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Tag: Nature (journal)

  • Scientists use tardigrade proteins for human health breakthrough

    Scientists use tardigrade proteins for human health breakthrough

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    Newswise — University of Wyoming researchers’ study of how microscopic creatures called tardigrades survive extreme conditions has led to a major breakthrough that could eventually make life-saving treatments available to people where refrigeration isn’t possible.

    Thomas Boothby, an assistant professor of molecular biology, and colleagues have shown that natural and engineered versions of tardigrade proteins can be used to stabilize an important pharmaceutical used to treat people with hemophilia and other conditions without the need for refrigeration — even amid high temperatures and other difficult conditions. The findings are detailed today (Monday) in Scientific Reports, an online, open access journal from the publishers of Nature.

    The pharmaceutical, human blood clotting Factor VIII, is an essential therapeutic used to treat genetic disease and instances of extreme bleeding. Despite being critical and effective in treating patients in these circumstances, Factor VIII has a serious shortcoming, in that it is inherently unstable. Without stabilization within a precise temperature range, Factor VIII will break down.

    “In underdeveloped regions, during natural disasters, during space flight or on the battlefield, access to refrigerators and freezers, as well as ample electricity to run this infrastructure, can be in short supply. This often means that people who need access to Factor VIII do not get it,” Boothby says. “Our work provides a proof of principle that we can stabilize Factor VIII, and likely many other pharmaceuticals, in a stable, dry state at room or even elevated temperatures using proteins from tardigrades — and, thus, provide critical live-saving medicine to everyone everywhere.”

    Measuring less than half a millimeter long, tardigrades — also known as water bears — can survive being completely dried out; being frozen to just above absolute zero (about minus 458 degrees Fahrenheit, when all molecular motion stops); heated to more than 300 degrees Fahrenheit; irradiated several thousand times beyond what a human could withstand; and even survive the vacuum of outer space. They are able to do so, in part, by manufacturing a sugar called trehalose and a protein called CAHS D.

    According to the research paper, Boothby and his colleagues fine-tuned the biophysical properties of both trehalose and CAHS D to stabilize Factor VIII, noting that CAHS D is most suitable for the treatment. The stabilization allows Factor VIII to be available in austere conditions without refrigeration, including repeated dehydration/rehydration, extreme heat and long-term dry storage.

    The researchers believe the same thing can be done with other biologics — pharmaceuticals containing or derived from living organisms — such as vaccines, antibodies, stem cells, blood and blood products.

    “This study shows that dry preservation methods can be effective in protecting biologics, offering a convenient, logistically simple and economically viable means of stabilizing life-saving medicines,” Boothby says. “This will be beneficial not only for global health initiatives in remote or developing parts of the world, but also for fostering a safe and productive space economy, which will be reliant on new technologies that break our dependence on refrigeration for the storage of medicine, food and other biomolecules.”

    Boothby and other researchers hope that their discoveries can be applied to address other societal and global health issues as well, including water scarcity. For example, their work might lead to better ways of generating engineered crops that can cope with harsh environments.

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    University of Wyoming

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  • A common metabolite may help treat autoimmune diseases

    A common metabolite may help treat autoimmune diseases

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    Newswise — Researchers have revealed the modulatory effect of the anti-inflammatory metabolite itaconate on T helper and T regulatory cells, which may lead to new therapeutic approaches to treating some autoimmune diseases.

    Autoimmune diseases occur when the immune system attacks its own body. There are more than eighty known types of autoimmune diseases. In many cases, autoimmune diseases can be treated by suppressing the immune system; however, a side effect of such treatment is that the patient has an increased risk of severe infectious diseases, which is a leading cause of death. Hence there is a need to establish novel therapies for autoimmune diseases to reduce the risk of infectious diseases. 

    A research team led by Professor Tatsuya Atsumi, Assistant Professor Michihito Kono and graduate student Kuniyuki Aso at Hokkaido University, along with Senior Lecturer Masatoshi Kanda at Sapporo Medical University, has studied the effect of the molecule itaconate on the immune system. Their findings, which have implications for treating autoimmune disorders, were published in the journal Nature Communications.

    “Multiple sclerosis (MS) and systemic lupus erythematosus are two of the many autoimmune diseases caused by a dysregulation of T cells,” Kono explained. “We were interested in two types of T cells: T helper 17 (Th17) and regulatory T (Treg) cells. These cells have the same origin but have opposite functions in autoimmune diseases, and cell metabolites modulate their action. The metabolite we focused on was itaconate (ITA), as it has been shown to have anti-inflammatory, antiviral, and antimicrobial effects.”

    The researchers showed that, in cell cultures, ITA inhibited the differentiation of Th17 cells which have the potential to elaborate autoimmune diseases, and promoted that of Treg cells, which can ameliorate them. Further, in mice models with experimental autoimmune encephalomyelitis, ITA reduced the disease symptoms. Further tests were conducted to confirm that this effect was due to its effect on T cells.

    Investigations into the mechanism of action of ITA revealed that it inhibits essential metabolic pathways, glycolysis, oxidative phosphorylation, and methionine metabolism in Th17 and Treg cells. “ITA inhibits these pathways by directly inhibiting the enzymes methionine adenosyltransferase and isocitrate dehydrogenase, resulting in change of S-adenosyl-L-methionine/S-adenosylhomocysteine ratio and 2-hydroxyglutarate levels,” Kono elaborated. “The altered cell metabolites also indirectly affect the chromatin accessibility of essential transcription factors and the synthesis of proteins required for the differentiation of Th17 and Treg cells.”

    “Our results explain the mechanisms that underlie the modulation of T cell differentiation,” he concluded. “This could eventually lead to simple therapeutic approaches which regulate T cell differentiation, thereby treating T cell-mediated autoimmune diseases.”

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    Hokkaido University

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  • New Class of Drugs Could Prevent Resistant COVID-19 Variants

    New Class of Drugs Could Prevent Resistant COVID-19 Variants

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    Newswise — The constant evolution of new COVID-19 variants makes it critical for clinicians to have multiple therapies in their arsenal for treating drug-resistant infections. Researchers have now discovered that a new class of oral drugs that acts directly on human cells can inhibit a diverse range of pathogenic SARS-CoV-2 strains.

    In their newly published study, the team found a novel mechanism through which the gene that expresses angiotensin converting enzyme-2 (ACE-2)—the cellular receptor to which SARS-CoV-2 binds so that it can enter and infect the cell—is turned on. They also found that a class of oral drugs currently in human clinical trials can block this pathway and potentially be a therapeutic for all SARS-CoV-2 variants, as well as any newly emerging SARS-like viruses. The team published its findings in Nature Genetics on March 8.

    Targeting these master regulatory complexes complements existing approaches and fills a need for a new drug class that can be exploited to help combat drug resistance and infection. -Craig Wilen, MD, PhD

    “Because of drug-resistant variants, we’re down to only one drug, Paxlovid, as far as our oral options,” says Craig Wilen, MD, PhD, associate professor of laboratory medicine and of immunobiology, and a member of Yale Cancer Center. “Targeting these master regulatory complexes complements existing approaches and fills a need for a new drug class that can be exploited to help combat drug resistance and infection.” Wilen and Cigall Kadoch, PhD, of Dana-Farber Cancer Institute, are co-senior authors of the study. The co-first authors are Jin Wei, PhD, postdoctoral scholar in the Wilen Lab, and Ajinkya Patil, MS, graduate student in the Kadoch Lab and the Program in Virology at Harvard Medical School.

    Researchers Identify Potential Anti-Viral Targets

    In a previous study published in 2021, Wilen’s team at Yale performed genetic screening to identify host factors that are essential for SARS-CoV-2 infection. One of the key players was the mammalian switch/sucrose non-fermentable (mSWI/SNF, also called BAF) chromatin remodeling complex, a group of over a dozen very conserved proteins that allow certain genes to turn on.

    “At that point, I’d never heard of it in the setting of virus infection, and we couldn’t understand why it was important for coronaviruses,” says Wilen. Thus, the group teamed up with experts on this complex, the Kadoch Lab at the Dana-Farber Cancer Institute and Harvard Medical School to find out how the protein complex acts to make cells susceptible to infection and if newly emerging drugs against these complexes could stunt viral infection.

    At the time they embarked on their collaborative work, the U.S. Food and Drug Administration had authorized six monoclonal antibody treatments for emergency use, yet none of these treatments work against the newest Omicron variants. This leaves clinicians with remdesivir, which can only be administered through an IV, limiting its use; molnupiravir, an oral drug that works similarly to remdesivir but only has 30 percent efficacy; and Paxlovid, an oral antiviral that works through inhibiting the viral protease. Paxlovid, Wilen says, is the mainstay of current treatment.

    “It’s a great drug that works well, but there has been some emerging drug resistance to it,” he says. “And currently, that is the only drug in our toolbox that we can give as an oral form.” The dwindling of effective treatments further highlights the critical need for a new class of drugs to add to the toolbox, and ideally, ones that are less susceptible to quick-acting resistance mechanisms.

    Blocking mSWI/SNF Protects Cells Against SARS-CoV-2

    First, the team discovered that disrupting mSWI/SNF complexes prevented viral entry into human cells. Because mSWI/SNF is known to regulate genes turning on and off, they then hypothesized that it might also play a role in activating the ACE-2 receptor. Next, they uncovered its mechanism: mSWI/SNF binds to another protein called HNF1A, a transcription factor, which directs it to the gene that encodes ACE-2. Upon disrupting mSWI/SNF complexes, the cell could no longer make ACE-2 and became resistant to infection by any virus that uses that receptor. This includes many coronaviruses.

    Small molecule inhibitors that target mSWI/SNF have already been developed by Kadoch-founded Foghorn Therapeutics and are in phase I clinical trials as a therapeutic for several cancers. Wilen and Kadoch found that this class of drugs was effective against multiple variants of SARS-CoV-2—including a remdesivir-resistant strain isolated from a Yale patient—without any adverse effects on the cell. “This is proof of principle that this can be a really important first- or second-line tool to combat drug resistance,” says Wilen.

    “Further, this speaks to the wide, multi-disease potential for pharmacologic modulation of chromatin remodeling complexes,” says Kadoch. “These molecular machines sit at the top of the pyramid in governing gene expression programs that go awry in many different human diseases—we are just at the tip of the iceberg in identifying and exploring their utility”.

    Wilen believes the drugs in these clinical trials can potentially be repurposed to inhibit both current and future coronaviruses. Furthermore, Wilen and Kadoch hope the work can provide insight into why certain people and specific cell types may be more susceptible to coronavirus than others. “Future work is needed to look at the underlying biology of why some people are asymptomatic while others experience severe infection and death,” Wilen says.

    COVID-19 will not be the last severe viral outbreak. Wilen’s lab studies coronaviruses circulating in wild bats, which he believes pose the highest risk for infecting humans and causing the next pandemic. Many of these viruses use ACE-2 as a receptor, which means that this new study may hold the key to slowing or stopping the next outbreak. “We’re going to have another pandemic, whether it’s in a few years or a decade. And we’re underprepared for it,” he says. “The best way to prepare is to have as many vaccines and drugs as possible ready to go so that we can combat the outbreak early with maximum effectiveness.”

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    Yale Cancer Center/Smilow Cancer Hospital

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  • New Class of Drugs May Prevent Infection by Wide Range of COVID-19 Variants

    New Class of Drugs May Prevent Infection by Wide Range of COVID-19 Variants

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    RESEARCH SUMMARY

    Publication: Nature Genetics https://www.nature.com/articles/s41588-023-01307-z

    Dana-Farber Cancer Institute author: Cigall Kadoch, PhD,

     

    Summary:

    A new class of oral drugs can inhibit a wide range of SARS-CoV-2 variants, researchers report, potentially identifying new antiviral agents providing broad activity against the constantly emerging new strains of the COVID-19 virus. The researchers discovered that the mammalian SWI/SNF (also called BAF) chromatin remodeling complex, a regulator of gene expression –controls the expression of the ACE2, the cellular receptor or “entry point” used by COVID-19 viruses.  When mSWI/SNF complexes were disrupted, the cell could no longer make ACE-2 receptor protein and became resistant to infection by any virus that uses that receptor. Kadoch’s work on mSWI/SNF complexes over the years has led to experimental drugs currently in phase 1 trials as anti-cancer agents. These oral drugs now are looking promising for use in COVID-19, since they can inhibit ACE2 activity and nearly completely block viral infection in multiple cell lines and human lung organoids.

    Impact:

    The formerly potent array of monoclonal antibody treatments for COVID-19 continue to lose their activity as new less-sensitve variants of the virus appear: indeed, one by one, they have gone off the market. The need for more broadly acting agents against new and drug-resistant viruses is great. With the identification of this new target – a druggable chromatin regulatory complex – inhibition of which prevents infection of host cells, Kadoch and co-author Craig Wilen, MD, PhD, of the Yale Cancer Center have found a promising novel approach to combating the constantly-changing SARS virus.

    Funding:

    This work was supported by NIH grants K08AI128043, Burroughs Wellcome Fund, Smith Family Foundation, Ludwig Family Foundation, Huffington Foundation, Mathers Foundation, Emergent Ventures Fast Grant, and NIH Director’s New Innovator Award 1DP2CA195762-01.

     

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    Dana-Farber Cancer Institute

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  • Sea level rise poses particular risk for Asian megacities

    Sea level rise poses particular risk for Asian megacities

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    Newswise — Sea level rise this century may disproportionately affect certain Asian megacities as well as western tropical Pacific islands and the western Indian Ocean, according to new research that looks at the effects of natural sea level fluctuations on the projected rise due to climate change.

    The study, led by scientists at the French National Center for Scientific Research (CNRS) and University of La Rochelle in France and co-authored by a scientist at the National Center for Atmospheric Research (NCAR), mapped sea level hotspots around the globe. The research team identified several Asian megacities that may face especially significant risks by 2100 if society emits high levels of greenhouse gases: Chennai, Kolkata, Yangon, Bangkok, Ho Chi Minh City, and Manila.

    Scientists have long known that sea levels will rise with increasing ocean temperatures, largely because water expands when it warms and melting ice sheets release more water into the oceans. Studies have also indicated that sea level rise will vary regionally because shifts in ocean currents will likely direct more water to certain coastlines, including the northeastern United States.

    What’s notable about the new study is the way it incorporates naturally occurring sea level fluctuations caused by such events as El Niño or changes in the water cycle (a process known as internal climate variability). By using both a computer model of global climate and a specialized statistical model, the scientists could determine the extent to which these natural fluctuations can amplify or reduce the impact of climate change on sea level rise along certain coastlines.

    The study showed that internal climate variability could increase sea level rise in some locations by 20-30% more than what would result from climate change alone, exponentially increasing extreme flooding events. In Manila, for example, coastal flooding events are predicted to occur 18 times more often by 2100 than in 2006, based solely on climate change. But, in a worst-case scenario, they could occur 96 times more often based on a combination of climate change and internal climate variability.

    Internal climate variability will also increase sea level rise along the west coasts of the United States and Australia.

    The study drew on a set of simulations conducted with the NCAR-based Community Earth System Model that assume society this century emits greenhouse gases at a high rate. The simulations were run at the NCAR-Wyoming Supercomputing Center.

    The paper stressed that the estimates of sea level rise come with considerable uncertainties because of the complex and unpredictable interactions in Earth’s climate system. But the authors said it’s critical for society to be aware of the potential of extreme sea level rise in order to develop effective adaptation strategies.

    “The internal climate variability can greatly reinforce or suppress the sea level rise caused by climate change,” said NCAR scientist Aixue Hu, who co-authored the paper. “In a worst-case scenario, the combined effect of climate change and internal climate variability could result in local sea levels rising by more than 50% of what is due to climate change alone, thus posing significant risks of more severe flooding to coastal megacities and threatening millions of people.” 

    The study was published in Nature Climate Change. It was supported by the French Research Agency, the U.S. Department of Energy, and the U.S. National Science Foundation, which is NCAR’s sponsor.

    This material is based upon work supported by the National Center for Atmospheric Research, a major facility sponsored by the National Science Foundation and managed by the University Corporation for Atmospheric Research. Any opinions, findings and conclusions or recommendations expressed in this material do not necessarily reflect the views of the National Science Foundation.

    About the article

    Title: Increased exposure of coastal cities to sea-level rise due to internal climate variability
    Authors: M. Becker, M. Karpytchev, and A. Hu
    Journal: Nature Climate Change

    On the web: news.ucar.edu
    On Twitter: @NCAR_Science

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    National Center for Atmospheric Research (NCAR)

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  • ‘Swarmalators’ better envision synchronized microbots

    ‘Swarmalators’ better envision synchronized microbots

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    Newswise — ITHACA, N.Y. — Imagine a world with precision medicine, where a swarm of microrobots delivers a payload of medicine directly to ailing cells. Or one where aerial or marine drones can collectively survey an area while exchanging minimal information about their location.

    One early step towards realizing such technologies is being able to simultaneously simulate swarming behaviors and synchronized timing – behaviors found in slime molds, sperm and fireflies, for example.

    In 2014, Cornell researchers first introduced a simple model of swarmalators – short for ‘swarming oscillator’ – where particles self-organize to synchronize in both time and space. In the study, “Diverse Behaviors in Non-uniform Chiral and Non-chiral Swarmalators,” which published Feb. 20 in the journal Nature Communications, they expanded this model to make it more useful for engineering microrobots, better understand existing, observed biological behaviors, and for theoreticians to experiment in this field.

    “We wanted a simple mathematical model that can lay the foundation for swarmalators in general, something that captures all of the complex emergent phenomena we see in natural and engineered swarms,” said Kirstin Petersen, the paper’s senior author, assistant professor and an Aref and Manon Lahham Faculty Fellow in the Department of Electrical and Computer Engineering in Cornell Engineering.

    Steven Ceron, Ph.D. ‘22, a former graduate student in Petersen’s lab, is the paper’s first author, and Kevin O’Keeffe Ph.D. ‘17, a former graduate student in applied mathematics, is a co-author.    

    O’Keeffe compared this model to the largest doll in a set of Russian dolls, with each smaller doll representing models capable of simulating more refined behaviors. “We’ve tried to come up with a model that is as simple as possible in the hope of capturing generic phenomena,” he said.

    The researchers simplified their model to work with just four mathematical constants linked together to produce diverse emergent behaviors, such as aggregation, dispersion, vortices, traveling waves, and bouncing clusters.

    The new model can mimic particles in nature that each operate at different natural frequencies, as some objects move slower and faster around a trajectory than others. The researchers also added chirality, or the ability for a particle to move in a circle, because many examples in nature, such as sperm, swim in circles and in vortices. And particles in the model exhibit local coupling, so they sense and respond only to their local neighbors.

    At its core, the model combines swarming behaviors with synchronization in time. Examples of swarming from nature include flocking birds or herds of stampeding buffalo, where individuals move together as a group. Synchronized timing can be found in cardiac pacemaker cells that fire an electric impulse in unison, shocking the heart into regular repeated beats. Sperm represent both phenomena together, as they can beat their tails in unison while swimming as a group. Fireflies are also known to fly in swarms while flashing in synchrony.

    “That’s what makes them swarmalators, because there’s two of the self-organizing forces going on at the same time,” O’Keeffe said.

    The model doesn’t try to model a specific real world swarmalator, such as sperm, robotic drones, or magnetic domain walls. Rather, it tries to model the behavior common to all those systems ­– it aims for generality, rather than specificity. As an example, the model was shown to reproduce behaviors found in microbial slime molds, which can operate as individual cells, but when starved will aggregate into a slug and eventually a fruiting body.

    “These very simple coupled mechanisms can potentially be implemented on swarms of tiny robots with very limited power, computational and memory resources, which in spite of their individual simplicity can work together to produce the complex swarming behaviors we predict in our model,” Petersen said. 

    One future application could be for precision medicine, where tiny magnetized insoluble particles could swarm and be synchronized in relation to each other and then controlled to deliver a payload to tissues in need of a therapy, O’Keeffe said.

    The study was funded by the National Science Foundation, the Packard Foundation and an Aref and Manon Lahham Faculty Fellowship.

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    Cornell University

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  • Mysteries of the Earth: FSU researchers predict how fast ancient magma ocean solidified

    Mysteries of the Earth: FSU researchers predict how fast ancient magma ocean solidified

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    BYLINE: Bill Wellock

    Newswise — Early in the formation of Earth, an ocean of magma covered the planet’s surface and stretched thousands of miles deep into its core. The rate at which that “magma ocean” cooled affected the formation of the distinct layering within the Earth and the chemical makeup of those layers.

    Previous research estimated that it took hundreds of million years for that magma ocean to solidify, but new research from Florida State University published in Nature Communications narrows these large uncertainties down to less than just a couple of million years.

    “This magma ocean has been an important part of Earth’s history, and this study helps us answer some fundamental questions about the planet,” said Mainak Mookherjee, an associate professor of geology in the Department of Earth, Ocean and Atmospheric Science.

    When magma cools, it forms crystals. Where those crystals end up depends on how viscous the magma is and the relative density of the crystals. Crystals that are denser are likely to sink and thus change the composition of the remaining magma. The rate at which magma solidifies depends on how viscous it is. Less viscous magma will lead to faster cooling, whereas a magma ocean with thicker consistency will take a longer time to cool.

    Like this research, previous studies have used fundamental principles of physics and chemistry to simulate the high pressures and temperatures in the Earth’s deep interior. Scientists also use experiments to simulate these extreme conditions. But these experiments are limited to lower pressures, which exist at shallower depths within the Earth. They don’t fully capture the scenario that existed in the planet’s early history, where the magma ocean extended to depths where pressure is likely to be three times higher than what experiments can reproduce.

    To overcome those limitations, Mookherjee and collaborators ran their simulation for up to six months in the high-performance computing facility at FSU as well as at a National Science Foundation computing facility. This eliminated much of the statistical uncertainties in previous work.

    “Earth is a big planet, so at depth, pressure is likely to be very high,” said Suraj Bajgain, a former post-doctoral researcher at FSU who is now a visiting assistant professor at Lake Superior State University. “Even if we know the viscosity of magma at the surface, that doesn’t tell us the viscosity hundreds of kilometers below it. Finding that is very challenging.”

    The research also helps explain the chemical diversity found within the Earth’s lower mantle. Samples of lava — the name for magma after it breaks through the surface of the Earth — from ridges at the bottom of the ocean floor and volcanic islands like Hawaii and Iceland crystallize into basaltic rock with similar appearances but distinct chemical compositions, a situation that has long perplexed Earth scientists.

    “Why do they have distinct chemistry or chemical signals?” Mookherjee said. “Since the magma originates from underneath the Earth’s surface, that means the source of the magma there has chemical diversity. How did that chemical diversity begin in the first place, and how has it survived over geological time?”

    The starting point of chemical diversity in the mantle can be successfully explained by a magma ocean in the Earth’s early history with low viscosity. Less viscous magma led to the rapid separation of the crystals suspended within it, a process often referred to as fractional crystallization. That created a mix of different chemistry within the magma, rather than a uniform composition.

    Doctoral student Aaron Wolfgang Ashley from FSU as well as Dipta Ghosh and Bijaya Karki from the Department of Geology and Geophysics at Louisiana State University were co-authors of this paper.

    This work was funded by the National Science Foundation.

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    Florida State University

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  • SLAC, Stanford researchers make a new type of quantum material with a dramatic distortion pattern

    SLAC, Stanford researchers make a new type of quantum material with a dramatic distortion pattern

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    Newswise — Researchers at the Department of Energy’s SLAC National Accelerator Laboratory and Stanford University have created a new type of quantum material whose atomic scaffolding, or lattice,  has been dramatically warped into a herringbone pattern.

    The resulting distortions are “huge” compared to those achieved in other materials, said Woo Jin Kim, a postdoctoral researcher at the Stanford Institute for Materials and Energy Sciences (SIMES) at SLAC who led the study. 

    “This is a very fundamental result, so it’s hard to make predictions about what may or may not come out of it, but the possibilities are exciting,” said SLAC/Stanford Professor and SIMES Director Harold Hwang. 

    “Based on theoretical modeling from members of our team, it looks like the new material has intriguing magnetic, orbital and charge order properties that we plan to investigate further,” he said. Those are some of the very properties that scientists think give quantum materials their surprising characteristics. 

    The research team described their work in a paper published in Nature today.

    High-rises versus octahedrons

    The herringbone-patterned material is the first demonstration of something called the Jahn-Teller (JT) effect in a layered material with a flat, planar lattice, like a high-rise building with evenly spaced floors.  

    The JT effect addresses the dilemma an electron faces when it approaches an ion – an atom that’s missing one or more electrons. 

    Just like a ball rolling along the ground will stop and settle in a low spot, the electron will seek out and occupy the vacancy in the atom’s electron orbitals that has the lowest energy state. But sometimes there are two vacancies with equally low energies. What then? 

    If the ion is in a molecule or embedded in a crystal, the JT effect distorts the surrounding atomic lattice in a way that leaves only one vacancy at the lowest energy state, solving the electron’s problem, Hwang said. 

    And when the whole crystal lattice consists of JT ions, in some cases the overall crystal structure warps, so the electron’s dilemma is cooperatively solved for all the ions. 

    That’s what happened in this study.

    “The Jahn-Teller effect creates strong interactions between the electrons and between the electrons and the lattice,” Hwang said. “This is thought to play key roles in the physics of a number of quantum materials.” 

    The JT effect had already been demonstrated for single molecules and for 3D crystalline materials that consist of ions arranged in octahedral or tetrahedral structures. In fact, JT oxides based on manganese or copper exhibit colossal magnetoresistance and high-temperature superconductivity – leading scientists to wonder what would happen in materials based on other elements or having a different structure.

    In this study, the SIMES researchers turned a material made of cobalt, calcium and oxygen (CaCoO2.5), which has a different stacking of octahedral and tetrahedral layers and is known as brownmillerite,  into a layered material (CaCoO2) where the JT effect could take hold. They did it with a chemical trick developed at SIMES a few years ago to make the superconductivity-nickel-oxide-material”>first nickel oxide superconductor.

    Pulling out Jenga blocks

    Kim synthesized a thin film of brownmillerite and chemically removed single layers of oxygen atoms from its lattice, much like players carefully remove blocks from a Jenga tower. The lattice collapsed and settled into a flat, planar configuration with alternating layers containing negatively charged cobalt ions ­– the JT ions ­– and positively charged calcium ions. 

    Each cobalt ion tried to pull calcium ions from the layers above and below it, Kim said. 

    “This tug-of-war between adjacent layers led to a beautiful pattern of distortions that reflects the best and most harmonious compromise between the forces at play,” he said. “And the resulting lattice distortions are huge compared to those in other materials ­– equal to 25% of the distance between ions in the lattice.”

    Hwang said the research team will be exploring this remarkable new electronic configuration with X-ray tools available at SLAC and elsewhere. “We also wonder what will happen if we can dope this material – replacing some atoms with others to change the number of electrons that are free to move around,” he said. “There are many exciting possibilities.”

    Researchers from Cornell University, the Pohang Accelerator Laboratory in South Korea and the Center for Nanoscale Materials Sciences, a DOE Office of Science user facility at Oak Ridge National Laboratory, contributed to this work. It received major funding from the DOE Office of Science and the Gordon and Betty Moore Foundation’s Emergent Phenomena in Quantum Systems Initiative. 

     


    SLAC is a vibrant multiprogram laboratory that explores how the universe works at the biggest, smallest and fastest scales and invents powerful tools used by scientists around the globe. With research spanning particle physics, astrophysics and cosmology, materials, chemistry, bio- and energy sciences and scientific computing, we help solve real-world problems and advance the interests of the nation.

    SLAC is operated by Stanford University for the U.S. Department of Energy’s Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time.

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    SLAC National Accelerator Laboratory

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  • UCLA Health tip sheet: Pesticides & Parkinson’s symptoms; Gender-affirming hormones improve mental health; Body composition & cardiovascular disease

    UCLA Health tip sheet: Pesticides & Parkinson’s symptoms; Gender-affirming hormones improve mental health; Body composition & cardiovascular disease

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    UCLA Health Tip Sheet Feb. 21, 2023

    Below is a brief roundup of news and story ideas from the experts at UCLA Health. For more information on these stories or for help on other stories, please contact us at [email protected].

    Body composition, not BMI, may signal risk for cardiovascular disease  Body mass index has long been a measure of a person’s risk of developing cardiovascular disease, but body composition and its role in the disease have not been well studied. In a new study, UCLA researchers predicted higher fat mass would be linked to higher levels of coronary artery calcification (CAC) — a marker of subclinical cardiovascular disease – and higher fat-free mass would be linked to lower levels of CAC. Using computed tomography scans and bioelectrical impedance analysis to study CAC and body composition in 3,129 non‐Hispanic Whites, Blacks, Hispanics, and Chinese patients, the researchers unexpectedly found that higher fat-free mass and, to a lesser extent, higher fat mass were linked to high levels of CAC. The researchers cautioned that bioelectrical impedance analysis could not identify the quality of fat or fat-free mass. Given these findings, the researchers say measuring body composition rather than using BMI to assess obesity may be a better approach to evaluating cardiovascular disease risk. Read the study published Feb. 8, 2023 in the Journal of the American Heart Association.

    Bariatric surgery reduces risks of hospitalization for heart failure Bariatric surgery has been found to reverse the ill effects of diabetes and may be protective against obesity-related cancers. Because obesity rates are on the rise across the globe, UCLA researchers set out to study other health benefits weight loss surgeries confer, in particular the link between the procedures and acute heart failure hospitalizations. After analyzing data from the Nationwide Readmissions Database from 2016 to 2019, the researchers found bariatric surgery was associated with lower odds of being hospitalized with acute heart failure. Among patients hospitalized with acute heart failure, prior bariatric surgery was associated with lower risks of death, prolonged ventilation, and acute renal failure. Beyond the health benefits, those who had undergone surgery stayed one fewer day in the hospital and incurred about $1,200 less in hospital costs compared to age matched cohorts. Read the study in Surgery for Obesity and Related Diseases. 

    Pesticides may also worsen Parkinson’s symptoms: While researchers have consistently found an association between pesticide exposure and higher risk of developing Parkinson’s disease, there has been little study of whether such exposure can accelerate the course of the disease. In a new study of 53 pesticides associated with Parkinson’s onset, researchers led by UCLA assistant professor of neurology Kimberly Paul, PhD, identified 10 pesticides that are associated with faster progression of motor and non-motor symptoms. Furthermore, exposure to six of those pesticides was associated with worsening of multiple endpoints researchers measured. Two pesticides, copper sulfate (pentahydrate) and MCPA (dimethylamine salt), were associated with all three endpoints measured: motor function, cognitive function, and depressive symptoms. Read the study in the journal Science of the Total Environment.

    Repurposing an old drug for a rare disease: A drug used to treat epilepsy, retigabine, may help manage episodic attacks of paralysis in patients with the rare inherited muscle disease Hypokalemic Periodic Paralysis (HypoPP), according to a new study that tested retigabine in genetically engineered mice. There’s a strong need to identify new HypoPP treatments since existing ones only improve symptoms in about half of patients and have considerable side effects. HypoPP is often marked by reduced potassium levels in the blood during episodes of muscle weakness. While it was known that retigabine affects a potassium channel that plays an important role in the heart and brain, the channel wasn’t previously known to exist in skeletal muscle. However, the new study led by Dr. Stephen C. Cannon, chair of the physiology department at the UCLA David Geffen School of Medicine, found that retigabine helps stabilize the membrane potential of skeletal muscle, thereby protecting against attacks of muscle weakness. Read the study, published online Jan. 30, in the journal Brain.

    Women treated with thrombectomy for pulmonary embolism fare worse A new study led by UCLA researchers analyzed the different outcomes in men and women with a pulmonary embolism who are treated by a percutaneous pulmonary artery thrombectomy- a procedure in which a catheter is placed in a patient’s lung to dissolve or remove a blood clot. After analysis of a national cohort of US patients from an inpatient claims-based database, researchers reported that women had higher rates of procedural bleeding, vascular complications, and needed more blood transfusions compared to men. They also found that women had higher in-hospital death rates and were more likely to go a nursing home or an assisted living facility instead of returning home after discharge. Given these disparities in outcomes, study authors are calling for more sex-based research. Read the study in the January 1, 2023 issue of CHEST. 

    A new clue about Parkinson’s progression The transmission of misfolded proteins in the brain is a key mechanism for the progression of various neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease. Chao Peng, PhD, an assistant professor of neurology, found a novel mechanism that regulates the transmission of one of these pathological proteins, misfolded alpha-synuclein, which leads to disease progression in Parkinson’s. This mechanism is the discovery that many modifications that a cell makes in these proteins alter their ability for transmission in the brain and disease progression. This discovery not only provides critical insights into disease mechanism but also facilitates the development of novel therapy for neurodegenerative diseases. Read the study, published Jan. 23, in Nature Neuroscience.

    Urban heat islands, redlining and kidney stones The persistent rise in kidney stone prevalence in recent decades has prompted much speculation as to the causes. There has been some discussion about the effect of heat on nephrolithiasis. A review of recent data suggests that heat may play a role in stone formation on a large scale and among African-Americans in particular. A new UCLA-led study led by Dr. Kymora B. Scotland states that African-Americans are the race/ancestry group with faster rates of increasing incidence and prevalence of kidney stones. Researchers also found that urban heat islands in the United States have resulted in part from the effects of redlining, a practice of systematic segregation and racism in housing that led to the development of neighborhoods with substantial disparities in environmental conditions. Dr. Scotland and her team hypothesize that the increased temperatures experienced by residents in redlined communities, many of whom are African American may contribute to the 150% increase in the prevalence of kidney stones in African Americans in recent decades. Read the study in the January 1, 2023 issue of Current Opinion in Nephrology and Hypertension.

    Gender-affirming hormones tied to mental health for transgender youth Transgender and nonbinary teens who receive gender-affirming hormones experience improvement in body satisfaction, life satisfaction and less depression and anxiety than before treatment. These findings are according to newly-published research by a four-site prospective, observational study and co-authored by Marco A. Hidalgo, PhD. Dr. Hidalgo is a clinical psychologist and Associate Clinical Professor of Medicine at the David Geffen School of Medicine at UCLA. Read the study published January 19, 2023 in the New England Journal of Medicine.

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  • Astrophysics: Scientists observe high-speed star formation

    Astrophysics: Scientists observe high-speed star formation

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    Newswise — Gas clouds in the Cygnus X Region, a region where stars form, are composed of a dense core of molecular hydrogen (H2) and an atomic shell. These ensembles of clouds interact with each other dynamically in order to quickly form new stars. That is the result of observations conducted by an international team led by scientists at the University of Cologne’s Institute of Astrophysics and at the University of Maryland. Until now, it was unclear how this process precisely unfolds. The Cygnus X region is a vast luminous cloud of gas and dust approximately 5,000 light years from Earth. Using observations of spectral lines of ionized carbon (CII), the scientists showed that the clouds have formed there over several million years, which is a fast process by astronomical standards. The results of the study ‘Ionized carbon as a tracer for the assembly of interstellar clouds’ will appear in the next issue of Nature Astronomy. The paper is already accessible online.

    The observations were carried out in an international project led by Dr Nicola Schneider at the University of Cologne and Prof Alexander Tielens at the University of Maryland as part of the FEEDBACK programme on board the flying observatory SOFIA (Stratospheric Observatory for Infrared Astronomy). The new findings modify previous perceptions that this specific process of star formation is quasi-static and quite slow. The dynamic formation process now observed would also explain the formation of particularly massive stars.

    By comparing the distribution of ionized carbon, molecular carbon monoxide and atomic hydrogen, the team found that the shells of interstellar gas clouds are made of hydrogen and collide with each other at speeds of up to twenty kilometres per second. “This high speed compresses the gas into denser molecular regions where new, mainly massive stars form. We needed the CII observations to detect this otherwise ‘dark’ gas,” said Dr Schneider. The observations show for the first time the faint CII radiation from the periphery of the clouds, which could not be observed before. Only SOFIA and its sensitive instruments were capable of detecting this radiation.

    SOFIA was operated by NASA and the German Aerospace Center (DLR) until September 2022. The observatory consisted of a converted Boeing 747 with a built-in 2.7-metre telescope. It was coordinated by the German SOFIA Institute (DSI) and the Universities Space Research Association (USRA). SOFIA observed the sky from the stratosphere (above 13 kilometres) and covered the infrared region of the electromagnetic spectrum, just beyond what humans can see. The Boeing thus flew above most of the water vapour in the Earth’s atmosphere, which otherwise blocks out infrared light. This allowed the scientists to observe a wavelength range that is not accessible from Earth. For the current results, the team used the upGREAT receiver installed on SOFIA in 2015 by the Max Planck Institute for Radio Astronomy in Bonn and the University of Cologne.

    Even though SOFIA is no longer in operation, the data collected so far are essential for basic astronomical research because there is no longer an instrument that extensively maps the sky in this wavelength range (typically 60 to 200 micrometres). The now active James Webb Space Telescope observes in the infrared at shorter wavelengths and focuses on spatially small areas. Therefore, the analysis of the data collected by SOFIA is ongoing and continues to provide important insights – also regarding other star-forming regions: “In the list of FEEDBACK sources, there are other gas clouds in different stages of evolution, where we are now looking for the weak CII radiation at the peripheries of the clouds to detect similar interactions as in the Cygnus X region,” Schneider concluded.

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  • The unnecessary burden of war

    The unnecessary burden of war

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    Newswise — Governments could help millions of people and save a lot of money with targeted energy subsidies. Different kinds of households around the world suffer in various ways from the exorbitant energy prices and need different kinds of support, says Klaus Hubacek from the University of Groningen, the Netherlands, in a new study that was published on 16 February in Nature Energy.

    All around the world, households are affected by soaring energy prices due to the war in Ukraine. But these households are affected in different ways: ‘This depends on their income level, how they spend their money, and how and where the products that they are using are being produced,’ explains Hubacek, Professor of Science, Technology, and Society. 

    Poverty

    ‘Our study is one of the very first that quantifies—at an unprecedented level of detail—the impacts of the energy crisis, including its impact on households, within many countries and with a global reach,’ says Hubacek. ‘Without such detailed knowledge, it is impossible to know who to help and how. If the governments were to use this as a guide, they could save a lot of money.’

    The increased fossil fuel prices potentially push millions of people into poverty, or even extreme poverty. Government measures to subsidize towering energy bills for households are inefficient because they do not take enough details into account. ‘If you look at the responses of governments, for example in Germany, the UK, the US, or the Netherlands, they have been using policies that do not sufficiently help those who need it most,’ states Hubacek. ‘Meanwhile they spend lots of money on people who don’t need it. That really frustrates me.’

    Food

    Energy prices affect households in two ways. Directly, through high energy bills, and indirectly, through the goods and services that became more expensive due to fossil fuel use in their supply chains. ‘So, for example, if you use a cell phone in the Netherlands you need direct energy, which is not a lot,’ explains Hubacek. ‘But a cell phone is made of many different components that come from Japan, China, Austria, the US, and so on.’ Therefore higher energy prices effect the price of a new smart phone indirectly.

    The same is true for food: energy prices push up costs for fertilizer, transport, etcetera. Energy inputs are required in production and transportation all the way to the final product. The rising costs of energy are passed on to the consumer through the price of the product, thus indirectly increasing the burden on households.

    Straw

    Because different households spend their money on different things, the kind of burden that the energy price shock imposes varies as well. ‘We show this in detail in our paper,’ says Hubacek. ‘For example, in some countries it is the increase in food prices that affects households most, in other cases it’s mobility, and so on. Knowing what causes the increased costs exactly allows you to really subsidize the products and services that put the highest pressure on households.’

    For both high- and low-income countries, the indirect energy costs impose the biggest burden, whereas for middle-income countries, direct energy costs have the biggest impact. A possible explanation is that in high- and low-income countries, households’ direct energy availability is uniform, according to Yuru Guan, one of Hubacek’s PhD students and first author of the paper. Therefore, they are affected more by consumption patterns of other goods. ‘For example, Dutch people basically use natural gas for heating, so when energy prices increase, everyone suffers from the same rate of increase in direct energy costs,’ explains Guan.

    In middle-income countries, households show larger disparities when it comes to the availability of energy. ‘In China, the rich have access to natural gas for heating, while the poorest burn coal or even straw,’ continues Guan. Therefore, the total burden on household expenditure is dominated by direct energy costs.

    Windfall tax

    Hubacek makes another point. He suspects that the increase of energy prices due to the Russian invasion in Ukraine wouldn’t have been as extreme if better policies had been made before. ‘Governments could have saved money by helping people with lower incomes to insulate their houses instead of digging for coal and investing in LNG terminals that are hugely inefficient,’ says Hubacek. ‘Now they invest in a very expensive infrastructure that we shouldn’t have in the first place if we take climate change seriously.’

    Governments could moreover increase their income relatively easy. ‘Energy companies’ profits have increased considerably since the onset of the war,’ according to Hubacek. ‘And many other sectors benefited as well. They increase their prices more than required to cover the extra energy costs, thus increasing their profits.’ Special windfall and carbon taxes could help enormously in the fight against poverty. ‘It’s all linked,’ says Hubacek. ‘Polluting sectors could be taxed and the money could be used to help poor households. It’s simple. It’s just politically difficult.’

    It is up to policy makers to make decisions that take the bigger picture into account, and to not just stick plasters. ‘However, there is no free lunch,’ as Hubacek puts it. ‘Renewable energy contributes to climate change as well. So the focus should be on policies that fight poverty and energy use in the long term.

    Reference: Yuru Guan, Jin Yan, Yuli Shan, Yannan Zhou, Ye Hang, Ruoqi Li, Yu Liu, Binyuan Liu, Qingyun Nie, Benedikt Bruckner, Kuishuang Feng en Klaus Hubacek. Burden of the global energy price crisis on households, Nature Energy, 16 February 2023

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    University of Groningen

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  • Extracts from two wild plants inhibit COVID-19 virus, study finds

    Extracts from two wild plants inhibit COVID-19 virus, study finds

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    Newswise — Two common wild plants contain extracts that inhibit the ability of the virus that causes COVID-19 to infect living cells, an Emory University study finds. Scientific Reports published the results — the first major screening of botanical extracts to search for potency against the SARS-CoV-2 virus.

    In laboratory dish tests, extracts from the flowers of tall goldenrod (Solidago altissima) and the rhizomes of the eagle fern (Pteridium aquilinum) each blocked SARS-CoV-2 from entering human cells.

    The active compounds are only present in miniscule quantities in the plants. It would be ineffective, and potentially dangerous, for people to attempt to treat themselves with them, the researchers stress. In fact, the eagle fern is known to be toxic, they warn.

    “It’s very early in the process, but we’re working to identify, isolate and scale up the molecules from the extracts that showed activity against the virus,” says Cassandra Quave, senior author of the study and associate professor in Emory School of Medicine’s Department of Dermatology and the Center for the Study of Human Health. “Once we have isolated the active ingredients, we plan to further test for their safety and for their long-range potential as medicines against COVID-19.”

    Quave is an ethnobotanist, studying how traditional people have used plants for medicine to identify promising new candidates for modern-day drugs. Her lab curates the Quave Natural Product Library, which contains thousands of botanical and fungal natural products extracted from plants collected at sites around the world.

    Caitlin Risener, a PhD candidate in Emory’s Molecular and Systems Pharmacology graduate program and the Center for the Study of Human Health, is first author of the current paper.

    In previous research to identify potential molecules for the treatment of drug-resistant bacterial infections, the Quave lab focused on plants that traditional people had used to treat skin inflammation.

    Given that COVID-19 is a newly emerged disease, the researchers took a broader approach. They devised a method to rapidly test more than 1,800 extracts and 18 compounds from the Quave Natural Product Library for activity against SARS-CoV-2.

    “We’ve shown that our natural products library is a powerful tool to help search for potential therapeutics for an emerging disease,” Risener says. “Other researchers can adapt our screening method to search for other novel compounds within plants and fungi that may lead to new drugs to treat a range of pathogens.”

    SARS-CoV-2 is an RNA virus with a spike protein that can bind to a protein called ACE2 on host cells. “The viral spike protein uses the ACE2 protein almost like a key going into a lock, enabling the virus to break into a cell and infect it,” Quave explains.

    The researchers devised experiments with virus-like particles, or VLPs, of SARS-CoV-2, and cells programmed to overexpress ACE2 on their surface. The VLPs were stripped of the genetic information needed to cause a COVID-19 infection. Instead, if a VLP managed to bind to an ACE2 protein and enter a cell, it was programmed to hijack the cell’s machinery to activate a fluorescent green protein.

    A plant extract was added to the cells in a petri dish before introducing the viral particles. By shining a fluorescent light on the dish, they could quickly determine whether the viral particles had managed to enter the cells and activate the green protein.   

    The researchers identified a handful of hits for extracts that protected against viral entry and then homed in on the ones showing the strongest activity: Tall goldenrod and eagle fern. Both plant species are native to North America and are known for traditional medicinal uses by Native Americans.

    Additional experiments showed that the protective power of the plant extracts worked across four variants of SARS-CoV-2: Alpha, theta, delta and gamma.

    To further test these results, the Quave lab collaborated with co-author Raymond Schinazi, Emory professor of pediatrics, director of Emory’s Division of Laboratory of Biochemical Pharmacology and co-director of the HIV Cure Scientific Working Group within the NIH-sponsored Emory University Center for AIDS Research. A world leader in antiviral development, Schinazi is best known for his pioneering work on breakthrough HIV drugs.

    The higher biosecurity rating of the Schinazi lab enabled the researchers to test the two plant extracts in experiments using infectious SARS-CoV-2 virus instead of VLPs. The results confirmed the ability of the tall goldenrod and eagle fern extracts to inhibit the ability of SARS-CoV-2 to bind to a living cell and infect it.

    “Our results set the stage for the future use of natural product libraries to find new tools or therapies against infectious diseases,” Quave says.

    As a next step, the researchers are working to determine the exact mechanism that enables the two plant extracts to block binding to ACE2 proteins.

    For Risener, one of the best parts about the project is that she collected samples of tall goldenrod and eagle fern herself. In addition to gathering medicinal plants from around the globe, the Quave lab also makes field trips to the forests of the Joseph W. Jones Research Center in South Georgia. The Woodruff Foundation established the center to help conserve one of the last remnants of the unique longleaf pine ecosystem that once dominated the southeastern United States.

    “It’s awesome to go into nature to identify and dig up plants,” Risener says. “That’s something that few graduate students in pharmacology get to do. I’ll be covered in dirt from head to toe, kneeling on the ground and beaming with excitement and happiness.”

    She also assists in preparing the plant extracts and mounting the specimens for the Emory Herbarium.

    “When you collect a specimen yourself, and dry and preserve the samples, you get a personal connection,” she says. “It’s different from someone just handing you a vial of plant material in a lab and saying, ‘Analyze this.’”

    After graduating, Risener hopes for a career in outreach and education for science policy surrounding research into natural compounds. A few of the more famous medicines derived from botanicals include aspirin (from the willow tree), penicillin (from fungi) and the cancer therapy Taxol (from the yew tree).

    “Plants have such chemical complexity that humans probably couldn’t dream up all the botanical compounds that are waiting to be discovered,” Risener says. “The vast medicinal potential of plants highlights the importance of preserving ecosystems.”

    Co-authors of the current paper include: Sumin Woo, Tharanga Samarakoon, Marco Caputo and Emily Edwards (the Quave lab and Emory’s Center for the Study of Human Health); Keivan Zandi, Shu Ling Goh and Jessica Downs-Bowen (the Schinazi lab); Kier Klepzig (Joseph W. Jones Research Center); and Wendy Applequist (Missouri Botanical Garden).

    Funding for the paper was provided by the Marcus Foundation, the NIH-funded Center for AIDS Research and the NIH National Center for Complementary and Integrative Health.

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    Emory University

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  • A second chance to protect wetlands

    A second chance to protect wetlands

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    Newswise — Wetlands are among the most threatened ecosystems in the world. A new study, published in Nature, has found that the loss of wetland areas around the globe since 1700 has likely been overestimated. This is good news overall, however, the global picture hides significant variations, with several regions and distinct wetland types under significant levels of pressure. For instance, temperate river floodplains have been highly impacted while remote boreal-arctic peatlands remain comparatively unharmed. While wetland conversion and degradation has slowed globally, it continues apace in some regions, such as Indonesia, where large swaths of land are being cleared for oil palm plantations and other agricultural uses. This new global perspective on wetland loss can help prioritize conservation and restoration actions.


    Historical reconstruction provides new insights
    Now understood to be vital sources of water purification, groundwater recharge, and carbon storage, wetlands were historically seen as unproductive areas teeming with disease-bearing insects and good only for draining to grow crops or harvest peat for fuel or fertilizer. Over time, unrelenting drainage for conversion to farmland and urban areas along with alteration caused by fires and groundwater extraction have made wetlands among the world’s most threatened ecosystems.

    Until now, a lack of historical data has hindered efforts to understand the full global impact of wetland loss, forcing scientists to make estimates based on incomplete collections of regional data. In a first of its kind historical reconstruction, the team, bringing together researchers from Stanford, Cornell, and McGill universities, combed through thousands of records of wetland drainage and land-use changes in 154 countries, mapping the distribution of drained and converted wetlands onto maps of present-day wetlands to get a picture of what the original wetland areas might have looked like in 1700.

    Decline in wetlands – less than previously thought

    The researchers found that the area of wetland ecosystems has declined by between 21-35% since 1700 due to human intervention. That’s far less than the 50-87% losses estimated by some previous studies. The lower estimate likely results from the study’s expanded focus beyond regions with historically high wetland losses, and its avoidance of large and possibly misleading extrapolations. Still, the authors estimate that at least 3.4 million square kilometres of wetlands have been lost globally over the past 300 years—an area about the size of India. Five countries with the highest losses, USA, China, India, Russia, and Indonesia, alone account for over 40% of global losses.

    “Many regions of the world have sustained dramatically high wetland losses, but our results suggest that losses are lower than previously thought once aggregated globally. Yet, it remains urgent to halt and reverse the conversion and degradation of wetlands, particularly in high-loss regions. The geographic disparities in losses are critical because the disappearance of ecosystem services caused by wetland drainage in one location cannot be replaced by the existence of wetlands elsewhere,” said lead author Etienne Fluet-Chouinard, a postdoctoral associate in Stanford’s Department of Earth System Science at the time of the research, who conceived of this study during his master’s degree in McGill’s Department of Geography.

    Another chance to act on wetland loss

    “Wetlands, in their natural state, are among the most important ecosystems to regulate our water resources, which benefits both humans and the environment,” adds coauthor Bernhard Lehner, a global hydrologist at McGill University. “Discovering that fewer wetlands have been historically lost than we previously thought gives us a second chance to take action to ensure wetland cover does not decline further. As part of that, we need to improve our capacity to map their past and current extents and monitor their status using satellites. This will allow us to establish meaningful conservation goals and restoration targets.


    About McGill University

    Founded in Montreal, Quebec, in 1821, McGill University is Canada’s top ranked medical doctoral university. McGill is consistently ranked as one of the top universities, both nationally and internationally. It is a world-renowned institution of higher learning with research activities spanning two campuses, 11 faculties, 13 professional schools, 300 programs of study and over 40,000 students, including more than 10,200 graduate students. McGill attracts students from over 150 countries around the world, its 12,800 international students making up 31% of the student body. Over half of McGill students claim a first language other than English, including approximately 19% of our students who say French is their mother tongue.

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  • Mosquito’s DNA could provide clues on gene expression, regulation

    Mosquito’s DNA could provide clues on gene expression, regulation

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    Newswise — HOUSTON – (Feb. 9, 2023) – When it comes to DNA, one pesky mosquito turns out to be a rebel among species.

    Researchers at Rice University’s Center for Theoretical Biological Physics (CTBP) are among the pioneers of a new approach to studying DNA. Instead of focusing on chromosomes as linear sequences of genetic code, they’re looking for clues on how their folded 3D shapes might determine gene expression and regulation.

    For most living things, their threadlike chromosomes fold to fit inside the nuclei of cells in one of two ways. But the chromosomes of the Aedes aegypti mosquito — which is responsible for the transmission of tropical diseases such as denguechikungunyazikamayaro and yellow fever — defy this dichotomy, taking researchers at the CTBP by surprise.

    The Aedes aegypti’s chromosomes organize as fluid-yet-oriented “liquid crystals,” different from all other species, according to their study published in Nature Communications.

    “Understanding DNA is a key to understanding how life works,” said Rice theoretical physicist Peter Wolynes, a co-author on the study. “We are only just beginning to learn how the 3D architecture of chromosomes influences the functioning of genomes.”

    A 2021 collaborative study co-led by a team from the CTBP and published in Science reported that chromosomes display one of two structural patterns when cells are not dividing, the stage in the cell life cycle known as interphase.

    “In a ‘type two’ genome architecture — like that found in humans and chickens, for instance — chromosomes form territories and don’t mix together that much,” said Vinícius Contessoto, a CTBP research scientist who is a lead co-author on the latest study and was also a co-author on the 2021 study.

    The still-unknown forces that keep active and inactive parts of “type two” chromosomes separate from each other during interphase behave like those that prevent oil and water from mixing together.

    “In a ‘type one’ architecture, like that found in yeast or in many plants, the regions of the chromosomes known as centromeres come together, folding them into an intermeshed, hairpin-like structure, polarized with telomeres ” said José Onuchic, Rice’s Harry C. and Olga K. Wiess Professor of Physics and Astronomy, and a professor of chemistry and biosciences.

    “Something that’s surprising to me is that even though so many different species have been mapped, they still largely fall into one of these two different classes,” Wolynes said. “The Aedes aegypti mosquito is the first real outlier.”

    The genome of the Aedes aegypti is roughly half the length of the human genome and is organized into six large chromosomes, as opposed to humans’ 46. “We used to think that the chromosomes of the mosquito did not form territories, but in fact they do form these elongated territories,” Contessoto said.

    “During interphase, ‘type two’ chromosomes are really very fluid, disordered things balled up into droplet-shaped territories,” said Wolynes, Rice’s Bullard-Welch Foundation Professor of Science and a professor of chemistry, of biochemistry and cell biology, of physics and astronomy, and of materials science and nanoengineering and co-director of the CTBP.

    The chromosomes of the Aedes aegypti mosquito display fluid characteristics, separating from one another like liquid droplets of oil and water. At the same time, they are partially condensed by compaction forces, which gives them an unusual shape, oriented like an overlong football, suggesting their consistency is also similar to that of a crystal.

    Moreover, if force is applied to a regular “type two” nucleus and it is deformed, the organization of the chromosomes inside remains unaffected. “It’s like poking a water balloon — it reverts to its prior shape. But when we poke the nucleus of the mosquito cells, the chromosomes’ patterns inside change dramatically,” said Onuchic.

    “This is an intriguing feature of ‘type one’ chromosome architecture that suggests there is a possible mechanism linking gene regulation to mechanical inputs on the cell,” said Onuchic. In 2020, he and collaborators confirmed the existence of a mechanism connecting genome structure to gene expression.

    Other co-authors of the new study are Erez Lieberman Aiden, a Rice adjunct assistant professor of computer science and an assistant professor of computational and applied mathematics, an associate professor of molecular and human genetics and a principal investigator in the joint Rice/Baylor College of Medicine Center for Genome Architecture; Olga Dudchenko, an assistant professor in the Center for Genome Architecture and former CTBP postdoctoral fellow; and Michele Di Pierro, an assistant professor of physics at Northeastern University. All are CTBP members.

    The research was supported by the National Science Foundation (2019745, 2210291, 2019276, 2021795); the Welch Foundation (C-1792, Q-1866); the Cancer Prevention and Research Institute of Texas; the São Paulo State Research Foundation and Higher Education Personnel, and Higher Education Personnel Improvement Coordination (2016/13998-8, 2017/09662-7); the D.R. Bullard-Welch Chair at Rice (C-0016); the McNair Medical Institute Scholar Award; the National Institutes of Health (UM1HG009375, RM1HG011016-01A1, R35GM146852); and the AMD HPC Fund.

    -30-

    This release can be found online at news.rice.edu.

    Follow Rice News and Media Relations via Twitter @RiceUNews.

    Peer-reviewed paper:

    Interphase chromosomes of the Aedes aegypti mosquito are liquid crystalline and can sense mechanical cues | Nature Communications | DOI: 10.1038/s41467-023-35909-2

    https://doi.org/10.1038/s41467-023-35909-2

    Authors: Vinícius Contessoto, Olga Dudchenko, Erez Lieberman Aiden, Peter Wolynes, José Onuchic and Michele Di Pierro

    Image downloads:

    https://news-network.rice.edu/news/files/2023/02/CTBP_NatureCommunications_image1_LG.jpg

    CAPTION: 3D simulation of the genome structure of the Aedes aegypti mosquito. The elongated territories formed by each of the six chromosomes are color-coded and shown separately (bottom) and together as part of the whole genome (top). (Image adapted from Nature Communications, https://doi.org/10.1038/s41467-023-35909-2, under a Creative Commons Attribution 4.0 International License.)

    https://news-network.rice.edu/news/files/2023/02/CTBP_NatureCommunications_image2_LG.jpg
    CAPTION: The image shows the effects of applying tension to cell nuclei on contacts between the chromosomes of both the human and mosquito genomes (red and white squares), with corresponding 3D simulations (colorful stringlike structures). The human interphase chromosome is less sensitive to mechanical cues than the mosquito interphase chromosome. (Image adapted from Nature Communications, https://doi.org/10.1038/s41467-023-35909-2, under a Creative Commons Attribution 4.0 International License.)

    https://news-network.rice.edu/news/files/2023/02/230203_Vinicius-Contessoto_LG.jpg
    CAPTION: Vinícius Contessoto is a researcher in the Center for Biological Theoretical Physics at Rice University. (Photo by Gustavo Raskosky/Rice University)

    https://news-network.rice.edu/news/files/2023/02/230203_Onuchic_LG.jpg
    CAPTION: José Onuchic is the Harry C. and Olga K. Wiess Chair of Physics and professor of chemistry and biosciences at Rice University. (Photo by Gustavo Raskosky/Rice University)

    https://news-network.rice.edu/news/files/2023/02/230203_ContessotoOnuchic_LG.jpg
    CAPTION: Vinícius Contessoto (left) and José Onuchic are lead co-authors on the study published last month in Nature Communications. (Photo by Gustavo Raskosky/Rice University)

    Related stories:

    NSF extends Physics of Living Systems network at Rice:
    https://news2.rice.edu/2021/09/27/nsf-extends-physics-of-living-systems-network-at-rice/

    Biologists construct a ‘periodic table’ for cell nuclei:
    https://news.rice.edu/news/2021/biologists-construct-periodic-table-cell-nuclei

    At our cores, we’re all strengthened by ‘dumbbells’:
    https://news.rice.edu/news/2020/our-cores-were-all-strengthened-dumbbells

    Snake-like proteins can wrangle DNA:
    https://news.rice.edu/news/2020/snake-proteins-can-wrangle-dna

    Ring-shaped protein complex wrangles DNA:
    https://news2.rice.edu/2018/11/02/ring-shaped-protein-complex-wrangles-dna/

    Links:

    BioScience Research Collaborative: https://brc.rice.edu/

    Center for Theoretical Biological Physics: https://ctbp.rice.edu/

    Department of Chemical and Biomolecular Engineering: https://chbe.rice.edu/

    Department of Chemistry: https://chemistry.rice.edu/

    Department of Physics and Astronomy: https://physics.rice.edu/

    George R. Brown School of Engineering: https://engineering.rice.edu

    Ken Kennedy Institute: https://kenkennedy.rice.edu/

    Wiess School of Natural Sciences: https://naturalsciences.rice.edu

    Wolynes Research Lab: https://wolynes.rice.edu/

    Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation’s top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 4,552 undergraduates and 3,998 graduate students, Rice’s undergraduate student-to-faculty ratio is just under 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for lots of race/class interaction and No. 1 for quality of life by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger’s Personal Finance.

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    Rice University

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  • Protein droplets may cause many types of genetic disease

    Protein droplets may cause many types of genetic disease

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    Newswise — Most proteins localize to distinct protein-rich droplets in cells, also known as “cellular condensates”. Such proteins contain sequence features that function as address labels, telling the protein which condensate to move into. When the labels get screwed up, proteins may end up in the wrong condensate. According to an international team of researchers from clinical medicine and basic biology, this could be the cause of many unresolved diseases. The findings appeared in the journal Nature.

    Patients with BPTA syndrome have characteristically malformed limbs featuring short fingers and additional toes, missing tibia bones in their legs and reduced brain size. As the researchers found out, BPTAS is caused by a special genetic change that causes an essential protein to migrate to the nucleolus, a large proteinaceous droplet in the cell nucleus. As a result, the function of the nucleolar condensate is inhibited and developmental disease develops.

    “What we discovered in this one disease might apply to many more disorders. It is likely not a rare unicorn that exists only once. We just could not see the phenomenon until now because we did not know how to look for it,” says Denise Horn, a clinical geneticist at the Institute of Medical and Human Genetics at Charité – Universitätsmedizin Berlin.

    In collaboration with scientists at the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin, the University Hospital Schleswig-Holstein (UKSH), and contributors from all around the world, the team is pushing open a door to new diagnoses that could lead to the elucidation of numerous other diseases as well as possible future therapies.

    “We discovered a new mechanism that could be at play in a wide range of diseases, including hereditary diseases and cancer,” says Denes Hnisz, Research Group Leader at the MPIMG. “In fact, we have discovered over 600 similar mutations, 101 of which are known to be associated with different disorders.”

    “The actual work is just starting now,” adds human geneticist Malte Spielmann of UKSH in Lübeck and Kiel. “We will find many more genes with such disease-causing mutations and can now test their mode of action.”

    An unusual mutation

    Affected individuals have complex and striking malformations of the limbs, face, and nervous and bone systems, only partially described by the already-long disease name “brachyphalangy-polydactyly-tibial aplasia/hypoplasia syndrome” (BPTAS).

    “With fewer than ten documented cases worldwide, the disease is not only rare, but ultra-rare,” says Martin Mensah, clinical geneticist at the Institute of Medical and Human Genetics at Charité. To track down the cause, he and his colleagues decoded the genome of five affected individuals and found that the gene for the protein HMGB1 was altered in all patients.

    This protein has the task of organizing the genetic material in the cell nucleus and facilitates the interaction of other molecules with the DNA, for example to read genes.

    In mice, a complete loss of the gene on both chromosomes is catastrophic and leads to death of the embryo. In some patients with only one copy mutated, however, the cells are using the intact copy on the other chromosome, resulting only in mild neurodevelopmental delay. But the newly discovered cases did not fit this scheme.

    “All five unrelated individuals featured the same ultra-rare disorder and had virtually the same mutation”, says Mensah, who is a fellow of the Clinician Scientist Program operated by the Berlin Institute of Health at Charité (BIH) and Charité. “This is why we are sure that the HMGB1 mutation is the cause of the disease. However, at that point, we had no clue how the gene product functionally caused disease, especially given that loss-of-function mutations were reported to result in other phenotypes.”

    Charged protein extensions

    A closer look revealed that different mutations of HMGB1 have different consequences. The sequencing data showed that in the affected individuals with the severe malformations, the reading frame for the final third of the HMGB1 gene is shifted.

    After translation to protein, the corresponding region is now no longer equipped with negative but with positively charged amino acid building blocks. This can happen if a number of genetic letters not divisible by three is missing in the sequence, because exactly three consecutive letters always code for one building block of the protein.

    However, the tail part of the protein does not have a defined structure. Instead, this section hangs out of the molecule like a loose rubber band. The purposes of such protein tails (also called “intrinsically disordered regions”) are difficult to study because they often become effective only in conjunction with other molecules. So how might their mutation lead to the observed disease?

    Protein droplets in the cell

    To answer this question, the medical researchers approached biochemists Denes Hnisz and Henri Niskanen at the MPIMG, who work with cellular condensates that control important genes. These droplet-like structures behave much like the oil and vinegar droplets in a salad dressing. Composed of a large number of different molecules, they are separated from their surroundings and can undergo dynamic changes.

    “We think condensates are formed in the cell for practical reasons,” Niskanen explains. Molecules for a specific task are grouped together in this way, say to read a gene. For this task alone, he says, several hundred proteins need to somehow make their way to the right place.

    “Intrinsically disordered regions, which tend not to have an obvious biochemical role, are thought to be responsible for forming condensates,” Niskanen says, giving an example to describe how important the physical properties of the protein extensions are in this regard. “I can easily make a ball from many loose rubber bands that holds together relatively tightly and that can be taken apart with little effort. A ball of smooth fishing line or sticky tape, on the other hand, would behave quite differently.”

    Solidifying droplets

    The nucleolus within the cell nucleus is also a condensate, which appears as a diffuse dark speck under the microscope. This is where many proteins with positively charged tails like to linger. Many of these provide the machinery required for protein synthesis, making this condensate essential for cellular functions.

    The mutant protein HMGB1 with its positively charged molecular tail is attracted to the nucleolus as well, as the team observed from experiments with isolated protein and with cell cultures.

    But since the mutated protein region has also gained an oily, sticky part, it tends to clump. The nucleolus loses its fluid-like properties and increasingly solidifies, which Niskanen was able to observe under the microscope. This impaired the vital functions of the cells – with the mutated protein, more cells in a culture died compared to a culture of cells without the mutation.

    Combing through databases

    The research team then searched databases of genomic data from thousands of individuals looking for similar incidents. In fact, the scientists were able to identify more than six hundred similar mutations in 66 proteins, in which the reading frame had been shifted by a mutation in the protein tail, making it both more positively charged and more “greasy”. Of the mutations, 101 had previously been linked to several different disorders.

    For a cell culture assay, the team selected 13 mutant genes. In 12 out of 13 cases, the mutant proteins had a preference to localize into the nucleolus. About half of the tested proteins impaired the function of the nucleolus, resembling the disease mechanism of BPTA syndrome.

    New explanations for existing diseases

    “For clinical research, our study could have an eye-opening effect,” says Malte Spielmann, who led the research together with Denes Hnisz and Denise Horn. “In the future, we can certainly elucidate the causes of some genetic diseases and hopefully one day treat them.”

    However, “congenital genetic diseases such as BPTAS are almost impossible to cure even with our new knowledge”, says Horn. “Because the malformations already develop in the womb, they would have to be treated with drugs before they develop. This would be very difficult to do.”

    But tumor diseases are also predominantly genetically determined, adds Hnisz: “Cellular condensates and the associated phase separation are a fundamental mechanism of the cell that also plays a role in cancer. The chances of developing targeted therapies for this are much better.”

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    Max Planck Society (Max-Planck-Gesellschaft)

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  • Scientists detect molten rock layer hidden under earth’s tectonic plates

    Scientists detect molten rock layer hidden under earth’s tectonic plates

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    Newswise — Scientists have discovered a new layer of partly molten rock under the Earth’s crust that might help settle a long-standing debate about how tectonic plates move. 

    Researchers had previously identified patches of melt at a similar depth. But a new study led by The University of Texas at Austin revealed for the first time the layer’s global extent and its part in plate tectonics.

    The research was published Feb. 6, 2023, in the journal Nature Geoscience

    The molten layer is located about 100 miles from the surface and is part of the asthenosphere, which sits under the Earth’s tectonic plates in the upper mantle. The asthenosphere is important for plate tectonics because it forms a relatively soft boundary that lets tectonic plates move through the mantle. 

    The reasons why it is soft, however, are not well understood. Scientists previously thought that molten rocks might be a factor. But this study shows that melt, in fact, does not appear to notably influence the flow of mantle rocks.   

    “When we think about something melting, we intuitively think that the melt must play a big role in the material’s viscosity,” said Junlin Hua, a postdoctoral fellow at UT’s Jackson School of Geosciences who led the research. “But what we found is that even where the melt fraction is quite high, its effect on mantle flow is very minor.”

    According to the research, which Hua began as a graduate student at Brown University, the convection of heat and rock in the mantle are the prevailing influence on the motion of the plates. Although the Earth’s interior is largely solid, over long periods of time, rocks can shift and flow like honey. 

    Showing that the melt layer has no influence on plate tectonics means one less tricky variable for computer models of the Earth, said coauthor Thorsten Becker, a professor at the Jackson School.

    “We can’t rule out that locally melt doesn’t matter,” said Becker, who designs geodynamic models of the Earth at the Jackson School’s University of Texas Institute for Geophysics. “But I think it drives us to see these observations of melt as a marker of what’s going on in the Earth, and not necessarily an active contribution to anything.”

    The idea to look for a new layer in Earth’s interior came to Hua while studying seismic images of the mantle beneath Turkey during his doctoral research. 

    Intrigued by signs of partly molten rock under the crust, Hua compiled similar images from other seismic stations until he had a global map of the asthenosphere. What he and others had taken to be an anomaly was in fact commonplace around the world, appearing on seismic readings wherever the asthenosphere was hottest. 

    The next surprise came when he compared his melt map with seismic measurements of tectonic movement and found no correlation, despite the molten layer encompassing almost half the Earth. 

    “This work is important because understanding the properties of the asthenosphere and the origins of why it’s weak is fundamental to understanding plate tectonics,” said coauthor Karen Fischer, a seismologist and professor at Brown University who was Hua’s Ph.D. advisor when he began the research.

    The research was funded by the U.S. National Science Foundation. Collaborating institutions included the UT Oden Institute for Computational Engineering and Sciences and Cornell University.

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    University of Texas at Austin (UT Austin)

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  • Abandoning wood cook stoves would be great for Africa, if families could afford it

    Abandoning wood cook stoves would be great for Africa, if families could afford it

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    Newswise — DURHAM, N.C. — Replacing traditional biomass-burning cookstoves across sub-Saharan Africa could save more than 463,000 lives and US $66 billion in health costs annually, according to a new analysis of the most socially optimal cooking technologies in Africa.

    But the promise of those outcomes alone may not be enough to hasten the adoption of cleaner alternatives, the researchers warn.

    The study, published in the open source journal Nature Sustainabilityused a geospatial model to determine the best cooking options by location across the continent, weighing factors such as availability and cost of fuel, time spent gathering fuels and preparing meals, and impacts on health and the environment. In the model, everyone using a traditional cookstove – around 83 percent of households in sub-Saharan Africa, comprising nearly 1 billion people – would switch to stoves that delivered more benefits to both households and society.

    “From both a social perspective and a private perspective, it would be optimal for most of these households to use cleaner technologies,” says Marc Jeuland, Ph.D., an associate professor of global health and public policy at Duke who led the research. “And so that’s telling you that these polluting technologies are extremely damaging.”

    Traditional stoves typically burn wood or other solid fuels, generating indoor air pollution and climate-altering emissions. Cooking regularly on such stoves can cause respiratory disease, as well as contribute to global warming and deforestation. Stoves fueled by electricity or even liquid petroleum gas (LPG) mitigate those risks while also offering efficiencies in time and labor. Many African households using traditional stoves spend more than an hour a day gathering fuel to prepare meals, Jeuland notes.

    Despite those advantages, adoption of cleaner alternatives has been sluggish in Africa, which has lagged other regions in the transition away from polluting cooking technologies. In fact, according to the World Bank’s 2022 Energy Progress Report, the number of people using biomass-burning cookstoves actually increased by 50 percent between 2000 and 2020, as population growth outpaced conversion.

    Jeuland and colleagues describe the situation as a “severe market failure” that calls for new policies and incentives to stimulate growth of cleaner technologies.

    “Just because something may be beneficial from a social or private perspective doesn’t necessarily mean it’s affordable,” Jeuland says. The up-front cost of purchasing a new stove and ongoing fuel costs “are going to continue to be a barrier for many households in sub-Saharan Africa unless you really reduce those costs through subsidies of some form.”

    Jeuland favors subsidies that would reduce the cost of conversion for most families to “close to zero.” He also believes wealthy nations should help foot the bill, since a wide-scale shift to cleaner cooking technologies would lessen a climate problem that those countries bear the most responsibility for creating.

    “If rural Africans continue to harvest firewood for cooking, the contribution to climate change is pretty minimal. But because those damages are accumulating, the rich world should be paying to avoid them,” Jeuland says.

    But affordability is not the only obstacle. Many parts of Africa do not have reliable electricity or infrastructure to deliver gas for LPG stoves, Jeuland says. The researchers’ model, designed by a team of energy systems engineers at the KTH Royal Institute of Technology in Sweden, accounted for regional infrastructure differences, picking the technology best suited for each location’s unique circumstances.

    In the model selecting for the highest net benefits, about two-thirds of households across sub-Saharan Africa would be best off using LPG stoves, with another 30 percent, mostly in urban areas where grid power is available, using electric. Smaller populations in the poorest and most remote locations would use biogas or improved biomass stoves, which burn more cleanly than traditional cookstoves. Even when factoring only benefits to the household, the model suggests eight in ten people in sub-Saharan Africa should switch to cleaner technologies.

    The results can help governments and nonprofits target their efforts to encourage conversion, Jeuland says. Doing more to inform people about the potential benefits of switching and developing technologies that are well-suited to local cultures and customs will also be critical, he adds.

    But one other area Jeuland would like to explore is how to influence who is at the table when household cooking preferences are discussed. In traditional societies where women and children are exerting most of the cooking labor, men still often make most of the financial decisions.

    “Women tend to not have as much bargaining power, and their preferences are down-weighted in these households,” Jeuland says. “And so we need to be thinking about how to empower women in these decisions.”

    This research was partially supported by the Clean Cooking Alliance and The Royal Institute of Technology

    CITATION: “A Geospatial Approach to Understanding Clean Cooking Challenges in Sub-Saharan Africa,” Babak Khavari, Camilo Ramirez, Merc Jeuland, Francesco Fuso Nerini. Nature Sustainability, Jan. 12, 2023. DOI: 10.1038/s41893-022-01039-8

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  • Autonomous driving: New algorithm distributes risk fairly

    Autonomous driving: New algorithm distributes risk fairly

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    Newswise — Technical realization is not the only obstacle to be mastered before autonomously driving vehicles can be allowed on the street on a large scale. Ethical questions play an important role in the development of the corresponding algorithms: Software has to be able to handle unforeseeable situations and make the necessary decisions in case of an impending accident. Researchers at TUM have now developed the first ethical algorithm to fairly distribute the levels of risk rather than operating on an either/or principle. Approximately 2,000 scenarios involving critical situations were tested, distributed across various types of streets and regions such as Europe, the USA and China. The research work published in the journal “Nature Machine Intelligence” is the joint result of a partnership between the TUM Chair of Automotive Technology and the Chair of Business Ethics at the TUM Institute for Ethics in Artificial Intelligence (IEAI).

    Maximilian Geisslinger, a scientist at the TUM Chair of Automotive Technology, explains the approach: “Until now, autonomous vehicles were always faced with an either/or choice when encountering an ethical decision. But street traffic can’t necessarily be divided into clear-cut, black and white situations; much more, the countless gray shades in between have to be considered as well. Our algorithm weighs various risks and makes an ethical choice from among thousands of possible behaviors – and does so in a matter of only a fraction of a second.”

    More options in critical situations

    The basic ethical parameters on which the software’s risk evaluation is oriented were defined by an expert panel as a written recommendation on behalf of the EU Commission in 2020. The recommendation includes basic principles such as priority for the worst-off  and the fair distribution of risk among all road users. In order to translate these rules into mathematical calculations, the research team classified vehicles and persons moving in street traffic based on the risk they present to others and on the respective willingness to take risks. A truck for example can cause serious damage to other traffic participants, while in many scenarios the truck itself will only experience minor damage. The opposite is the case for a bicycle. In the next step the algorithm was told not to exceed a maximum acceptable risk in the various respective street situations. In addition, the research team added variables to the calculation which account for responsibility on the part of the traffic participants, for example the responsibility to obey traffic regulations.

    Previous approaches treated critical situations on the street with only a small number of possible maneuvers; in unclear cases the vehicle simply stopped. The risk assessment now integrated in the researchers’ code results in more possible degrees of freedom with less risk for all. An example will illustrate the approach: An autonomous vehicle wants to overtake a bicycle, while a truck is approaching in the oncoming lane. All the existing data on the surroundings and the individual participants are now utilized. Can the bicycle be overtaken without driving in the oncoming traffic lane and at the same time maintaining a safe distance to the bicycle? What is the risk posed to each respective vehicle, and what risk do these vehicles constitute to the autonomous vehicle itself? In unclear cases the autonomous vehicle with the new software always waits until the risk to all participants is acceptable. Aggressive maneuvers are avoided, while at the same time the autonomous vehicle doesn’t simply freeze up and abruptly jam on the brakes. Yes and No are irrelevant, replaced by an evaluation containing a large number of options.

    “The sole consideration of traditional ethical theories resulted in a dead end”

    “Until now, often traditional ethical theories were contemplated to derive morally permissible decisions made by autonomous vehicles. This ultimately led to a dead end, since in many traffic situations there was no other alternative than to violate one ethical principle,” says Franziska Poszler, scientist at the TUM Chair of Business Ethics. “In contrast, our framework puts the ethics of risk at the center. This allows us to take into account probabilities to make more differentiated assessments.”

    The researchers emphasized the fact that even algorithms that are based on risk ethics – although they can make decisions based on the underlying ethical principles in every possible traffic situation – they still cannot guarantee accident-free street traffic. In the future it will additionally be necessary to consider further differentiations such as cultural differences in ethical decision-making.

    Software now to be tested in street traffic

    Until now the algorithm developed at TUM has been validated in simulations. In the future the software will be tested on the street using the research vehicle EDGAR. The code embodying the findings of the research activities is available as Open Source software. TUM is thus contributing to the development of viable and safe autonomous vehicles.

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    Technical University of Munich

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  • Researchers identify the neurons that synchronise female preferences with male courtship songs in fruit flies

    Researchers identify the neurons that synchronise female preferences with male courtship songs in fruit flies

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    Newswise — When it comes to courtship, it is important to ensure that one is interacting with a member of the same species. Animals use multiple sensory systems to confirm that potential mates are indeed suitable, with acoustic communication playing an important role in their decision making.   

    Although these differences have previously been reported at the behavioral level, it is not known how the neuronal circuitry underlying this decision-making has diverged between species. Now, in a new publication in Scientific Reports, a research group at Nagoya University in Japan has investigated how the auditory processing pathway has evolved and diverged between fruit fly species.  

    Males of several species of Drosophila (fruit flies), which are regularly used in neuroscience research, vibrate their wings rhythmically during courtship, producing a courtship song. The temporal components of these songs differ between species, allowing female flies to distinguish between potential mates. 

    “Identifying complex features, such as rhythm, requires information processing that involves not only the auditory organs but also neural circuits,” explains Yuki Ishikawa, the lecturer leading the project. “However, interspecies comparisons of the mechanism of rhythm discrimination have not been studied before because they require a more precise approach than just studying peripheral auditory organs.” 

    To find out what happens in the neural circuits during courtship, Professor Azusa Kamikouchi, Lecturer Yuki Ishikawa, and Graduate Student Takuro Ohashi of the Graduate School of Science first played songs with different rhythms to females of two closely related species of fruit flies (Drosophilia melanogaster and Drosophilia simulans), which have different courtship songs, to see which tones the females found acceptable. Confirming previous reports, the researchers found that Drosophilia simulans females preferred songs with distinct temporal components to those of Drosophilia melanogaster. 

    Building on these behavioral data, the researchers next used calcium imaging to determine how a specific subset of auditory neurons, called AMMC-B1, responded to different courtship songs between the species. They found that the responses of these neurons did indeed differ between species, and that these differences were consistent with previously observed behavioral responses.  

    “This is the first study to clarify how the evolution of the mechanism for distinguishing between rhythms of the same sound occurs,” explains Dr. Ishikawa. “Rhythmic information processing in neural circuits differs between fruit fly species. Using mathematical modeling, we have shown that this species difference may be due to a change in the balance between facilitation and inhibition in neural circuits.” 

    Despite the differences at the behavioral level, the group found that the overall characteristics of AMMC-B1 neurons are similar between the two species. This suggests that the properties of the neural circuit, at least in its early stages, are evolutionarily conserved. Thus, even in different species, they appear to be encoded by similar genes. These findings support the theory that the species-specificity of such neuronal cell groups emerged at a later stage of the auditory information- processing neural circuits. 

    “Drosophila melanogaster has neural mechanisms that are widely shared among animals,” Ishikawa said. “It is one of the most advanced animals for brain research because of the wealth of existing genetic tools. By introducing these tools into Drosophila simulans, this study was the first to make detailed interspecies comparisons of auditory neural circuits. By transferring these methods and results to closely related species, we can begin to study how information processing has evolved in the animal brain. We hope that the method established in this study will contribute to understanding the full picture of how mechanisms in the auditory brain have evolved.” 

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    Nagoya University

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  • Researchers reveal microscopic quantum correlations of ultracold molecules

    Researchers reveal microscopic quantum correlations of ultracold molecules

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    Newswise — Physicists are increasingly using ultracold molecules to study quantum states of matter. Many researchers contend that molecules have advantages over other alternatives, such as trapped ions, atoms or photons. These advantages suggest that molecular systems will play important roles in emerging quantum technologies. But, for a while now, research into molecular systems has advanced only so far because of long-standing challenges in preparing, controlling and observing molecules in a quantum regime.  

    Now, as chronicled in a study published this week in Nature, Princeton researchers have achieved a major breakthrough by microscopically studying molecular gases at a level never before achieved by previous research. The Princeton team, led by Waseem Bakr, associate professor of physics, was able to cool molecules down to ultracold temperatures, load them into an artificial crystal of light known as an optical lattice, and study their collective quantum behavior with high spatial resolution such that each individual molecule could be observed.  

    “We prepared the molecules in the gas in a well-defined internal and motional quantum state. The strong interactions between the molecules gave rise to subtle quantum correlations which we were able to detect for the first time,” said Bakr.  

    This experiment has profound implications for fundamental physics research, such as the study of many-body physics, which looks at the emergent behavior of ensembles of interacting quantum particles. The research also might accelerate the development of large-scale quantum computer systems. 

    In the quest to build large-scale quantum systems, both for quantum computing and for more general scientific applications, researchers have used a variety of different alternatives—everything from trapped ions and atoms to electrons confined in “quantum dots.” The goal is to transform these various alternatives into what are called qubits, which are the building blocks of a quantum computer system. Quantum computers have much greater computing power and capacity—exponentially greater—than classical computer systems, and can solve problems classical computers have difficulty solving.  

    Although so far no single type of qubit has emerged as the front-runner, Bakr and his team believe that molecular systems, while less explored than other platforms, hold particular promise.

    One important advantage of using molecules in experimental settings—and especially as potential qubits—is the fact that molecules can store quantum information in an abundance of new ways not available to single atoms. For example, even for a simple molecule made of just two atoms, which can be visualized as a tiny dumbbell, quantum information can be stored in the rotational motion of the dumbbell or the shaking of its constituent atoms relative to each other. Another advantage of molecules is that they often have long-range interactions; they can interact with other molecules many sites away in an optical lattice, whereas atoms, for example, can only interact if they occupy the same site.

    When using molecules to study many-body physics, these advantages are expected to enable researchers to explore fascinating new quantum phases of matter in these synthetic systems. However, a major problem, which Bakr and his team have been able to overcome in this experiment, is the microscopic characterization of these quantum states.

    “The ability to probe the gas at the level of individual molecules is the novel aspect of our research,” said Bakr. “When you’re able to look at individual molecules, you can extract a lot more information about the many-body system.”  

    What Bakr means by extracting more information is the ability to observe and document the subtle correlations that characterize molecules in a quantum state—for example, correlations of their positions in the lattice or their rotational states.  

    “Researchers had prepared molecules in the ultracold regime before, but they couldn’t measure their correlations because they couldn’t see the single molecules,” said Jason Rosenberg, a graduate student in Princeton’s Department of Physics and the co-lead author of the paper. “By seeing each individual molecule, we can really characterize and explore the different quantum phases that are expected to emerge.”  

    While researchers have been studying many-body physics with atomic quantum gases for over two decades, molecular quantum gases have been much harder to tame. Unlike atoms, molecules can store energy by vibrating and rotating in many different ways. These various excitations are known as “degrees of freedom”—and their abundance is the characteristic that makes molecules difficult to control and manipulate experimentally.  

    “In order to study molecules in a quantum regime, we need to control all their degrees of freedom and place them in a well-defined quantum mechanical state,” said Bakr.  

    The researchers accomplished this precise level of control by first cooling two atomic gases of sodium and rubidium down to incredibly low temperatures that are measured in nanokelvins, or temperatures one-billionth of a degree Kelvin. At these ultracold temperatures, each of the two gases transition into a state of matter known as a Bose-Einstein condensate. In this ultracold environment, the researchers coax the atoms into pairing up into sodium-rubidium molecules in a well-defined internal quantum state. Then they use lasers to transfer the molecules into their absolute ground state where all rotations and vibrations of the molecules are frozen.

    To maintain the quantum behavior of the molecules, they are isolated in a vacuum chamber and held in an optical lattice made of standing waves of light.  

    “We interfere a set of laser beams together and, from this, we create a corrugated landscape resembling an ‘egg carton’ in which the molecules sit,” said Rosenberg.

    In the experiment, the researchers captured about one hundred molecules in this “egg carton” lattice. Then the researchers pushed the system out of equilibrium—and tracked what happened in the strongly interacting system. 

    “We gave the system a sudden ‘nudge,’” said Lysander Christakis, a graduate student and co-lead author of the paper. “We allowed the molecules to interact and build up quantum entanglement. This entanglement is reflected in subtle correlations, and the ability to probe the system at this microscopic level allows us to reveal these correlations—and learn about them.”    

    Entanglement is one of the most fascinating—and perplexing— properties of many-body quantum states. It describes a property of the subatomic world in which quantum elements—whether molecules, electrons, photons, or whatever—become inextricably linked with each other no matter the distance separating them. Entanglement is especially significant in quantum computing because it acts as a sort of computational multiplier. It is the crucial ingredient underlying the exponential speedup in solving problems with quantum computers.

    The unparalleled control the researchers achieved in preparing and detecting the molecules has clear implications for quantum computing. But the researchers emphasize that, ultimately, the experiment is not necessarily about creating the most advanced qubits. Rather, it is, most importantly, a huge step forward in fundamental physics research.  

    “This research opens up a lot of possibilities to study really interesting problems in many-body physics,” said Christakis. “What we’ve demonstrated here is a complete platform for using ultracold molecules as a system to study complex quantum phenomena.”  

    Rosenberg concurred. “In this experiment, the molecules were frozen into individual sites on the lattice and quantum information was only stored in the rotational states of the molecules. Moving forward, it will be exciting to explore a whole other realm of interesting phenomena that appear when you allow the molecules to ‘hop’ from site to site. Our research has opened the door to investigating ever more exotic states of matter that can be prepared with these molecules, and now we can characterize them very well,” he concluded.  

    Other members of the Princeton team are graduate student Ravin Raj; postdoctoral research associate Zoe Yan; undergraduate Sungjae Chi; and theorists Alan Morningstar, postdoctoral fellow at Stanford University, and David Huse, Princeton’s Cyrus Fogg Brackett Professor of Physics. The research was supported by the National Science Foundation and the David and Lucile Packard Foundation.

    The study, “Probing site-resolved correlations in a spin system of ultracold molecules,” by Lysander Christakis, Jason S. Rosenberg, Ravin Raj, Sungjae Chi, Alan Morningstar, David A. Huse, Zoe Z. Yan, and Waseem S. Bakr was published online in Nature, on February 1, 2023. DOI: 10.1038/s41586-022-05558-4.

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