In the study, published this week in Nature Genetics, researchers used CRISPR technology to test the impact of every human gene on SARS-CoV-2 infections in human lung cells. Their findings revealed new pathways that the virus relies on to infect cells, as well as the antiviral pathways that help protect against viral infection. Notably, they showed that mucins — the main component of mucus found in the lungs — seem to help block the SARS-CoV-2 virus from entering our cells.

“Our data suggest that mucins play a key role in restricting SARS-CoV-2 infection by acting as a barrier to viruses that are attempting to access our lung epithelial cells,” said Scott Biering, the study’s co-lead author and a postdoctoral researcher in Eva Harris’s lab at UC Berkeley’s School of Public Health. “Further, our data suggest that mucin expression levels in an individual’s lungs may impact COVID-19 disease progression.”

Patrick Hsu — cofounder of the Arc Institute and Berkeley assistant professor of bioengineering, Deb Faculty Fellow and Innovative Genomics Institute Investigator — is the principal investigator of the study, which brought together researchers from 10 institutions. Harris, professor of public health at UC Berkeley, and Silvana Konermann, assistant professor at Stanford University School of Medicine, were co-senior authors of the study. Other collaborators contributed from Stanford University, the University of North Carolina at Chapel Hill, Yale School of Medicine and Cornell University, and spanned disciplines ranging from immunology, bioengineering, epidemiology, molecular biology and genetics.

Together, the researchers were trying to determine how the SARS-CoV-2 virus enters human cells and replicates so efficiently during illness. They also wanted to identify specific defense mechanisms in human cells that might be able to fight infection, which could inspire new therapeutic strategies.

Researchers discovered that MUC1 and MUC4, types of mucins found in lung cell membranes, defend lung cells from infection. This finding is important because previous studies had suggested that an accumulation of mucus could be the reason why some people became seriously ill with COVID-19 — since the mucus can make it difficult for people to breathe — and proposed using drugs to deplete mucus. This Berkeley-led study suggests that such a strategy could interfere with mucins that provide a valuable defense mechanism against SARS-CoV-2 infection.

Still, mucins are complex, and more research is needed to fully understand them. The researchers discovered that other mucins — MUC5AC and MUC5B — which are secreted into the mucus lining of the lungs, either do nothing to stop SARS-CoV-2 infection or can even promote viral infection.

According to Biering, both the type and amount of mucus that each person produces may result in different outcomes for SARS-CoV-2 infection — and lead to different treatment strategies.

“Somebody who produces a lot of the right type of mucus could be very protected. But somebody who produces a lot of the wrong type of mucus might have more risk of infection,” said Biering. “And somebody who produces very little of the right type also could be at more risk.”

This is also the first study in which researchers looked at how the SARS-CoV-2 virus interacts with human lung cells, marking a critical advancement in COVID-19 research.

“It is well known that virus infection can be promoted or inhibited by our own proteins,” said Biering. “But this is the first time that a systematic investigation of these host cell proteins has been conducted in human lung epithelial cells for SARS-CoV-2 infection.”

Past studies of SARS-CoV-2 infection have used cell types that do not naturally contain the receptors or other pathways that the virus uses to infect our lungs. For this study, researchers wanted to use a more relevant cell type, human epithelial cells called Calu-3, found on the inner surface of the lung. Though this cell line is extremely challenging to work with, researchers managed to gain a more accurate understanding of the biology involved in human SARS-CoV-2 infections.

“[Using Calu-3 cells] was a huge advancement, given that these are very representative of the first cells the virus contacts and infects in humans, and it revealed new pathways not seen in other cell lines,” said co-lead author Sylvia Sarnik, an assistant specialist in Hsu’s lab at the time of the study. “Overall, this study is a step forward in understanding viral infection pathways and paves the way for research toward better treatments in the future.”

The researchers conducted genome-wide CRISPR gain-of-function and loss-of-function screening to eliminate or overexpress every gene in the human genome. Then they measured the impact of these gene expression changes on SARS-CoV-2 infection in human lung epithelial cells. Importantly, many of the genes highlighted by this screen have yet to be investigated experimentally, providing a starting point for future work.

“You can run these massively parallel ‘Hunger Games’-style experiments on human cells to see which genes you can change to tune the ability of our lung cells to survive or grow when the virus infects them,” said Hsu.

“Our screen successfully identified hundreds of genes that were important for replication of SARS-CoV-2 and hundreds of genes that could restrict SARS-CoV-2,” said Biering. “In this study, we chose to focus on understanding the role of these mucin proteins.”

The researchers identified mucin glycoproteins as key restriction factors for infection in cells, both in mouse models and potentially in humans.

Researchers also studied how mucins would interact with other respiratory viruses, including influenza A virus, human parainfluenza virus, common cold coronaviruses and respiratory syncytial virus. As with SARS-CoV-2, the results were unpredictable.

“What we showed was mucins are broadly antiviral, but the story is actually much more complicated than that,” said Hsu. “In fact, in some viruses, we found that mucin overexpression actually seemed to increase infectivity.”

Future work will be critical to better understand how viruses interact with mucins, but, for now, these findings provide an important starting point. “This study helped us learn more about the virus and opened new avenues for research to further investigate druggable targets,” said Sarnik.

Fast Grants, the National Institutes of Health and the Centers for Disease Control and Prevention helped support this research.

A dense, collapsed star spinning 707 times per second — making it one of the fastest spinning neutron stars in the Milky Way galaxy — has shredded and consumed nearly the entire mass of its stellar companion and, in the process, grown into the heaviest neutron star observed to date.

Weighing this record-setting neutron star, which tops the charts at 2.35 times the mass of the sun, helps astronomers understand the weird quantum state of matter inside these dense objects, which — if they get much heavier than that — collapse entirely and disappear as a black hole.

“We know roughly how matter behaves at nuclear densities, like in the nucleus of a uranium atom,” said Alex Filippenko, Distinguished Professor of Astronomy at the University of California, Berkeley. “A neutron star is like one giant nucleus, but when you have one-and-a-half solar masses of this stuff, which is about 500,000 Earth masses of nuclei all clinging together, it’s not at all clear how they will behave.”

Roger W. Romani, professor of astrophysics at Stanford University, noted that neutron stars are so dense — 1 cubic inch weighs over 10 billion tons — that their cores are the densest matter in the universe short of black holes, which because they are hidden behind their event horizon are impossible to study. The neutron star, a pulsar designated PSR J0952-0607, is thus the densest object within sight of Earth.

The measurement of the neutron star’s mass was possible thanks to the extreme sensitivity of the 10-meter Keck I telescope on Maunakea in Hawai’i, which was just able to record a spectrum of visible light from the hotly glowing companion star, now reduced to the size of a large gaseous planet. The stars are about 3,000 light years from Earth in the direction of the constellation Sextans.

Discovered in 2017, PSR J0952-0607 is referred to as a “black widow” pulsar — an analogy to the tendency of female black widow spiders to consume the much smaller male after mating. Filippenko and Romani have been studying black widow systems for more than a decade, hoping to establish the upper limit on how large neutron stars/pulsars can grow.

“By combining this measurement with those of several other black widows, we show that neutron stars must reach at least this mass, 2.35 plus or minus 0.17 solar masses,” said Romani, who is a professor of physics in Stanford’s School of Humanities and Sciences and member of the Kavli Institute for Particle Astrophysics and Cosmology. “In turn, this provides some of the strongest constraints on the property of matter at several times the density seen in atomic nuclei. Indeed, many otherwise popular models of dense-matter physics are excluded by this result.”

If 2.35 solar masses is close to the upper limit of neutron stars, the researchers say, then the interior is likely to be a soup of neutrons as well as up and down quarks — the constituents of normal protons and neutrons — but not exotic matter, such as “strange” quarks or kaons, which are particles that contain a strange quark.

“A high maximum mass for neutron stars suggests that it is a mixture of nuclei and their dissolved up and down quarks all the way to the core,” Romani said. “This excludes many proposed states of matter, especially those with exotic interior composition.”

Romani, Filippenko and Stanford graduate student Dinesh Kandel are co-authors of a paper describing the team’s results that has been accepted for publication by The Astrophysical Journal Letters.

How large can they grow?

Astronomers generally agree that when a star with a core larger than about 1.4 solar masses collapses at the end of its life, it forms a dense, compact object with an interior under such high pressure that all atoms are smashed together to form a sea of neutrons and their subnuclear constituents, quarks. These neutron stars are born spinning, and though too dim to be seen in visible light, reveal themselves as pulsars, emitting beams of light — radio waves, X-rays or even gamma rays — that flash Earth as they spin, much like the rotating beam of a lighthouse.

“Ordinary” pulsars spin and flash about once per second, on average, a speed that can easily be explained given the normal rotation of a star before it collapses. But some pulsars repeat hundreds or up to 1,000 times per second, which is hard to explain unless matter has fallen onto the neutron star and spun it up. But for some millisecond pulsars, no companion is visible.

One possible explanation for isolated millisecond pulsars is that each did once have a companion, but it stripped it down to nothing.

“The evolutionary pathway is absolutely fascinating. Double exclamation point,” Filippenko said. “As the companion star evolves and starts becoming a red giant, material spills over to the neutron star, and that spins up the neutron star. By spinning up, it now becomes incredibly energized, and a wind of particles starts coming out from the neutron star. That wind then hits the donor star and starts stripping material off, and over time, the donor star’s mass decreases to that of a planet, and if even more time passes, it disappears altogether. So, that’s how lone millisecond pulsars could be formed. They weren’t all alone to begin with — they had to be in a binary pair — but they gradually evaporated away their companions, and now they’re solitary.”

The pulsar PSR J0952-0607 and its faint companion star support this origin story for millisecond pulsars.

“These planet-like objects are the dregs of normal stars which have contributed mass and angular momentum, spinning up their pulsar mates to millisecond periods and increasing their mass in the process,” Romani said.

“In a case of cosmic ingratitude, the black widow pulsar, which has devoured a large part of its mate, now heats and evaporates the companion down to planetary masses and perhaps complete annihilation,” said Filippenko.

Spider pulsars include redbacks and tidarrens

Finding black widow pulsars in which the companion is small, but not too small to detect, is one of few ways to weigh neutron stars. In the case of this binary system, the companion star — now only 20 times the mass of Jupiter — is distorted by the mass of the neutron star and tidally locked, similar to the way our moon is locked in orbit so that we see only one side. The neutron star-facing side is heated to temperatures of about 6,200 Kelvin, or 10,700 degrees Fahrenheit, a bit hotter than our sun, and just bright enough to see with a large telescope.

Filippenko and Romani turned the Keck I telescope on PSR J0952-0607 on six occasions over the last four years, each time observing with the Low Resolution Imaging Spectrometer in 15-minute chunks to catch the faint companion at specific points in its 6.4-hour orbit of the pulsar. By comparing the spectra to that of similar sun-like stars, they were able to measure the orbital velocity of the companion star and calculate the mass of the neutron star.

Filippenko and Romani have examined about a dozen black widow systems so far, though only six had companion stars bright enough to let them calculate a mass. All involved neutron stars less massive than the pulsar PSR J0952-060. They’re hoping to study more black widow pulsars, as well as their cousins: redbacks, named for the Australian equivalent of black widow pulsars, which have companions closer to one-tenth the mass of the sun; and what Romani dubbed tidarrens — where the companion is around one-hundredth of a solar mass — after a relative of the black widow spider. The male of this species, Tidarren sisyphoides, is about 1% of the female’s size.

“We can keep looking for black widows and similar neutron stars that skate even closer to the black hole brink. But if we don’t find any, it tightens the argument that 2.3 solar masses is the true limit, beyond which they become black holes,” Filippenko said.

“This is right at the limit of what the Keck telescope can do, so barring fantastic observing conditions, tightening the measurement of PSR J0952-0607 likely awaits the 30-meter telescope era,” added Romani.

Other co-authors of the ApJ Letters paper are UC Berkeley researchers Thomas Brink and WeiKang Zheng. The work was supported by the National Aeronautics and Space Administration (80NSSC17K0024, 80NSSC17K0502), the Christopher R. Redlich Fund, the TABASGO Foundation, and UC Berkeley’s Miller Institute for Basic Research in Science.

The scientists found a way to build high-temperature superconducting magnets that are made of material that conducts electricity with little or no resistance at temperatures warmer than before. Such powerful magnets would more easily fit within the tight space inside spherical tokamaks, which are shaped more like a cored apple than the doughnut-like shape of conventional tokamaks, and are being explored as a possible design for future fusion power plants.

Since the magnets could be positioned apart from other machinery in the spherical tokamak’s central cavity to corral the hot plasma that fuels fusion reactions, researchers could repair them without having to take anything else apart. “To do this, you need a magnet with a stronger magnetic field and a smaller size than current magnets,” said Yuhu Zhai, a principal engineer at PPPL and lead author of a paper reporting the results in IEEE Transactions on Applied Superconductivity. “The only way you do that is with superconducting wires, and that’s what we’ve done.”

Fusion, the power that drives the sun and stars, combines light elements in the form of plasma — the hot, charged state of matter composed of free electrons and atomic nuclei — that generates massive amounts of energy. Scientists are seeking to replicate fusion on Earth for a virtually inexhaustible supply of safe and clean power to generate electricity.

High-temperature superconducting magnets have several advantages over copper magnets. They can be turned on for longer periods than copper magnets can because they don’t heat up as quickly, making them better suited for use in future fusion power plants that will have to run for months at a time. Superconducting wires are also powerful, able to transmit the same amount of electrical current as a copper wire many times wider while producing a stronger magnetic field.

The magnets could also help scientists continue to shrink the size of tokamaks, improving performance and reducing construction cost. “Tokamaks are sensitive to the conditions in their central regions, including the size of the central magnet, or solenoid, the shielding, and the vacuum vessel,” said Jon Menard, PPPL’s deputy director for research. “A lot depends on the center. So if you can shrink things in the middle, you can shrink the whole machine and reduce cost while, in theory, improving performance.”

These new magnets take advantage of a technique refined by Zhai and researchers at Advanced Conductor Technologies, the University of Colorado, Boulder, and the National High Magnetic Field Laboratory, in Tallahassee, Florida. The technique means that the wires do not need conventional epoxy and glass fiber insulation to ensure the flow of electricity. While simplifying construction, the technique also lowers costs. “The costs to wind the coils are much lower because we don’t have to go through the expensive and error-prone epoxy vacuum-impregnation process,” Zhai said. “Instead, you’re directly winding the conductor into the coil form.”

Moreover, “high-temperature superconducting magnets can help spherical tokamak design because the higher current density and smaller windings provide more space for support structure that helps the device withstand the high magnetic fields, enhancing operating conditions,” said Thomas Brown, a PPPL engineer who contributed to the research. “Also, the smaller, more powerful magnets give the machine designer more options to design a spherical tokamak with geometry that could enhance overall tokamak performance. We’re not quite there yet but we’re closer, and maybe close enough.”

This research was supported by the U.S. Department of Energy (Small Business Innovation Research and Laboratory Directed Research and Development).

Story Source:

Materials provided by DOE/Princeton Plasma Physics Laboratory. Original written by Raphael Rosen. Note: Content may be edited for style and length.

About 565 million years ago, however, the magnetic field’s strength decreased to 10 percent of its strength today. Then, mysteriously, the field bounced back, regaining its strength just before the Cambrian explosion of multicellular life on Earth.

What caused the magnetic field to bounce back?

According to new research from scientists at the University of Rochester, this rejuvenation happened within a few tens of millions of years — rapid on geological timescales — and coincided with the formation of Earth’s solid inner core, suggesting that the core is likely a direct cause.

“The inner core is tremendously important,” says John Tarduno, the William R. Kenan, Jr., Professor of Geophysics in the Department of Earth and Environmental Sciences and dean of research for Arts, Sciences & Engineering at Rochester. “Right before the inner core started to grow, the magnetic field was at the point of collapse, but as soon as the inner core started to grow, the field was regenerated.”

In the paper, published in Nature Communications, the researchers determined several key dates in the inner core’s history, including a more precise estimate for its age. The research provides clues about the history and future evolution of Earth and how it became a habitable planet, as well as the evolution of other planets in the solar system.

Unlocking information in ancient rocks

Earth is composed of layers: the crust, where life is situated; the mantle, Earth’s thickest layer; the molten outer core; and the solid inner core, which is, in turn, composed of an outermost inner core and an innermost inner core.

Earth’s magnetic field is generated in its outer core, where swirling liquid iron causes electric currents, driving a phenomenon called the geodynamo that produces the magnetic field.

Because of the magnetic field’s relationship to Earth’s core, scientists have been trying for decades to determine how Earth’s magnetic field and core have changed throughout our planet’s history. They cannot directly measure the magnetic field due to the location and extreme temperatures of materials in the core. Fortunately, minerals that rise to Earth’s surface contain tiny magnetic particles that lock in the direction and intensity of the magnetic field at the time the minerals cool from their molten state.

To better constrain the age and growth of the inner core, Tarduno and his team used a CO₂ laser and the lab’s superconducting quantum interference device (SQUID) magnetometer to analyze feldspar crystals from the rock anorthosite. These crystals have minute magnetic needles within them that are “perfect magnetic recorders,” Tarduno says.

By studying the magnetism locked in ancient crystals — a field known as paleomagnetism — the researchers determined two new important dates in the history of the inner core:

• 550 million years ago: the time at which the magnetic field began to renew rapidly after a near collapse 15 million years before that. The researchers attribute the rapid renewal of the magnetic field to the formation of a solid inner core that recharged the molten outer core and restored the magnetic field’s strength.
• 450 million years ago: the time at which the growing inner core’s structure changed, marking the boundary between the innermost and outermost inner core. These changes in the inner core coincide with changes around the same time in the structure of the overlying mantel, due to plate tectonics on the surface.

“Because we constrained the inner core’s age more accurately, we could explore the fact that the present-day inner core is actually composed of two parts,” Tarduno says. “Plate tectonic movements on Earth’s surface indirectly affected the inner core, and the history of these movements is imprinted deep within Earth in the inner core’s structure.”

Avoiding a Mars-like fate

Better understanding the dynamics and growth of the inner core and the magnetic field has important implications, not only in uncovering Earth’s past and predicting its future, but in unraveling the ways in which other planets might form magnetic shields and sustain the conditions necessary to harbor life.

Researchers believe that Mars, for example, once had a magnetic field, but the field dissipated, leaving the planet vulnerable to solar wind and the surface ocean-less. While it is unclear whether the absence of a magnetic field would have caused Earth to meet the same fate, “Earth certainly would’ve lost much more water if Earth’s magnetic field had not been regenerated,” Tarduno says. “The planet would be much drier and very different than the planet today.”

In terms of planetary evolution, then, the research emphasizes the importance of a magnetic shield and a mechanism to sustain it, he says.

“This research really highlights the need to have something like a growing inner core that sustains a magnetic field over the entire lifetime — many billions of years — of a planet.”