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Wednesday, 3 June 2020

Turn Scary Math Into Beautiful Pictures Using This New Tool


Some people look at an equation and see a bunch of numbers and symbols; others see beauty. Thanks to a new tool created at Carnegie Mellon University, anyone can now translate the abstractions of mathematics into beautiful and instructive illustrations.

The tool enables users to create diagrams simply by typing an ordinary mathematical expression and letting the software do the drawing. Unlike a graphing calculator, these expressions aren't limited to basic functions, but can be complex relationships from any area of mathematics.

The researchers named it Penrose after the noted mathematician and physicist Roger Penrose, who is famous for using diagrams and other drawings to communicate complicated mathematical and scientific ideas.



"Some mathematicians have a talent for drawing beautiful diagrams by hand, but they vanish as soon as the chalkboard is erased," said Keenan Crane, an assistant professor of computer science and robotics. "We want to make this expressive power available to anyone."

Diagrams are often underused in technical communication, since producing high-quality, digital illustrations is beyond the skill of many researchers and requires a lot of tedious work.

Penrose addresses these challenges by enabling diagram-drawing experts to encode how they would do it in the system. Other users can then access this capability using familiar mathematical language, leaving the computer to do most of the grunt work.

The researchers will present Penrose at the SIGGRAPH 2020 Conference on Computer Graphics and Interactive Techniques, which will be held virtually this July because of the COVID-19 pandemic.

"We started off by asking: 'How do people translate mathematical ideas into pictures in their head?'" said Katherine Ye, a Ph.D. student in the Computer Science Department. "The secret sauce of our system is to empower people to easily 'explain' this translation process to the computer, so the computer can do all the hard work of actually making the picture."

Once the computer learns how the user wants to see mathematical objects visualized -- a vector represented by a little arrow, for instance, or a point represented as a dot -- it uses these rules to draw several candidate diagrams. The user can then select and edit the diagrams they want from a gallery of possibilities.

The research team developed a special programming language for this purpose that mathematicians should have no trouble learning, Crane said.

"Mathematicians can get very picky about notation," he explained. "We let them define whatever notation they want, so they can express themselves naturally."



An interdisciplinary team developed Penrose. In addition to Ye and Crane, the team included Nimo Ni and Jenna Wise, both Ph.D students in CMU's Institute for Software Research (ISR); Jonathan Aldrich, a professor in ISR; Joshua Sunshine, an ISR senior research fellow; cognitive science undergraduate Max Krieger; and Dor Ma'ayan, a former master's student at the Technion-Israel Institute of Technology.

"Our vision is to be able to dust off an old math textbook from the library, drop it into the computer and get a beautifully illustrated book -- that way more people understand," Crane said, noting that Penrose is a first step toward this goal.



Bibliography:

Carnegie Mellon Tool Automatically Turns Math Into Pictures

Link

Tuesday, 2 June 2020

When Astrocytes Go Rogue: Why Do The Brain's Support Cells Turn Into Neuron Killers?


A new study published today in Neuron led by The New York Stem Cell Foundation (NYSCF) Research Institute's Valentina Fossati, PhD, creates astrocytes - an integral support cell in the brain - from stem cells and shows that in disease-like environments, these normally helpful cells can turn into neuron-killers.

"We can now create stem cells from any individual and see in the dish how astrocytes play a role in diseases like multiple sclerosis, Parkinson's, and Alzheimer's," remarked NYSCF CEO Susan L. Solomon. "This will shed new light on the devastating process of neurodegeneration, pointing us towards effective treatments for this growing group of patients."



Creating Astrocytes from Stem Cells

Astrocytes, star-shaped cells that make up more than half the cells in the central nervous system, belong to a category of brain cells called glia which provide vital support for neurons in the brain. Astrocytes aid in metabolic processes, regulate connectivity of brain circuits, participate in inflammatory signaling, and help regulate blood flow across the blood-brain barrier, among other duties. They are a crucial component of brain function but are often overlooked in research and drug development, although recent mounting evidence implicates them in many neurological diseases.

Most studies of astrocytes have been done in mouse models, but it has been shown that mouse astrocytes are not quite the same as human astrocytes. This means that many aspects of human astrocyte function, including some behaviors that may be relevant to disease, are not fully captured by mouse models.

"The field needed a reliable method for making human astrocytes from stem cells so that we can better investigate how they may be contributing to neurodegenerative diseases," explained Dr. Fossati, a Senior Research Investigator at the NYSCF Research Institute. "Previously, drugs that failed have not specifically targeted astrocytes. Now, drugs targeting astrocyte malfunctions can be identified using patient cells."

Dr. Fossati's team built on their previously published protocols for converting stem cells into glial cells such as microglia (the brain's immune cells) and oligodendrocytes (cells that aid in neuronal communication) to identify a protein marker, CD49f, that is expressed in astrocytes and can be used to isolate them from mixed cell populations in a lab dish or the human brain, facilitating downstream research.

"We were excited to see that our stem-cell-derived astrocytes isolated with CD49f behaved the way typical astrocytes do: they take up glutamate, respond to inflammation, engage in phagocytosis - which is like 'cell eating' - and encourage mature firing patterns and connections in neurons," said Dr. Fossati.

The team also confirmed that CD49f is present in astrocytes found in human brain tissue.

"We looked at human brain tissue samples from both a healthy donor and a patient with Alzheimer's disease and found that these astrocytes also expressed CD49f - suggesting that this protein is a reliable indicator of astrocyte identity in both health and disease."



When Astrocytes Go Rogue

Armed with a protocol for creating functional astrocytes from stem cells, the team then turned their attention to how these astrocytes begin to misbehave in disease.

Recent work from Shane Liddelow, PhD, of New York University (NYU), a collaborator on the study, found that astrocytes can 'go rogue,' becoming toxic to the neurons they typically support.

"We observed in mice that astrocytes in inflammatory environments take on a reactive state, actually attacking neurons rather than supporting them," explained Dr. Liddelow, Assistant Professor of Neuroscience and Physiology and of Ophthalmology at the NYU Grossman School of Medicine. "We found evidence of reactive astrocytes in the brains of patients with neurodegenerative diseases, but without a human stem cell model, it wasn't possible to figure out how they were created and what they are doing in patient brains."

Dr. Fossati sought to use her human stem cell model to determine if what Dr. Liddelow observed in mice could also be happening in humans. Her team exposed healthy stem-cell-derived astrocytes to inflammation - essentially mimicking the environment of the brain in neurodegenerative diseases - collected their byproducts, and then exposed these secretions to healthy neurons.

"What we saw in the dish confirmed what Dr. Liddelow saw in mice: the neurons began to die," said Dr. Fossati. "Observing this 'rogue astrocyte' phenomenon in a human model of disease suggests that it could be happening in actual patients and opens the door for new therapeutics that intervene in this process."

The team also saw that stem-cell-derived astrocytes exposed to inflammation lost their typical astrocyte functions: they did not support neuronal maturation or firing very well, and they didn't uptake as much glutamate. They also changed their morphology, losing their characteristic 'long arms' and taking on a more constricted star-like shape.

"Along with secreting a toxin that kills neurons, we also saw that stem-cell-derived astrocytes in disease-like environments simply do not perform their typical jobs as well, and that could lead to neuronal dysfunction," noted Dr. Fossati. "For example, since they do not take up glutamate properly, too much glutamate is likely left around the neurons, which could cause a neuron to atrophy, and that's something we can potentially target in new therapies."



Altogether, these findings open up exciting new avenues of study and provide researchers with a new system to explore mechanisms of disease.

"I'm looking forward to using our new system to further explore the intricacies of astrocyte function in Alzheimer's, multiple sclerosis, Parkinson's, and other diseases," remarked Dr. Fossati. "We have already seen intriguing behaviors that may explain how neurodegeneration occurs, and I am hopeful that this work will point us toward new treatment opportunities for these patients."


Bibliography:

Barbar, L., Jain, T., Zimmer, M., Kruglikov, I., Sadick, J. S., Wang, M., Kalpana, K., Rose, I. V. L., Burstein, S. R., Rusielewicz, T., Nijsure, M., Guttenplan, K. A., Domenico, A. di, Croft, G., Zhang, B., Nobuta, H., Hébert, J. M., Liddelow, S. A., & Fossati, V. (2020).

CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes.

Neuron, 0(0).

DOI: https://doi.org/10.1016/j.neuron.2020.05.014

Monday, 1 June 2020

Scientists announced a 'nuclear' periodic table


A staple in every science classroom is the periodic table of elements, and for many it is their first introduction to the vast mysteries of the natural world.

Now physicists from Kyoto University have unveiled a new table that provides a different perspective on the building blocks of the universe. While the traditional table is based on the behavior of electrons in an atom, this new table is based on the protons in the nucleus.

"The periodic table of the elements is one of the most significant achievements in science, and in its familiar form it is based on the shell structure of electron orbitals in atoms," explains Yoshiteru Maeno, one of the co-developers of the new table.



"But atoms are comprised of two types of charged particles that designate each element: electrons orbiting the core and protons in the core itself."

The team's new 'Nucletouch' table -- also available as a 3D model -- was announced recently in the journal Foundations of Chemistry.

Over 150 years have passed since Dmitri Mendeleev discovered the periodic law that lead him to propose the classic periodic table. He even had the foresight to add space for elements that were still unknown in his time.

"Fundamentally, it comes down to the electrons in each atom. Atoms are considered to be stable when electrons completely fill their 'shell' of orbits around the nucleus," continues Maeno.

"So-called 'noble gases', inert elements such as helium, neon, and argon, rarely react with other elements. Their most stable electron numbers are 2, 10, 18, 36, and so on."

Maeno decribes these as atomic 'magic numbers', and importantly the same principle can also be applied to protons. Imagining that protons in a nucleus exist in 'orbits' may seem like a stretch, but the discovery of the concept was awarded the 1963 Nobel prize in physics.

Protons have different stable magic numbers: 2, 8, 20, 28, and so on. Among these are familiar elements such at helium, oxygen, and calcium. The Nucletouch table places these 'magic nuclei' at its center, providing a new perspective on the elements.

"Similar to electrons, when nuclear orbits are filled with protons, they form stable nuclei, analogous to the noble-gas elements," says collaborator Kouichi Hagino.



"In our nuclear periodic table, we also see that nuclei tend to be spherically-shaped near the magic numbers, but deformed as you move away from them."

The team made the table to highlight alternative ways to illustrate the laws of nature, and hopes that enthusiasts and academics alike will find something to enjoy and learn from this fresh new look at an old friend.


Bibliography:

K. Hagino, Y. Maeno.

A nuclear periodic table.

Foundations of Chemistry, 2020;

DOI: 10.1007/s10698-020-09365-5

Sunday, 31 May 2020

Increased fertility for women with Neanderthal gene, study suggests


One in three women in Europe inherited the receptor for progesterone from Neandertals -- a gene variant associated with increased fertility, fewer bleedings during early pregnancy and fewer miscarriages. This is according to a study published in Molecular Biology and Evolution by researchers at the Max Planck Institute for Evolutionary Anthropology in Germany and Karolinska Institutet in Sweden.

"The progesterone receptor is an example of how favourable genetic variants that were introduced into modern humans by mixing with Neandertals can have effects in people living today," says Hugo Zeberg, researcher at the Department of Neuroscience at Karolinska Institutet and the Max Planck Institute for Evolutionary Anthropology, who performed the study with colleagues Janet Kelso and Svante Pääbo.

Progesterone is a hormone, which plays an important role in the menstrual cycle and in pregnancy. Analyses of biobank data from more than 450,000 participants -- among them 244,000 women -- show that almost one in three women in Europe have inherited the progesterone receptor from Neandertals. Twenty-nine percent carry one copy of the Neandertal receptor and three percent have two copies.



Favourable effect on fertility

"The proportion of women who inherited this gene is about ten times greater than for most Neandertal gene variants," says Hugo Zeberg. "These findings suggest that the Neandertal variant of the receptor has a favourable effect on fertility."

The study shows that women who carry the Neandertal variant of the receptor tend to have fewer bleedings during early pregnancy, fewer miscarriages, and give birth to more children. Molecular analyses revealed that these women produce more progesterone receptors in their cells, which may lead to increased sensitivity to progesterone and protection against early miscarriages and bleeding.


Bibliography:

Svante Pääbo, Janet Kelso, Hugo Zeberg.

The Neandertal Progesterone Receptor.

Molecular Biology and Evolution, 2020;

DOI: 10.1093/molbev/msaa119

Saturday, 30 May 2020

Cells Inside Cells: The Bacteria That Live in Cancer Cells


Cancer cells are comfy havens for bacteria. That conclusion arises from a rigorous study of over 1,000 tumor samples of different human cancers. The study, headed by researchers at the Weizmann Institute of Science, found bacteria living inside the cells of all the cancer types – from brain to bone to breast cancer – and even identified unique populations of bacteria residing in each type of cancer. The research suggests that understanding the relationship between a cancer cell and its “mini-microbiome” may help predict the potential effectiveness of certain treatments or may point, in the future, to ways of manipulating those bacteria to enhance the actions of anticancer treatments.

Dr. Ravid Straussman of the Institute’s Molecular Cell Biology Department had, several years ago, discovered bacteria lurking within human pancreatic tumor cells; these bacteria were shown to protect cancer cells from chemotherapy drugs by “digesting” and inactivating these drugs. When other studies also found bacteria in tumor cells, Straussman and his team wondered whether such hosting might be the rule, rather than the exception. To find out, Drs. Deborah Nejman and Ilana Livyatan in Straussman’s group and Dr. Garold Fuks of the Physics of Complex Systems Department worked together with a team of oncologists and researchers around the world. The work was also led by Dr. Noam Shental of the Mathematics and Computer Science Department of the Open University of Israel.



Ultimately, the team would produce a detailed study describing, in high resolution, the bacteria living in these cancers – brain, bone, breast, lung, ovary, pancreas, colorectal and melanoma. They discovered that every single cancer type, from brain to bone, harbored bacteria and that different cancer types harbor different bacteria species. It was the breast cancers, however, that had the largest number and diversity of bacteria. The team demonstrated that many more bacteria can be found in breast tumors compared to the normal breast tissue surrounding these tumors, and that some bacteria were preferentially found in the tumor tissue rather than in the normal tissue surrounding it.

To arrive at these results, the team had to overcome several challenges. For one, the mass of bacteria in a tumor sample is relatively small, and the researchers had to find ways to focus on these tiny cells-within-cells. They also had to eliminate any possible outside contamination. To this end they used hundreds of negative controls and created a series of computational filters to remove the traces of any bacteria that could have come from outside the tumor samples.

The team was able to grow bacteria directly from human breast tumors, and their results proved that the bacteria found in these tumors are alive. Electron microscopy visualization of these bacteria demonstrated that they prefer to nestle up in a specific location inside the cancer cells – close to the cell nucleus.

This electron microscope image reveals the bacteria living in a tumor cell


Different cells for different bacteria

The team also reported that bacteria can be found not only in cancer cells, but also in immune cells that reside inside tumors. “Some of these bacteria could be enhancing the anticancer immune response, while others could be suppressing it – a finding that may be especially relevant to understanding the effectiveness of certain immunotherapies,” says Straussman. Indeed, when the team compared the bacteria from groups of melanoma samples, they found that different bacteria were enriched in those melanoma tumors that responded to immunotherapy as compared to those that had a poor response.

Straussman thinks that the study can also begin to explain why some bacteria like cancer cells and why each cancer has its own typical microbiome: The differences apparently come down to the choice of amenities offered in each kind of tumor-cell environment. That is, the bacteria may live off certain metabolites that are overproduced by or stored within the specific tumor types. For example, when the team compared the bacteria found in lung tumors from smokers with those from patients who had never smoked, they found variances. These differences stood out more clearly when the researchers compared the genes of these two groups of bacteria: Those from the smokers’ lung cancer cells had many more genes for metabolizing nicotine, toluene, phenol and other chemicals that are found in cigarette smoke.

In addition to showing that some of the most common cancers shelter unique populations of bacteria within their cells, the researchers believe that the methods they have developed to identify signature microbiomes with each cancer type can now be used to answer some crucial questions about the roles these bacteria play: Are the bacteria freeloaders on the cancer cell’s surplus metabolites, or do they provide a service to the cell? At what stage do they take up residence? How do they promote or hinder the cancer’s growth? What are the effects that they have on response to a wide variety of anticancer treatments?



“Tumors are complex ecosystems that are known to contain, in addition to cancer cells, immune cells, stromal cells, blood vessels, nerves, and many more components, all part of what we refer to as the tumor microenvironment. Our studies, as well as studies by other labs, clearly demonstrate that bacteria are also an integral part of the tumor microenvironment. We hope that by finding out how exactly they fit into the general tumor ecology, we can figure out novel ways of treating cancer,” Straussman says.


Bibliography:

Nejman, D., Livyatan, I., Fuks, G., Gavert, N., Zwang, Y., Geller, L. T., . . . Straussman, R. (2020).

The human tumor microbiome is composed of tumor type–specific intracellular bacteria.

Science, 368(6494), 973-980.

doi: 10.1126/science.aay9189

Friday, 29 May 2020

Exploiting viruses to attack cancer cells


An adenovirus is now better able to target and kill cancer cells due to the addition of an RNA stabilizing element.

Hokkaido University scientists have made an adenovirus that specifically replicates inside and kills cancer cells by employing special RNA-stabilizing elements. The details of the research were published in the journal Cancers.

Much research in recent years has investigated genetically modifying adenoviruses to kill cancers, with some currently being tested in clinical trials. When injected, these adenoviruses replicate inside cancer cells and kill them. Scientists are trying to design more efficient viruses, which are better able to target cancer cells while leaving normal cells alone.



Hokkaido University molecular oncologist Fumihiro Higashino led a team of scientists to make two new adenoviruses that specifically target cancer cells. To do this, they used ‘adenylate-uridylate-rich elements’ (AREs), which are signals in RNA molecules known to enhance the rapid decay of messenger RNAs (mRNAs) in human cells. “AREs make sure that mRNAs don’t continue to code for proteins unnecessarily in cells,” explains Higashino. “Genes required for cell growth and proliferation tend to have AREs.”

Under certain stress conditions, however, ARE-containing mRNAs can become temporarily stabilized allowing the maintenance of some necessary cell processes. ARE-mRNAs are also stabilized in cancer cells, supporting their continuous proliferation.

Higashino and his team inserted AREs from two human genes into an adenovirus replicating gene, making the new adenoviruses: AdARET and AdAREF. “The idea behind the insertion is that the AREs will stabilize the killer adenoviruses, allowing them to replicate only inside cancer cells but not in normal healthy ones,” says Higashino.

Indeed, AdARET and AdAREF were both found to replicate inside and kill cancer cells in the laboratory, while they hardly affected normal cells. Tests confirmed that the specific replication in cancer cells was due to stabilization of the viral genes with AREs, which did not happen in the healthy cells.

The AdARET killed cancer cells (A549, H1299, and C33A) in a dose-dependent manner while normal cells (BJ and WI38) were largely unaffected particularly with small doses of AdARET. Living cells were stained blue. MOI indicates the number of virus particles per cell. (Yohei Mikawa et al., Cancers, May 11, 2020)

The scientists then injected human cancer cells under the skin of nude mice, which then developed into tumors. When AdARET and AdAREF were injected into the tumors, they resulted in a significant reduction in tumor size.

This wasn’t the first time for the team to test the use of AREs in adenoviruses. In a previous study, another scientist used an ARE belonging to a different gene and found this adenovirus worked specifically in cancers containing a mutation in a gene called RAS. AdARET and AdAREF, on the other hand, were found to be effective against cancer cells without a mutated RAS gene, making the viruses applicable to a wider range of cancer cells.



“Since ARE-mRNA stability has also been reported in diseases other than cancer, we think the viruses we engineered could also have potential for treating diseases related to inflammations, viral infection, hypoxia, and ultraviolet irradiation,” says Higashino.


Bibliography:

Yohei Mikawa, Mohammad Towfik Alam, Elora Hossain, Aya Yanagawa-Matsuda, Tetsuya Kitamura, Motoaki Yasuda, Umma Habiba, Ishraque Ahmed, Yoshimasa Kitagawa, Masanobu Shindoh, Fumihiro Higashino.

Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA. 

Cancers, 2020; 12 (5): 1205

DOI: 10.3390/cancers12051205

Thursday, 28 May 2020

Theoretical Chemist's Predictions Become a Reality


Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other complex structures by shaping 2D layers into the desired forms. Thomas Heine, Professor for Theoretical Chemistry at TU Dresden, is working on the prediction of such innovative materials. Their properties can be precisely calculated using modern methods of computational chemistry, even before they have been realized in the laboratory.

This research is particularly interesting for 2D polymers: their lattice type is defined by the shape of their building blocks, and those can be selected from the almost infinite variety of plane organic molecules which match the required structure. A particularly interesting example is the kagome lattice, which consists of the corners and edges of a trihexagonal tiling. In 2019, Yu Jing and Thomas Heine proposed to synthesize such 2D polymers from triangular organic molecules (so-called triangulenes). These materials have a combined honeycomb-kagome structure (see figure). Their calculations suggest that these 2D structures combine the properties of graphene (quasi massless charge carriers) with those of superconductors (flat electronic bands).



Now the Italian materials scientist Giorgio Contini and his international team have succeeded in synthesizing this 2D honeycomb kagome polymer, as published in Nature Materials earlier this week. An innovative surface synthesis method made it possible to produce crystals of such high quality that they were suitable for the experimental characterization of electronic properties. Indeed, the predicted fascinating topological properties were revealed. Thus, for the first time, it could be experimentally proven that topological materials can be realized via 2D polymers.

Research on 2D polymers is thus placed on a solid basis. The kagome lattice described here is only one example out of hundreds of possibilities to connect plane molecules to regular lattices. For some of these variants, other interesting electronic properties have already been predicted theoretically. This opens up numerous new possibilities for theorists and experimentalists in chemistry and physics to develop materials with previously unknown properties.

Prof. Heine explains: "These results show that 2D polymers can be materials with useful electronic properties, although their structures are much more wide-meshed than regular electronic materials, with distances of more than one nanometer between the lattice points. The prerequisite is that the materials are of excellent structural quality. This includes a high crystallinity and a very low defect density. Another important contribution of the colleagues around Prof. Contini is that, although the 2D polymers were produced on a metal surface, they can be detached and transferred to any other substrate, such as silicon oxide or mica, and thus be incorporated into electronic devices".


Bibliography:

Yu Jing and Thomas Heine.

"Making 2D Topological Polymers a reality"

Nature Materials.

DOI: Nature

Wednesday, 27 May 2020

Researchers Discover How Protein Can Inhibit Cancer Development in Mice


Proteins are found throughout our cells and regulate a lot of biological processes that are important for our survival. But some of them also regulate processes that can make us sick. Now, an international research team, with researchers from the University of Copenhagen at the forefront, has achieved a much better understanding of one such protein.

In a new study, the researchers discovered how the protein PP2A works at the molecular level, and how it inhibits the development of tumors in mice. The new results have been published in the scientific journal, the EMBO Journal.



“We call PP2A a household protein because it is found almost everywhere. In everything living – from simple yeast cells to complex cells in humans. PP2A removes phosphate groups on other proteins, and now we have found these proteins and how PP2A, via one of these proteins, inhibits cancer development”, says Jakob Nilsson, Professor at the Novo Nordisk Foundation Center for Protein Research.


Turned-off enzyme

According to the researchers, there is a great deal of interest from both the academic research community and from the pharmaceutical industry for the protein PP2A because it is well-known that PP2A is a so-called tumor suppressor that suppresses tumors. But precisely which proteins PP2A regulates in order to inhibit cancer have so far not been known. Now, the researchers have gained detailed insight into this.

“The new thing about our study is that we show how PP2A selects the phosphate groups that shall be removed from other proteins. And then at the same time, we show that PP2A turns off an enzyme named ADAM17. This shutdown of ADAM17 results in inhibition of tumour growth in mice”, explains Associate Professor Marie Kveiborg from the Biotech Research and Innovation Centre.

The researchers have used advanced methods to show that PP2A can turn off the activity of ADAM17 on the outside of the cell by removing phosphate groups from the part of ADAM17 that is located inside the cell.

The researchers' illustration of PP2A binding to ADAM17 whcich cleaves other proteins such as the growth factor EGF which again binds the receptor EGFR and stimulates cell growth.

The function is inhibited

Normally, ADAM17 sits as a pair of molecular scissors in the cell's outer membrane and cleaves other proteins from the cell surface – for example, growth factors that will then stimulate cell growth. But that function ceases when PP2A removes the phosphate groups from ADAM17.

The researchers already knew from previous studies that ADAM17 stimulates a variety of cancers, including breast and bowel cancer. But this is the first time that PP2A has been shown to actively turn off ADAM17 activity.



Going forward, the researchers hope that their new cancer discovery will also apply to human tumors. For now, the next step for the researchers is to clarify whether substances that activate PP2A can be used to regulate ADAM17 activity. In addition, the researchers also want to look at how PP2A regulates other proteins that may be important for the understanding of its tumor suppressor function.


Bibliography:

Kruse et al. (2020). Mechanisms of Site-Specific Dephosphorylation and Kinase Opposition Imposed by PP2A Regulatory Subunits.

The EMBO Journal.

DOI: https://doi.org/10.15252/embj.2019103695

Tuesday, 26 May 2020

ALMA Discovers Massive Rotating Disk in Early Universe


In our 13.8 billion-year-old universe, most galaxies like our Milky Way form gradually, reaching their large mass relatively late. But a new discovery made with the Atacama Large Millimeter/submillimeter Array (ALMA) of a massive rotating disk galaxy, seen when the universe was only ten percent of its current age, challenges the traditional models of galaxy formation. This research appears on 20 May 2020 in the journal Nature.

Galaxy DLA0817g, nicknamed the Wolfe Disk after the late astronomer Arthur M. Wolfe, is the most distant rotating disk galaxy ever observed. The unparalleled power of ALMA made it possible to see this galaxy spinning at 170 miles (272 kilometers) per second, similar to our Milky Way.

"While previous studies hinted at the existence of these early rotating gas-rich disk galaxies, thanks to ALMA we now have unambiguous evidence that they occur as early as 1.5 billion years after the Big Bang," said lead author Marcel Neeleman of the Max Planck Institute for Astronomy in Heidelberg, Germany.



How did the Wolfe Disk form?

The discovery of the Wolfe Disk provides a challenge for many galaxy formation simulations, which predict that massive galaxies at this point in the evolution of the cosmos grew through many mergers of smaller galaxies and hot clumps of gas.

"Most galaxies that we find early in the universe look like train wrecks because they underwent consistent and often 'violent' merging," explained Neeleman. "These hot mergers make it difficult to form well-ordered, cold rotating disks like we observe in our present universe."

In most galaxy formation scenarios, galaxies only start to show a well-formed disk around 6 billion years after the Big Bang. The fact that the astronomers found such a disk galaxy when the universe was only ten percent of its current age, indicates that other growth processes must have dominated.

"We think the Wolfe Disk has grown primarily through the steady accretion of cold gas," said J. Xavier Prochaska, of the University of California, Santa Cruz and coauthor of the paper. "Still, one of the questions that remains is how to assemble such a large gas mass while maintaining a relatively stable, rotating disk."

Star formation

The team also used the National Science Foundation's Karl G. Jansky Very Large Array (VLA) and the NASA/ESA Hubble Space Telescope to learn more about star formation in the Wolfe Disk. In radio wavelengths, ALMA looked at the galaxy's movements and mass of atomic gas and dust while the VLA measured the amount of molecular mass -- the fuel for star formation. In UV-light, Hubble observed massive stars. "The star formation rate in the Wolfe Disk is at least ten times higher than in our own galaxy," explained Prochaska. "It must be one of the most productive disk galaxies in the early universe."

A 'normal' galaxy

The Wolfe Disk was first discovered by ALMA in 2017. Neeleman and his team found the galaxy when they examined the light from a more distant quasar. The light from the quasar was absorbed as it passed through a massive reservoir of hydrogen gas surrounding the galaxy -- which is how it revealed itself. Rather than looking for direct light from extremely bright, but more rare galaxies, astronomers used this 'absorption' method to find fainter, and more 'normal' galaxies in the early universe.



"The fact that we found the Wolfe Disk using this method, tells us that it belongs to the normal population of galaxies present at early times," said Neeleman. "When our newest observations with ALMA surprisingly showed that it is rotating, we realized that early rotating disk galaxies are not as rare as we thought and that there should be a lot more of them out there."

"This observation epitomizes how our understanding of the universe is enhanced with the advanced sensitivity that ALMA brings to radio astronomy," said Joe Pesce, astronomy program director at the National Science Foundation, which funds the telescope. "ALMA allows us to make new, unexpected findings with almost every observation."



Bibliography:

Marcel Neeleman & J. Xavier Prochaska, et al.

A Cold, Massive, Rotating Disk 1.5 Billion Years after the Big Bang.

Nature, 2020

DOI: 10.1038/s41586-020-2276-y

Monday, 25 May 2020

Scientists finally crack nature’s most common chemical bond


The most common chemical bond in the living world — that between carbon and hydrogen — has long resisted attempts by chemists to crack it open, thwarting efforts to add new bells and whistles to old carbon-based molecules.

Now, after nearly 25 years of work by chemists at the University of California, Berkeley, those hydrocarbon bonds — two-thirds of all the chemical bonds in petroleum and plastics — have fully yielded, opening the door to the synthesis of a large range of novel organic molecules, including drugs based on natural compounds.



“Carbon-hydrogen bonds are usually part of the framework, the inert part of a molecule,” said John Hartwig, the Henry Rapoport Chair in Organic Chemistry at UC Berkeley. “It has been a challenge and a holy grail of synthesis to be able to do reactions at these positions because, until now, there has been no reagent or catalyst that will allow you to add anything at the strongest of these bonds.”

Hartwig and other researchers had previously shown how to add new chemical groups at C-H bonds that are easier to break, but they could only add them to the strongest positions of simple hydrocarbon chains.

In the May 15 issue of the journal Science, Hartwig and his UC Berkeley colleagues described how to use a newly designed catalyst to add functional chemical groups to the hardest of the carbon-hydrogen bonds to crack: the bonds, typically at the head or tail of a molecule, where a carbon has three attached hydrogen atoms, what’s called a methyl group (CH3).

A catalyst (center) based on iridium (blue ball) can snip a hydrogen atom (white balls) off a terminal methyl group (upper and lower left) to add a boron-oxygen compound (pink and red) that is easily swapped out for more complicated chemical groups. The reaction works on simple hydrocarbon chains (top reaction) or more complicated carbon compounds (bottom reaction). The exquisite selectivity of this catalytic reaction is due to the methyl group (yellow) that has been added to the iridium catalyst. The black balls are carbon atoms; red is oxygen; pink is boron. (UC Berkeley image by John Hartwig). Credit: John Hartwig, UC Berkeley.


“The primary C-H bonds, the ones on a methyl group at the end of a chain, are the least electron-rich and the strongest,” he said. “They tend to be the least reactive of the C-H bonds.”

UC Berkeley postdoctoral fellow Raphael Oeschger discovered a new version of a catalyst based on the metal iridium that opens up one of the three C-H bonds at a terminal methyl group and inserts a boron compound, which can be easily replaced with more complex chemical groups. The new catalyst was more than 50 times more efficient than previous catalysts and just as easy to work with.

“We now have the ability to do these types of reactions, which should enable people to rapidly make molecules that they would not have made before,” Hartwig said. “I wouldn’t say these are molecules that could not have been made before, but people wouldn’t make them because it would take too long, too much time and research effort, to make them.”

The payoff could be huge. Each year, nearly a billion pounds of hydrocarbons are used by industry to make solvents, refrigerants, fire retardants and other chemicals and are the typical starting point for synthesizing drugs.

‘Expert surgery’ on hydrocarbons

To prove the utility of the catalytic reaction, UC Berkeley postdoctoral fellow Bo Su and his coworkers in the lab used it to add a boron compound, or borane, to a terminal, or primary, carbon atom in 63 different molecular structures. The borane can then be swapped out for any number of chemical groups. The reaction specifically targets terminal C-H bonds, but works at other C-H bonds when a molecule doesn’t have a terminal C-H.

“We make a boron-carbon bond using boranes as reagents — they’re just a couple steps away from ant poison, boric acid — and that carbon-boron bond can be converted into many different things,” Hartwig said. “Classically, you can make a carbon-oxygen bond from that, but you can also make a carbon-nitrogen bond, a carbon-carbon bond, a carbon-fluorine bond or other carbon-halogen bonds. So, once you make that carbon-boron bond, there are many different compounds that can be made.”

Organic chemist Varinder Aggarwal from the University of Bristol referred to the catalytic reaction as “expert surgery” and characterized UC Berkeley’s new technique as “sophisticated and clever,” according to the magazine Chemical and Engineering News

One potential application, Hartwig said, is altering natural compounds — chemicals from plants or animals that have useful properties, such as antibiotic activity — to make them better. Many pharmaceutical companies today are focused on biologics — organic molecules, such as proteins, used as drugs — that could also be altered with this reaction to improve their effectiveness.



“In the normal course, you would have to go back and remake all those molecules from the start, but this reaction could allow you to just make them directly,” Hartwig said. “This is one type of chemistry that would allow you to take those complex structures that nature makes that have an inherent biological activity and enhance or alter that biological activity by making small changes to the structure.”

He said that chemists could also add new chemical groups to the ends of organic molecules to prep them for polymerization into long chains never before synthesized.

“It could enable you to take molecules that would be naturally abundant, biosourced molecules like fatty acids, and be able to derivatize them at the other end for polymer purposes,” he said.

UC Berkeley’s long history with C-H bonds

Chemists have long tried to make targeted additions to carbon-hydrogen bonds, a reaction referred to as C-H activation. One still unachieved dream is to convert methane — an abundant, but often wasted, byproduct of oil extraction and a potent greenhouse gas — into an alcohol called methanol that can be used as a starting point in many chemical syntheses in industry.

In 1982, Robert Bergman, now a UC Berkeley professor emeritus of chemistry, first showed that an iridium atom could break a C-H bond in an organic molecule and insert itself and an attached ligand between the carbon and hydrogen. While a major advance in organic and inorganic chemistry, the technique was impractical — it required one iridium atom per C-H bond. Ten years later, other researchers found a way to use iridium and other so-called transition metals, like tungsten, as a catalyst, where a single atom could break and functionalize millions of C-H bonds.

Hartwig, who was a graduate student with Bergman in the late 1980s, continued to bang on unreactive C-H bonds and in 2000 published a paper in Science describing how to use a rhodium-based catalyst to insert boron at terminal C-H bonds. Once the boron was inserted, chemists could easily swap it out for other compounds. With subsequent improvements to the reaction and changing the metal from rhodium to iridium, some manufacturers have used this catalytic reaction to synthesize drugs by modifying different types of C-H bonds. But the efficiency for reactions at methyl C-H bonds at the ends of carbon chains remained low, because the technique required that the reactive chemicals also be the solvent.

With the addition of the new catalytic reaction, chemists can now stick chemicals in nearly any type of carbon-hydrogen bond. In the reaction, iridium snips off a terminal hydrogen atom, and the boron replaces it; another boron compound floats away with the released hydrogen atom. The team attached a new ligand to iridium — a methyl group called 2-methylphenanthroline — that accelerated the reaction by 50 to 80 times over previous results.



Hartwig acknowledges that these experiments are a first step. The reactions vary from 29% to 85% in their yield of the final product. But he is working on improvements.

“For us, it shows, yeah, you can do this, but we will need to make even better catalysts. We know that the ultimate goal is attainable if we can further increase our rates by a factor of 10, let’s say. Then, we should be able to increase the complexity of molecules for this reaction and achieve higher yields,” Hartwig said. “It is a little bit like a four-minute mile. Once you know that something can be accomplished, many people are able to do it, and the next thing you know, we’re running a three-and-three-quarter-minute mile.”


Bibliography:

Diverse functionalization of strong alkyl C–H bonds by undirected borylation.

Raphael Oeschger, Bo Su, Isaac Yu, Christian Ehinger, Erik Romero, Sam He,  John Hartwig.

Science  15 May 2020: Vol. 368, Issue 6492, pp. 736-741.

DOI: 10.1126/science.aba6146

Sunday, 24 May 2020

Researchers record world's fastest internet speed (44.2Tbps) from a single optical chip


Researchers from Monash, Swinburne and RMIT universities have successfully tested and recorded Australia’s fastest internet data speed, and that of the world, from a single optical chip – capable of downloading 1000 high definition movies in a split second.

Published in the prestigious journal Nature Communications, these findings have the potential to not only fast-track the next 25 years of Australia’s telecommunications capacity, but also the possibility for this home-grown technology to be rolled out across the world.

In light of the pressures being placed on the world’s internet infrastructure, recently highlighted by isolation policies as a result of COVID-19, the research team led by Dr Bill Corcoran (Monash), Distinguished Professor Arnan Mitchell (RMIT) and Professor David Moss (Swinburne) were able to achieve a data speed of 44.2 Terabits per second (Tbps) from a single light source.



This technology has the capacity to support the high-speed internet connections of 1.8 million households in Melbourne, Australia, at the same time, and billions across the world during peak periods.

Demonstrations of this magnitude are usually confined to a laboratory. But, for this study, researchers achieved these quick speeds using existing communications infrastructure where they were able to efficiently load-test the network.

They used a new device that replaces 80 lasers with one single piece of equipment known as a micro-comb, which is smaller and lighter than existing telecommunications hardware. It was planted into and load-tested using existing infrastructure, which mirrors that used by the NBN.

It is the first time any micro-comb has been used in a field trial and possesses the highest amount of data produced from a single optical chip.

“We’re currently getting a sneak-peak of how the infrastructure for the internet will hold up in two to three years’ time, due to the unprecedented number of people using the internet for remote work, socialising and streaming. It’s really showing us that we need to be able to scale the capacity of our internet connections,” said Dr Bill Corcoran, co-lead author of the study and Lecturer in Electrical and Computer Systems Engineering at Monash University.

“What our research demonstrates is the ability for fibres that we already have in the ground, thanks to the NBN project, to be the backbone of communications networks now and in the future. We’ve developed something that is scalable to meet future needs.



“And it’s not just Netflix we’re talking about here – it’s the broader scale of what we use our communication networks for. This data can be used for self-driving cars and future transportation and it can help the medicine, education, finance and e-commerce industries, as well as enable us to read with our grandchildren from kilometres away.”

To illustrate the impact optical micro-combs have on optimising communication systems, researchers installed 76.6km of ‘dark’ optical fibres between RMIT’s Melbourne City Campus and Monash University’s Clayton Campus. The optical fibres were provided by Australia’s Academic Research Network.

Within these fibres, researchers placed the micro-comb – contributed by Swinburne University, as part of a broad international collaboration – which acts like a rainbow made up of hundreds of high quality infrared lasers from a single chip. Each ‘laser’ has the capacity to be used as a separate communications channel.

Researchers were able to send maximum data down each channel, simulating peak internet usage, across 4THz of bandwidth.

Distinguished Professor Mitchell said reaching the optimum data speed of 44.2 Tbps showed the potential of existing Australian infrastructure. The future ambition of the project is to scale up the current transmitters from hundreds of gigabytes per second towards tens of terabytes per second without increasing size, weight or cost.

“Long-term, we hope to create integrated photonic chips that could enable this sort of data rate to be achieved across existing optical fibre links with minimal cost,” Distinguished Professor Mitchell said.

“Initially, these would be attractive for ultra-high speed communications between data centres. However, we could imagine this technology becoming sufficiently low cost and compact that it could be deployed for commercial use by the general public in cities across the world.”



Professor Moss, Director of the Optical Sciences Centre at Swinburne University, said: “In the 10 years since I co-invented micro-comb chips, they have become an enormously important field of research.

“It is truly exciting to see their capability in ultra-high bandwidth fibre optic telecommunications coming to fruition. This work represents a world-record for bandwidth down a single optical fibre from a single chip source, and represents an enormous breakthrough for part of the network which does the heaviest lifting. Micro-combs offer enormous promise for us to meet the world’s insatiable demand for bandwidth.”


Bibliography:

Bill Corcoran, Mengxi Tan, Xingyuan Xu, Andreas Boes, Jiayang Wu, Thach G. Nguyen, Sai T. Chu, Brent E. Little, Roberto Morandotti, Arnan Mitchell, David J. Moss.

Ultra-dense optical data transmission over standard fibre with a single chip source.

Nature Communications, 2020; 11 (1)

DOI: 10.1038/s41467-020-16265-x

Brain’s ‘updating mechanisms’ may create false memories


A new study shows that the brain can update or ‘edit’ poorly-formed memories with the wrong information, potentially causing confusion, anxiety disorders like PTSD and, in extreme cases, false memories.

The research, published in Current Biology, is one of the first comprehensive characterisations of poorly-formed memories and may offer a framework for science to explore different therapeutic approaches to fear, memory and anxiety disorders. It may also have implications for accuracy of some witness testimony.

Senior author Professor Bryce Vissel, from the UTS Centre for Neuroscience & Regenerative Medicine, said his team used novel behavioural, molecular and computational techniques to investigate memories that have not been well-formed, and how the brain deals with them.



He explained, "For memories to be useful, they have to have been well-formed during an event - that is, they have to accurately reflect what actually happened.

"However, in the real world many memories are likely to be inaccurate - especially in situations where the experience was brief, sudden or highly emotional, as can often occur during trauma. Inaccurate memories can also occur when the memory is poorly encoded, potentially as a result of subtle differences in how each person processes memory or because of disease like Alzheimer's or dementia."

Lead author Dr Raphael Zinn said, "Our findings are exciting because they show that memory updating mechanisms that become activated after recall can refine and improve memories.

"Surprisingly, we found that the same process can, in some circumstances, lead to incorrect updating of the memory. We also identify one molecular mechanism, called reconsolidation, which could be mediating this process.

"This suggests we might be able to target such updating mechanisms therapeutically to treat memory and anxiety disorders where memory formation is poor."

The 6-year study shows that the same mechanism that updates poor memories can also severely distort them if it occurs in the wrong situation.

Professor Vissel said these findings could be useful for understanding memory fallibility in everyday life; fear and memory disorders, post-traumatic stress disorder (PTSD); and situations where accurate recall is critical, like witness testimony in courtrooms.

"While these findings come from studies in mice, this research is likely to apply across many animals with developed brains, including other mammals and humans. They might also tie in with dementias, where the main memory-related problem is an apparent inability to form accurate new memories.



"Why is memory fallible? Our study suggests that when an individual forms a poor memory, the brain reactivates the memory in a similar situation and then updates it. Sometimes a poorly formed memory can be wrongly reactivated in a similar, but irrelevant, situation. The brain may then update the memory from that irrelevant situation, causing the memory to become incorrect - rather than creating a new and entirely different memory of the new situation."


Bibliography:

Zinn, R., Leake, J., Krasne, F. B., Corbit, L. H., Fanselow, M. S., & Vissel, B. (2020).

Maladaptive Properties of Context-Impoverished Memories.

Current Biology, S0960982220305546.

DOI: https://doi.org/10.1016/j.cub.2020.04.040

Saturday, 23 May 2020

How a Quantum Physicist Invented New Code to Achieve What Many Thought Was Impossible


A scientist at the University of Sydney has achieved what one quantum industry insider has described as "something that many researchers thought was impossible."

Dr Benjamin Brown from the School of Physics has developed a type of error-correcting code for quantum computers that will free up more hardware to do useful calculations. It also provides an approach that will allow companies like Google and IBM to design better quantum microchips.

He did this by applying already known code that operates in three-dimensions to a two-dimensional framework.

"The trick is to use time as the third dimension. I'm using two physical dimensions and adding in time as the third dimension," Dr Brown said. "This opens up possibilities we didn't have before."

His research is published today in Science Advances.

"It's a bit like knitting," he said. "Each row is like a one-dimensional line. You knit row after row of wool and, over time, this produces a two-dimensional panel of material."



Fault-tolerant quantum computers

Reducing errors in quantum computing is one of the biggest challenges facing scientists before they can build machines large enough to solve useful problems.

"Because quantum information is so fragile, it produces a lot of errors," said Dr Brown, a research fellow at the University of Sydney Nano Institute.

Completely eradicating these errors is impossible, so the goal is to develop a "fault-tolerant" architecture where useful processing operations far outweigh error-correcting operations.

"Your mobile phone or laptop will perform billions of operations over many years before a single error triggers a blank screen or some other malfunction. Current quantum operations are lucky to have fewer than one error for every 20 operations -- and that means millions of errors an hour," said Dr Brown who also holds a position with the ARC Centre of Excellence for Engineered Quantum Systems.

"That's a lot of dropped stitches."

Most of the building blocks in today's experimental quantum computers -- quantum bits or qubits -- are taken up by the "overhead" of error correction.

"My approach to suppressing errors is to use a code that operates across the surface of the architecture in two dimensions. The effect of this is to free up a lot of the hardware from error correction and allow it to get on with the useful stuff," Dr Brown said.

Dr Naomi Nickerson is Director of Quantum Architecture at PsiQuantum in Palo Alto, California, and unconnected to the research. She said: "This result establishes a new option for performing fault-tolerant gates, which has the potential to greatly reduce overhead and bring practical quantum computing closer."



Path to universal computation

Start-ups like PsiQuantum, as well as the big technology firms Google, IBM and Microsoft, are leading the charge to develop large-scale quantum technology. Finding error-correcting codes that will allow their machines to scale up is urgently needed.

Dr Michael Beverland, a senior researcher at Microsoft Quantum and also unconnected with the research, said: "This paper explores an exciting, exotic approach to perform fault-tolerant quantum computation, pointing the way towards potentially achieving universal quantum computation in two spatial dimensions without the need for distillation, something that many researchers thought was impossible."

Two-dimensional codes that currently exist require what Dr Beverland refers to as distillation, more precisely known as 'magic-state distillation'. This is where the quantum processor sorts through the multiple computations and extracts the useful ones.

This chews up a lot of computing hardware just suppressing the errors.

"I've applied the power of the three-dimensional code and adapted it to the two-dimensional framework," Dr Brown said.

Dr Brown has been busy this year. In March he published a paper in top physics journal Physical Review Letters with colleagues from EQUS and the University of Sydney. In that research he and colleagues developed a decoder that identifies and corrects more errors than ever before, achieving a world record in error correction.

"Identifying the more common errors is another way we can free up more processing power for useful computations," Dr Brown said.

Professor Stephen Bartlett is a co-author of that paper and leads the quantum information theory research group at the University of Sydney.



"Our group at Sydney is very focused on discovering how we can scale-up quantum effects so that they can power large-scale devices," said Professor Bartlett, who is also Associate Dean for Research in the Faculty of Science.

"Dr Brown's work has shown how to do this for a quantum chip. This type of progress will enable us to go from small numbers of qubits to very large numbers and build ultra-powerful quantum computers that will solve the big problems of tomorrow."


Bibliography:

Benjamin J. Brown.

A fault-tolerant non-Clifford gate for the surface code in two dimensions.


Science Advances, 2020

DOI: 10.1126/sciadv.aay4929

Detecting Red Blood Cell Damage in Real-time


According to the National Kidney Foundation, more than 37 million people are living with kidney disease.

The kidneys play an important role in the body, from removing waste products to filtering the blood. For people with kidney disease, dialysis can help the body perform these essential functions when the kidneys aren't working at full capacity.

However, red blood cells sometimes rupture when blood is sent through faulty equipment that is supposed to clean the blood, such as a dialysis machine. This is called hemolysis. Hemolysis also can occur during blood work when blood is drawn too quickly through a needle, leading to defective laboratory samples.

There is no reliable indicator that red blood cells are being damaged in a clinical setting until an individual begins showing symptoms, such as fever, weakness, dizziness or confusion.



University of Delaware mechanical engineer Tyler Van Buren and collaborating colleagues at Princeton University have developed a method to monitor blood damage in real-time.

"Our goal was to find a method that could detect red blood cell damage without the need for lab sample testing," said Van Buren, an assistant professor of mechanical engineering with expertise in fluid dynamics.

Detecting blood cell damage

In the body, red blood cells float in plasma alongside white blood cells and platelets. The plasma is naturally conductive and is efficient at passing an electric charge. Red blood cells are chock-full of hemoglobin, an oxygen-transporting protein, that also is conductive.

This hemoglobin is typically insulated from the body by the cell lining. But as red blood cells rupture, hemoglobin is released into the bloodstream, causing the blood to become more conductive.

"Think of the blood like a river and red blood cells like water balloons in that river," said Van Buren, who joined UD in 2019. "If you have electrons (negatively charged particles) waiting to cross the river, it is more difficult when there are a lot of water balloons present. This is because the rubber is insulated, so the blood will be less conductive. As the water balloons (or blood cells) break, there are fewer barriers and the blood becomes more conductive, making it easier for electrons to move from one side to the other."

This diagram depicts the way conductivity will change as blood cells break. The yellow dots represent electrons. The red circles represent blood cells. Viewing the graphic from left to right, one can see that when more blood cells are present, fewer electrons are able to get across. As blood cells break, there are fewer barriers and the blood becomes more conductive, making it easier for electrons to move from one side to the other.


In dialysis, a patient's blood is removed from the body, cleaned, then recirculated into the body. The researchers developed a simple experiment to see if they could measure the blood's mechanical resistance outside of the body.

To test their technique, the researchers circulated healthy blood through the laboratory system and gradually introduced mechanically damaged blood to see if it would change the conductive nature of the fluid in the system.

It did. The researchers saw a direct correlation between the conductivity of the fluid in the system and the amount of damaged blood included in the sample.

While this issue of damaged blood is very rare, the research team's method does introduce one potential way to indirectly monitor blood damage in the body during dialysis. The researchers theorize that if clinicians were able to monitor the resistance of a patient's blood going into a dialysis machine and coming out, and they saw a major change in resistance -- or conductivity -- there is good reason to believe the blood is being damaged.

"We are not doctors, we're mechanical engineers," said Van Buren. "This technique would need a lot more vetting before being applied in a clinical setting."

For example, Van Buren said the method wouldn't necessarily work across patient populations because an individual's blood conductivity is just that, individual.



In the future, Van Buren said it would be interesting to evaluate whether conductivity also could be used in place of lab sampling for applications outside of dialysis. For example, this might be useful in research aimed at understanding how blood cells may be damaged, both inside and outside of the body, and possible methods for prevention.

He also is curious whether this method could be used to evaluate and identify compromised blood samples on-site, saving time and money for hospitals or diagnostic laboratories, while eliminating the need for patients to make multiple trips to have blood drawn if there is a problem.


Bibliography:

A simple method to monitor hemolysis in real time

Tyler Van Buren, Gilad Arwatz & Alexander J. Smits

Scientific Reports volume 10, Article number: 5101

doi: 10.1038/s41598-020-62041-8

Friday, 22 May 2020

RESEARCHERS MAY HAVE UNCOVERED THE ACHILLES HEEL OF VIRUSES


Viruses have an exceptional ability to circumvent the body's immune system and cause diseases. The majority of people recover from a viral infection such as influenza, although the current COVID-19 pandemic demonstrates how dangerous viruses are when there is no effective vaccine or treatment.

Professor and virologist Søren Riis Paludan from the Department of Biomedicine at Aarhus University, Denmark, has been leading a research partnership between Aarhus University, the University of Oxford and the University of Gothenburg, which has brought us one step closer to understanding the tactics used by viruses when they attack the immune system.



Søren Riis Paludan heads a laboratory which carries out research into the immune system's ability to fight diseases caused by the herpes virus, influenza viruses and, most recently, SARS-CoV2, more commonly known as coronavirus.

In the new study, which has just been published in the scientific journal Journal of Experimental Medicine, the researchers have investigated how the herpes simplex virus circumvents the immune system in order to cause infections of the brain. This is a rare infection but one which has a high mortality rate among those who are affected.

"In the study, we found that the herpes simplex virus is capable of inhibiting a protein in the cells, known as STING, which is activated when there is a threat. When STING is inhibited, the body's immune system is also inhibited - the virus thereby puts the brakes on the body's brake, which is supposed to prevent us from becoming ill. Other viruses also make use of the same principle," says Søren Riis Paludan.

Søren Riis Paludan points out that though the study focuses on herpesviruses, there are parallels to the coronavirus. Interestingly, the same protein is also inhibited by many different viruses, including the coronavirus.

"This suggests that we have found an Achilles heel in the virus and the way it establishes infections in the body. Our results lead us to hope that if we can prevent viruses from blocking STING, then we can prevent the virus from replicating. That could pave the way for new principles for treatment of herpes, influenza and also the coronavirus," says Søren Riis Paludan.



He hopes that the research results can be used in the development of antiviral drugs and vaccines in the future.

"Previous studies have also shown that the coronavirus inhibits STING in the same way as the herpes virus. This suggests that we have found a common denominator for several types of virus, and that this is probably an important element in the development of treatment," he says.



Bibliography:

HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection
Chiranjeevi Bodda,

 Line S. Reinert, Stefanie Fruhwürth, Timmy Richardo, Chenglong Sun, Bao-cun Zhang, Maria Kalamvoki, Anja Pohlmann, Trine H. Mogensen, Petra Bergström, Lotta Agholme, Peter O’Hare, Beate Sodeik, Mads Gyrd-Hansen, Henrik Zetterberg, Søren R. Paludan

Exp Med (2020) 217 (7): e20191422. 

DOI: https://doi.org/10.1084/jem.20191422.

Thursday, 21 May 2020

ESO telescope sees signs of planet birth


Observations made with the European Southern Observatory’s Very Large Telescope (ESO’s VLT) have revealed the telltale signs of a star system being born. Around the young star AB Aurigae lies a dense disc of dust and gas in which astronomers have spotted a prominent spiral structure with a ‘twist’ that marks the site where a planet may be forming. The observed feature could be the first direct evidence of a baby planet coming into existence.

“Thousands of exoplanets have been identified so far, but little is known about how they form,” says Anthony Boccaletti who led the study from the Observatoire de Paris, PSL University, France. Astronomers know planets are born in dusty discs surrounding young stars, like AB Aurigae, as cold gas and dust clump together. The new observations with ESO’s VLT, published in Astronomy & Astrophysics, provide crucial clues to help scientists better understand this process.



“We need to observe very young systems to really capture the moment when planets form,” says Boccaletti. But until now astronomers had been unable to take sufficiently sharp and deep images of these young discs to find the ‘twist’ that marks the spot where a baby planet may be coming to existence.

The new images feature a stunning spiral of dust and gas around AB Aurigae, located 520 light-years away from Earth in the constellation of Auriga (The Charioteer). Spirals of this type signal the presence of baby planets, which ‘kick’ the gas, creating “disturbances in the disc in the form of a wave, somewhat like the wake of a boat on a lake,” explains Emmanuel Di Folco of the Astrophysics Laboratory of Bordeaux (LAB), France, who also participated in the study. As the planet rotates around the central star, this wave gets shaped into a spiral arm. The very bright yellow ‘twist’ region close to the centre of the new AB Aurigae image, which lies at about the same distance from the star as Neptune from the Sun, is one of these disturbance sites where the team believe a planet is being made.

Observations of the AB Aurigae system made a few years ago with the Atacama Large Millimeter/submillimeter Array (ALMA), in which ESO is a partner, provided the first hints of ongoing planet formation around the star. In the ALMA images, scientists spotted two spiral arms of gas close to the star, lying within the disc’s inner region. Then, in 2019 and early 2020, Boccaletti and a team of astronomers from France, Taiwan, the US and Belgium set out to capture a clearer picture by turning the SPHERE instrument on ESO’s VLT in Chile toward the star. The SPHERE images are the deepest images of the AB Aurigae system obtained to date.

With SPHERE's powerful imaging system, astronomers could see the fainter light from small dust grains and emissions coming from the inner disc. They confirmed the presence of the spiral arms first detected by ALMA and also spotted another remarkable feature, a ‘twist’, that points to the presence of ongoing planet formation in the disc. "The twist is expected from some theoretical models of planet formation,” says co-author Anne Dutrey, also at LAB. “It corresponds to the connection of two spirals  — one winding inwards of the planet’s orbit, the other expanding outwards — which join at the planet location. They allow gas and dust from the disc to accrete onto the forming planet and make it grow."



ESO is constructing the 39-metre Extremely Large Telescope, which will draw on the cutting-edge work of ALMA and SPHERE to study extrasolar worlds. As Boccaletti explains, this powerful telescope will allow astronomers to get even more detailed views of planets in the making. “We should be able to see directly and more precisely how the dynamics of the gas contributes to the formation of planets,” he concludes.



Bibliography:

A. Boccaletti, E. Di Folco, E. Pantin, A. Dutrey, S. Guilloteau, Y. W. Tang, V. Piétu, E. Habart, J. Milli, T. L. Beck, A.-L. Maire.

Possible evidence of ongoing planet formation in AB Aurigae. 

Astronomy & Astrophysics, 2020; 637: L5

DOI: 10.1051/0004-6361/202038008

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