Culture

Most people infected with SARS-CoV-2 are able to recover from the disease at home - even if they might experience very stressful disease progressions. Some have no symptoms at all. But about ten percent of those affected become so severely ill that they have to be treated in a hospital. The assumption that a weak immune system is behind a severe progression is short-sighted. Especially with critical progressions, the immune system works under intense pressure, but does not manage to control the virus.

A Berlin research group has now observed how SARS-CoV-2 uses an immune system defense mechanism to increasingly hijack the body's mucous membrane cells and multiply there. Their study has just appeared in the journal EMBO Molecular Medicine. "This may give us part of the explanation as to why the immune system has difficulty regulating or even defeating the infection in some people," says Dr. Julian Heuberger, scientist at the Division of Hepatology and Gastroenterology in Charité - Universitätsmedizin Berlin's Medical Department. He is the first author of the study and a member of an Emmy Noether Research Group led by PD Dr. Michael Sigal at Charité and the Berlin Institute for Medical Systems Biology (BIMSB), part of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC). For the study, the research group cooperated with researchers from the Max Planck Institute for Infection Biology (MPIIB), Freie Universität Berlin and Hong Kong University.

SARS-CoV-2 uses defense mechanism as a port of entry

Actually, the human body has a very effective defense mechanism against invaders, based on the interaction of various immune cells. T cells play an important role in this: When they encounter viruses in the organism, they destroy the affected cells. They also secrete the signaling molecule interferon-gamma (IFN-γ). On the one hand, IFN-γ fights infectious agents. On the other hand, it calls other immune cells to the scene.

Heuberger and his colleagues have now shown how SARS-CoV-2 can turn this protective mechanism mediated by IFN-γ into its opposite. For in addition to immune cells, the body's mucous membrane cells also respond to IFN-γ by forming more ACE2 receptors. SARS-CoV-2 needs these ACE2 receptors as a port of entry into the cells. Infected cells, in turn, make more ACE2. In this way, both the IFN-γ response of epithelial cells and the virus itself intensify the SARS-CoV-2 infection.

Cell differentiation observed in colon organoids

Patients infected with SARS-CoV-2 sometimes show gastrointestinal symptoms. In order to observe the immune cascade in the intestinal cells, Heuberger cultivated organoids of the human colon. An organoid is a kind of mini-organ in a petri dish, barely the size of a pinhead. The colon organoids are based on cells that come from intestinal biopsies. They grow in three-dimensionally arranged units and replicate the physiology of mucous membrane cells in the human intestinal tract. "These colon organoids are a very helpful tool," Heuberger emphasizes. "We can use them to explore the complex interplay of different signaling pathways that control cell differentiation from stem cells to specialized epithelial cells."

The scientists first treated the cultured intestinal cells with IFN-γ to simulate the body's immune response. Then they infected the organoids with SARS-CoV-2. Using gene expression analysis and a laser scanning microscope - a special optical microscope that scans a sample point by point - they were able to measure increased ACE2 expression in the organoids. In addition, quantitative polymerase chain reaction (PCR) detected increased virus production.

In other words, more IFN-γ means more ACE2. More ACE2 means more viruses can enter the cells. The more viruses that enter the cells, the more viruses produced. Thus, the immune response and the surface cell response to infection pave the way for SARS-CoV-2.

Balancing an excessive IFN-γ response with medication

"We hypothesize that a strong immune response may increase the susceptibility of mucous membrane cells to SARS-CoV-2," says the head of the study, Dr. Michael Sigal. He directs the Gastrointestinal Barrier, Regeneration and Carcinogenesis Lab at Charité and the MDC and is a gastroenterologist at Charité. "If the IFN-γ concentration is higher from the outset or the infection triggers a very excessive production of IFN-y, the viruses probably have an easier time entering the cells." However, the conditions under which this actually happens must still be investigated in clinical trials.

The results of the study carry the idea of a treatment approach for severe COVID-19 courses, Heuberger feels: "One possible strategy could be to balance the IFN-γ response with drugs." However, this would first require a very detailed analysis of the mechanisms underlying the IFN-γ response.

Computing - Modeling COVID dynamics

To better understand the spread of SARS-CoV-2, the virus that causes COVID-19, Oak Ridge National Laboratory researchers have harnessed the power of supercomputers to accurately model the spike protein that binds the novel coronavirus to a human cell receptor.

These simulations also shed light on the ligand molecules that can inhibit such binding, pointing the way to potential drug therapies.

An ultrafast quantum chemical modeling method provides information about the critical electronic interactions between protein and ligand chemicals, going beyond the classical interaction models that are normally employed in computational drug discovery.

The findings will enable accurate predictions of the performance of currently available inhibitors and inform the future development of even more potent, novel inhibitor compounds, demonstrating the effectiveness of quantum chemical approaches in simulation for drug discovery.

"Quantum mechanics on supercomputers accelerates computational COVID-19 drug discovery by accurately describing inhibitor-virus protein interactions," said ORNL's Stephan Irle.

Media contact: Scott Jones, 865.241.6491, jonesg@ornl.gov

Image: https://www.ornl.gov/sites/default/files/2021-02/toc_notext.png

Caption: ORNL has modeled the spike protein that binds the novel coronavirus to a human cell for better understanding of the dynamics of COVID-19. Credit: Stephan Irle/ORNL, U.S. Dept. of Energy

Climate - Permafrost lost

A study by Oak Ridge National Laboratory, the University of Copenhagen, the National Park Service and the U.S. Geological Survey showed that hotter summers and permafrost loss are causing colder water to flow into Arctic streams, which could impact sensitive fish and other wildlife.

To understand trends observed in 11 Alaskan streams, ORNL researchers modeled the flow of water through the semi-frozen landscape during summer months. Usually, permafrost forms an icy barrier that keeps groundwater flow to the topmost layer of soil, which allows the water to warm with summer air temperatures.

Researchers found that as thawing permafrost sinks lower beneath the surface, groundwater flows deeper underground and, therefore, stays colder.

"In this ecosystem, the lateral flow of water strongly influences stream levels and temperatures," said ORNL's Scott Painter, "but it is often neglected in models. Our Amanzi-ATS model provides a detailed representation of the physics that impact groundwater supplying Arctic streams."

Media contact: Kim Askey, 865.576.2841, askeyka@ornl.gov

Image: https://www.ornl.gov/sites/default/files/2021-02/permafrost_melt_labeled.gif

Caption: ORNL researchers used the award-winning Amanzi-ATS model to simulate groundwater flow in Arctic ecosystems. As thawing permafrost sinks lower beneath the surface, groundwater flows deeper underground and, therefore, stays colder as it flow into streams. Credit: Michelle Lehman/ORNL, U.S. Dept. of Energy

Manufacturing - Taking the heat

Oak Ridge National Laboratory researchers have demonstrated that a new class of superalloys made of cobalt and nickel remains crack-free and defect-resistant in extreme heat, making them conducive for use in metal-based 3D printing applications.

Metal materials have proven to be cost-effective for manufacturing, and deploying them for use in additive processes could enable the production of innovative, complex designs with minimal material waste. However, these materials are primarily used in energy, space and nuclear applications that also produce extreme heat environments.

In a study, researchers processed the cobalt and nickel class of superalloys and proved that they remained crack-free in electron-beam and laser-melting 3D printing processes.

"The challenge has been producing alloys that don't crack in the heat," ORNL's Mike Kirka said. "These superalloys have the material properties necessary for challenging environments, because they not only successfully withstood the heat but also retained strength when stretched."

Media contact: Jennifer Burke, 865.414.6835, burkejj@ornl.gov

Image: https://www.ornl.gov/sites/default/files/2021-02/2019-P05612-2.jpg

Caption: A 3D printed turbine blade demonstrates the use of the new class of nickel-based superalloys that can withstand extreme heat environments without cracking or losing strength. Credit: ORNL/U.S. Dept. of Energy

Researchers have discovered that the use of Cytoglobin (CYGB) as an intravenous drug could delay liver fibrosis progression in mice.

CYGB, discovered in 2001 by Professor Norifumi Kawada, is present in hepatic stellate cells, the cells that produce fibrotic molecules such as collagens when the liver has acute or chronic inflammation induced by different etiologies. The enhancement of CYGB on these cells or the injection of recombinant CYGB has the effect of suppressing liver damage and cirrhosis. These findings published in the February 2021 issue of the journal Hepatology.

Anti-fibrotic therapy remains an unmet medical need in human chronic liver diseases. A research team led by Professor Norifumi Kawada, Osaka City University (OCU), reported the novel anti-fibrotic properties of CYGB, a respiratory protein expressed in hepatic stellate cells (HSCs), the main cell type involved in liver fibrosis. In mice with advanced liver fibrosis, both enhancement of CYGB or recombinant CYGB injection can suppress hepatocyte damage and liver fibrosis. In chimera mice with a human liver, the injected CYGB did not show any adverse side effects.

"Fixing the liver after injury is a highly orchestrated, coordinated process, and inhibiting the fibrosis could return the liver to a healthy condition," said Norifumi Kawada, M.D., Ph.D., Dean of OCU Medical School and senior author of the study.

Liver injury starts with hepatocyte damage, following several conditions including inflammatory cell infiltration, activation of HSCs, and the production of harmful reactive oxygen species (ROSs). Dr. Kawada, along with Le Thi Thanh Thuy, PhD., OCU scientist, and their colleagues, observed that when they culture human HSCs under recombinant human CYGB treatment, it can enter the cellular organelles, hunt the harmful ROSs, and prevent the activation of HSCs leading to inhibit collagen production.

To identify potential treatment strategies, Dr. Kawada and his team developed several animal models of liver injury and investigated how the liver responds to CYGB regulation and treatment.

In both mouse models of bile flow obstruction induced cholestasis and high fat diet induced fatty liver disease, the absence of CYGB made the liver injury more severe, however, when CYGB was enhanced, the liver injury subsided.

In the next set of experiments, Dr. Kawada and his group tried to generate two other mouse models of advanced liver fibrosis using different chemical agents and applied recombinant human CYGB protein by intravenous injection. Interestingly, the therapeutic protein dramatically suppressed liver injuries, inflammation and fibrosis without any side effects.

Using the results of this research as a foothold, the research team hopes to start clinical trials using this new anti-fibrotic therapy.

Between January 2012 and March 2018, there were an average of 1,000 failures each year at large North American gas power plants due to unscheduled fuel shortages and fuel conservation interruptions. This is a problem as the power grid depends on reliable natural gas delivery from these power plants in order to function. More than a third of all U.S. electricity is generated from natural gas. New research now indicates that these fuel shortages are not due to failures of pipelines and that in certain areas of the country a change in how gas is purchased can significantly reduce generator outages.

The paper, "What Causes Natural Gas Fuel Shortages at U.S. Power Plants?" by researchers at Carnegie Mellon University and the North American Electric Reliability Corporation, was published in Energy Policy.

Gas shortages at generators have caused simultaneous failures of several power plants. Physical failures and disruptions of the natural gas pipeline network are rare; the authors found that they account for no more than 5% of the power plant generation lost to fuel shortages over the six years examined. The vast majority of the natural gas generator outages due to fuel unavailability were due to curtailment of gas when supplies were tight. In the Midwest and Mid-Atlantic states, natural gas was available but power plants that did not purchase firm contracts were out-prioritized by commercial and industrial customers.

"While it is unsurprising that plants using the spot market or interruptible pipeline contracts for their fuel were somewhat more likely to experience fuel shortages than those with firm contracts, these contracts can still make a big difference in reliability in certain regions," says Jay Apt, a Professor and the Co-Director of Carnegie Mellon's Electricity Industry Center, who co-authored the paper. "Still, firm contracts are not a solution for areas such as New England that have few gas pipelines and further discussion on other mitigation strategies should be explored."

Natural gas is increasingly used to generate power in the U.S. and the North American Electric Reliability Corporation (NERC) projects that the natural gas generating capacity will further expand by 12 GW over the next decade, about a 5% increase. Fuel shortages have been a problem at power plants that are used exclusively at times of peak demand, such as during extreme cold and hot weather, as well as at more heavily-used gas power plants. This indicates that fuel shortages affect the power grid's ability to operate whether it's responding to an emergency or merely serving load during normal operation.

Previous research has focused on technical reports from reliability organizations or regional transmission organizations. For the first time, researchers for this paper used historical data collected by NERC to examine fuel shortages between 2012 and 2018 at natural gas power plants in North America to determine their cause. The researchers' primary goal was to identify how many of these fuel shortage failures were caused by physical interruptions of gas flow as opposed to operational procedures on the pipeline network, such as gas service curtailment priority. They also sought to respond to policy questions regarding whether generators could mitigate fuel shortage failures by switching to firm pipeline contracts.

Along with analyzing the NERC data from 2012 - 2018, the researchers developed a systematic approach to match the NERC failure data to U.S. Energy Information Administration generator characteristic data in order to evaluate how gas pipeline system characteristics have historically affected natural gas fuel shortage failures. They calculated a time series of unscheduled, unavailable capacity due to fuel shortages and time-matched the beginning times of fuel shortage power plant failure events with time windows of pipeline failures to determine if pipeline failures could have caused fuel shortage outages at power plants. They then completed a similar process of spatial matching of power plants to gas trading hubs in order to assess the historical availability of natural gas for transactions by power plants.

Ultimately, the researchers observed that both plants with firm contracts and plants without firm contracts experienced fuel shortages and conservation interruptions, but that non-firm plants were overrepresented in the fuel shortage failure data. This suggests that curtailment priority on pipeline networks is the likely reason for most correlated failures. However, the data also suggests that firm contracts will not solve everything and other strategies should be explored, especially in areas such as New England where the pipeline network has historically been constrained.

DALLAS - Feb. 16, 2021 - A study that identifies how a coronavirus protein called Nsp1 blocks the activity of genes that promote viral replication provides hope for new COVID-19 treatments.

Since the start of the pandemic, scientists have worked endlessly to understand SARS-CoV-2, the coronavirus that causes COVID-19. Even with the arrival of vaccines, the virus is still spreading and there is a need to develop alternative therapies. Scientists hope to achieve this by studying how SARS-CoV-2 infects cells and propagates itself while avoiding the body's natural immune system.

Now researchers at UT Southwestern have added another piece to this puzzle with their study published in Science Advances.

"When a virus infects a cell, the way the host cell reacts is to alter cellular pathways (or networks) in certain ways to counteract the viral infection. Viruses can target many of these pathways to favor their own replication," says Beatriz Fontoura, Ph.D., professor of cell biology at UTSW and corresponding author of the paper.

Viruses replicate by suppressing the host cell's genes in favor of their own. One way they do this is by blocking the export of messenger RNA (mRNA) from the nucleus of the cell to another compartment called the cytoplasm. Some of these RNAs code for proteins that can only be made by the cell in the cytoplasm. So, by blocking their export from the nucleus, viruses prevent some proteins from being made (e.g., antiviral proteins) and simultaneously free up the cell's machinery for their own replication.

"We've been studying the NS1 protein of the influenza virus and we have shown that one of its functions is to block mRNA nuclear export. Due to some similarities between NS1 from flu and Nsp1 from coronaviruses in their roles in suppressing antiviral response in the host cell, we decided to test whether these two proteins shared a similar function," says Ke Zhang, Ph.D., a postdoctoral researcher in Fontoura's lab and first author of the paper.

The researchers landed on the protein Nsp1. Coronavirus Nsp1 has been described as a multifunctional protein capable of altering viral replication and suppressing the production of other proteins, some of which are involved in immune response. Fontoura's group sought to find out how Nsp1 does this and if it uses a mechanism similar to that of the influenza virus protein NS1.

Indeed, the group found that like NS1 from influenza, SARS-CoV-2 Nsp1 inhibits host cell mRNA nuclear export by binding to the export factor NXF1. This new role of Nsp1 complements the protein's other function, blocking host cell mRNA translation into protein. By obstructing two steps that lead to the production of proteins, Nsp1 suppresses a cell's ability to respond to the viral infection, allowing SARS-CoV-2 to replicate. So what would happen, researchers wondered, if Nsp1 could be stopped from performing one of these functions?

In a proof-of-principle experiment, the researchers infected cells with SARS-CoV-2 and added an excess of NXF1 to see if this would block virus replication. Strikingly, that's exactly what they found. When the cells had access to more NXF1 than the SARS-CoV-2 virus could suppress, the cells were able to stop the virus from multiplying.

The study offers insight into the mechanism behind how coronaviruses, and SARS-CoV-2 in particular, are able to promote their replication inside host cells. Understanding this mechanism provides a building block for potential therapeutics.

"If you find a way to block the interaction between Nsp1 and NXF1 or increase the amount of NXF1 in the cell, you'll get mRNAs out of the nucleus and may get a protective effect, as suggested by our experiments," says Fontoura.

COVID-19 treatments focus on management of symptoms while the body fights off the infection with its natural defenses. A key area of interest in viral therapies is to target the infected cells to stop the virus from replicating. Focusing on Nsp1 or its interaction with NXF1 represents a possible way to do this.

"We still need to know more, like the structure of Nsp1 bound to NXF1, which would shed light on how this blocks mRNA export and how we can revert it," says Zhang. "The research is promising, but in order to develop therapies down the line, we first need to better understand the mechanism."

TUCSON, Ariz. -- The ongoing pandemic has had a significant and alarming trend of increased alcohol use and abuse - especially among younger adults, males and those who have lost their jobs - according to a new study by University of Arizona Health Sciences researchers.

Research led by William "Scott" Killgore, PhD, professor of psychiatry in the UArizona College of Medicine - Tucson and director of the Social, Cognitive and Affective Neuroscience Lab, found that hazardous alcohol use and likely dependence increased every month for those under lockdowns compared to those not under restrictions.

"Being under lockdown during a worldwide pandemic has been hard on everyone, and many people are relying on greater quantities of alcohol to ease their distress," said Dr. Killgore. "We found that younger people were the most susceptible to increased alcohol use during the pandemic, which could set them on the dangerous path toward long-term alcohol dependence."

The paper, "Alcohol dependence during COVID-19 lockdowns," was recently published in the journal Psychiatry Research.

Between April and September 2020, Dr. Killgore and UArizona co-authors Sara Cloonan, Emily Taylor, Daniel Lucas and Natalie Dailey, PhD, surveyed 5,931 adults from all 50 states and the District of Columbia. Each month, roughly 1,000 participants completed the Alcohol Use Disorders Identification Test (AUDIT), a 10-item questionnaire that is used to detect hazardous drinking in adults.

The questions assess the frequency and quantity of alcohol consumed, behaviors associated with dependence, and harm resulting from alcohol use, and provide scores that range from 0 to 40. Scores from 8 to 14 suggest hazardous or harmful alcohol consumption, a score of 15 or more indicates the likelihood of alcohol dependence, and a score of 20 or more implies severe alcohol use disorder.

People under lockdown posted increases for all three thresholds, with hazardous alcohol use rising from 21.0% in April to 40.7% in September and probable alcohol dependence rising from 7.9% to 29.1%. For those scoring 20 or higher, usage that is considered severe alcohol dependence, percentages for those under lockdown increased from 3.9% in April to 17.4% by September.

For all three thresholds, the percentages for those not under lockdown restrictions were essentially unchanged.

Dr. Killgore says the surge in alcohol use comes with several risks, not only to the individual, but also to the family.

"Being cooped up with family for weeks and months without a break can be difficult, but when excess alcohol gets mixed in, it can become a recipe for increased aggressive behavior and domestic violence," Dr. Killgore said. "I worry about the effect on families and children."

For the individual, there are numerous health problems associated with alcohol dependence, including risks of cancer, liver disease, injury, mental health problems and early death. Additionally, employers may also be affected by an individual's excessive alcohol use.

"Many of us are working from home, but this is not the same thing as being productive from home. The use of alcohol while 'on the job' at home is likely to reduce productivity at a time when the country needs us to be doing everything we can to sustain the economy," he added. "Having a few drinks while 'on the clock' at home can lead to a situation of 'presenteeism,' which means that a person may be sitting through Zoom meetings and responding to a few emails, but may not actually be contributing productively to their job. This could severely hamper our ability to pull out of this crisis quickly and on a strong economic footing."

Astronomers have tested a method for reconstructing the state of the early Universe by applying it to 4000 simulated universes using the ATERUI II supercomputer at the National Astronomical Observatory of Japan (NAOJ). They found that together with new observations the method can set better constraints on inflation, one of the most enigmatic events in the history of the Universe. The method can shorten the observation time required to distinguish between various inflation theories.

Just after the Universe came into existence 13.8 billion years ago, it suddenly increased more than a trillion, trillion times in size, in less than a trillionth of a trillionth of a microsecond; but no one knows how or why. This sudden "inflation," is one of the most important mysteries in modern astronomy. Inflation should have created primordial density fluctuations which would have affected the distribution of where galaxies developed. Thus, mapping the distribution of galaxies can rule out models for inflation which don't match the observed data.

However, processes other than inflation also impact galaxy distribution, making it difficult to derive information about inflation directly from observations of the large-scale structure of the Universe, the cosmic web comprised of countless galaxies. In particular, the gravitationally driven growth of groups of galaxies can obscure the primordial density fluctuations.

A research team led by Masato Shirasaki, an assistant professor at NAOJ and the Institute of Statistical Mathematics, thought to apply a "reconstruction method" to turn back the clock and remove the gravitational effects from the large-scale structure. They used ATERUI II, the world's fastest supercomputer dedicated to astronomy simulations, to create 4000 simulated universes and evolve them through gravitationally driven growth. They then applied this method to see how well it reconstructed the starting state of the simulations. The team found that their method can correct for the gravitational effects and improve the constraints on primordial density fluctuations.

"We found that this method is very effective," says Shirasaki. "Using this method, we can verify of the inflation theories with roughly one tenth the amount of data. This method can shorten the required observing time in upcoming galaxy survey missions such as SuMIRe by NAOJ's Subaru Telescope."

The short message service Twitter has played a prominent role in US politics in recent weeks and months and attracted a lot of attention. Even in business, Twitter users' tweets are being closely followed and used as a basis for decision-making. A new study shows that venture capitalists can also be influenced by Twitter sentiment when valuing start-up companies from the high-tech sector. "However, the sentiment signals on Twitter say nothing about the long-term investment success of such a start-up. Patent applications, for example, are much better suited for this," said Professor Andranik Tumasjan from Johannes Gutenberg University Mainz (JGU) in Germany. He conducted the study together with Professor Reiner Braun and Dr. Barbara Stolz from the Technical University of Munich. The results were published in the renowned Journal of Business Venturing.

Twitter as a globally established information platform in the business and technology sector

The researchers' main question was whether and how strongly venture capitalists may be influenced by media hypes. "Out of all social media platforms, Twitter is the most suitable medium for such a study in the business and technology sector," emphasized Tumasjan. Founded in 2006, the microblogging service is now the world's most important social media platform for the short-term exchange of information on new technologies and trends, such as artificial intelligence and business activities in general. Twitter sentiment could therefore also influence venture capitalists' start-up valuations. "Young start-up companies are particularly difficult to value when they have just been launched, as nothing has yet been produced or sold. This means that there is a huge amount of uncertainty involved when venture capitalists decide whether to invest in tech start-ups," explained Tumasjan.

But can Twitter sentiment actually predict the valuations and long-term success of high-tech start-ups? The research team analyzed over 400,000 English-language tweets about 37 different technologies and more than 4,600 venture capital financing rounds between 2008 and 2017. The tweets were analyzed using VADER, a dictionary specifically designed to measure social media sentiment. "This gives us an objective indicator of Twitter sentiment and how people are talking about a particular technology," said Tumasjan. The study included a total of 4,005 US companies that were on average about five years old. The venture capitalists' start-up valuations were assessed using the so-called pre-money valuation. The long-term success of an investment in a start-up was measured by an initial public offering (IPO) or acquisition of a start-up.

Twitter sentiment is a "weak signal," whereas patents are a "strong signal"

The results show that Twitter sentiment about technology do, in fact, significantly predict the venture capital valuations of young high-tech companies whose business model is based on these technologies. However, Twitter cannot predict long-term investment success as indicated by a start-up's IPO or acquisition. "Twitter sentiment is a comparatively novel signal in venture capital financing, and it is at the same time only a weak signal in comparison to patents," resumed Tumasjan. Patents and patent applications have been shown to be strong signals for years, as they are associated with both the valuation and the long-term investment success.

In summary, from the perspective of start-up founders Twitter hype of a technology or trend may be beneficial to obtain a higher capital valuations. However, Professor Andranik Tumasjan recommends that venture capitalists should not let themselves be distracted by Twitter sentiment and should instead focus on other signals, such as patents. This also applies to experienced venture capitalists: according to the study, they are not immune to Twitter hype either.

Andranik Tumasjan studied at Ludwig-Maximilians-Universität München and received both his doctorate and postdoctoral degree in management from the Technical University of Munich. He has been a professor and head of the Management and Digital Transformation (MDT) research group at Johannes Gutenberg University Mainz since 2017. His research focuses on how digital technologies and trends influence management and the emergence of new organizational, leadership, and business models as well as entrepreneurial opportunities. One current focus of his research is the potential of blockchain technology. In previous studies, he investigated to what extent Twitter sentiment can predict events such as political elections and stock market movements.

These observations might be useful for the future development of new antibacterial strategies. The team reports in the journal Applied and Environmental Microbiology on 12 February 2021.

Bacterial groups in search of food

We commonly know predator-prey relationships from the animal kingdom, but they are also a survival strategy of certain bacteria: bacterial predators actively kill bacteria of other species in order to feed on them. The predatory species include many myxobacteria, which are widespread in the soil and display unique behavioural patterns: many cells assemble into large groups and go in search of food together or, in the event of nutrient limitation, build three-dimensional fruiting bodies. "The motility mechanisms of myxobacteria are very well investigated, but there are still many unanswered questions on the molecular processes of predation and their significance in complex bacteria communities," says Christine Kaimer.

The Bochum-based biology team is investigating bacterial predation behaviour using the model of the soil bacterium Myxococcus xanthus, which is known to use a wide range of different microorganisms as prey. "We wondered, which mechanisms these predators use to kill structurally different prey bacteria," explains Kaimer. "To address this, we carefully observed the predation behaviour of M. xanthus against different prey under the microscope and also compared the efficacy of the different protein fractions of the predator cells."

Direct contact or contact in combination with proteins

The experiments have shown that several mechanisms are combined in different ways: the prey cells are initially killed by a predator cell in direct cell-cell contact. For gram-negative prey bacteria with a thin cell wall, this is sufficient to dissolve the cell and access the nutrients inside. To break down gram-positive prey bacteria with a thick cell wall, the predator needs additional proteins, which are realeased into the surrounding area. "The formation of larger predator groups seems to be particularly important for this," explains Christine Kaimer.

These findings provide an important starting point to further reveal bacterial predation mechanisms. In the future, the researchers hope to gain insights into the dynamic interactions in bacterial communities and possibly obtain impulses for the development of new antibacterial strategies.

Leukemia is caused by leukemic stem cells which are resistant to most known therapies. Relapses are also due to this resistance. Leukemic stem cells arise from normal blood-forming (hematopoietic) stem cells. Because they are closely related, leukemic and hematopoietic stem cells share many of the same signaling pathways. If the proliferation of leukemic stem cells is to be stopped, it is crucial to find signaling pathways that are active only in the leukemic stem cell, but not the normal one. With this goal in mind, Prof. Adrian Ochsenbein and his team are conducting research at the Department of Medical Oncology at Inselspital, Bern University Hospital. The latest discovery, the so-called LIGHT/LTbR pathway, is presented in Sabine Höpner's article published today in Nature Communications.

A new approach to controlling leukemic stem cells

In normal blood formation, the LIGHT/LTbR signaling pathway plays no role in hematopoietic stem cells. It is important in maintaining stem cell function only in situations of increased demand, such as after chemotherapy. In contrast, leukemic stem cells always rely on this signaling pathway. The LIGHT/LTbR signaling pathway leads to increased symmetric cell division and thus proliferation of leukemic stem cells. If the pathway is blocked with monoclonal antibodies, for example, the stem cells lose their stem cell function and die. Furthermore, the LIGHT binding site is significantly more abundant in leukemic stem cells than in normal stem cells. In laboratory experiments, animals with leukemia survived significantly longer when the newly discovered signaling pathway had been blocked.

The latest contribution is a beacon of hope for future leukemia treatment

The results published show that multiple receptor/ligand pairs are involved in the maintenance of leukemic stem cells. The researchers believe that the new approach (blocking LIGHT) may lead to an improved therapy of various types of leukemia in the future.

Therapy with medications that aim to block various immune receptors and ligands has revolutionized the treatment of cancer diseases. However, important drugs used to treat solid tumors are not effective in treating leukemia. Therefore, the CD70/CD27 and LIGHT/LTbR signaling pathways that we have defined represent an important advance in improving immunotherapy in myeloid leukemia. Research groups at Stanford have developed antibodies against CD47 that activate another immune signaling pathway (phagocytosis). These new drugs are already in phase II development for the treatment of acute myeloid leukemia.

A polymer that is custom designed to produce light that penetrates murky environments has shown promise in bioimaging trials, where it can detect nano-sized particles underneath the surface of realistic tissue models.

Recent studies have demonstrated that fluorescent probes -- light-emitting materials that attach to tiny targets such as cells -- are particularly useful for bioimaging when they radiate in the shortwave infrared (SWIR) region of the optical spectrum. Because this type of fluorescent light penetrates deeper into biological objects without being absorbed or scattered, SWIR probes can be spotted farther into tissue than conventional emitters. These features have enabled SWIR probes to capture high-resolution images of structures located deep within the body, such as brain tissue, without the hazards of x-rays.

Satoshi Habuchi and his colleagues are working to improve fluorescent imaging by expanding the type of probes capable of producing SWIR radiation. Currently, most bright SWIR emitters are either semiconductor quantum dots or rare-earth-doped nanoparticles that are unsuitable for many specimens because of their toxic side-effects. On the other hand, materials that are more biocompatible, such as organic dyes, are usually not intense enough to be seen inside tissue.

To resolve this issue, KAUST researchers turned to polymers having "donor-acceptor" structures, a layout where electron-rich components alternate with electron-poor portions along a conductive molecular chain. "This distribution promotes charge transfer along the polymer backbone, which is a very effective way to obtain SWIR light," explains Hubert Piwon?ski, the study's lead author.

The team chose two donor-acceptor polymers with ideal characteristics for SWIR emission and then developed a precipitation procedure that fused the compounds into tiny polymer spheres, or "dots", just a few nanometers wide. Optical characterizations revealed these materials had exceptionally bright SWIR emissions that were easily spotted in biological tissue models.

"Per volume, our particles have a brightness value larger than almost all other SWIR emitters reported so far," says Habuchi. "This enabled detection of nanometer-sized polymer dots in specimens one millimeter thick."

In addition, the new polymer dots that fluoresce only for a nanosecond can produce low-noise images with single-molecule sensitivity due to high throughput detection of emitted fluorescence. The ability to visualize single probes at fast acquisition rates could benefit researchers looking to capture processes in tissues and organs as they happen.

"There are huge opportunities for new probes and imaging modalities capable of addressing the dynamics of molecules in living systems, and our polymer dots are a big step toward single-particle tissue imaging," says Piwon?ski.

Our universe is dominated by a mysterious matter known as dark matter. Its name comes from the fact that dark matter does not absorb, reflect or emit electromagnetic radiation, making it difficult to detect.

Now, a team of researchers has investigated the strength of dark matter scattered across the smallest galaxies in the universe using stellar kinematics.

"We discovered that the strength of dark matter is quite small, suggesting that dark matter does not easily scatter together," said professor Kohei Hayashi, lead author of the study.

Much is unknown about dark matter, but theoretical and experimental research, from particle physics to astronomy, are elucidating more about it little by little.

One prominent theory surrounding dark matter is the "self-interacting dark matter (SIDM) theory." It purports that dark matter distributions in galactic centers become less dense because of the self-scattering of dark matter.

However, supernova explosions, which occur toward the end of a massive star's life, can also form less dense distributions. This makes it challenging to distinguish whether it is the supernova explosion or the nature of dark matter that causes a less dense distribution of dark matter.

To clarify this, Hayashi and his team focused on ultra-faint dwarf galaxies. Here a few stars exist, rendering the influences of supernova explosions negligible.

Their findings showed that dark matter is dense at the center of the galaxy, challenging the basic premise of SIDM. Images from the dwarf galaxy Segue 1 revealed high dark matter density at the center of the galaxy, and that scattering is limited.

"Our study showed how useful stellar kinematics in ultra-faint dwarf galaxies are for testing existing theories on dark matter," noted Hayashi. "Further observations using next-generation wide-field spectroscopic surveys with the Subaru Prime Focus Spectrograph, will maximize the chance of obtaining dark matter's smoking gun."

Both Earth and Mars currently have oxidising atmospheres, which is why iron-rich materials in daily life develop rust (a common name for iron oxide) during the oxidation reaction of iron and oxygen. The Earth has had an oxidising atmosphere for approximately two and a half billion years, but before that, the atmosphere of this planet was reducing - there was no rust.

The transition from a reduced planet to an oxidised planet is referred to as the Great Oxidation Event or GOE. This transition was a central part of our planet's evolution, and fundamentally linked to the evolution of life here - specifically to the prevalence of photosynthesis that produced oxygen. Planetary geologists at HKU have discovered that Mars underwent a great oxygenation event of its own - billions of years ago, the red planet was not so red.

The discovery was published recently in Nature Astronomy in a paper led by research postgraduate student Jiacheng LIU and his advisor Associate Professor Dr Joe MICHALSKI, both affiliated with the Research Division for Earth and Planetary Science and Laboratory for Space Research. The researchers used infrared remote sensing and spectroscopy to measure the molecular vibration of the material on the Martian surface from orbit, in order to reveal the mineralogy and geochemistry of ancient rocks on Mars. Through detailed comparisons of infrared remote sensing data and data collected in the laboratory here on Earth, the team showed that ancient rocks on Mars exposed at the surface had been weathered under reducing conditions, indicating a reduced atmosphere did exist.

Many people are aware that Mars is cold and dry now, but ~ 3.5 billion years ago, it was warmer and wetter. It was warm enough to allow the formation of river channels, lakes and minerals that formed by interaction with water. Scientists who have used mathematical models to constrain the conditions of an early Martian atmosphere, have concluded that greenhouse warming occurred, but they also concluded from their models that the greenhouse must have included reduced gases rather than carbon dioxide, implied that a reducing atmosphere might have existed. Yet until now, there has not been any evidence that the reduced atmosphere of early Mars actually occurred. This work indicates that it did exist.

This project involved detailed infrared remote sensing of Mars, using infrared spectroscopy to map minerals in exposed, weathered rock units. The work was built on detailed analysis of weathered volcanic rocks in Hainan Island in southwestern China, where thick sequences of basalt, similar to volcanic rocks on Mars occur. Jiacheng Liu analysed the altered rocks systematically using infrared spectroscopy in the laboratory and produced a paper on that research published recently in Applied Clay Science.

"Jiacheng has carried out a truly excellent PhD project, built on careful analysis in the laboratory and application of those laboratory results to remote sensing of Mars," Dr Michalski commented, "Jiacheng has built on his detailed work on samples from Hainan Island to show that similar mineralogical trends occurred in rocks on Mars."

Assistant Professor Dr Ryan MCKENZIE from Research Division for Earth and Planetary Science is also impressed by these findings. "This is a rather remarkable study with findings that will significantly impact how we understand the early evolution of terrestrial planets and their surface environments. The transition from a reducing to oxidising atmosphere on Earth ~2.5 billion years ago was only possible because the existence of life, as oxygen is a waste product of metabolic processes like photosynthesis. Without microbes producing oxygen, it would not accumulate in our atmosphere, and we could not be here. While there are certainly differences in the local conditions Mars and Earth have been subjected to during their evolutionary histories, my mind can't help but start thinking about what Jiancheng's results may mean for a potential early Martian biosphere," Dr McKenzie remarked.

As China's first mission to Mars Tianwen-1 is underway - has successfully arrived in Mars orbit on February 10 and set to land on Mars in May 2021, scientists are preparing for an exciting year of Mars exploration and discovery. This work demonstrates how spectroscopy and remote sensing lead to fundamental discoveries of significant importance for understanding Mars' history. As we begin to understand the most ancient history of Mars, researchers are ready to directly search of any signatures that life might have once existed on ancient Mars, and HKU plans to be at the centre of this great scientific adventure.

Osaka, Japan - All chemistry students are taught about the periodic table, an organization of the elements that helps you identify and predict trends in their properties. For example, science fiction writers sometimes describe life based on the element silicon because it is in the same column in the periodic table as carbon.

However, there are deviations from expected periodic trends. For example, lead and tin are in the same column in the periodic table and thus should have similar properties. However, whilst lead-acid batteries are common in cars, tin-acid batteries don't work. Nowadays we know that this is because most of the energy in lead-acid batteries is attributable to relativistic chemistry but such chemistry was unknown to the researchers who originally proposed the periodic table.

Relativistic chemistry is difficult to study in the superheavy elements, because such elements are generally produced one at a time in nuclear fission reactions and deteriorate quickly. Nevertheless, having the ability to study the chemistry of superheavy elements could uncover new applications for superheavy elements and for common lighter elements, such as lead and gold.

In a recent study in Nature Chemistry, researchers from Osaka University studied how single atoms of superheavy rutherfordium metal react with two classes of common bases. Such experiments will help researchers use relativistic principles to better utilize the chemistry of many elements.

"We prepared single atoms of rutherfordium at RIKEN accelerator research facility, and attempted to react these atoms with either hydroxide bases or amine bases," explains Yoshitaka Kasamatsu, lead author on the study. "Radioactivity measurements indicated the end result."

Researchers can better understand relativistic chemistry from such experiments. For example, rutherfordium forms precipitate compounds with hydroxide base at all concentrations of base, yet its homologues zirconium and hafnium in high concentrations. This difference in reactivity may be attributable to relativistic chemistry.

"If we had a way to produce a pure rutherfordium precipitate in larger quantities, we could move forward with proposing practical applications," says senior author Atsushi Shinohara. "In the meantime, our studies will help researchers systematically explore the chemistry of superheavy elements."

Relativistic chemistry explains why bulk gold metal is not silver-colored, as one would expect based on periodic table predictions. Such chemistry also explains why mercury metal is a liquid at room temperature, despite periodic table predictions. There may be many unforeseen applications that arise from learning about the chemistry of superheavy elements. These discoveries will depend on newly reported protocols and ongoing fundamental studies such as this one by Osaka University researchers.

For the first time, a research team led by Lund University in Sweden has mapped out exactly what happens when spruce bark beetles use their sense of smell to find trees and partners to reproduce with. The hope is that the results will lead to better pest control and protection of the forest in the future.

The Eurasian spruce bark beetle uses its sense of smell to locate trees and partners. The odours are captured via odorant receptors (proteins) in their antennae. Researchers have long understood the connection, but so far they have not known exactly which receptors bind to what pheromones. This is key knowledge for the long-term development of more effective and environmentally friendly pesticides and bark beetle traps used to protect the forest.

The research team were able to characterize the response of odorant receptors in bark beetles for the first time. They identified 73 different receptors in the antennae of the Eurasian spruce bark beetle (Ips typographus), and succeeded in characterizing the odour response in two of the receptors. One responds to the pheromone ipsenol, the other to ipsdienol.

"A large number of different bark beetle species use these pheromones when communicating with scents, so the fact that we have been able to to characterize them is a breakthrough", says Martin N Andersson who led the research group consisting of researchers in Lund, Germany and the Czech Republic.

The two receptors are thus the first ever to be characterized in bark beetles. To put the result into context, Martin N Andersson says that within the entire insect order Coleoptera beetles, with more than 300,000 species on Earth, only three odour receptors had been characterized previously.

"Our results indicate that the pheromone receptors of different beetle species are evolutionarily unrelated, at least in the few species that have been studied. We also show that the odour response in these receptors is very specific, and we are the first in the world to be able to show exactly where in the receptors the pheromones are likely to bind", he says.

The results could make it possible to develop better and more environmentally friendly pest control methods. One approach is to try to find other odours that bind even better to the two receptors than ipsenol and ipsdienol. If such odours can be found, they can hopefully be used to disrupt the pheromone communication of spruce bark beetles - either by a stronger activation of the receptor compared with the natural pheromone, or by blocking the receptor.

Another way could be to use the two characterized receptors in a biosensor that is under development. This would quickly locate spruce bark beetles and thus be able to identify infested trees before the bark beetles spread.

According to Martin N Andersson, the practical applications are a few years away.

"Screening for better substances can begin in 2021. If we find something, the results must be confirmed in the lab and then evaluated in the field, and that would take two or three years. Using it in biosensors for monitoring and detection will probably take longer than that. However, our discovery means that the process can now begin", he concludes.