Since the coronavirus pandemic began in early 2020, several more-infectious variants of SARS-CoV-2, the virus that causes COVID-19, have emerged. The original, or wild-type, virus was followed by the alpha variant, which became widespread in the United States in early 2021, and subsequently the delta variant, which is the most prevalent strain circulating today. The variants have acquired mutations that help them infect people and spread more easily. Many of the mutations affect the spike protein, which the virus uses to get into cells. Scientists have been trying to understand how these changes alter the virus’s function.

“Throughout the pandemic, NIDCR researchers have applied their expertise in the oral health sciences to answer key questions about COVID-19,” said NIDCR Director Rena D’Souza, D.D.S., Ph.D. “This study offers fresh insights into the greater infectivity of the alpha and delta variants and provides a framework for the development of future therapies.”

The outer surface of SARS-CoV-2 is decorated with spike proteins, which the virus uses to attach to and enter cells. Before this can happen, though, the spike protein must be activated by a series of cuts, or cleavages, by host proteins, starting with the furin enzyme. In the alpha and delta variants, mutations to the spike protein appear to enhance furin cleavage, which is thought to make the virus more effective at entering cells.

Studies have shown that in some cases protein cleavage can be decreased by the addition of bulky sugar molecules — a process carried out by enzymes called GALNTs — next to the cleavage site. Ten Hagen’s team wondered if this happens to the SARS-CoV-2 spike protein, and, if so, whether it changes the protein’s function.

To find out, the scientists studied the effects of GALNT activity on spike protein in fruit fly and mammalian cells. The experiments showed that one enzyme, GALNT1, adds sugars to wild-type spike protein, and this activity reduces furin cleavage. By contrast, mutations to the spike protein, like those in the alpha and delta variants, decrease GALNT1 activity and increase furin cleavage. This suggested that GALNT1 activity may partially suppress furin cleavage in wild-type virus, and that the alpha and delta mutations overcome this effect, allowing furin cleavage to go unchecked.

Further experiments supported this idea. The researchers expressed either wild-type or mutated spike in cells grown in a dish. They observed the cells’ tendency to fuse with their neighbors, a behavior that may facilitate spread of the virus during infection. The scientists found that cells expressing mutated spike protein fused with neighbors more often than cells with the wild-type spike. Cells with wild-type spike also fused less often in the presence of GALNT1, suggesting that its activity may limit spike protein function.

“Our findings indicate that the alpha and delta mutations overcome the dampening effect of GALNT1 activity, which may enhance the virus’s ability to get into cells,” said Ten Hagen.

To see if this process might also occur in people, the team analyzed RNA expression in cells from healthy volunteers. The researchers found wide expression of GALNT1 in lower and upper respiratory tract cells that are susceptible to SARS-CoV-2 infection, indicating that the enzyme could influence infection in humans. The scientists theorized that individual differences in GALNT1 expression could affect virus spread.

“This study suggests that GALNT1 activity may modulate viral infectivity and provides insight into how mutations in the alpha and delta variants may influence this,” Ten Hagen said. The knowledge could inform future efforts to develop new interventions.

This research was supported by the NIDCR Division of Intramural Research. Support also came from the intramural program of the National Institute of Environmental Health Sciences.

Inflammation is a natural and vital response of our immune system to danger signals and tissue damage. Inflammatory processes help the body to eliminate the triggers, for example bacteria, and to initiate repair mechanisms. Terminating this inflammatory reaction quickly and in a coordinated manner is just as important, however, as otherwise there is a risk of developing chronic inflammatory conditions such as rheumatoid arthritis or Crohn’s disease. One of the important factors for resolving the inflammatory reaction is the elimination of damaged and dead cells, a process that was not very well understood until now. New inflammation can occur if these cells are allowed to accumulate.

How waste from inflammation is disposed of

A research team led by Prof. Gerhard Krönke at the Department of Medicine 3 — Rheumatology and Immunology at Universitätsklinikum Erlangen has now succeeded in gaining a better understanding of the fundamental molecular mechanisms involved. The researchers investigated the function of macrophages at the site where inflammation occurs. These cells are capable of ingesting large quantities of cellular waste and digesting and eliminating the molecular components of this waste in their mitochondria, also referred to as the powerhouse of the cell.

The scientists were able to demonstrate that the danger signal interleukin 33, which is released from damaged cells, triggers lasting changes to the metabolism of macrophages, so that their waste disposal capacity significantly increases. The sheer quantity of waste produced during the inflammatory reaction places the mitochondria under severe strain, and they produce increased quantities of damaging oxygen radicals as a result. Interleukin 33 regulates the function of the mitochondria by initiating a process known as uncoupling in these cell components and protecting them from overloading. ‘This enables the macrophages to ‘let off steam’ and carry on ingesting waste without interruption despite the heavy strain placed upon them, resolving the inflammation processes as a result,’ explains Maria Faas, lead author of the article recently published in the journal ‘Immunity’.

Protection of mitochondria as a new approach for therapy for inflammation

The findings of the FAU team could pave the way for new approaches for treating chronic inflammatory conditions. ‘It may be possible to accelerate and support the resolution of inflammatory processes in the long term by influencing the cell metabolism of the macrophages and deliberately uncoupling their mitochondria,’ explains Prof. Gerhard Krönke. Interestingly, substances that positively influence the cell metabolism of macrophages have already been discovered. However, they have not yet been approved for use in chronic inflammatory conditions and must undergo further clinical trials. The investigations and experiments were conducted as part of the DFG collaborative research centre CRC 1181 ‘Switching points for resolving inflammation’ and the DFG research group FOR2886 PANDORA (Pathways triggering Autoimmunity and Defining Onset of early Rheumatoid Arthritis). Maria Faas also received a scholarship as part of the DFG research training group 1660 (Key signals of adaptive immune response).

Story Source:

Materials provided by Friedrich-Alexander-Universität Erlangen-Nürnberg. Note: Content may be edited for style and length.

In a paper published recently in Nature Communications, the authors, including experts from China’s Tsinghua University, the Carnegie Institution for Science and Caltech, said that most of the current electricity demand in advanced, industrialized nations can be met by some combination of wind and solar power. But that positive finding comes with the caveat that extra efforts are going to be necessary to completely satisfy the countries’ requirements.

Most reliable systems, which are dominated by wind power, are capable of meeting electricity requirements in the countries studied 72 to 91 percent of the time, even without energy storage, according to the study. With the addition of 12 hours of energy storage capacity, systems become dominated by solar power and can satisfy demand 83 to 94 percent of hours.

“Wind and solar could meet more than 80 percent of demand in many places without crazy amounts of storage or excess generating capacity, which is the critical point,” said co-author Steve Davis, UCI professor of Earth system science. “But depending on the country, there may be many multi-day periods throughout the year when some demand will need to be met by energy storage and other non-fossil energy sources in a zero-carbon future.”

The team analyzed 39 years’ worth of hourly energy demand data from 42 major countries to evaluate the adequacy of wind and solar power resources to serve their needs. They found that a full conversion to sustainable power resources can be easier for larger, lower-latitude countries, which can rely on solar power availability throughout the year.

The researchers highlighted Germany as an example of a relatively smaller country, in terms of land mass, at higher latitude which will make it more challenging to meet its electricity needs with wind and solar resources.

“Historic data show that countries that are farther from the equator can occasionally experience periods called ‘dark doldrums’ during which there is very limited solar and wind power availability,” said lead author Dan Tong, assistant professor of Earth system science at Tsinghua University. “One recent occurrence of this phenomenon in Germany lasted for two weeks, forcing Germans to resort to dispatchable generation, which in many cases is provided by fossil fuel-burning plants.”

Among the approaches the researchers suggested to alleviate this problem are a building up generating capacity that exceeds annual demand, developing long-term storage capabilities and pooling resources of multiple nations on a continental land mass.

“Europe provides a good example,” said Tong, who began her work on this study as a post-doctoral scholar in UCI’s Department of Earth System Science. “A lot of consistency and reliability could be provided by a system that includes solar resources from Spain, Italy and Greece with bountiful wind available in the Netherlands, Denmark and the Baltic region.”

The researchers found that a wind and solar power system could provide about 85 percent of the total electricity demand of the United States, and that amount could also be increased through capacity overbuilding, addition of batteries and other storage methods, and connecting with other national partners on the North American continent.

“Around the world, there are some definite geophysical constraints on our ability to produce net-zero carbon electricity,” said Davis. “It comes down to the difference between the difficult and the impossible. It will be hard to completely eliminate fossil fuels from our power generation mix, but we can achieve that goal when technologies, economics and socio-political will are aligned.”

Dissipationless electric energy transport — also known as superconductivity — is seen as a beacon of hope for the energy industry. Since its discovery more than 100 years ago, scientists around the world have been investigating this well-known quantum phenomenon, which, however, requires the electrons in metals to be cooled to ultra-low temperatures. A team of scientists from the Cluster of Excellence ct.qmat-Complexity and Topology in Quantum Matter at the Universities of Dresden and Würzburg has now made a remarkable discovery: In certain superconducting metals, a compound of four electrons ensures that a completely new state of matter is created. Until now, only electron pairs were known to play a role in superconductivity. The discovery by the research team led by Prof. Hans-Henning Klauss of Technische Universität Dresden is therefore considered a milestone for materials research. The research results have been published in the journal Nature Physics.

Electron family surprises researchers

In quantum physics, superconductivity, discovered as early as in 1911, is probably the best-known phenomenon to date. Its theoretical foundations are understood since the 1950s. It is essential that electrons at ultra-low temperatures no longer move through a metal individually, but as pairs. Electron pairs do not collide with the atomic lattice, so that they can transport their charge without any loss of energy.

When the Dresden researchers led by Henning Klauss experimentally investigated the superconducting metal Ba_1-xK_xFe₂As₂ from the class of iron pnictides, they initially suspected a mistake: “When we discovered that suddenly four electrons instead of two were forming a bond, we first believed it was a measurement error. But the more methods we used to confirm the result, the clearer it became that this had to be a new phenomenon: all data are consistent with the same result. Now we know that the four particle electron family in certain metals creates a completely new state of matter when cooled to ultra-low temperatures. What this will lead to in the future will become clear over the next few years,” comments Dresden physicist Hans-Henning Klauss.

Results tested for more than two years

Already about ten years ago, it was theoretically predicted that there could be an unusual state of matter in certain superconducting metals, in which four instead of two electrons play a role. The international research team of the Cluster of Excellence ct.qmat has now provided the first experimental evidence. It was scrutinized for two years using seven different methods.

“We first discovered the new state of matter in a Swiss particle accelerator. We were then able to confirm our results with six other methods on site in Dresden and at Stockholm University. The great location advantage of Dresden is the short distances: I can bring my sample almost on foot to a Leibniz Institute or Helmholz Center,” emphasizes the project’s lead experimenter, Dr. Vadim Grinenko of TU Dresden. The theoretical interpretation of the measurement results comes from the Swedish physicist Prof. Egor Babaev.

New type of superconductivity possible

The discovery of iron pnictides as a class of materials particularly suitable for superconductivity already triggered a worldwide research boom in physics and materials science starting in 2008. The energy industry has high hopes for the popular quantum phenomenon because up to 15 percent of energy is lost in conventional energy transport due to transport resistance. “If you could actually transport electricity across the country in superconducting metals at room temperature, about ten large power plants would be superfluous right away,” says Klauss. However, basic research — such as Prof. Klauss’ — is concerned with understanding the underlying physics and can at best speculate about future applications.

“One can assume that our results will lead to a whole new line of research, looking for other metals with four connected electrons, for example, or exploring how materials need to be changed to create an electron family,” Klauss explains. “In purely theoretical terms, a whole new type of superconductivity would also be possible with our electron family. The only thing that is certain is that iron pnictides are well suited for technologies such as quantum sensors due to their new aggregate state.”

International participation

In addition to Prof. Hans-Henning Klauss, Dr. Vadim Grinenko of TU Dresden and Prof. Egor Babaev of the Royal Institute of Technology in Stockholm were significantly involved in the current research findings. The experiments were carried out at the Swiss Paul Scherrer Institute in Villigen as well as at the Leibniz Institute for Solid State and Materials Research in Dresden, the high-field magnet laboratory of the Helmholtz Center Dresden-Rossendorf and the AIST Institute in Tsukuba in Japan.

Human genetic material contains more than 20,000 different genes. But each cell only uses a fraction of the information stored in this genome. Hence, cells have to control precisely which genes they use. If not, cancer or embryonal growth disorder may develop. So-called transcription factories play a central role in the selection of active genes. “These factories are molecular clusters in the nucleus that combine the correct selection of active genes and the read-out of their sequence at a central location,” Lennart Hilbert explains. The Junior Professor for Systems Biology/Bioinformatics at the Zoological Institute (ZOO) of KIT also heads a working group at KIT’s Institute of Biological and Chemical Systems — Biological Information Processing (IBCS-BIP).

Setup and Start within a Few Seconds

For decades, cellular and molecular biologists have studied how transcription factories are set up and taken into operation within a few seconds. Results obtained so far suggest relevance of processes known from industrial and technical polymer and liquid materials only. Current research focuses on phase separation as a central mechanism. In everyday life, phase separation can be observed when separating oil from water. It has not yet been clear, however, how exactly phase separation contributes to the setup of transcription factories in living cells.

Researchers from KIT’s Institute of Biological and Chemical Systems (IBCS), Zoological Institute (ZOO), Institute of Applied Physics (APH), and Institute of Nanotechnology (INT), in cooperation with scientists from FAU and MPZPM in Erlangen and the University of Illinois at Urbana-Champaign/USA, have now gained new findings on the formation of transcription factories: It is similar to the condensation of liquids. This is reported in Molecular Systems Biology. The first co-authors are Agnieszka Pancholi of IBCS-BIP and ZOO and Tim Klingberg of FAU and MPZPM.

Latest Light Microscopy Combined with Computer Simulations

In their publication, the researchers point out that condensation to form transcription factories resembles steamy glasses or windows. Liquid condenses in the presence of a receptive surface only, but then very quickly. In the living cell, specially marked areas of the genome are used as condensation surfaces. The liquid-coated areas allow for the adhesion of relevant gene sequences and additional molecules that eventually activate the adhering genes. These findings were obtained by interdisciplinary cooperation. Zebrafish embryos were studied with latest light microscopes developed by Professor Gerd Ulrich Nienhaus’s Chair at APH. These observations were then linked to computer simulations at the FAU Chair for Mathematics headed by Professor Vasily Zaburdaev. Combination of observations and simulations makes the condensation process reproducible and explains how living cells can set up transcription factories rapidly and reliably.

New understanding of condensed liquids in living cells recently resulted in entirely new approaches to treating cancer and diseases of the nervous system. These approaches are now being pursued by startups developing new drugs. Other research activities focus on the use of DNA sequences as digital data storage systems. Meanwhile, principle feasibility of DNA-based data storage systems has been demonstrated by several working groups. Reliable storage and read-out of information in such DNA storage media still represent big challenges. “Our work shows how the biological cell organizes such processes rapidly and reliably. The computer simulations and functional concepts developed by us can be transferred directly to artificial DNA systems and can support their design,” Lennart Hilbert says.

Story Source:

Materials provided by Karlsruhe Institute of Technology. Note: Content may be edited for style and length.

“Heterotopic ossification is an incredibly debilitating condition for which we have no truly effective therapies,” said study leader Benjamin Levi, M.D., Associate Professor of Surgery and in the Children’s Medical Center Research Institute at UT Southwestern and the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research. “To be able to prevent HO from occurring after an injury while also decreasing pain would be a substantial step forward.”

HO occurs in a significant number of patients with musculoskeletal injuries or who undergo some surgeries. For example, about 20% of patients undergoing an initial hip replacement develop this abnormal bone growth, and for a second replacement of the same hip, that number rises to up to 80%. HO is also common in patients with large-area burns, traumatic elbow injuries, spinal cord injuries, and pelvic fractures, where it causes contractures that limit mobility. Although pain during healing is an obvious feature of these injuries and surgeries, Dr. Levi explained, it’s been unclear whether pain-sensing nerves play a role in its development.

To investigate this question, Dr. Levi and Johns Hopkins colleague Aaron W. James, M.D., Ph.D., co-led a team of researchers from six institutions to determine how HO is affected by sensory nerves. Using a mouse model, the researchers observed that sciatic nerve axons — long extensions of neurons — grew into the injury site before HO occurred. When the nerve axons were not present, HO did not develop.

In an effort to identify the signal that draws sensory nerve axons into the injury site, the researchers surveyed gene activity to determine which genes might be over- or under-producing proteins after injury. They found that the amount of one protein, called nerve growth factor (NGF), increased several-fold after injury, and it came from cells on the outside of blood vessels. Because nerve fibers usually travel the same routes as blood vessels, NGF seemed like a likely beacon to draw axons in.

Sure enough, when the researchers used a genetic technique to shut down NGF- signaling at the injury site, HO did not develop. The researchers achieved similar success by using small molecules or an investigational drug to block TrkA, the receptor to which NGF binds.

Dr. Levi noted that several drugs that aim to relieve pain by blocking NGF are currently in phase 3 clinical trials at other institutions. These drugs could serve a dual purpose in patients at risk for HO by preventing this condition from developing.

Story Source:

Materials provided by UT Southwestern Medical Center. Note: Content may be edited for style and length.

Dr. Fan Zhang, associate professor of physics in the School of Natural Sciences and Mathematics, is an author of a study published on Oct. 6 in the journal Nature that demonstrates the exotic behavior in bilayer graphene, which is a naturally occurring, two-atom thin layer of carbon atoms arranged in two honeycomb lattices stacked together.

The quantum Hall effect is a macroscopic phenomenon in which the transverse resistance in a material changes by quantized values in a stepwise fashion. It occurs in two-dimensional electron systems at low temperatures and under strong magnetic fields. In the absence of an external magnetic field, however, a 2D system may spontaneously generate its own magnetic field, for example, through an orbital ferromagnetism that is produced by interactions among electrons. This behavior is called the quantum anomalous Hall effect.

“When the rare quantum anomalous Hall effect was investigated previously, the materials studied were complex,” Zhang said. “By contrast, our material is comparably simple, since it just consists of two layers of graphene and occurs naturally.”

Dr. Thomas Weitz, an author of the study and a professor at the University of Göttingen, said: “Additionally, we found quite counterintuitively that even though carbon is not supposed to be magnetic or ferroelectric, we observed experimental signatures consistent with both.”

In research published in 2011, Zhang, a theoretical physicist, predicted that bilayer graphene would have five competing ground states, the most stable states of the material that occur at a temperature near absolute zero (minus 273.15 degrees Celsius or minus 459.67 degrees Fahrenheit). Such states are driven by the mutual interaction of electrons whose behavior is governed by quantum mechanics and quantum statistics.

“We predicted that there would be five families of states in bilayer graphene that compete with each other to be the ground state. Four have been observed in the past. This is the last one and the most challenging to observe,” Zhang said.

In experiments described in the Nature article, the researchers found eight different ground states in this fifth family that exhibit the quantum anomalous Hall effect, ferromagnetism and ferroelectricity simultaneously.

“We also showed that we could choose among this octet of ground states by applying small external electric and magnetic fields as well as controlling the sign of charge carriers,” Weitz said.

The ability to control the electronic properties of bilayer graphene to such a high degree might make it a potential candidate for future low-dissipation quantum information applications, although Zhang and Weitz said they are primarily interested in revealing the “beauty of fundamental physics.”

“We predicted, observed, elucidated and controlled a quantum anomalous Hall octet, where three striking quantum phenomena — ferromagnetism, ferroelectricity and zero-field quantum Hall effect — can coexist and even cooperate in bilayer graphene,” Zhang said. “Now we know we can unify ferromagnetism, ferroelectricity and the quantum anomalous Hall effect in this simple material, which is amazing and unprecedented.”

Other authors of the Nature article include UT Dallas physics doctoral student Tianyi Xu and researchers from the University of Göttingen and the Ludwig Maximilian University of Munich.

Zhang’s research is funded by the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory and the National Science Foundation.

Story Source:

Materials provided by University of Texas at Dallas. Original written by Amanda Siegfried. Note: Content may be edited for style and length.