Daily Archives: 8 Feb 2021

Material science

Researchers Develop Flexible Crystal, Paving the Way For More Efficient Bendable Electronics (Material Science)

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A team of researchers led by Nanyang Technological University, Singapore (NTU Singapore) has developed a new material, that when electricity is applied to it, can flex and bend forty times more than its competitors, opening the way to better micro machines. 

Conversely, when it is bent, it generates electricity very effectively and could be used for better “energy harvesting” – potentially recharging batteries in gadgets just from everyday movements.

The novel material is both electrostrictive and piezoelectric. Its electrostrictive properties means it can change shape when an electric current is applied, while piezoelectric means the material can convert pressure into electric charges.

NTU Prof Fan Hong Jin (left) with PhD student Mr Hu Yuzhong, both holding the new piezoelectric crystal which can flex up to 40 times more than conventional ferroelectric crystals when electricity is applied. © NTU Singapore

When an electric field is applied, the atoms that make up electrostrictive materials shift, causing the material to deform and flex. When piezoelectrics are compressed, the pressure is converted to electric charges which accumulate in the material. 

The scientists found that when an electric field is applied, the new hybrid material could be strained up to 22 per cent, the highest strain reported in a piezoelectric material so far. This far surpasses conventional piezoelectric materials that only deform up to 0.5 per cent when a current is passed through it. The new material is also more energy-efficient than other piezoelectric and electrostrictive materials.

Piezoelectric materials are commonly used in guitars, loudspeakers, sensors and electric motors. For instance, a piezoelectric pick-up is a device used in an electric guitar to convert the vibrations from the strings into an electric signal, which is then processed for music recording or to be amplified through loudspeakers. 

Ferroelectric crystals were first discovered in 1920 and have been used to make piezoelectrics for over 70 years, as they are easily integrated into electrical devices. 

However, they are brittle and inflexible, bending only 0.5 per cent, which largely limits their application in electronic devices such as actuators (parts that convert an electric control signal into mechanical motion, for example, a valve that opens and closes).

A profile photo of Professor Junling Wang from the Southern University of Science and Technology, China, a former NTU professor at the School of Materials Science and Engineering, who is a co-author of the paper. © NTU Singapore

Some ferroelectrics also contain lead, which is toxic, and its presence in piezoelectric devices is one of the reasons why electronic waste is challenging to recycle. Traditional ferroelectrics such as perovskite oxides are also unsuitable for flexible electrical devices that are in contact with the skin, such as wearable biomedical devices that track heart rate.    

Published in the scientific journal Nature Materials last month, the new material was created at NTU by Professor Fan Hong Jin from the School of Physical & Mathematical Sciences and his team, including his PhD student Mr Hu Yuzhong who is the first author of this paper. Also part of the team is Professor Junling Wang from the Southern University of Science and Technology, China, a former NTU professor at the School of Materials Science and Engineering. 

Prof Fan said, “Being more than 40 times more flexible than similar electrostrictive materials, the new ferroelectric material may be used in highly efficient devices such as actuators and sensors that flex when an electric field is applied. With its superior piezoelectric properties, the material can also be used in mechanical devices that harvest energy when bent, which will be useful to recharge wearable devices.

“We think we can substantially improve on this performance in future by further optimising the chemical composition, and we believe this type of material could play a key role in the development of wearable devices for the Internet of Things (IOT), one of the key technologies enabling the 4th Industrial Revolution.” 

Developing a flexible ferroelectric material

To develop a flexible ferroelectric material, the researchers modified the chemical structure of a hybrid ferroelectric compound C6H5N(CH3)3CdCl3, or PCCF in short, which can potentially bend up to a hundred times more than traditional ferroelectrics. 

To increase the material’s range of movement further, the scientists modified the chemical makeup of the compound by substituting some of its chlorine (Cl) atoms for bromine (Br), which has a similar size to chlorine, to weaken the chemical bonds at specific points in the structure. This made the material more flexible without affecting its piezoelectric qualities.  

The new material is easy to manufacture, requiring only solution-based processing in which the crystal forms as the liquid evaporates, unlike typical ferroelectric crystals that require the use of high-powered lasers and energy to form. 

When an electric field was applied to the new PCCF compound, the atoms in it shifted substantially more than the atoms in most conventional ferroelectrics, straining up to 22 per cent far more than conventional piezoelectric materials.

Other authors of the paper include researchers from NTU’s School of Materials Science and Engineering, Facility for Analysis, Characterisation, Testing and Simulation (FACTS), Soochow University and Southern University of Science and Technology, China.

Featured image: A close up of the new piezoelectric crystal developed by NTU scientists, which can flex up to 40 times more than the conventional ferroelectric crystals typically used in small actuators and sensors. © NTU Singapore

Reference:
Titled “Ferroelastic-switching-driven large shear strain and piezoelectricity in a hybrid ferroelectric”, the paper is published in Nature Materials (Jan 2021). https://www.nature.com/articles/s41563-020-00875-3

Provided by Nanyang Technological University

Chemistry

Understanding Catalytic Couplings: Not All Synergies Are Simple (Chemistry)

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Negishi cross-coupling reactions have been widely used to form C-C bonds since the 1970s and are often perceived as the result of two metals (i.e zinc and palladium/nickel) working in synergy. But like all relationships, there is more under the surface than what we first expected. PhD student Craig Day and Dr. Rosie Somerville from the Martin group at ICIQ have delved into the Negishi cross-coupling of aryl esters using nickel catalysis to understand how this reaction works at the molecular level and how to improve it. The results have been published in Nature Catalysis.

Compared to palladium, nickel has the advantage of being readily available transition metal, with unique chemical properties that allow for the activation of challenging bonds otherwise inaccessible by palladium cross-coupling endeavours. These characteristics make it attractive for the development of synthetic applications, and over the last decades, it has proven to be a rapid and reliable way to rapidly and reliably build up molecular complexity from simple and available precursors. To the researchers this Nature Catalysis paper provides a rationalisation of how and why nickel-catalysed cross-coupling reactions work at a level that wasn’t attempted before. “Our work provides an unprecedented look at the speciation of Ni catalysts in Negishi cross-coupling reactions, and have unraveled a counterintuitive dichotomy exerted by Zn(II) salts in catalytic activity. Given the important role exerted by Zn in a myriad of Ni-catalysed reactions, one might expect that these transformations obey similar principles to those described in our study, thus offering new vistas for designing new catalytic systems or outperform existing ones” explains Prof. Ruben Martin, ICIQ group leader and ICREA professor.

Using an organometallic approach to investigate and identify the nickel species involved in the catalytic cycle, the team has been able to isolate the individual intermediates and show how they are all connected in the catalytic cycle. This led them to contemplate there were other meaningful, although undesired, interactions happening between the two metals nickel and zinc. “The interaction between the two metals is required for the transformation, but it can also be deleterious in other ways. Chemists need to be aware of these problems to design better catalytic reactions,” quips Craig S. Day, PhD student in the group of Prof. Ruben Martín and first author of the paper.

The scientists have discovered there are three undesired off-cycle pathways happening: ligand scavenging, reduction-oxidation pathways and the formation of unorthodox Ni/Zn clusters. Although speculated for a long time, this work offers the first direct evidence of Ni-Zn interactions. In addition, the research shows the importance of the nature of the solvent used in the reaction as it plays a role in regulating the interactions of the catalyst and zinc species. In fact, looking further into the role of zinc in these systems, the researchers believe there is still more to be determined about how the properties of ligands affect the interactions among the catalytic couple.

Tying together all the concepts, the work easily extrapolates to other cross-couplings, opening up new avenues of research to explore the inner workings of different systems. “We’ve provided a model for how similar reactions should occur. Both in understanding how aryl-oxygen electrophiles can be functionalised and lessons in Ni-catalysed Negishi cross-coupling reactions” concludes Day.

Featured image: Overview of the catalytic transformation and key structures identified by the Martin group. Credit: Craig S. Day

Reference paper: Deciphering the dichotomy exerted by Zn(ii) in the catalytic sp2 C–O bond functionalization of aryl esters at the molecular level Day, Craig S.; Somerville, R.; Martin, R. Nat. Catalysis 2021. DOI: 10.1038/s41929-020-00560-3.

Provided by ICIQ

Neuroscience

As You Look Around, Mental Images Bounce Between Right and Left Brain (Neuroscience)

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Ask anyone from an NFL quarterback scanning the field for open receivers, to an air traffic controller monitoring the positions of planes, to a mom watching her kids run around at the park: We depend on our brain to hold what we see in mind, even as we shift our gaze around and even temporarily look away. This capability of “visual working memory” feels effortless, but a new MIT study shows that the brain works hard to keep up. Whenever a key object shifts across our field of view—either because it moved or our eyes did—the brain immediately transfers a memory of it by re-encoding it among neurons in the opposite brain hemisphere.

The finding, published in Neuron by neuroscientists at The Picower Institute for Learning and Memory, explains via experiments in animals how we can keep continuous track of what’s important to us, even though our visual system’s basic wiring requires mapping what we see on our left in the right side of our brain and what we see on our right in the left side of the brain.

“You need to know where things are in the real world, regardless of where you happen to be looking or how you are oriented at a given moment,” said study lead author Scott Brincat, a postdoctoral researcher in the lab of Picower Professor Earl Miller, the senior author. “But the representation that your brain gets from the outside world changes every time you move your eyes around.”

In their experiments, Brincat, Miller and co-authors found that when an object switches sides in the field of view, the brain rapidly employs a telltale change in the synchrony of brain wave frequencies to shepherd the memory information from one side of the brain to the other. The transfer, which occurs in mere milliseconds, recruits a new group of neurons in the prefrontal cortex of the opposite brain hemisphere to store the memory. This new ensemble of neurons encodes the object based on its new position, but the brain continues to recognize it as the object that used to be in the other hemisphere’s field of view.

That ability—to remember that something is the same thing no matter how it’s moving around relative to our eyes—is what gives us the freedom to control where we look, Miller said. Tampa Bay Buccaneers quarterback Tom Brady, for instance, can decide to shift his gaze from the left side of the field to the right side without having to fear that he’ll instantly forget that those left-side receivers are still there, even if changing the gaze position has substantially shifted them within, or even out of, his field of view.

“If you didn’t have that, we would just be simple creatures who could only react to whatever is coming right at us in the environment, that’s all,” Miller said. “But because we can hold things in mind, we can have volitional control over what we do.  We don’t have to react to something now, we can save it for later.”

Shifting sides

In the lab, the researchers measured the activity of hundreds of neurons in the prefrontal cortex of both brain hemispheres as animals played a game. They had to fix their gaze on one side of a screen as an image of an object (e.g. a banana) appeared briefly in the middle of the screen. The object thus appeared on one or the other side of their field of view, and due to the brain’s crossed wiring, it was processed in the opposite cortical hemisphere. The animal had to hold the image in mind, then indicate if a subsequently presented image was of a different object (e.g. an apple). On some trials, though, while the original object was held in working memory the animals were cued to switch their gaze from one side to the other, effectively changing which side of their field of view the remembered image was on.

Animals were accurate in remembering whether the images they were presented matched, but their performance suffered just a little bit in cases where they had to shift their gaze. Brincat said the error suggests that having to keep up with the shift is not as easy for the brain as it seems.

“It feels trivial to us, but it apparently isn’t,” he said.

To analyze their measurements in the brain, the team trained a computer program called a decoder to identify patterns in the raw data of neural activity that indicated the memory of the object image. As expected, that analysis showed that the brain encoded information about each image in the hemisphere opposite of where it was in the field of view. But more remarkably, it also showed that in cases where the animals shifted their gaze across the screen, neural activity encoding the memory information shifted from one brain hemisphere to the other.

The team also measured the overall rhythms of the neurons’ collective activity, or brain waves. They found that the transfer of a memory from one hemisphere to the other consistently occurred with a signature change in those rhythms. As the transfer occurred, the synchrony across hemispheres of very low frequency “theta” waves (~4-10 Hz) and high frequency “beta” waves (~17-40 Hz) rose and the synchrony of “alpha/beta” waves (~11-17 Hz) declined.

This push-and-pull pattern of rhythms closely resembles one that Miller’s lab has found in many studies of how the cortex employs rhythms to transmit information. Increases in the combination of very low and higher frequency rhythms allows sensory information (i.e. representations of what the animal just saw) to be encoded or recalled. A power increase in the alpha/beta frequency range inhibits that encoding, acting as a sort of gate on sensory information processing.

“This is another form of gating,” Miller said. “This time alpha/beta is gating the memory transfer between hemispheres.”

Spotting a surprise

While the rhythm patterns seemed consistent with prior studies, the researchers were surprised by another finding of the study: Given the same object image in the same spot in the field of view, the prefrontal cortex employed different neurons if it was initially seen at that location vs. transferred from the other hemisphere. In other words, animals seeing a banana in the left side of their vision recruited a different neural ensemble to represent that memory than they did if the banana was previously seen on the right and then transferred to that spot.

To Miller, the finding has an intriguing implication. Neuroscientists once thought that individual neurons were the basic unit of function in the brain and more recently have begun to think that instead ensembles of neurons are. The new findings, however, suggest that even the same information could still be encoded by different, arbitrarily assembled ensembles.

“Perhaps even ensembles aren’t the functional units of the brain,” Miller speculated. “So what is the functional unit of the brain? It’s the computational space that brain network activity creates.”

In addition to Brincat and Miller the paper’s other authors are Jacob Donoghue, Meredith Mahnke, Simon Kornblith and Mikael Lundqvist.

The National Institute of Mental Health, Office of Naval Research, the JPB Foundation, and the National Institute of General Medical Sciences funded the research.

Featured image: Visual memories transfer from one hemisphere to the other when a mental image shifts across the field of view. Illustration credit: Jessica Bell.

Reference: Scott L. Brincat, Jacob A. Donoghue, Meredith K. Mahnke et al., “Interhemispheric transfer of working memories”, Neuron, 2021 DOI: https://doi.org/10.1016/j.neuron.2021.01.016 https://www.cell.com/neuron/fulltext/S0896-6273(21)00038-6

Provided by Picower Institute

Medicine

New Clues to How SARS-CoV-2 Infects Cells (Medicine)

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The molecular details of how SARS-CoV-2 enters cells and infects them are still not clear. Researchers at Uppsala University have tested the bioinformatic predictions made by another research group and have identified receptors that could be important players in the process. The results are presented in the journal Science Signaling and at the AAAS Annual Meeting held this week.

The spike protein of SARS-CoV-2 binds the protein ACE2 on the outside of the human cell. This triggers a series of events that leads to invasion of the cell by the virus. The molecular details of this process have remained obscure despite much research on SARS-CoV-2 and other coronaviruses. Moreover, ACE2 is not present in human lung cells, which would suggest that different players are involved when the virus infects these cells.

A recent study by researchers at Uppsala University sheds some new light on the issues. The study was published back-to-back with a study by an international team led by Dr Toby Gibson at the European Molecular Biology Laboratory (EMBL) in Heidelberg. The Gibson study predicted potential interactions that could be of importance for the entry of Sars-CoV-2 into the cell.

The researchers at Uppsala University tested the bioinformatic predictions in vitro and could show that ACE2 and the potential co-receptor integrin beta3 interact with important players involved in endocytosis and autophagy – cellular processes of uptake and disposal of substances. This means that these processes might be hijacked by the virus during infection.

“The Gibson team is world leading in terms of the bioinformatic analysis of these types of interactions, and we were excited to follow up on their predictions,” says Professor Ylva Ivarsson, who headed the Uppsala study. “Our results also helped them to improve their analysis. It was an easy decision to engage in this project, as our lab has a strong interest in host-pathogen protein-protein interactions.”

The research is also presented at the AAAS Annual Meeting held this week: From the Journal: New Biochemical Clues in Cell Receptors Help Explain How SARS-CoV-2 May Hijack Human Cells.

Reference: Kliche et al. (2021) Cytoplasmic short linear motifs in ACE2 and integrin β3 link SARS-CoV-2 host cell receptors to mediators of endocytosis and autophagy Sci. Signal. 14, eabf1117 https://stke.sciencemag.org/content/14/665/eabf1117.full

Provided by Uppsala University

Biology

What Rules Govern The Structure of Membraneless Organelles? (Biology)

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A study in Nature Communications outlines physical rules regulating the architecture of these liquid organelles.

In cells, numerous important biochemical functions take place within spherical chambers made from proteins and RNA.

These compartments are akin to specialized rooms inside a house, but their architecture is radically different: They don’t have walls. Instead, they take the form of liquid droplets that don’t have a membrane, forming spontaneously, similar to oil droplets in water. Sometimes, the droplets are found alone. Other times, one droplet can be found nested inside of another. And these varying assemblies can regulate the functions the droplets perform.

A study published on Feb. 8 in Nature Communications explores how these compartments, also known as membraneless organelles (MLOs) or biomolecular condensates, form and organize themselves.

The research lays out physical rules controlling the arrangement of various types of synthetic MLOs created using just three kinds of building materials: RNA and two different proteins, a prion-like polypeptide (PLP) and an arginine-rich polypeptide (RRP).

The project brought together a team from the University at Buffalo and Iowa State University.

University at Buffalo physics PhD student Taranpreet Kaur is first author of the new study in Nature Communications. Credit: Douglas Levere / University at Buffalo

“Different condensates can coexist inside the cells,” says first author Taranpreet Kaur, a PhD student in physics in the UB College of Arts and Sciences. “They can be detached, attached to another condensate, or completely embedded within one another. So how is the cell controlling this? We found two different mechanisms that allowed us to control the architecture of synthetic membraneless organelles formed inside a test tube. First, the amount of RNA in the mixture helps to regulate the morphology of the organelles. The other factor is the amino acid sequence of the proteins involved.”

“These two factors impact how sticky the surfaces of the condensates are, changing how they interact with other droplets,” says Priya Banerjee, PhD, UB assistant professor of physics, and one of two senior authors of the paper. “In all, we have shown using a simple system of three components that we can create different kinds of organelles and control their arrangement in a predictive manner. We suspect that such mechanisms may be employed by cells to arrange different MLOs for optimizing their functional output.”

Davit Potoyan, PhD, assistant professor of chemistry at Iowa State University, is the study’s other senior author.

Addressing questions in cell biology

Priya Banerjee, University at Buffalo assistant professor of physics. The Banerjee lab studies membraneless organelles.

The experiments were done on model systems made from RNA and proteins floating in a buffer solution. But the next step in the research — already underway — is to conduct similar studies inside a living cell.

“Going back to our motivations in researching MLOs, the big questions that started the field were questions in cell biology: How do cells organize their internal space?” Banerjee says. “The principles we uncover here contribute to the knowledge base that will improve understanding in this area.”

Research on MLOs could lead to advancements in fields such as synthetic cell research or new materials for drug delivery.

“We are in the process of learning the biomolecular grammar that may be a universal language used by cells for taming their inner cellular complexity. We hope one day to utilize this knowledge to engineer artificial protocells with custom-designed functionalities inspired by nature,” Potoyan says.

In addition to Banerjee, Potoyan and Kaur, co-authors of the study included Iowa State University chemistry postdoctoral researcher Muralikrishna Raju; UB physics PhD student Ibraheem Alshareedah; and UB physics postdoctoral researcher Richoo Davis.

The study was supported by the National Institute of General Medical Sciences, part of the U.S. National Institutes of Health, and the U.S. National Science Foundation (NSF). The team also received assistance from two NSF-funded resources: The UB North Campus Confocal Imaging Facility, and the Extreme Science and Engineering Discovery Environment.

Study co-authors Taranpreet Kaur (left) and Ibraheem Alshareedah, both physics PhD students at the University at Buffalo, prepare a microfluidic flow chamber for optical microscopy experiments. Credit: Douglas Levere / University at Buffalo

Featured image: A fluorescence microscopy image shows two types of immiscible biomolecular condensates (green and red) sticking to one another. A new study outlines physical rules regulating how such condensates, made from RNA and proteins, form and interact with one another. Credit: Taranpreet Kaur

Reference: Kaur, T., Raju, M., Alshareedah, I. et al. Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies. Nat Commun 12, 872 (2021). https://www.nature.com/articles/s41467-021-21089-4 https://doi.org/10.1038/s41467-021-21089-4

Provided by University at Buffalo

Psychiatry

Researchers Showed Brain Protein That Causes Alzheimer’s Actually Protects Against the Disease (Psychiatry)

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Findings from a new study on Alzheimer’s disease (AD), led by researchers at the University of Saskatchewan (USask), could eventually help clinicians identify people at highest risk for developing the irreversible, progressive brain disorder and pave the way for treatments that slow or prevent its onset.

The research, published in the journal Scientific Reports in early January, has demonstrated that a shorter form of the protein peptide believed responsible for causing AD (beta-amyloid 42, or Aβ42) halts the damage-causing mechanism of its longer counterpart.

“While Aβ42 disrupts the mechanism that is used by brain cells to learn and form memories, Aβ38 completely inhibits this effect, essentially rescuing the brain cells,” said molecular neurochemist Darrell Mousseau, professor in USask’s Department of Psychiatry and head of the Cell Signalling Laboratory.

Previous studies have hinted that Aβ38 might not be as bad as the longer form, said Mousseau, but their research is the first to demonstrate it is actually protective.

“If we can specifically take out the Aβ42 and only keep the Aβ38, maybe that will help people live longer or cause the disease to start later, which is what we all want.”

Aβ42 is toxic to cells, disrupts communication between cells, and over time accumulates to form deposits called plaques. This combination of factors is believed responsible for causing AD. Experts have long thought that all forms of Aβ peptides cause AD, despite the fact that clinical trials have shown removing these peptides from the brains of patients does not prevent or treat the disease.

Mousseau said the idea behind the study was simple enough: If two more amino acids is bad, what about two less?

“We just thought: Let’s compare these three peptides, the 40 amino acid one that most people have, the 42 amino acid that we think is involved in Alzheimer’s, and this 38 one, the slightly shorter version,” said Mousseau, who is Saskatchewan Research Chair in Alzheimer disease and related dementias, a position co-funded by the Saskatchewan Health Research Foundation and the Alzheimer Society of Saskatchewan.

The project confirmed the protective effects of the shorter protein across a variety of different analyses: in synthetic versions of the protein in test tubes; in human cells; in a worm model widely used for studying aging and neurodegeneration; in tissue preparations used to study membrane properties and memory; and in brain samples from autopsies. In the brain samples, they also found that men with AD who had more Aβ42 and less Aβ38 died at an earlier age. The fact that they didn’t see this same pattern in samples from women suggests the protein peptide behaves differently in men and women. 

The USask team also included Maa Quartey and Jennifer Nyarko from the Cell Signalling Lab (Department of Psychiatry), Jason Maley at the Saskatchewan Structural Sciences Centre, Carlos Carvalho in the Department of Biology, and Scot Leary in the Department of Biochemistry, Microbiology and Immunology. Joseph Buttigieg at the University of Regina and Matt Parsons at Memorial University of Newfoundland were also part of the research team.

While Mousseau wasn’t surprised to see that the shorter form prevents the damage caused by the longer version, he said he was a little taken aback at how significant an effect it had.

“As soon as you put Aβ38 into it, it brings it back up to control levels, completely inhibiting the toxic effects of Aβ42. That’s what was pleasantly surprising.” 

Featured image: Molecular neurochemist Darrell Mousseau is a professor in USask’s Department of Psychiatry and head of the Cell Signalling Laboratory. (Photo: University of Saskatchewan)

Reference: Quartey, M.O., Nyarko, J.N.K., Maley, J.M. et al. The Aβ(1–38) peptide is a negative regulator of the Aβ(1–42) peptide implicated in Alzheimer disease progression. Sci Rep 11, 431 (2021). https://doi.org/10.1038/s41598-020-80164-w https://www.nature.com/articles/s41598-020-80164-w

Provided by University of Saskatchewan

Astronomy

Sagittarius A East: Rare Blast’s Remains Discovered in Milky Way Center (Astronomy)

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  • Scientists have discovered the first evidence for a rare type of stellar explosion, or supernova in the Milky Way.
  • This intriguing object lies near the center of our galaxy in a supernova remnant called Sagittarius A East (Sgr A East).
  • Chandra data revealed that Sgr A East may belong to a special group of Type Ia supernovas.
  • This result helps astronomers understand the different ways that white dwarf stars can explode.

Astronomers have found evidence for an unusual type of supernova near the center of the Milky Way galaxy, as reported in our latest press release. This composite image contains data from NASA’s Chandra X-ray Observatory (blue) and the NSF’s Very Large Array (red) of the supernova remnant called Sagittarius A East, or Sgr A East for short. This object is located very close to the supermassive black hole in the Milky Way’s center, and likely overruns the disk of material surrounding the black hole.

Researchers were able to use Chandra observations targeting the supermassive black hole and the region around it for a total of about 35 days to study Sgr A East and find the unusual pattern of elements in the X-ray signature, or spectrum. An ellipse on the annotated version of the images outlines the region of the remnant where the Chandra spectra were obtained.

The X-ray spectrum of Sgr A East show that it is a strong candidate for the remains of a so-called Type Iax supernova, a special class of Type Ia supernova explosions that are used to accurately measure distances across space and study the expansion of the Universe.

Astronomers are still debating the cause of Type Iax supernova explosions, but the leading theory is that they involve thermonuclear reactions that travel much more slowly through the star than in normal Type Ia supernovas. This relatively slow walk of the blast leads to weaker explosions and, hence, different amounts of elements produced in the explosion. The researchers found this distinctive pattern of elements in the Chandra observations of Sgr A East.

Sagittarius A East (labeled) (Credit: X-ray: NASA/CXC/Nanjing Univ./P. Zhou et al. Radio: NSF/NRAO/VLA)

In other galaxies, scientists observe that Type Iax supernovas occur at a rate that is about one third that of Type Ia supernovas. In the Milky Way, there have been three confirmed Type Ia supernova remnants and two candidates that are younger than 2,000 years. If Sgr A East is younger than 2,000 years and is a Type Iax supernova, this study suggests that our Galaxy is in alignment with respect to the relative numbers of Type Iax supernovas seen in other galaxies.

Previous studies had argued that Sgr A East was the remnant from the collapse of a massive star, which is a wholly different category of supernova, although a normal Type Ia supernova had not been ruled out. The latest study conducted with this deep Chandra data argue against both the massive star and the normal Type Ia interpretations.

These results will be published on Wednesday February 10th, 2021 in The Astrophysical Journal, and a preprint is available online. The authors of the paper are Ping Zhao (Nanjing University in China, and previously at the University of Amsterdam), Shing-Chi Leung (California Institute of Technology), Zhiyuan Li (Nanjing University), Ken’ichi Nomoto (The University of Tokyo in Japan), Jacco Vink (University of Amsterdam), and Yang Chen (Nanjing University).

NASA’s Marshall Space Flight Center manages the Chandra program. The Smithsonian Astrophysical Observatory’s Chandra X-ray Center controls science from Cambridge Massachusetts and flight operations from Burlington, Massachusetts.

Featured image: X-ray: NASA/CXC/Nanjing Univ./P. Zhou et al. Radio: NSF/NRAO/VLA

Reference: Ping Zhou, Shing-Chi Leung, Zhiyuan Li, Ken’ichi Nomoto, Jacco Vink, Yang Chen, “Chemical abundances in Sgr A East: evidence for a Type Iax supernova remnant”, 2021, ApJ, accepted; arXiv:2006.15049 https://arxiv.org/abs/2006.15049

Provided by Chandra X-ray Observatory

Medicine

Bernese Researchers Create Sophisticated Lung-on-chip (Medicine)

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In collaboration with clinical partners from the Inselspital, researchers from the ARTORG Center for Biomedical Research of the University of Bern have developed a second-generation lung-on-chip model with life-size dimension alveoli in a stretchable membrane, made of purely biological material. The new model reproduces key aspects of the lung tissue architecture not found in previous lungs-on-chip. This opens up new possibilities for basic pneumological research, understanding lung pathologies, drug screening and precision medicine.

The lung is a complex organ whose main function is to exchange gases. It is the largest organ in the human body and plays a key role in the oxygenation of all the organs. Due to its structure, cellular composition and dynamic microenvironment, is difficult to mimic in vitro. 

A specialized laboratory of the ARTORG Center for Biomedical Engineering Research, University of Bern, headed by Olivier Guenat has developed a new generation of in-vitro models called organs-on-chip for over 10 years, focusing on modeling the lung and its diseases. After a first successful lung-on-chip system exhibiting essential features of the lung, the Organs-on-Chip (OOC) Technologies laboratory has now developed a purely biological next-generation lung-on-chip in collaboration with the Helmholtz Centre for Infection Research in Germany and the Thoracic Surgery and Pneumology Departments at Inselspital.

A fully biodegradable life-sized air-blood-barrier

Pauline Zamprogno, who developed the new model for her PhD thesis at the OOC, summarizes its characteristics: “The new lung-on-chip reproduces an array of alveoli with in vivo like dimensions. It is based on a thin, stretchable membrane, made with molecules naturally found in the lung: collagen and elastin. The membrane is stable, can be cultured on both sides for weeks, is biodegradable and its elastic properties allow mimicking respiratory motions by mechanically stretching the cells.”

Prof. Dr. Olivier Guenat, Head Organs-on-Chip Technologies, ARTORG Center for Biomedical Engineering Research, University of Bern. © Andres Burkhard / ARTORG Center for Biomedical Engineering

By contrast to the first generation, which was also built by the team around Olivier Guenat, the developed system reproduces key aspects of the lung extracellular matrix (ECM): Its composition (cells support made of ECM proteins), its structure (array of alveoli with dimension similar to those found in vivo + fiber structure) and its properties (biodegradability, a key aspect to investigating barrier remodeling during lung diseases such as IPF or COPD). Additionally, the fabrication process is simple and less cumbersome than that of a polydimethylsiloxane stretchable porous membrane from the first-generation lung-on-chip.

Broad potential clinical applications

Cells to be cultured on the new chip for research are currently obtained from cancer patients undergoing lung resections at the Inselspital Department of Thoracic Surgery. Department Head Ralph Schmid sees a double advantage in the system: “The second generation lung-on-chip can be seeded with either healthy or diseased lung alveolar cells. This provides clinicians with both a better understanding of the lung’s physiology and a predictive tool for drug screening and potentially also for precision medicine, identifying the specific therapy with the best potential of helping a particular patient.”

Dr. Pauline Zamprogno, PostDoc Organs-on-Chip Technologies, ARTORG Center for Biomedical Engineering Research, University of Bern. © zvg

“The applications for such membranes are broad, from basic science investigations into lung functionalities and pathologies, to identifying new pathways, and to a more efficient discovery of potential new therapies”, says Thomas Geiser, Head of the Department of Pneumology at the Inselspital and Director of Teaching and Research of the Insel Gruppe. 

Powerful alternative to animal models in research

As an additional plus, the new lung-on-chip can reduce the need for pneumological research based on animal models. “Many promising drug candidates successfully tested in preclinical models on rodents have failed when tested in humans due to differences between the species and in the expression of a lung disease,” explains Olivier Guenat. “This is why, in the long term, we aim to reduce animal testing and provide more patient-relevant systems for drug screening with the possibility of tailoring models to specific patients (by seeding organs-on-chip with their own cells).”

Pauline Zamprogno at the Organs-on-Chip Culture Laboratory of the ARTORG Center. © Adrian Moser

The new biological lung-on-chip will be further developed by Pauline Zamprogno and her colleagues from the OOC Technologies group to mimic a lung with idiopathic pulmonary fibrosis (IPF), a chronic disease of the lung leading to progressive scarring of the lung tissue within the framework of a research project funded by the Swiss 3R Competence Center (3RCC). “My new project consists in the development of an IPF-on- chip model based on the biological membrane. So far, we have develop a healthy air-blood barrier. Now it’s time to use it to investigate a real biological question,” says Zamprogno.

Video: The new lung-on-chip is a team development of the Organs-on-Chip Technologies of the ARTORG Center for Biomedical Engineering Research, University of Bern, with the Departments of Thoracic Surgery and Pneumology Inselspital, Bern University Hospital, and the Helmholtz Centre for Infection Research in Germany.

Video: This is how the new membrane works. © Artem Lopyrev / ARTORG Center for Biomedical Engineering Research

Featured image: Immunostaining of patients cell cultures on a second-generation lung-on-chip. © Pauline Zamprogno, ARTORG Center for Biological Engineering Research

Reference: Zamprogno, P., Wüthrich, S., Achenbach, S. et al.: Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane. Commun Biol 4, 168 (2021). https://www.nature.com/articles/s42003-021-01695-0 https://doi.org/10.1038/s42003-021-01695-0

Provided by University of Bern

Medicine

Study Describes the Diversity of Genetic Changes That Cause Inherited Kidney Disease (Medicine)

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A study has described genetic changes in patients with the most common form of hereditary kidney disease that affects an estimated 12.5 million people worldwide. The research, which focussed on Polycystic Kidney Disease (PKD) in Ireland, provides insights into PKD that will assist doctors and patients in the management of this of inherited condition.

The study, led by researchers from the RCSI University of Medicine and Health Sciences, is published in the European Journal of Human Genetics.

In the research, a cohort of 169 patients with PKD in Ireland were analysed. The genetic changes were identified in up to 83% of cases. It is the first time that the diversity of genetic causes of PKD in Ireland have been described. The results will better assist doctors in identifying patients who may require transplantation or dialysis. The findings also have important implications for people who have a family history of PKD and are planning a family or considering kidney donation.

“This study is hugely important in providing us with an insight into the genetic landscape of Polycystic Kidney Disease, the most common form of inherited kidney disease in the world,” said first author on the study Dr Katherine Benson, School of Pharmacy and Biomolecular Sciences, RCSI.

“Our findings have implications for the prognosis of patients by helping us to further identify why the disease may progress more rapidly in some cases and how we can reduce the burden of inherited kidney disease in future.”

The study was carried out by a team of researchers and clinician scientists under the supervision of senior authors Prof. Gianpiero Cavalleri, Professor of Human Genetics at RCSI and Prof. Peter Conlon, Associate Professor of Medicine at RCSI and Consultant Nephrologist at Beaumont Hospital.

The study was supported by an Enterprise Partnership Scheme Fellowship Award from The Irish Research Council, in conjunction with Punchestown Kidney Research Fund. The research was also funded by the Beaumont Hospital Foundation and the Royal Irish Academy.

Reference: Benson, K.A., Murray, S.L., Senum, S.R. et al. The genetic landscape of polycystic kidney disease in Ireland. Eur J Hum Genet (2021). https://www.nature.com/articles/s41431-020-00806-5 https://doi.org/10.1038/s41431-020-00806-5

Provided by RCSI