Monday, January 11, 2021

Physician-pharmacist collaboration may increase adherence to opioid addiction treatment

NIH/NATIONAL INSTITUTE ON DRUG ABUSE

NIH-supported pilot study found team-based approach may improve buprenorphine care.

WHAT:

A collaborative approach to treating opioid use disorder that relies heavily on community pharmacists is feasible and may increase adherence and participant satisfaction, according to a pilot study published today in Addiction. The study was supported by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, through the NIDA Center for the Clinical Trials Network.

Most people with opioid use disorder who would benefit from medication do not receive it. Buprenorphine is a safe and effective medication that has been used in opioid addiction treatment for nearly two decades, but providers must complete training and receive a special waiver in order to prescribe buprenorphine to treat opioid use disorder. In the United States, fewer than 10% of primary care providers are authorized to prescribe buprenorphine, and more than 20 million people in the United States live in a county without a buprenorphine-waivered physician. This lack of access is a significant barrier to treatment, especially to people in underserved communities.

To help address treatment gaps, investigators studied the transfer of care of 71 participants using buprenorphine maintenance therapy for opioid use disorder from waivered physicians to trained community pharmacists. About 90% of people in the United States live within five miles of a community pharmacy.

Researchers from Duke University, Durham, North Carolina, and their collaborators found nearly 89% of participants remained in the study and 95.3% adhered to the daily medication regimen. During the 6-month trial, no opioid-related emergencies or hospitalizations were reported. The proportion of opioid-positive urine drug screens was less than 5% at month 6 among participants who completed all urine drug screens in the study. Participants, physicians, and pharmacists alike reported high rates of satisfaction with the program.

Investigators recruited 71 adults currently receiving office-based buprenorphine treatment for opioid use disorder in the Raleigh-Durham, N.C., area from March to December 2018. Six physicians and six community pharmacists took part in the trial. The initial treatment phase, in which the buprenorphine dose is gradually increased until a satisfactory daily dose is reached, was carried out under the care of a waivered physician. Then, participants attended monthly maintenance visits in which pharmacists dispensed buprenorphine, assessed how well the medication was working, and provided counseling and referrals to specialists as needed. Pharmacists then provided feedback to the partnering physician to adjust buprenorphine dosage as needed.

The researchers concluded that the pilot study offers strong support for advancing physician-pharmacist team-based approaches to leverage the abundant resource of community pharmacies in expanding access to opioid use disorder treatment with buprenorphine. Larger clinical trials are needed to establish strategies and approaches to most effectively implement team-based buprenorphine care and respond to the needs of diverse clinical settings and populations.

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Article

Wu, L-T et al. Buprenorphine physician?pharmacist collaboration in the management of patients with opioid use disorder: Results from a multi-site study of the National Drug Abuse Treatment Clinical Trials Network. Addiction. January 11, 2021.

The paper will be available at https://onlinelibrary.wiley.com/doi/abs/10.1111/add.15353.

WHO:

Nora Volkow, M.D., director of NIDA, is available for comment.

To learn more about NIDA's National Drug Abuse Treatment Clinical Trials Network, go to NIDA's Clinical Trials Network website: https://www.drugabuse.gov/about-nida/organization/cctn/clinical-trials-network-ctn.

For more information, contact the NIDA press office at media@nida.nih.gov or 301-443-6245. Follow NIDA on Twitter and Facebook.

About the National Institute on Drug Abuse (NIDA): NIDA is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world's research on the health aspects of drug use and addiction. The Institute carries out a large variety of programs to inform policy, improve practice, and advance addiction science. For more information about NIDA and its programs, visit http://www.drugabuse.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIH...Turning Discovery Into Health®

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Unveiling the double origin of cosmic dust in the distant Universe

An international team of researchers develops a new method for the study of large, massive, dusty galaxies and sheds new light on the physical processes involved in the production of dust in these 'giants'

SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI

Research News

Two billion years after the Big Bang, the Universe was still very young. However, thousands of huge galaxies, rich in stars and dust, were already formed. An international study, led by SISSA - Scuola Internazionale Superiore di Studi Avanzati, now explains how this was possible. Scientists combined observational and theoretical methods to identify the physical processes behind their evolution and, for the first time, found evidence for a rapid growth of dust due to a high concentration of metals in the distant Universe. The study, published in Astronomy&Astrophysics, offers a new approach to investigate the evolutionary phase of massive objects.

Since their initial discovery 20 years ago, very distant and massive galaxies that form prodigious amount of young stars - so-called dusty (star-forming) galaxies - represent a serious challenge for astronomers: "On one hand, they are difficult to detect because they reside in dense regions of the distant Universe and contain dusty particles which absorb most of the optical light radiated by young stars", explains Darko Donevski, postdoctoral fellow at SISSA. "On the other hand, many of these dusty 'giants' have been formed when the Universe was very young, sometimes even less than 1 billion years-old, and scientists have been wondering how could such large amount of dust have been produced so early in time".

The study of these exotic objects is now possible thanks to the Atacama Large Millimeter/submillimeter Array (ALMA). This interferometer of 66 telescopes in the Atacama Desert of northern Chile is able to detect the infrared light which penetrates the dusty clouds, revealing the presence of newly forming stars. However, the origin of large amount of dust at early cosmic time is still an open question to astronomers. "Throughout many years scientists thought that production of cosmic dust was exclusively due to supernovae explosion. However, recent theoretical works suggest that dust can also grow through collisions of particles of cold, metal-rich gas which fills the galaxies," explains the researcher.

An international team of researchers from institutions based in Europe, US, Canada and South Africa, led by Donevski, combined observational and theoretical methods to study 300 distant, dusty galaxies in order to unveil the origin of these "Giants". In particular, they inferred the physical properties of these dusty galaxies by fitting their spectral energy distributions. "We found a huge amount of dust mass in most of our galaxies. Our estimates showed that supernovae explosions could not be responsible for all of it and a part had to be produced through particle collisions in the gaseous metal-rich environment around massive stars, as previously supposed by theoretical models" says Donevski. "This is the first time that observational data support the existence of both production mechanisms."

Scientists also looked at dust to star mass ratio over time to study how efficiently galaxies create and destroy dust during their evolution. "This allowed us to identify dust life cycle in two different populations of galaxies: normal, so-called 'main-sequence', galaxies, which are slowly evolving, and more extreme, rapidly evolving galaxies, called 'starbursts'", said Lara Pantoni, PhD student at SISSA, who developed the analytic model used for data interpretation. The model shows the great potential in describing differences in these two groups of observed galaxies. "Interestingly, we also showed that irrespective of their distance, stellar mass or size, compact 'starburst' galaxies always have dust-to-stellar mass ratio higher than the normal galaxies."

To fully evaluate the observational findings, the team of astronomers also confronted their data with the state-of-the-art galaxy simulations. They used SIMBA, a new suite that simulates the formation and evolution of millions of galaxies since the beginning of the Universe to present time, tracking all their physical properties, including dust mass. "Up to now, theoretical models had problems in matching both galaxy dust and stellar properties simultaneously. However, our new cosmological simulation suite, SIMBA, could reproduce most of the observed data," explains Desika Narayanan, professor of astronomy at the University of Florida and member of the DAWN institute in Copenhagen.

"Our study shows that dust production in 'giants' is dominated by very rapid growth of particles through their collisions with gas. Thus, it provides the first strong proof that dust formation occurs both during stars death and in the space between these massive stars, as assumed from theoretical studies," concludes Donevski. "Moreover, it offers a new mixed approach to investigate the evolution of massive objects in the distant Universe that will be tested with future space telescopes such as the James Webb Space Telescope."

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Video Interview with D. Donevski:
https://bit.ly/3qc60WK

'Galaxy-sized' observatory sees potential hints of gravitational waves

UNIVERSITY OF COLORADO AT BOULDER

Research News

Scientists have used a "galaxy-sized" space observatory to find possible hints of a unique signal from gravitational waves, or the powerful ripples that course through the universe and warp the fabric of space and time itself.

The new findings, which appeared recently in The Astrophysical Journal Letters, hail from a U.S. and Canadian project called the North American Nanohertz Observatory for Gravitational Waves (NANOGrav).

For over 13 years, NANOGrav researchers have pored over the light streaming from dozens of pulsars spread throughout the Milky Way Galaxy to try to detect a "gravitational wave background." That's what scientists call the steady flux of gravitational radiation that, according to theory, washes over Earth on a constant basis. The team hasn't yet pinpointed that target, but it's getting closer than ever before, said Joseph Simon, an astrophysicist at the University of Colorado Boulder and lead author of the new paper.

"We've found a strong signal in our dataset," said Simon, a postdoctoral researcher in the Department of Astrophysical and Planetary Sciences. "But we can't say yet that this is the gravitational wave background."

In 2017, scientists on an experiment called the Laser Interferometer Gravitational-Wave Observatory (LIGO) won the Nobel Prize in Physics for the first-ever direct detection of gravitational waves. Those waves were created when two black holes slammed into each other roughly 130 million lightyears from Earth, generating a cosmic shock that spread to our own solar system.

That event was the equivalent of a cymbal crash--a violent and short-lived blast. The gravitational waves that Simon and his colleagues are looking for, in contrast, are more like the steady hum of conversation at a crowded cocktail party.

Detecting that background noise would be a major scientific achievement, opening a new window to the workings of the universe, he added. These waves, for example, could give scientists new tools for studying how the supermassive black holes at the centers of many galaxies merge over time.

"These enticing first hints of a gravitational wave background suggest that supermassive black holes likely do merge and that we are bobbing in a sea of gravitational waves rippling from supermassive black hole mergers in galaxies across the universe," said Julie Comerford, an associate professor of astrophysical and planetary science at CU Boulder and NANOGrav team member.

Simon will present his team's results at a virtual press conference on Monday at the 237th meeting of the American Astronomical Society.

Galactic lighthouses

Through their work on NANOGrav, Simon and Comerford are part of a high stakes, albeit collaborative, international race to find the gravitational wave background. Their project joins two others out of Europe and Australia to make up a network called the International Pulsar Timing Array.

Simon said that, at least according to theory, merging galaxies and other cosmological events produce a steady churn of gravitational waves. They're humungous--a single wave, Simon said, can take years or even longer to pass Earth by. For that reason, no other existing experiments can detect them directly.

"Other observatories search for gravitational waves that are on the order of seconds," Simon said. "We're looking for waves that are on the order of years or decades."

He and his colleagues had to get creative. The NANOGrav team uses telescopes on the ground not to look for gravitational waves but to observe pulsars. These collapsed stars are the lighthouses of the galaxy. They spin at incredibly fast speeds, sending streams of radiation hurtling toward Earth in a blinking pattern that remains mostly unchanged over the eons.

Simon explained that gravitational waves alter the steady pattern of light coming from pulsars, tugging or squeezing the relative distances that these rays travel through space. Scientists, in other words, might be able to spot the gravitational wave background simply by monitoring pulsars for correlated changes in the timing of when they arrive at Earth.

"These pulsars are spinning about as fast as your kitchen blender," he said. "And we're looking at deviations in their timing of just a few hundred nanoseconds."

Something there

To find that subtle signal, the NANOGrav team strives to observe as many pulsars as possible for as long as possible. To date, the group has observed 45 pulsars for at least three years and, in some cases, for well over a decade.

The hard work seems to be paying off. In their latest study, Simon and his colleagues report that they've detected a distinct signal in their data: Some common process seems to be affecting the light coming from many of the pulsars.

"We walked through each of the pulsars one by one. I think we were all expecting to find a few that were the screwy ones throwing off our data," Simon said. "But then we got through them all, and we said, 'Oh my God, there's actually something here.'"

The researchers still can't say for sure what's causing that signal. They'll need to add more pulsars to their dataset and observe them for longer periods to determine if it's actually the gravitational wave background at work.

"Being able to detect the gravitational wave background will be a huge step but that's really only step one," he said. "Step two is pinpointing what causes those waves and discovering what they can tell us about the universe."

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NANOGrav is a U.S. National Science Foundation Physics Frontiers Center. It is co-directed by Maura McLaughlin of West Virginia University and Xavier Siemens of Oregon State University.

Robot displays a glimmer of empathy to a partner robot

Columbia engineers create a robot that learns to visually predict how its partner robot will behave, displaying a glimmer of empathy. This "Robot Theory of Mind" could help robots get along with other robots--and humans--more intuitively.

COLUMBIA UNIVERSITY SCHOOL OF ENGINEERING AND APPLIED SCIENCE

VIDEO: SHORT HIGH-LEVEL VIDEO DESCRIPTION OF THE COLUMBIA ENGINEERING "ROBOT THEORY OF MIND " PROJECT (AUDIO NARRATIONS INCLUDED). view more
CREDIT: CREATIVE MACHINES LAB/COLUMBIA ENGINEERING
Video of "Robot Theory of Mind" [video] | EurekAlert! Science News

New York, NY--January 11, 2021--Like a longtime couple who can predict each other's every move, a Columbia Engineering robot has learned to predict its partner robot's future actions and goals based on just a few initial video frames.

When two primates are cooped up together for a long time, we quickly learn to predict the near-term actions of our roommates, co-workers or family members. Our ability to anticipate the actions of others makes it easier for us to successfully live and work together. In contrast, even the most intelligent and advanced robots have remained notoriously inept at this sort of social communication. This may be about to change.

The study, conducted at Columbia Engineering's Creative Machines Lab led by Mechanical Engineering Professor Hod Lipson, is part of a broader effort to endow robots with the ability to understand and anticipate the goals of other robots, purely from visual observations.

The researchers first built a robot and placed it in a playpen roughly 3x2 feet in size. They programmed the robot to seek and move towards any green circle it could see. But there was a catch: Sometimes the robot could see a green circle in its camera and move directly towards it. But other times, the green circle would be occluded by a tall red carboard box, in which case the robot would move towards a different green circle, or not at all.

After observing its partner puttering around for two hours, the observing robot began to anticipate its partner's goal and path. The observing robot was eventually able to predict its partner's goal and path 98 out of 100 times, across varying situations--without being told explicitly about the partner's visibility handicap.

CAPTION

An actor robot runs on a playpen trying to catch the visible green food, while an observer machine learns to predict the actor robot's behavior purely through visual observations. Although the observer can always see the green foods, the actor, from its own perspective, cannot due to occlusions.

CREDIT

Creative Machines Lab/Columbia Engineering

"Our initial results are very exciting," says Boyuan Chen, lead author of the study, which was conducted in collaboration with Carl Vondrick, assistant professor of computer science, and published today by Nature Scientific Reports. "Our findings begin to demonstrate how robots can see the world from another robot's perspective. The ability of the observer to put itself in its partner's shoes, so to speak, and understand, without being guided, whether its partner could or could not see the green circle from its vantage point, is perhaps a primitive form of empathy."

When they designed the experiment, the researchers expected that the Observer Robot would learn to make predictions about the Subject Robot's near-term actions. What the researchers didn't expect, however, was how accurately the Observer Robot could foresee its colleague's future "moves" with only a few seconds of video as a cue.

The researchers acknowledge that the behaviors exhibited by the robot in this study are far simpler than the behaviors and goals of humans. They believe, however, that this may be the beginning of endowing robots with what cognitive scientists call "Theory of Mind" (ToM). At about age three, children begin to understand that others may have different goals, needs and perspectives than they do. This can lead to playful activities such as hide and seek, as well as more sophisticated manipulations like lying. More broadly, ToM is recognized as a key distinguishing hallmark of human and primate cognition, and a factor that is essential for complex and adaptive social interactions such as cooperation, competition, empathy, and deception.

In addition, humans are still better than robots at describing their predictions using verbal language. The researchers had the observing robot make its predictions in the form of images, rather than words, in order to avoid becoming entangled in the thorny challenges of human language. Yet, Lipson speculates, the ability of a robot to predict the future actions visually is not unique: "We humans also think visually sometimes. We frequently imagine the future in our mind's eyes, not in words."

Lipson acknowledges that there are many ethical questions. The technology will make robots more resilient and useful, but when robots can anticipate how humans think, they may also learn to manipulate those thoughts.

"We recognize that robots aren't going to remain passive instruction-following machines for long," Lipson says. "Like other forms of advanced AI, we hope that policymakers can help keep this kind of technology in check, so that we can all benefit."

CAPTION

Predictions from the observer machine: the observer sees the left side video and predicts the behavior of the actor robot shown on the right. With more information, the observer can correct its predictions about the actor's final behaviors.

CREDIT

Creative Machines Lab/Columbia Engineering

About the Study

The study is titled "Visual Behavior Modelling for Robotic Theory of Mind"

Authors are: Boyuan Chen, Carl Vondrick and Hod Lipson, Mechanical Engineering and Computer Science, Columbia Engineering.

The study was supported by NSF NRI 1925157 and DARPA MTO grant L2M Program HR0011-18-2-0020.

The authors declare no financial or other conflicts of interest.

LINKS:

Paper: http://www.nature.com/articles/s41598-020-77918-x
DOI: 10.1038/s41598-020-77918-x
VIDEO: https://youtu.be/f2U7_jZVxcU
PROJECT WEBSITE: https://www.creativemachineslab.com/robot-visual-behavior-modeling.html
https://engineering.columbia.edu/faculty/hod-lipson
http://www.cs.columbia.edu/~bchen/
https://me.columbia.edu/
https://www.cs.columbia.edu/
http://engineering.columbia.edu/

Columbia Engineering

Columbia Engineering, based in New York City, is one of the top engineering schools in the U.S. and one of the oldest in the nation. Also known as The Fu Foundation School of Engineering and Applied Science, the School expands knowledge and advances technology through the pioneering research of its more than 220 faculty, while educating undergraduate and graduate students in a collaborative environment to become leaders informed by a firm foundation in engineering. The School's faculty are at the center of the University's cross-disciplinary research, contributing to the Data Science Institute, Earth Institute, Zuckerman Mind Brain Behavior Institute, Precision Medicine Initiative, and the Columbia Nano Initiative. Guided by its strategic vision, "Columbia Engineering for Humanity," the School aims to translate ideas into innovations that foster a sustainable, healthy, secure, connected, and creative humanity.

Computer scientists: We wouldn't be able to control super intelligent machines

New findings from theoretical computer science

MAX PLANCK INSTITUTE FOR HUMAN DEVELOPMENT

Research News

We are fascinated by machines that can control cars, compose symphonies, or defeat people at chess, Go, or Jeopardy! While more progress is being made all the time in Artificial Intelligence (AI), some scientists and philosophers warn of the dangers of an uncontrollable superintelligent AI. Using theoretical calculations, an international team of researchers, including scientists from the Center for Humans and Machines at the Max Planck Institute for Human Development, shows that it would not be possible to control a superintelligent AI. The study was published in the Journal of Artificial Intelligence Research.

Suppose someone were to program an AI system with intelligence superior to that of humans, so it could learn independently. Connected to the Internet, the AI may have access to all the data of humanity. It could replace all existing programs and take control all machines online worldwide. Would this produce a utopia or a dystopia? Would the AI cure cancer, bring about world peace, and prevent a climate disaster? Or would it destroy humanity and take over the Earth?

Computer scientists and philosophers have asked themselves whether we would even be able to control a superintelligent AI at all, to ensure it would not pose a threat to humanity. An international team of computer scientists used theoretical calculations to show that it would be fundamentally impossible to control a super-intelligent AI.

"A super-intelligent machine that controls the world sounds like science fiction. But there are already machines that perform certain important tasks independently without programmers fully understanding how they learned it. The question therefore arises whether this could at some point become uncontrollable and dangerous for humanity", says study co-author Manuel Cebrian, Leader of the Digital Mobilization Group at the Center for Humans and Machines, Max Planck Institute for Human Development.

Scientists have explored two different ideas for how a superintelligent AI could be controlled. On one hand, the capabilities of superintelligent AI could be specifically limited, for example, by walling it off from the Internet and all other technical devices so it could have no contact with the outside world -- yet this would render the superintelligent AI significantly less powerful, less able to answer humanities quests. Lacking that option, the AI could be motivated from the outset to pursue only goals that are in the best interests of humanity, for example by programming ethical principles into it. However, the researchers also show that these and other contemporary and historical ideas for controlling super-intelligent AI have their limits.

In their study, the team conceived a theoretical containment algorithm that ensures a superintelligent AI cannot harm people under any circumstances, by simulating the behavior of the AI first and halting it if considered harmful. But careful analysis shows that in our current paradigm of computing, such algorithm cannot be built.

"If you break the problem down to basic rules from theoretical computer science, it turns out that an algorithm that would command an AI not to destroy the world could inadvertently halt its own operations. If this happened, you would not know whether the containment algorithm is still analyzing the threat, or whether it has stopped to contain the harmful AI. In effect, this makes the containment algorithm unusable", says Iyad Rahwan, Director of the Center for Humans and Machines.

Based on these calculations the containment problem is incomputable, i.e. no single algorithm can find a solution for determining whether an AI would produce harm to the world. Furthermore, the researchers demonstrate that we may not even know when superintelligent machines have arrived, because deciding whether a machine exhibits intelligence superior to humans is in the same realm as the containment problem.

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The study "Superintelligence cannot be contained: Lessons from Computability Theory" was published in the Journal of Artificial Intelligence Research. Other researchers on the study include Andres Abeliuk from the University of Southern California, Manuel Alfonseca from the Autonomous University of Madrid, Antonio Fernandez Anta from the IMDEA Networks Institute and Lorenzo Coviello.

Core design strategy for fire-resistant batteries

Development of a strategy for reducing 'electrolyte-electrode interface resistance,' which limits the commercialization of all-solid-state batteries; new material design strategy to increase performance by improving the cathode material

NATIONAL RESEARCH COUNCIL OF SCIENCE & TECHNOLOGY

Research News

IMAGE: SCHEME OF EXPOSED CRYSTAL FACETS OF CUBIC STRUCTURES WITH (100), (110), AND (111) ORIENTATIONS. view more
CREDIT: KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY(KIST)

All-solid-state batteries are the next-generation batteries that can simultaneously improve the stability and capacity of existing lithium batteries. The use of non-flammable solid cathodes and electrolytes in such batteries considerably reduces the risk of exploding or catching fire under high temperatures or external impact and facilitates high energy density, which is twice that of lithium batteries. All-solid-state batteries are expected to become a game changer in the electric vehicle and energy storage device markets. Despite these advantages, the low ionic conductivity of solid electrolytes combined with their high interfacial resistance and rapid deterioration reduce battery performance and life, thus limiting their commercialization.

The Korea Institute of Science and Technology (KIST) is proud to announce that the research team of Dr. Sang-baek Park at the Center for Energy Materials Research, in collaboration with the research team of Professor Hyun-jung Shin of Sungkyunkwan University, has developed a breakthrough material design strategy that can overcome the problem of high interfacial resistance between the solid electrolyte and the cathode, which is an obstacle to the commercialization of all-solid-state batteries.

Unique physical phenomena occur at the interface where two different substances meet. Unlike the atoms inside the bulk of a substance, which hold hands with other atoms around themselves and form stable bonds, the atoms at the interface, having no neighboring atom of the same substance on one side, are likely to form a different atomic arrangement.

In all-solid-state batteries having a solid electrode-solid electrolyte interface, a phenomenon occurs that disturbs the atomic arrangement and limits charge transfer, thereby increasing resistance and accelerating deterioration. Methods of coating an appropriate material on the surface of the cathode and the electrolyte or inserting an intermediate layer are currently being studied to solve the above-mentioned problem. However, this further increases the costs and lowers the overall activity and energy density of the batteries.

In order to solve these problems, the KIST-Sungkyunkwan University joint research team first systematically identified the crystal structure of the material that directly affects the solid interface. Using epitaxial film technology (a semiconductor manufacturing technology) to grow a thin film along the direction in which the crystals of the substrate were formed, cathode films having different exposed crystal planes were obtained under varying conditions. The effect of the exposed crystal plane on the interface between the solid electrolyte and the cathode material was analyzed in detail, disregarding other factors such as particle size and contact area that could affect the result.

The results indicated that the leakage of the transition metal from the cathode material into the electrolyte was suppressed by the closely-packed structure of the exposed crystal plane, which improved the stability of the all-solid-state battery. In addition, when the interface of the crystals was arranged in parallel with the direction of movement of the electrons, the movement of ions and electrons along the crystals was not hindered, resulting in reduced resistance and improved output.

"This means that improving the cathode material itself by increasing the density of the crystal plane and adjusting the direction of the interface between the crystals can ensure high performance and stability," said Dr. Sang-baek Park, KIST. "We plan to accelerate the development of all-solid-state battery materials by overcoming the instability of the solid electrolyte and solid cathode interface and imparting improved ion-charge exchange characteristics through this study, which has investigated the mechanism of all-solid-state battery degradation."

CAPTION

Photo and scheme of an ASSLB configuration for an LNMO thin film cathode.

CREDIT

Korea Institute of Science and Technology(KIST)

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This research was carried out as a major project of KIST with the support of the Ministry of Science and ICT (MSIT). The results of this study were published in the latest issue of "Nano Energy" (IF: 16.602, the highest rating of 4.299% by JCR), an international journal in the field of nanotechnology.

Acta Pharmaceutica Sinica B volume 10, issue 12 publishes

COMPUSCRIPT LTD

Research News

IMAGE: ACTA PHARMACEUTICA SINICA B VOLUME 10, ISSUE 12 PUBLISHES view more
CREDIT: ACTA PHARMACEUTICA SINICA B

The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association, Acta Pharmaceutica Sinica B (APSB) is a monthly journal, in English, which publishes significant original research articles, rapid communications and high quality reviews of recent advances in all areas of pharmaceutical sciences -- including pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis and pharmacokinetics.

Chloroplasts on the move

How different plants can share their genetic material with each other

MAX-PLANCK-GESELLSCHAFT

Research News

IMAGE: A NATURAL STEM GRAFT BETWEEN A BEECH (FRONT) AND A MAPLE (BACK) IN A FOREST NEAR MONROE, NEW JERSEY (LEFT PICTURE), AND AN SIMILAR STEM GRAFT BETWEEN TWO TOBACCO PLANTS... view more
CREDIT: MPI-MP, NATURE 511

The genetic material of plants, animals and humans is well protected in the nucleus of each cell and stores all the information that forms an organism. For example, information about the size or color of flowers, hair or fur is predefined here. In addition, cells contain small organelles that contain their own genetic material. These include chloroplasts in plants, which play a key role in photosynthesis, and mitochondria, which are found in all living organisms and represent the power plants of every cell. But is the genetic material actually permanently stored within one cell? No! As so far known, the genetic material can migrate from cell to cell and thus even be exchanged between different organisms. Researchers at the Max Planck Institute of Molecular Plant Physiology (MPI-MP) in Potsdam have now been able to use new experimental approaches to show for the first time how the genetic material travels. They published their results in the journal Science Advances.

After a short time, the two partners grow together at the graft junction, resulting in a physiological connection between the two plants. "We were able to observe that genome transfer from cell to cell occurs in both directions with high frequency at this site", explains Dr. Alexander Hertle, first author of the study.

Using a new experimental setup, the researchers were able to observe structural changes in the cell walls in the wound tissue of the graft site. "The cell walls formed protrusions, creating junctions between the two partners. The size of those created pores allows the migration of an entire plastid. Therefore, the genome does not migrate freely, but encapsulated from cell to cell," Hertle continues. However, to actually make this possible, the plastids have to shrink and become mobile. These rod-shaped plastids are equal to an amoeba and grow back to normal size after transfer into the target tissue.

The researchers have thus uncovered a new pathway for intercellular exchange of very large cell structures, which may also be used by parasitic plants, such as mistletoe, to carry out gene exchange with their host. In addition, it now needs to be clarified whether mitochondria and the nuclear genome also use similar transfer mechanisms.

The transfer of genetic material occurs quite frequently in plants. This can either result in a new combination of the genetic material, or alternatively the recipient cell can establish both genetic variants in parallel. This union of two different genomes, called allopolyploidization, is very interesting in evolutionary terms, as it leads to the formation of new plant species and is widespread in many plant groups. Many important crops, such as bread and durum wheat, oats, cotton, canola, coffee, and tobacco have such combined genomes from at least two crossed species.

In order to understand the mechanisms of genome transfer from cell to cell, the researchers led by Ralph Bock at MPI-MP conducted experiments with tobacco plants using grafting, which is commonly used in agriculture. Here, two different tobacco plants were grafted onto each other and the cells of the junction were observed microscopically in real time. To differentiate between the genome of nucleus and plastids, fluorescent reporter proteins were integrated and expressed from both genomes and the researchers used a trick using a specialization of the chloroplasts. In the plastids, a gene is integrated by transformation that encodes a chloroplast-specific fluorescence protein, which is produced exclusively in plastids and cannot leave them. This creates an absolutely specific and stable label for the plastids.

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Original publication

Alexander P. Hertle, Benedikt Haberl, Ralph Bock
Horizontal genome transfer by cell-to-cell travel of whole organelles
Science Advances
01 Jan 2021: Vol. 7, no. 1, eabd8215

Breakthrough on diarrhea virus opens up for new vaccines

UMEA UNIVERSITY

Research News

IMAGE: ILLUSTRATION FROM CRYO-ELECTRON MICROSCOPE IMAGE OF THE ENTERIC ADENOVIRUS HADV-F41. view more
CREDIT: IMAGE: KARIM RAFIE

"The findings provide an increased understanding of how the virus gets through the stomach and intestinal system. Continued research can provide answers to whether this property can also be used to create vaccines that ride 'free rides' and thus be given in edible form instead of as syringes," says Lars-Anders Carlson, researcher at Umeå University.

The virus that the researchers have studied is a so-called enteric adenovirus. It has recently been clarified that enteric adenoviruses are one of the most important factors behind diarrhea among infants, and they are estimated to kill more than 50,000 children under the age of five each year, mainly in developing countries.

Most adenoviruses are respiratory, that is, they cause respiratory disease, while the lesser-known enteric variants of adenovirus instead cause gastrointestinal disease. The enteric adenoviruses therefore need to be equipped to pass through the acidic environment of the stomach without being broken down, so that they can then infect the intestines.

With the help of the advanced cryo-electron microscope available in Umeå, the researchers have now managed to take such detailed images of an enteric adenovirus that it has been possible to put a three-dimensional puzzle that shows what the virus looks like right down to the atomic level. The virus is one of the most complex biological structures studied at this level. The shell that protects the virus' genome when it is spread between humans consists of two thousand protein molecules with a total of six million atoms.

The researchers were able to see that the enteric adenovirus manages to keep its structure basically unchanged at the low pH value found in the stomach. They could also see other differences compared to respiratory adenoviruses in how a particular protein is altered in the shell of the virus as well as new clues to how the virus packs its genome inside the shell. All in all, it provides an increased understanding of how the virus manages to move on to create disease and death.

"The hope is that you will be able to turn the ability that this unpleasant virus has to get to something that can instead be used as a tool to fight disease, perhaps even COVID-19. This is a step in the right direction, but it is still a long way off," says Lars-Anders Carlson.

Several of the new vaccines being tested against COVID-19 are based on genetically modified adenovirus. Today, these adenovirus-based vaccines must be injected to work in the body. If a vaccine could instead be based on enteric adenovirus, the vaccine might be given in edible form. This would, of course, facilitate large-scale vaccination.

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The virus that the researchers have studied is called HAdV-F41. The study is published in the scientific journal Science Advances. It is a collaboration between Lars-Anders Carlson's and Niklas Arnberg's research groups at Umeå University.

Bacterium produces pharmaceutical all-purpose weapon

Study should significantly facilitate research into the promising substance

UNIVERSITY OF BONN

Research News

IMAGE: FROM LEFT: DR. RENÉ RICHARZ WITH AN AGAR PLATE CONTAINING THE BACTERIUM, CORNELIA HERMES WITH AN EXTRACT OBTAINED FROM THE BACTERIUM, AND WORKING GROUP LEADER DR. MAX CRÜSEMANN. A CORALBERRY... view more
CREDIT: © AG CRÜSEMANN / UNIVERSITY OF BONN

For some years, an active substance from the leaves of an ornamental plant has been regarded as a possible forerunner of a new group of potent drugs. So far, however, it has been very laborious to manufacture it in large quantities. That could now change: Researchers at the University of Bonn (Germany) have identified a bacterium that produces the substance and can also be easily cultivated in the laboratory. The results are published in the journal Nature Communications.

The coralberry currently once again adorns many living rooms: In winter it bears bright red fruits, which make it a popular ornamental plant at this time of year. For pharmacists, however, it is interesting for a different reason: It contains an active substance that has emerged in recent years as a beacon of hope against asthma and certain types of cancer.

Unfortunately, obtaining the substance with the cryptic name FR900359 (abbreviated: FR) in larger quantities is rather laborious. Cultivating the plants in greenhouses takes many weeks; moreover, the yield can vary enormously depending on the specimen. Incidentally, they do not produce the active ingredient themselves, but have bacteria in their leaves that do it for them. "However, these only grow in the coralberry and cannot be cultivated in the laboratory," explains Dr. Max Crüsemann of the Institute of Pharmaceutical Biology at the University of Bonn.

Complex assembly line

Manufacturing FR is a complex undertaking. The bacteria have a special assembly line for this purpose, in which a number of enzymes work hand in hand. The bacterial genetic makeup specifies how this assembly line must be set up. "We have now searched huge databases for other microorganisms that also have these genes for FR synthesis," Crüsemann explains. "In the process, we came across another bacterium. Unlike its coralberry relative, it does not grow in plants, but in soil and is easily propagated in culture media."

This finding should greatly facilitate the production of FR in the future. However, it also allows more detailed insights into how the active substance works. "We have known for several years that FR inhibits an important group of signaling molecules in cells, the Gq proteins," explains Cornelia Hermes of the Institute of Pharmaceutical Biology. "That makes FR extremely effective: To date, no other compound is known to inhibit Gq proteins with similar potency."

Hermes is pursuing her doctoral studies in the group of Max Crüsemann and Prof. Gabriele König and, together with her colleague Dr. René Richarz, was responsible for a large part of the study now published. One of the questions the researchers explored was, why FR is such a good inhibitor. The molecule consists of two parts, the actual core and a side chain that is attached to it like an arm. Both are produced separately and then linked together. "The side chain is essential for the function of FR," Crüsemann explains. "When it is absent or even slightly modified, the inhibitory effect on Gq proteins decreases significantly."

Central control station in the cell

The function of Gq proteins in the cell is similar to that of the emergency call center of a city: They are the place where various signals from outside the cell converge. This activates them and then in turn certain metabolic processes are switched on or off. Instead of inhibiting numerous signaling pathways, it is therefore sufficient to inhibit the Gq protein in order to achieve a therapeutic effect. This means that FR is extremely effective, but also, if it were administered to the whole body, very toxic. "The goal is therefore to administer FR only to cells with pathologically altered behavior," Crüsemann explains. Bacterial genes can be easily and specifically modified nowadays. "In this way, we can in principle generate FR variants with specific properties, such as those that are transported precisely to certain cells in the body and only do their work there," says the pharmaceutical biologist.

The history of the FR molecule is therefore likely to be extended by another chapter as a result of the study: The active substance was discovered more than 30 years ago by Japanese researchers. In 2015, its biological mode of action was described by the research groups led by Professors Gabriele M. König and Evi Kostenis at the Institute of Pharmaceutical Biology. This work now forms the basis for a research group of the German Research Foundation (DFG). Today, more and more research groups around the world are exploring the potential of the molecule. With the newly discovered bacterium, they now have a new tool at hand.

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Publication: Cornelia Hermes, René Richarz, Daniel A. Wirtz, Julian Patt, Wiebke Hanke, Stefan Kehraus, Jan Hendrik Voß, Jim Küppers, Tsubasa Ohbayashi, Vigneshwaran Namasivayam, Judith Alenfelder, Asuka Inoue, Peter Mergaert, Michael Gütschow, Christa E. Müller, Evi Kostenis, Gabriele M. König & Max Crüsemann:
Thioesterase-mediated side chain transesteri ?cation generates potent Gq signaling inhibitor FR900359; Nature Communications; DOI: 10.1038/s41467-020-20418-3

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Monday, January 11, 2021

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Acta Pharmaceutica Sinica B volume 10, issue 12 publishes

Chloroplasts on the move

Breakthrough on diarrhea virus opens up for new vaccines

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