Sunday, July 24, 2022

Venomous! New pit viper discovered in Jiuzhaigou National Nature Reserve, China

Peer-Reviewed Publication

PENSOFT PUBLISHERS

Holotype of Gloydius lateralis 

IMAGE: HOLOTYPE OF GLOYDIUS LATERALIS view more 

CREDIT: SHENG-CHAO SHI

Jiuzhaigou National Nature Reserve, a World Heritage Site, lies in the transition zone from the eastern edge of the Qinghai-Tibet Plateau to the Sichuan Basin in Sichuan Province, China, and occupies an area of 651 km2. The reserve is covered with well-preserved original forests, and numerous alpine lakes. Beautiful and picturesque, it is home to some rare animals, such as the Giant Panda (Ailuropoda melanoleuca) and Golden Snub-nosed Monkey (Rhinopithecus roxellana).

The herpetological di­versity, in contrast to the mammals, is relatively low in the area due to the harsh alpine environment. To find out more about it, and to investigate the post-earthquake ecological system in the region, a group of researchers conducted a series of investigations in Jiuzhaigou National Nature Reserve. During their herpetological surveys, they collected some specimens of Gloydius, a genus of venomous pit vipers endemic to Asia, from Zharu Valley.

After running morphological and phylogenetic analyses, the scientists found out that these specimens in fact belonged to a yet-to-be-described species.

“The new species is morphologically similar, and phylogenetically closely related to G. swildanother recently described species from Heishui, Aba, Sichuan, but differs from it by having larger eyes (related to the head) and a continuous regular brown stripe on each dorsolateral side of the body,” explained the corresponding author, Dr Jingsong Shi.

“Thus, we named it after its unique color pattern: Gloydius lateralis.”

CAPTION

Holotype of Gloydius lateralis

CREDIT

Sheng-chao Shi

The newly described snake feeds on small mammals, such as mice, and “is active on sunny days by the roadside in a hot, dry valley”, the researchers write in their study, which was published in the open-access scientific journal ZooKeys.

“The discovery of G. lateralis provides new insights into the diversity and the distribution patterns of Asian pit vipers”, they write, suggesting that the formation of the Qinghai-Tibet Plateau might be one of the key factors to the geographical isolation of the alpine pit vipers in southwest China.

Jiuzhaigou National Nature Reserve, where G. lateralis was found, receives millions of tourists every year. “The only known habitat of the new species is Zharu Valley, and it is now under touristic development,” the researchers point out. “Thus, warning signs are still needed to remind visitors to watch out for the venomous pit viper, since this and another pit viper species, Protobothrops jerdo­nii, are often found in grass or bushes on both sides of roads.”

Snakes’ thermoregulation needs make them more prone to vehicle collisions, which is why the research team highlights the necessity to remind drivers to slow down in order to avoid road killings.

 

Original source:

Zhang M-H, Shi S-C, Li C, Yan P, Wang P, Ding L, Du J, Plenković-Moraj A, Jiang J-P, Shi J-S (2022) Exploring cryptic biodiversity in a world heritage site: a new pitviper (Squamata, Viperidae, Crotalinae) from Jiuzhaigou, Aba, Sichuan, China. ZooKeys 1114: 59–76. https://doi.org/10.3897/zookeys.1114.79709

New method can improve explosion detection


Peer-Reviewed Publication

UNIVERSITY OF ALASKA FAIRBANKS

Computers can be trained to better detect distant nuclear detonations, chemical blasts and volcano eruptions by learning from artificial explosion signals, according to a new method devised by a University of Alaska Fairbanks scientist.

The work, led by UAF Geophysical Institute postdoctoral researcher Alex Witsil, was published recently in the journal Geophysical Research Letters

Witsil, at the Geophysical Institute’s Wilson Alaska Technical Center, and colleagues created a library of synthetic infrasound explosion signals to train computers in recognizing the source of an infrasound signal. Infrasound is at a frequency too low to be heard by humans and travels farther than high-frequency audible waves.

“We used modeling software to generate 28,000 synthetic infrasound signals, which, though generated in a computer, could hypothetically be recorded by infrasound microphones deployed hundreds of kilometers from a large explosion,” Witsil said.

The artificial signals reflect variations in atmospheric conditions, which can alter an explosion’s signal regionally or globally as the sound waves propagate. Those changes can make it difficult to detect an explosion's origin and type from a great distance.

Why create artificial sounds of explosions rather than use real-world examples? Because explosions haven’t occurred at every location on the planet and the atmosphere constantly changes, there aren’t enough real-world examples to train generalized machine-learning detection algorithms.  

“We decided to use synthetics because we can model a number of different types of atmospheres through which signals can propagate,” Witsil said. “So even though we don't have access to any explosions that happened in North Carolina, for example, I can use my computer to model North Carolina explosions and build a machine-learning algorithm to detect explosion signals there.”

Today, detection algorithms generally rely on infrasound arrays consisting of multiple microphones close to each other. For example, the international Comprehensive Test Ban Treaty Organization, which monitors nuclear explosions, has infrasound arrays deployed worldwide. 

“That's expensive, it's hard to maintain, and a lot more things can break,” Witsil said.

Witsil’s method improves detection by making use of hundreds of single-element infrasound microphones already in place around the world.  That makes detection more cost-effective.

The machine-learning method broadens the usefulness of single-element infrasound microphones by making them capable of detecting more subtle explosion signals in near real-time. Single-element microphones currently are useful only for retroactively analyzing known and typically high-amplitude signals, as they did with January’s massive eruption of the Tonga volcano. 

Witsil’s method could be deployed in an operational setting for national defense or natural hazards mitigation.

This work was funded by the Defense Threat Reduction Agency.


CONTACTS:

• Alex Witsil, University of Alaska Fairbanks Geophysical Institute, ajwitsil@alaska.edu.

• Rod Boyce, University of Alaska Fairbanks Geophysical Institute, 907-474-7185, rcboyce@alaska.edu

Halos and dark matter: A recipe for discovery

No, scientists still don’t know what dark matter is. But MSU scientists helped uncover new physics while looking for it.

Peer-Reviewed Publication

MICHIGAN STATE UNIVERSITY

EAST LANSING, Mich. – About three years ago, Wolfgang “Wolfi” Mittig and Yassid Ayyad went looking for the universe’s missing mass, better known as dark matter, in the heart of an atom.

Their expedition didn’t lead them to dark matter, but they still found something that had never been seen before, something that defied explanation. Well, at least an explanation that everyone could agree on. 

“It’s been something like a detective story,” said Mittig, a Hannah Distinguished Professor in Michigan State University’s Department of Physics and Astronomy and a faculty member at the Facility for Rare Isotope Beams, or FRIB

“We started out looking for dark matter and we didn’t find it,” he said. “Instead, we found other things that have been challenging for theory to explain.”

So the team got back to work, doing more experiments, gathering more evidence to make their discovery make sense. Mittig, Ayyad and their colleagues bolstered their case at the National Superconducting Cyclotron Laboratory, or NSCL, at Michigan State University. 

Working at NSCL, the team found a new path to their unexpected destination, which they detailed June 28 in the journal Physical Review Letters. In doing so, they also revealed interesting physics that’s afoot in the ultra-small quantum realm of subatomic particles. 

In particular, the team confirmed that when an atom’s core, or nucleus, is overstuffed with neutrons, it can still find a way to a more stable configuration by spitting out a proton instead.

Shot in the dark

Dark matter is one of the most famous things in the universe that we know the least about. For decades, scientists have known that the cosmos contains more mass than we can see based on the trajectories of stars and galaxies. 

For gravity to keep the celestial objects tethered to their paths, there had to be unseen mass and a lot of it — six times the amount of regular matter that we can observe, measure and characterize. Although scientists are convinced dark matter is out there, they have yet to find where and devise how to detect it directly.

“Finding dark matter is one of the major goals of physics,” said Ayyad,  a nuclear physics researcher at the Galician Institute of High Energy Physics, or IGFAE, of the University of Santiago de Compostela in Spain. 

Speaking in round numbers, scientists have launched about 100 experiments to try to illuminate what exactly dark matter is, Mittig said.

“None of them has succeeded after 20, 30, 40 years of research,” he said.

“But there was a theory, a very hypothetical idea, that you could observe dark matter with a very particular type of nucleus,” said Ayyad, who was previously a detector systems physicist at NSCL.

This theory centered on what it calls a dark decay. It posited that certain unstable nuclei, nuclei that naturally fall apart, could jettison dark matter as they crumbled.

So Ayyad, Mittig and their team designed an experiment that could look for a dark decay, knowing the odds were against them. But the gamble wasn’t as big as it sounds because probing exotic decays also lets researchers better understand the rules and structures of the nuclear and quantum worlds. 

The researchers had a good chance of discovering something new. The question was what that would be.

Help from a halo

When people imagine a nucleus, many may think of a lumpy ball made up of protons and neutrons, Ayyad said. But nuclei can take on strange shapes, including what are known as halo nuclei. 

Beryllium-11 is an example of a halo nuclei. It’s a form, or isotope, of the element beryllium that has four protons and seven neutrons in its nucleus. It keeps 10 of those 11 nuclear particles in a tight central cluster. But one neutron floats far away from that core, loosely bound to the rest of the nucleus, kind of like the moon ringing around the Earth, Ayyad said.

Beryllium-11 is also unstable. After a lifetime of about 13.8 seconds, it falls apart by what’s known as beta decay. One of its neutrons ejects an electron and becomes a proton. This transforms the nucleus into a stable form of the element boron with five protons and six neutrons, boron-11.

But according to that very hypothetical theory, if the neutron that decays is the one in the halo, beryllium-11 could go an entirely different route: It could undergo a dark decay.

In 2019, the researchers launched an experiment at Canada’s national particle accelerator facility, TRIUMF, looking for that very hypothetical decay. And they did find a decay with unexpectedly high probability, but it wasn’t a dark decay.

It looked like the beryllium-11’s loosely bound neutron was ejecting an electron like normal beta decay, yet the beryllium wasn’t following the known decay path to boron. 

The team hypothesized that the high probability of the decay could be explained if a state in boron-11 existed as a doorway to another decay, to beryllium-10 and a proton. For anyone keeping score, that meant the nucleus had once again become beryllium. Only now it had six neutrons instead of seven.

“This happens just because of the halo nucleus,” Ayyad said. “It’s a very exotic type of radioactivity. It was actually the first direct evidence of proton radioactivity from a neutron-rich nucleus.”

But science welcomes scrutiny and skepticism, and the team’s 2019 report was met with a healthy dose of both. That “doorway” state in boron-11 did not seem compatible with most theoretical models. Without a solid theory that made sense of what the team saw, different experts interpreted the team’s data differently and offered up other potential conclusions.

“We had a lot of long discussions,” Mittig said. “It was a good thing.”

As beneficial as the discussions were — and continue to be — Mittig and Ayyad knew they’d have to generate more evidence to support their results and hypothesis. They’d have to design new experiments.

The NSCL experiments

In the team’s 2019 experiment, TRIUMF generated a beam of beryllium-11 nuclei that the team directed into a detection chamber where researchers observed different possible decay routes. That included the beta decay to proton emission process that created beryllium-10.

For the new experiments, which took place in August 2021, the team’s idea was to essentially run the time-reversed reaction. That is, the researchers would start with beryllium-10 nuclei and add a proton. 

Collaborators in Switzerland created a source of beryllium-10, which has a half-life of 1.4 million years, that NSCL could then use to produce radioactive beams with new reaccelerator technology. The technology evaporated and injected the beryllium into an accelerator and made it possible for researchers to make a highly sensitive measurement.

When beryllium-10 absorbed a proton of the right energy, the nucleus entered the same excited state the researchers believed they discovered three years earlier. It would even spit the proton back out, which can be detected as signature of the process.

“The results of the two experiments are very compatible,” Ayyad said.

That wasn’t the only good news. Unbeknownst to the team, an independent group of scientists at Florida State University had devised another way to probe the 2019 result. Ayyad happened to attend a virtual conference where the Florida State team presented its preliminary results, and he was encouraged by what he saw. 

“I took a screenshot of the Zoom meeting and immediately sent it to Wolfi,” he said. “Then we reached out to the Florida State team and worked out a way to support each other.”

The two teams were in touch as they developed their reports, and both scientific publications now appear in the same issue of Physical Review Letters. And the new results are already generating a buzz in the community.

“The work is getting a lot of attention. Wolfi will visit Spain in a few weeks to talk about this,” Ayyad said.

An open case on open quantum systems

Part of the excitement is because the team’s work could provide a new case study for what are known as open quantum systems. It’s an intimidating name, but the concept can be thought of like the old adage, “nothing exists in a vacuum.”

Quantum physics has provided a framework to understand the incredibly tiny components of nature: atoms, molecules and much, much more. This understanding has advanced virtually every realm of physical science, including energy, chemistry and materials science.

Much of that framework, however, was developed considering simplified scenarios. The super small system of interest would be isolated in some way from the ocean of input provided by the world around it. In studying open quantum systems, physicists are venturing away from idealized scenarios and into the complexity of reality.

Open quantum systems are literally everywhere, but finding one that’s tractable enough to learn something from is challenging, especially in matters of the nucleus. Mittig and Ayyad saw potential in their loosely bound nuclei and they knew that NSCL, and now FRIB could help develop it.

NSCL, a National Science Foundation user facility that served the scientific community for decades, hosted the work of Mittig and Ayyad, which is the first published demonstration of the stand-alone reaccelerator technology. FRIB, a U.S. Department of Energy Office of Science user facility that officially launched on May 2, 2022 is where the work can continue in the future. 

“Open quantum systems are a general phenomenon, but they’re a new idea in nuclear physics,” Ayyad said. “And most of the theorists who are doing the work are at FRIB.”

But this detective story is still in its early chapters. To complete the case, researchers still need more data, more evidence to make full sense of what they’re seeing. That means Ayyad and Mittig are still doing what they do best and investigating.

“We’re going ahead and making new experiments,” said Mittig. “The theme through all of this is that it’s important to have good experiments with strong analysis.”

NSCL was a national user facility funded by the National Science Foundation, supporting the mission of the Nuclear Physics program in the NSF Physics Division.

Michigan State University (MSU) operates the Facility for Rare Isotope Beams (FRIB) as a user facility for the U.S. Department of Energy Office of Science (DOE-SC), supporting the mission of the DOE-SC Office of Nuclear Physics. Hosting what is designed to be the most powerful heavy-ion accelerator, FRIB enables scientists to make discoveries about the properties of rare isotopes in order to better understand the physics of nuclei, nuclear astrophysics, fundamental interactions and applications for society, including in medicine, homeland security and industry.

The U.S. Department of Energy Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of today’s most pressing challenges. For more information, visit energy.gov/science.

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Michigan State University has been advancing the common good with uncommon will for more than 165 years. One of the world's leading research universities, MSU pushes the boundaries of discovery to make a better, safer, healthier world for all while providing life-changing opportunities to a diverse and inclusive academic community through more than 200 programs of study in 17 degree-granting colleges.

For MSU news on the Web, go to MSUToday. Follow MSU News on Twitter at twitter.com/MSUnews.

Light polarization creates art, explains mathematical concepts

Color visualization illustrates birefringence, polarization, retardance

Peer-Reviewed Publication

AMERICAN INSTITUTE OF PHYSICS

The stochastic stress-induced birefringence within plastic spoons left in the hot sun is visualized through polarization-filtered coloration 

IMAGE: THE STOCHASTIC STRESS-INDUCED BIREFRINGENCE WITHIN PLASTIC SPOONS LEFT IN THE HOT SUN IS VISUALIZED THROUGH POLARIZATION-FILTERED COLORATION. THE SPOONS ARE PLACED BETWEEN A PAIR OF CO-ALIGNED POLARIZER SHEETS IN AN OPEN-GATE ARRANGEMENT, WITH A BACKING OF PARCHMENT PAPER TO ACT AS A DIFFUSER FOR SUNLIGHT ILLUMINATION. view more 

CREDIT: AARON SLEPKOV, TRENT UNIVERSITY

WASHINGTON, July 22, 2022 – The polarization of light underpins a variety of recent technological innovations, including 3D cinema and LCDs. In LCDs, tiny electronically controllable liquid crystal elements are sandwiched between polarizers. If, instead, other transparent polarization-altering films – like cellophane gift wrap and packaging tape – are placed between a set of polarizers, an array of polarization-filtered colors can be observed.

In the American Journal of Physics, by AIP Publishing, Aaron Slepkov, from Trent University in Canada, explores the physics of how such colors emerge, how they can be controlled, and why subtle changes in viewing angle, sample orientation, and the order of layers of films between polarizers can have dramatic effects on the observed colors.

The research emphasizes visual examples of concepts related to birefringence, such as addition, subtraction, and order-of-operations. For example, the noncommutative nature of birefringent addition is typically illustrated using formal matrix mathematics. However, in this case, the researchers use color visualization.

"I use a visual language of coloration to illustrate subtle physics that is often only demonstrated mathematically," said Slepkov.

He was inspired, in part, by the work of artist Austine Wood Comarow, who made a career in applying polarization-filtered coloring techniques in fine art. Austine coined the term "polage," or polarization of collage, to refer to her art.

Austine created a wide array of works using sophisticated layering of cut cellophane and other birefringent polymer films, interspersed with layers of film polarizers. Her pieces range from small stand-alone pieces that fit on a shelf to massive career-spanning installations in institutions, such as the Disney Epcot Center in 1981 and the Gyeongsangnam-do Institute of Science Education, in Jinju, South Korea, in 2017.

"In this work, I clarify the link between polarization filtering and the observed colors. I demonstrate how various aspects of birefringence in common household films provide opportunities and challenges for their use in art," said Slepkov.

To create polarization-filtered color, all that is needed is a birefringent sample sandwiched between polarizers that form a polarization gate. Many household items can provide a kaleidoscopic array of colors and patterns.

Transparent plastic cutlery, for instance, provide a classic demonstration, where localized strain in the polymer structure results in differential birefringence, observable through a polarization gate. Likewise, somewhat randomly folded kitchen cling wrap, gift basket film, and layered adhesive tape can form intricate images reminiscent of stained-glass windows.

"The manipulation of birefringent films for the purpose of creating color images is fun and intellectually stimulating. Much of the nuanced physics of polarization, birefringence, retardance, and color theory can be observed in this accessible yet expansive endeavor," said Slepkov.

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The article "Painting in polarization" is authored by Aaron Slepkov. The article will appear in the American Journal of Physics on July 22, 2022 (DOI: 10.1119/5.0087800). After that date, it can be accessed at https://aip.scitation.org/doi/full/10.1119/5.0087800.

ABOUT THE JOURNAL

The American Journal of Physics is devoted to the instructional and cultural aspects of physics. The journal informs physics education globally with member subscriptions, institutional subscriptions, such as libraries and physics departments, and consortia agreements. It is geared to an advanced audience, primarily at the college level. Contents include novel approaches to laboratory and classroom instruction, insightful articles on topics in classical and modern physics, apparatus, and demonstration notes, historical or cultural topics, resource letters, research in physics education, and book reviews. See https://aapt.scitation.org/journal/ajp.

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PFAS FOREVER CHEMICALS

Research examines effects of embryonic exposure to environmental pollutants on risk of diabetes


UMass Amherst scientist awarded $2.44 million grant renewal from NIH

Grant and Award Announcement

UNIVERSITY OF MASSACHUSETTS AMHERST

Environmental health scientist 

IMAGE: ALICIA TIMME-LARAGY IS AN ASSOCIATE PROFESSOR IN THE UMASS AMHERST SCHOOL OF PUBLIC HEALTH AND HEALTH SCIENCES. view more 

CREDIT: UMASS AMHERST

A University of Massachusetts Amherst environmental health scientist has received a $2.44 million, five-year grant renewal from the National Institutes of Health (NIH) to continue her research into how embryonic exposure to certain common pollutants may put people at risk for diabetes and other metabolic health conditions later in life. 

Alicia Timme-Laragy, associate professor in the School of Public Health and Health Sciences, examines the impact on the developing pancreas of early life-stage exposures to two common per and polyfluoroalkylated substances (PFAS) chemicals, found in waterproof and nonstick household products, and the PFAS-containing aqueous film-forming foam (AFFF), used to fight flammable-liquid fires. These so-called “forever chemicals” take decades to break down in the environment and have contaminated drinking water worldwide. 

“A lot of people are working actively to understand what the long-term health implications are of these compounds,” Timme-Laragy says. “We’re trying to contribute to the scope of knowledge on what these compounds do, and I think we have a unique opportunity with our model and experimental protocols.”

Timme-Laragy and her research team, including UMass colleague John Clark, a professor of environmental toxicology in Veterinary and Animal Sciences (VASCI), use transgenic zebrafish to study the effects of these toxic chemicals on embryonic development.

“We are able to study in real time the effects on a very small subset of cells in live, transparent zebrafish embryos,” she says. “It’s a unique opportunity.”

The researchers will build on one of their key previous findings showing that oxidative stress created from the chemical exposures results in malformations of the developing pancreatic islet, which contains beta cells (β-cells) responsible for synthesizing, storing and releasing insulin.

“We want to better understand these mechanisms and the functional implications of these malformations,” says Timme-Laragy, who uses state-of-the-art imaging techniques including confocal microscopy at the Institute of Applied Life Sciences’ Light Microscopy Facility.

Pancreatic malformations, which occur in an estimated 10% of the population, are associated with type 1 and type 2 diabetes, as well as obesity and pancreatitis. In zebrafish exposed to PFAS chemicals, preliminary data have shown elevated levels of fructosamine, a clinical biomarker of diabetes in humans.

“That certainly suggests to us that there are long-term implications for development of diabetes later on,” Timme-Laragy says. “We want to understand the mechanisms involved within the beta cells and track individual fish that have malformed islets and see what are the effects on glucose homeostasis and the implications for overall growth and metabolism.”

Ultimately, the researchers hope to be able to predict the effects of other exposures once they understand the mechanisms occurring in the cells. They also hope to add to the evidence base on the health effects of PFAS chemicals.

The grant summary concludes, “This work will have a sustained and powerful impact on the fields of developmental toxicology, redox biology and the developmental origins of health and disease, and provides critical advances towards developing science-based PFAS guidelines, targets for clinical interventions and public health policies.”

Companies must invest to avoid a supply chain scandal or pay the price in lost consumers  

Peer-Reviewed Publication

UNIVERSITY OF SURREY

If a supply chain scandal does hit, customers want companies they buy from to act – and a combination of actions, not limited to firing their supplier – is the best way to minimise lost consumers. Apologies are not enough. 

Professor Sabine Benoit from Surrey Business School said:  

"Our research shows that companies need to do something – and that could include parting ways with a supplier if there's a scandal.  

"Customers will blame major firms for supply chain scandals – and this inherited blame will affect whether they buy from the firm in the future." 

Traditionally, supply chain managers have been encouraged to support their suppliers when wrongdoing is discovered in their supply chains. However, for many firms, this is not always a realistic option because it can be time-consuming and expensive.  

This research has found that firms also have the option to sack or monitor their suppliers – and this has the same effect on customers' buying intentions.  

Professor Benoit added:  

"Our research has found that taking one action – either monitoring and supporting suppliers to do better or moving on from them – will help to build trust and confidence in the major firm but purchasing intention only returns to 75% of what it was before the scandal hit. 

"The best option if a scandal does hit is for companies to double-down on their response by sacking the supplier who caused the scandal and work to support their remaining suppliers, then consumers' trust will start to rebuild, resulting in the best outcome possible – with purchasing intention rising to 85% of what it was before the scandal hit. 

"What this means for major companies is that consumers expect their brands to be doing good in the world – and there's a right way and a wrong way to handle supply chain scandal with a direct impact on the company's bottom line." 

The research, published by the Journal of Supply Chain Management, was carried out over a period of five years by authors in the United Kingdom, Germany and the United States. 

 

ENDS 

Note to Editors: 

  • There is an animated video explaining the research. 

  • The University of Surrey is a research-intensive university producing world-leading research that transforms lives and changes the world for the better. A focus on research that makes a difference to the world has contributed to Surrey being ranked 55th in the world in the Times Higher Education (THE) University Impact Rankings 2022, which assesses more than 1,400 universities' performance against the United Nations' Sustainable Development Goals (SDGs).   

Researchers determine the complex structure of the receptors related to the addictive effects of opioids

Receptors, macrostructures and pharmacological activity

Peer-Reviewed Publication

UNIVERSITY OF BARCELONA

UB SCIENTIFIC TEAM 

IMAGE: FROM LEFT TO RIGHT, THE EXPERTS NATÀLIA LLOPART, ESTEFANÍA MORENO, VERÒNICA CASADÓ AND VICENT CASADÓ. view more 

CREDIT: UNIVERSITY OF BARCELONA

A study published in the journal Pharmacological Research reveals the oligomeric molecular structure of the MOR-Gal1R complex, a component present in the brain which is involved in the analgesic and addictive effects of certain opioids. The study includes the participation of the experts Vicent Casadó, Estefanía Moreno and Verònica Casadó-Anguera, from the Molecular Neuropharmacology Research Group of the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB).

The study is coordinated by the experts Vicent Casadó (UB-IBUB), Leonardo Pardo (UAB), Leigh Daniel Plant (Boston Northeastern University, United States) and Sergi Ferré (National Institute on Drug Abuse, NIH, United States).This preclinical study, based on the use of cellular models and leading biophysical, biochemical and pharmacological techniques (total internal reflection fluorescence microscopy, TIRF), has been distinguished for its scientific interest in the website of the NIH’s National Institute on Drug Abuse.

Receptors, macrostructures and pharmacological activity

Gal1R and MOR receptors belong to the family of G protein-coupled receptors (GPCRs) that take part in the transduction of different cellular signals and the control of essential cell functions. These structures can form dimers —homodimers or heterodimers— that determine functional and pharmacological properties that are different from those of the individual components.

The study shows different in vitro evidences that reveal the preference of Gal1R and MOR receptors to form homodimeric complexes (MOR-MOR or Gal1R-Gal1R) in cell cultures when they are expressed separately. When expressed together, tetrameric complexes (heterotetramers) are formed by homodimers of both receptors (MOR-MOR-Gal1R-Gal1R-Gal1R).

"This heterotetrameric structure is even more complex because when the homodimers of both receptors join to form the MOR-MOR macrocomplex, the interaction and corresponding signalling is maintained by means of their characteristic G protein (the G protein inhibitory to adenylate cyclase or Gi)", says Vicent Casadó, member of the Department of Biochemistry and Molecular Biomedicine and the IBUB.

"However, Gal1R-Gal1R exchanges its characteristic inhibitory G-protein for the adenylyl cyclase-stimulating G-protein (Gs). This higherorder oligomeric complex contains more than 10 protein subunits considering the four receptors, the two heterotrimeric G-proteins and the adenylyl cyclase enzyme on which both G-proteins act to up- or down-regulate the intracellular levels of the cyclic AMP messenger", adds the expert. Determining the molecular characteristics of this macrostructure would explain the molecular mechanism by which the neuropeptide galanin —which has neurotrophic and neuroprotective properties— causes a decrease in the release of dopamine into the nucleus accumbens induced by opioids, as described by the same team (Journal of Neuroscience, 2016).

"This would be possible because when the Gal1R ligand binds to the heteromer, it activates the Gs protein, which interacts with the same adenylyl cyclase that was inhibited by the MOR-activated Gi protein, so it counteracts the secondary effects that opioid ligands have in activating the MOR receptors in the ventral tegmental area", says researcher Estefanía Moreno, member of the Department of Biochemistry and Molecular Biomedicine and IBUB.

Searching for new non-addictive drugs

In previous studies, the team from the Faculty of Biology and the IBUB had already showed that the greater proportion of analgesic —and not euphoric— effects of methadone administration make this compound the most indicated non-addictive option for the treatment of chronic pain (Journal of Clinical Investigation, 2019). This could be explained by the fact that methadone acts preferentially on MOR receptors when they do not form heteromers with Gal1R receptors, and therefore, its effect is mainly peripheral.

"Now, knowing this tetrameric macrostructure of the receptor complex —in addition to the differential capacities of opioid ligands to activate MOR depending on the formation of oligomeric complexes with other receptors— will facilitate the future design of opioid drugs that can bind with a greater affinity or can bind more effectively the signal pathways with mu-opioid receptor homodimers than with the MOR-Gal1R heterotetramers”, notes researcher Verònica Casadó-Anguera.

Specifically, it would be about μ-opioid receptor drugs capable of discriminating between homodimers of these compounds and their heterotetramers with galanin receptors. "It is also possible to design a strategy that combines opioid ligands with Gal1R ligands that bind to the heterotetramer and inhibit the activation of the dopamine system and, therefore, addiction. Thus, these therapies are expected to have a greater analgesic effect and less addictive activity", concluded the research team.

POSTMODERN ALCHEMY

Porous crystals bind fluorine-containing greenhouse gases

Heidelberg researchers develop new crystalline materials that adsorb polyfluorinated hydrocarbons on their surface

Peer-Reviewed Publication

HEIDELBERG UNIVERSITY

Porous crystals 

IMAGE: IN THE BACKGROUND: LIGHT MICROSCOPY IMAGES OF THE SINGLE-CRYSTAL STRUCTURES OF THE SHAPE-PERSISTENT ORGANIC CAGE COMPOUND. IN THE FRONT: BALL-AND-STICK MODEL OF THE SINGLE-CRYSTAL STRUCTURE, GREY: CARBON, WHITE: HYDROGEN, RED: OXYGEN, BLUE: NITROGEN, GREEN: FLUORINE. view more 

CREDIT: PROF. DR. MICHAEL MASTALERZ

Emissions of greenhouse gases contribute significantly to global warming. Not only carbon dioxide (CO2) but also fluorine-containing gases – including so-called per- or polyfluorinated hydrocarbons, or PFCs – have a significant share in this development. Researchers at the Institute of Organic Chemistry of Heidelberg University led by Prof. Dr Michael Mastalerz recently developed new crystalline materials that can selectively adsorb the molecules of such carbon-fluorine bonds. The Heidelberg researchers hope that these porous crystals may be useful for targeted binding and recovery of PFCs.

Polyfluorinated carbons are organic compounds of various lengths in which the hydrogen atoms of alkanes are partly or fully replaced by fluorine atoms. These atoms are chemically highly stable. They are not ubiquitous in nature and are used mainly for etching processes in the semiconductor industry, in eye surgery, and in medical diagnostics as contrast enhancers for certain ultrasound examinations. “Unlike CO2, which is integrated in natural material cycles, PFCs accumulate in the atmosphere and stay there for several thousands of years before breaking down,” stresses Prof. Mastalerz. Compared to carbon dioxide, PFCs thus have a much greater global warming potential – the impact of one PFC molecule is virtually equal to 5,000 to 10,000 CO2 molecules. According to the researcher, that makes polyfluorinated hydrocarbons a permanent problem that is not only contributing to global warming now but accelerating it as well.

With his research group at the Institute of Organic Chemistry of Heidelberg University, Prof. Mastalerz has developed a new type of crystalline material that can adsorb polyfluorinated hydrocarbons highly selectively, i.e., binding them to its interior surface. The porous crystals are based on shape-persistent organic cage compounds that carry fluorine-containing side chains on the interconnected struts. These side chains react according to the “like attracts like” principle via fluorine-fluorine interactions with the PFC molecules, ensuring they are deposited on the inner surface of the material. In their experiments, the Heidelberg researchers proved that the crystals they developed bind certain fluorine-containing gases such as octafluoropropane or octafluorocyclobutane approximately 1,500 to 4,000 times more strongly than dinitrogen, the main component of air. According to Prof. Mastalerz, these numbers represent extraordinarily high selectivities to bind such PFCs.

Currently Prof. Mastalerz and his team are working on further increasing the selectivity of the crystals and transferring the process to other fluorinated gases, such as those used in medical anaesthesia. “I see enormous potential for development in this area,” emphasises the researcher. He hopes that the adsorbent can be used for recovery of polyfluorinated hydrocarbons at their point of use.

The German Research Foundation funded the research. The research results were published in “Advanced Materials”.