Cancer Research, NIH/NCI R01 CA 201444, P30 CA-16042, UL1TR000124-02, P50 CA211015, NIH/NCATS UL1TR001855 and UL1TR000130 via the SC-CTSI.

Reference: Etan Orgel, Celia Framson, Rubi Buxton, Jiyoon Kim, Gang Li, Jonathan Tucci, David R. Freyer, Weili Sun, Matthew J. Oberley, Christina Dieli-Conwright, Steven D. Mittelman; Caloric and nutrient restriction to augment chemotherapy efficacy for acute lymphoblastic leukemia: the IDEAL trial. Blood Adv 2021; 5 (7): 1853–1861. doi: https://doi.org/10.1182/bloodadvances.2020004018

Provided by Children’s Hospital Los Angeles

About Children’s Hospital Los Angeles

Founded in 1901, Children’s Hospital Los Angeles is the highest-ranked children’s hospital in California and fifth in the nation on the prestigious U.S. News & World Report Honor Roll of best children’s hospitals. U.S. News ranks Children’s Hospital Los Angeles in all 10 specialty categories. Clinical care at the hospital is led by physicians who are faculty members of the Keck School of Medicine of USC through an affiliation dating from 1932.The hospital also operates the largest pediatric residency training program at a freestanding children’s hospital in the Western United States. The Saban Research Institute of Children’s Hospital Los Angeles is home to all basic, translational, clinical and community research conducted at the hospital, allowing proven discoveries to quickly reach patients. Our mission: to create hope and build healthier futures. To learn more, follow us on Facebook, Instagram, LinkedIn, YouTube and Twitter, and visit our blog at CHLA.org/blog.

Medicine

Study Finds Why Some Cancer Drugs May be Ineffective (Medicine)

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A possible explanation for why many cancer drugs that kill tumor cells in mouse models won’t work in human trials has been found by researchers with The University of Texas Health Science Center at Houston (UTHealth) School of Biomedical Informatics and McGovern Medical School.

The research was published today in Nature Communications.

In the study, investigators reported the extensive presence of mouse viruses in patient-derived xenografts (PDX). PDX models are developed by implanting human tumor tissues in immune-deficient mice, and are commonly used to help test and develop cancer drugs.

“What we found is that when you put a human tumor in a mouse, that tumor is not the same as the tumor that was in the cancer patient,” said W. Jim Zheng, PhD, professor at the School of Biomedical Informatics and senior author on the study. “The majority of tumors we tested were compromised by mouse viruses.”

Using a data-driven approach, researchers analyzed 184 data sets generated from sequencing PDX samples. Of the 184 samples, 170 showed the presence of mouse viruses.

The infection is associated with significant changes in tumors, and Zheng says that could affect PDX as a drug testing model for humans.

“When scientists are looking for a way to kill a tumor using the PDX model, they assume the tumor in the mouse is the same as cancer patients, but they are not. It makes the results of a cancer drug look promising when you think the medication kills the tumor – but in reality, it will not work in human trial, as the medication kills the virus-compromised tumor in mouse,” Zheng said.

He hopes his findings will change researchers’ approach to find a way to kill tumor cells. 

“We all share the common goal of hoping to find a cure for cancer. There are 210 ongoing NIH-funded projects relevant to PDX models, with a combined annual fiscal year budget of over $116 million. We need to tighten up quality control and use models that are not compromised so that the treatments we give to future patients are effective,” Zheng said.

This work is a collaboration between the Texas Therapeutics Institute, Institute of Molecular Medicine (IMM) at McGovern Medical School, and the Data Science and Informatics Core for Cancer Research at the School of Biomedical Informatics.

“As a team, we synergized the strengths of McGovern Medical School’s virology research and School of Biomedical Informatics’ data analysis expertise, and it has led to the success of this project,” said Zhiqiang An, PhD, co-senior author of the study, professor and Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical School.

The study is partly supported by the Cancer Prevention and Research Institute of Texas through grant RP170668, RP150551, and RP190561; the National Institutes of Health through grants 1UL1TR003167 and R01AG066749; and the Welch Foundation AU-0042-20030616.

Other UTHealth authors on the study include Hua Xu, PhD, professor and director of the Center for Computational Biomedicine at the School of Biomedical Informatics; Xuejun Fan, MD, PhD, research scientist with Texas Therapeutics Institute and the IMM at McGovern Medical School; Jay-Jiguang Zhu, MD, PhD, professor and director of neuro-oncology at McGovern Medical School and with UTHealth Neurosciences; Tong-Ming Fu, PhD, with the Texas Therapeutic Institute and and IMM at McGovern Medical School; Jiaqian Wu, PhD, associate professor of neurosurgery at McGovern Medical School; and Ningyan Zhang, PhD, professor with the Texas Therapeutic Institute and the IMM at McGovern Medical School.

Featured image: Researchers with UTHealth have found a possible explanation for why many cancer drugs that kill tumor cells in mouse models won’t work in human trials. (Photo by Getty Images)

Provided by UTHealth

Medicine

Replacing What Was Lost: A Novel Cell Therapy for Type I Diabetes Mellitus (Medicine)

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Type I Diabetes Mellitus (T1D) is an autoimmune disorder leading to permanent loss of insulin-producing beta-cells in the pancreas. In a new study, researchers from The University of Tokyo developed a novel device for the long-term transplantation of iPSC-derived human pancreatic beta-cells.

T1D develops when autoimmune antibodies destroy pancreatic beta-cells that are responsible for the production of insulin. Insulin regulates blood glucose levels, and in the absence of it high levels of blood glucose slowly damage the kidneys, eyes and peripheral nerves. Because the body loses the ability to produce insulin over time, the current mainstay of treatment for T1D is to inject insulin. An exciting research endeavor over the past decade has been to find ways to replace lost beta-cells by means of cell therapy.

“Cell therapy is an exciting, but challenging, approach to treat type I diabetes mellitus,” says lead author of the study Professor Shoji Takeuchi. “The challenge arises from the difficulty to make large amounts of human beta-cells in a dish, and more importantly, to achieve safe and effective transplantation. In this study, we wanted to develop a novel construct that enables successful transplantation of beta-cells in the long-term.”

To achieve their goal, the researchers developed a lotus-root-shaped cell-encapsulated construct (LENCON) and packaged it with human iPSC-derived pancreatic beta-cells, which are a limitless cell source and allow for the production of any number of beta-cells. The necessity for such an encapsulation technique arises from the fact that immune cells of the recipient could destroy the newly transplanted cells. To prevent this from happening, the researchers constructed the LENCON graft with millimeter thickness. The millimeter-thick graft diameters have previously been shown to mitigate the body’s immune response to a foreign body. At millimeter thickness, oxygen and nutrients could not be supplied to the center of the cells, but by using a lotus root shape, the cells were placed only near the edge of the graft where oxygen and nutrients can diffuse sufficiently, creating an environment in which the cells could survive, even in the millimeter-thick graft.

Having designed the LENCON, the question was if it would effectively control blood glucose levels in the long-term without provoking an immune response. To address this question, the researchers transplanted the construct in immunodeficient and immunocompetent diabetic mice. The former helped investigate the efficacy of the graft on controlling blood glucose levels in the absence of an immune response, while the latter approach tackled both goals. The researchers found that LENCON was able to maintain normal blood glucose levels for more than 180 days in the former mice, and was able to be removed without adhesion after more than one year of transplantation in the latter mice.

“These are striking results that show how LENCON can successfully and safely be used in the setting of type I diabetes mellitus. Our results suggest that LENCON could offer a novel option for cell therapy for type I diabetes mellitus,” says the first author of the study Dr. Fumisato Ozawa.

The article, “Lotus-root-shaped cell-encapsulated construct as a retrieval graft for long-term transplantation of human iPSC-derived β-cells” was published in iScience at DOI: 10.1016/j.isci.2021.102309

Featured image: Researchers from The University of Tokyo develop a novel device for the safe and effective transplantation of human induced pluripotent stem cell (iPSC)-derived pancreatic beta-cells in type I diabetes mellitus © Institute of Industrial Science, the University of Tokyo

Provided by IIS University of Tokyo

Planetary Science

NASA OSIRIS-REx’s Final Asteroid Observation Run (Planetary Science)

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NASA’s OSIRIS-REx mission is on the brink of discovering the extent of the mess it made on asteroid Bennu’s surface during last fall’s sample collection event. On Apr. 7, the OSIRIS-REx spacecraft will get one last close encounter with Bennu as it performs a final flyover to capture images of the asteroid’s surface. While performing the flyover, the spacecraft will observe Bennu from a distance of about 2.3 miles (3.7 km) – the closest it’s been since the Touch-and-Go Sample Collection event on Oct. 20, 2020.

The OSIRIS-REx team decided to add this last flyover after Bennu’s surface was significantly disturbed by the sample collection event. During touchdown, the spacecraft’s sampling head sunk 1.6 feet (48.8 centimeters) into the asteroid’s surface and simultaneously fired a pressurized charge of nitrogen gas. The spacecraft’s thrusters also mobilized a substantial amount of surface material during the back-away burn. Because Bennu’s gravity is so weak, these various forces from the spacecraft had a dramatic effect on the sample site – launching many of the region’s rocks and a lot of dust in the process. This final flyby of Bennu will provide the mission team an opportunity to learn how the spacecraft’s contact with Bennu’s surface altered the sample site and the region surrounding it.

The single flyby will mimic one of the observation sequences conducted during the mission’s Detailed Survey phase in 2019. OSIRIS-REx will image Bennu for 5.9 hours, which is just over a full rotation period of the asteroid. Within this timeframe, the spacecraft’s PolyCam imager will obtain high-resolution images of Bennu’s northern and southern hemispheres and its equatorial region. The team will then compare these new images with the previous high-resolution imagery of the asteroid obtained during 2019.

Most of the spacecraft’s other science instruments will also collect data during the flyover, including the MapCam imager, the OSIRIS-REx Thermal Emission Spectrometer (OTES), the OSIRIS-REx Visible and Infrared Spectrometer (OVIRS), and the OSIRIS-REx Laser Altimeter (OLA). Exercising these instruments will give the team a chance to assess the current state of each science instrument onboard the spacecraft, as dust coated the instruments during the sample collection event. Understanding the health of the instruments is also part of NASA’s evaluation of possible extended mission opportunities after the sample is delivered to Earth.

After the Bennu flyby, it will take several days for the data from the flyover to be downlinked to Earth. Once the data are downlinked, the team will inspect the images to understand how OSIRIS-REx disturbed the asteroid’s surface material. At this point, the team will also be able to evaluate the performance of the science instruments.

The spacecraft will remain in asteroid Bennu’s vicinity until May 10, when the mission will enter its Return Cruise phase and begin its two-year journey back to Earth. As it approaches Earth, the spacecraft will jettison the Sample Return Capsule (SRC) that contains the rocks and dust collected from Bennu. The SRC will then travel through the Earth’s atmosphere and land under parachutes at the Utah Test and Training Range on Sep. 24, 2023.

Once recovered, the capsule will be transported to the curation facility at the agency’s Johnson Space Center in Houston, where the sample will be removed for distribution to laboratories worldwide, enabling scientists to study the formation of our solar system and Earth as a habitable planet.

NASA’s Goddard Space Flight Center in Greenbelt, Maryland, provides overall mission management, systems engineering, and the safety and mission assurance for OSIRIS-REx. Dante Lauretta of the University of Arizona, Tucson, is the principal investigator, and the University of Arizona also leads the science team and the mission’s science observation planning and data processing. Lockheed Martin Space in Denver built the spacecraft and provides flight operations. Goddard and KinetX Aerospace are responsible for navigating the OSIRIS-REx spacecraft. OSIRIS-REx is the third mission in NASA’s New Frontiers Program, which is managed by NASA’s Marshall Space Flight Center in Huntsville, Alabama, for the agency’s Science Mission Directorate in Washington.

Featured image: This artist’s concept shows the planned flight path of NASA’s OSIRIS-REx spacecraft during its final flyby of asteroid Bennu, which is scheduled for April 7. Credits: NASA/Goddard/University of Arizona

Provided by NASA

Medicine

U of A Team Identifies Protein That Blocks Body’s Ability to Clear Bad Cholesterol (Medicine)

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Researchers are now looking to develop a drug that will boost existing statin drugs to prevent heart disease.

A team of researchers at the University of Alberta has uncovered a long-sought link in the battle to control cholesterol and heart disease.

The protein that interferes with low-density lipoprotein (LDL) receptors that clear “bad” cholesterol from the blood was identified in findings recently published in Nature Communications by Dawei Zhang, associate professor of pediatrics in the Faculty of Medicine & Dentistry. Excess LDL cholesterol can lead to atherosclerosis—a narrowing and hardening of arteries—and ultimately, heart attack.

“We have known for many years that these receptors could be cleaved, but nobody knew which protein was responsible,” said Zhang. “There had been several attempts around the world but nobody else was successful.”

Now that the culprit has been identified, Zhang’s lab is already at work to find a drug to target the protein, allowing the receptors to clear more LDL. 

A cholesterol-reducing class of drugs called statins—Lipitor and Crestor are two well-known brand names—has been shown to reduce cardiac events by 20 to 40 per cent, but they have side-effects that mean they can’t be given in high enough doses to work for everyone. The new drug would be used in combination with statins to boost their effect, Zhang said.

A serendipitous discovery 

Zhang’s team stumbled upon the role of the protein—membrane type 1 matrix metalloproteinase—by accident while studying another protein involved in heart function. They then set out to repeat and confirm their findings in mouse, rat and human cells, working in collaboration with researchers in China and other faculty members at the U of A. Their study was funded by the Heart and Stroke Foundation of Canada and the Canadian Institutes of Health Research. Zhang is also a member of the Women and Children’s Health Research Institute.

The protein has other critical physiological functions, Zhang explained, so his lab will work to identify and focus on the specific region within the protein that acts on the LDL receptor. They are also working with a new technique to further target their potential drug so it will work only within the liver, further reducing the likelihood of unwanted side-effects. Their early results are encouraging, Zhang said.

Zhang noted the protein is also critical for cancer tumour invasion, so the team will collaborate with U of A oncology experts to learn more.

“The one protein is a shared risk factor for the two most common diseases in humans—cancer and cardiovascular disease,” he said. “We will explore whether we can target one protein to reduce the incidence of the two most common human diseases.”

Featured image: U of A researcher Dawei Zhang was part of an international team that identified the protein that interferes with the body’s ability to get rid of “bad” cholesterol, which could point the way to better treatments to prevent heart disease. (Photo: Faculty of Medicine & Dentistry)

Reference: Alabi, A., Xia, XD., Gu, HM. et al. Membrane type 1 matrix metalloproteinase promotes LDL receptor shedding and accelerates the development of atherosclerosis. Nat Commun 12, 1889 (2021). https://doi.org/10.1038/s41467-021-22167-3

Provided by University of Alberta

Neuroscience

Disrupted Biochemical Pathway in the Brain Linked to Bipolar Disorder (Neuroscience)

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Bipolar disorder affects millions of Americans, causing dramatic swings in mood and, in some people, additional effects such as memory problems.

While bipolar disorder is linked to many genes, each one making small contributions to the disease, scientists don’t know just how those genes ultimately give rise to the disorder’s effects.

However, in new research, scientists at the University of Wisconsin–Madison have found for the first time that disruptions to a particular protein called Akt can lead to the brain changes characteristic of bipolar disorder. The results offer a foundation for research into treating the often-overlooked cognitive impairments of bipolar disorder, such as memory loss, and add to a growing understanding of how the biochemistry of the brain affects health and disease.

The Cahill lab and their colleagues at Michigan State University published their findings March 24 in Neuron.

Akt is a kinase, a type of protein that adds tags of the molecule phosphate to other proteins. These phosphate tags can act as on or off switches, changing how other proteins work, ultimately influencing vital functions. In neurons, those functions can include how cells signal to one another, which can affect thinking and mood. When the Akt pathway is revved up, a lot of other proteins get phosphate tags. When it’s quieter, those phosphate tags are absent.

The researchers discovered that men with bipolar disorder have reduced activity of this pathway, known at Akt-mTOR, in a brain region crucial for attention and memory. And when the researchers disrupted the pathway in mice, the rodents developed memory problems and crucial brain connections withered away, simulating changes in humans with bipolar disorder.

“This loss of Akt pathway function in people with bipolar disorder is probably contributing to cognitive impairment,” says Michael Cahill, a professor of neuroscience in the UW–Madison School of Veterinary Medicine, who led the research. “The idea is that maybe we can target pathways like this one pharmacologically to help alleviate core symptoms of bipolar disorder.”

To assess activity of the Akt pathway, the Cahill lab acquired brain tissue samples from deceased donors who had schizophrenia, bipolar disorder without psychosis, and bipolar disorder with psychosis, as well as healthy donors. The tissue samples came from the prefrontal cortex, known to control high-level functions, which is affected by bipolar disorder and the related disorder schizophrenia.

By measuring the number and variety of phosphate tags on proteins controlled by Akt in the tissue samples, the researchers could get a sense of the overall activity of the Akt-mTOR pathway.

Although they were originally expecting to see the biggest changes in patients with schizophrenia — which has the strongest genetic links to the Akt gene among the three related disorders — the researchers found that activity of the Akt-mTOR pathway was diminished in just one group of patients: men with bipolar disorder without psychosis.

“It was very different than we thought, which is kind of a good example of how in science you don’t really know what you’re going to get,” says Cahill.

After seeing this correlation between bipolar disorder and a quieter Akt pathway, Cahill’s group then asked what effect this diminished Akt pathway would have in the brain. To answer that question, they used viruses to deliver broken Akt proteins to the prefrontal cortexes of mice. The broken Akt proteins would override working ones, gumming up the Akt pathway.

In behavioral tests, the mice with gummed up Akt pathways demonstrated memory problems, no longer exploring changes to familiar environments.

Spending a lot of time investigating objects or other features that have changed their location is “their way of telling us that they recognize something is different,” says Cahill. “That was impaired when we disrupted the Akt pathway.”

But mice with less active Akt pathways still showed typical social behaviors, suggesting that the pathway wasn’t responsible for other high-level brain functions.

When the scientists looked in the brains of mice with diminished Akt pathways, they found that the connections that neurons use to interact with other neurons, known as dendritic spines, had withered.

Dendritic spines are like intersections between the roads that information in the brain travels on. “With the number of intersections being reduced, it’s harder to get where you want to go,” Cahill says.

That disrupting the Akt pathway in mice seemed to replicate aspects of bipolar disorder that also occur in humans — memory problems, weaker neuron connections —provides the first clear link from this gene to the effects of bipolar disorder.

Yet, many questions remain. Women with bipolar disorder did not show the same changes in Akt-mTOR activity as men did. Nor did people with bipolar disorder with psychosis or those with schizophrenia, despite similar genetic links between the Akt pathway and these disorders.

Untangling these differences and fleshing out the path from genes to disease will require much more research. For instance, many other genes contribute to bipolar disorder, and those genes may play a larger role in these groups.

Going forward, Cahill’s lab plans to follow individual circuits in the brain to discover just how the Akt pathway influences memory. That additional research should help unravel some of the enduring riddles surrounding bipolar disorder and how subtle genetic changes can lead to big differences in how people experience the world.

This work was supported in part by the National Institutes of Health (grants R21MH125227 and R01MH111604).

Reference: Amanda M. Vanderplow, Andrew L. Eagle, Bailey A. Kermath, Kathryn J. Bjornson, Alfred J. Robison, Michael E. Cahill, Akt-mTOR hypoactivity in bipolar disorder gives rise to cognitive impairments associated with altered neuronal structure and function, Neuron, 2021, , ISSN 0896-6273, https://doi.org/10.1016/j.neuron.2021.03.008. (https://www.sciencedirect.com/science/article/pii/S0896627321001562)

Provided by University of Winconsin–Madison

Planetary Science

Distant Stars Spiralling Towards a Collision Give Clues to the Forces That Bind Sub-atomic Particles (Planetary Science)

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Bath space scientists have found a new way to probe the internal structure of neutron stars, giving clues about the makeup of matter at an atomic level.

Space scientists at the University of Bath have found a new way to probe the internal structure of neutron stars, giving nuclear physicists a novel tool for studying the structures that make up matter at an atomic level.

Neutron stars are dead stars that have been compressed by gravity to the size of small cities. They contain the most extreme matter in the universe, meaning they are the densest objects in existence (for comparison, if Earth were compressed to the density of a neutron star, it would measure just a few hundred meters in diameter, and all humans would fit in a teaspoon). This makes neutron stars unique natural laboratories for nuclear physicists, whose understanding of the force that binds sub-atomic particles is limited to their work on Earth-bound atomic nuclei. Studying how this force behaves under more extreme conditions offers a way to deepen their knowledge.

Step in astrophysicists, who look to distant galaxies to unravel the mysteries of physics.

In a study described in the Monthly Notices of the Royal Astronomical Society, Bath astrophysicists have found that the action of two neutron stars moving ever faster as they spiral towards a violent collision gives a clue to the composition of neutron-star material. From this information, nuclear physicists will be in a stronger position to calculate the forces that determine the structure of all matter.

Resonance

It is through the phenomenon of resonance that the Bath team has made its discovery. Resonance occurs when force is applied to an object at its natural frequency, generating a large, often catastrophic, vibrational motion. A well-known example of resonance is found when an opera singer shatters a glass by singing loudly enough at a frequency that matches the oscillation modes of the glass.

When a pair of in-spiralling neutron stars reach a state of resonance, their solid crust – which is thought to be 10-billion times stronger than steel – shatters. This results in the release of a bright burst of gamma-rays (called a Resonant Shattering Flare) that can be seen by satellites. The in-spiralling stars also release gravitational waves that can be detected by instruments on Earth. The Bath researchers found that by measuring both the flare and the gravitational-wave signal, they can calculate the ‘symmetry energy’ of the neutron star.

Symmetry energy is one of the properties of nuclear matter. It controls the ratio of the sub-atomic particles (protons and neutrons) that make up a nucleus, and how this ratio changes when subjected to the extreme densities found in neutron stars. A reading for symmetry energy would therefore give a strong indication of the makeup of neutron stars, and by extension, the processes by which all protons and neutrons couple, and the forces that determine the structure of all matter.

The researchers stress that measurements obtained by studying the resonance of neutron stars using a combination of gamma-rays and gravitational-waves would be complementary to, rather than a replacement for, the lab experiments of nuclear physicists.

“By studying neutron stars, and the cataclysmic final motions of these massive objects, we’re able to understand something about the tiny, tiny nuclei that make up extremely dense matter,” said Bath astrophysicist Dr David Tsang. “The enormous difference in scale makes this fascinating.”

Astrophysics PhD student Duncan Neill, who led the research, added: “I like that this work looks at the same thing being studied by nuclear physicists. They look at tiny particles and we astrophysicists look at objects and events from many millions of light years away. We are looking at the same thing in a completely different way.”

Dr Will Newton, astrophysicist at the Texas A&M University-Commerce and project collaborator, said: “Though the force that binds quarks into neutrons and protons is known, how it actually works when large numbers of neutrons and protons come together is not well understood. The quest to improve this understanding is helped by experimental nuclear physics data, but all the nuclei we probe on Earth have similar numbers of neutrons and protons bound together at roughly the same density.

“In neutron stars, nature provides us with a vastly different environment to explore nuclear physics: matter made mostly of neutrons and spanning a wide range of densities, up to about ten times the density of atomic nuclei. In this paper, we show how we can measure a certain property of this matter – the symmetry energy – from distances of hundreds of millions of light years away. This can shed light on the fundamental workings of nuclei.”

Featured image: The physics of massive nuclei can be studied by measuring the ‘note’ at which tidal resonance between merging neutron stars causes the solid crust of the neutron stars to shatter © University of Bath

Reference: Duncan Neill, William G Newton, David Tsang, Resonant Shattering Flares as Multimessenger Probes of the Nuclear Symmetry Energy, Monthly Notices of the Royal Astronomical Society, 2021;, stab764, https://doi.org/10.1093/mnras/stab764

Provided by University of Bath

Psychology

Mimes Help Us ‘See’ Objects That Don’t Exist (Psychology)

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When we watch a mime seemingly pull rope, climb steps or try to escape that infernal box, we don’t struggle to recognize the implied objects — our minds automatically “see” them, a new study concludes.

To explore how the mind processes the objects mimes seem to interact with, Johns Hopkins University cognitive scientists brought the art of miming into the lab, concluding that invisible, implied surfaces are represented rapidly and automatically. The work appears today in the journal Psychological Science.

“Most of the time, we know which objects are around us because we can just see them directly. But what we explored here was how the mind automatically builds representations of objects that we can’t see at all but that we know must be there because of how they are affecting the world,” said senior author Chaz Firestone, an assistant professor who directs the university’s Perception & Mind Laboratory. “That’s basically what mimes do. They can make us feel like we’re aware of some object just by seeming to interact with it.”

In the experiments, 360 people were tested online. They watched clips where a character (Firestone himself) mimed colliding with a wall and stepping over a box in a way that suggested those objects were there, only invisible. Afterward, a black line appeared in the spot on the screen where the implied surface would have been. This line could be horizontal or vertical, so it either matched or didn’t match the orientation of the surface that had just been mimed. Participants had to quickly answer if the line was vertical or horizontal. The team found people responded significantly faster when the line aligned with the mimed wall or box, suggesting that the implied surface was actively represented in the mind – so much so that it affected responses to the real surface participants saw immediately after.

Participants had been told not to pay attention to the miming, but they couldn’t help but be influenced by those implied surfaces, said lead author Pat Little, who did the work as an undergraduate at Johns Hopkins, and is now a graduate student at New York University.

“Very quickly people realize that the mime is misleading them, and that there is no actual connection between what the person does and the type of line that appears,” Little said. “They think, ‘I should ignore this thing because it’s getting in my way’, but they can’t. That’s the key. It seems like our minds can’t help but represent the surface that the mime is interacting with – even when we don’t want to.”

The work is partly inspired by a phenomenon in psychology called the Stroop Effect, where the name for one color is written in ink of a different color (e.g., the word “red” is written in blue ink); when a person is given the task of saying the color of the ink (blue), they can’t help but read the mismatched text (red), which distracts them and slows them down. In this regard, miming is like reading: Just as you can’t help but read the text you see (even when you’re supposed to ignore it), you can’t help but  recognize the object being mimed, even when it’s getting in the way of another task.

While it could seem that the findings diminish the work of mimes – since it suggests our brains are going to imagine these objects automatically – the researchers insist mimes still deserve credit.

“This suggests that miming might be different from other kinds of acting,” Little said. “If the mime is skilled enough, understanding what’s going on doesn’t require any effort at all — you just get it automatically.”

The findings could also inform artificial intelligence related to vision.

“If you’re trying to build a self-driving car that can see the world and steer around objects, you want to give it all the best tools and tricks,” Firestone said. “This study suggests that, if you want a machine’s vision to be as sophisticated as ours, it’s not enough for it to identify objects that it can see directly — it also needs the ability to infer the existence of objects that aren’t even visible at all.”

The work was supported by the National Science Foundation (Grant #2021053), the Johns Hopkins Science of Learning Institute, and a STAR award from the Johns Hopkins Office of Undergraduate Research.

VIDEO: https://youtu.be/KA7Bu7Nbb6U

Reference: Little PC, Firestone C. Physically Implied Surfaces. Psychological Science. April 2021. doi:10.1177/0956797620939942

Provided by Johns Hopkins University