“Enzymes make life possible by catalyzing chemical transformations that otherwise would just take too long for an organism,” said Greg Weiss, UCI professor of chemistry and a co-corresponding author of the new study. “One of the transformations we’re really interested in is essential for all life on the planet — it’s the process by which DNA is copied and repaired.”

The molecule the UCI-led team studied is an enzyme called Taq, a name derived from the microorganism it was first discovered in, Thermos aquaticus. The molecule the UCI-led team studied is an enzyme called Taq, a name derived from the microorganism it was first discovered in, Thermos aquaticus. Taq replicates DNA. Polymerase chain reaction, the technique with thousands of uses from forensics to PCR tests to detect COVID-19, takes advantage of Taq.

The UCI-led team found that Taq, as it helps make new copies of DNA, behaves completely unlike what scientists previously thought. Instead of behaving like a well-oiled, efficient machine continuously churning out DNA copies, the enzyme, Weiss explained, acts like an indiscriminate shopper who cruises the aisles of a store, throwing everything they see into the shopping cart.

“Instead of carefully selecting each piece to add to the DNA chain, the enzyme grabs dozens of misfits for each piece added successfully,” said Weiss. “Like a shopper checking items off a shopping list, the enzyme tests each part against the DNA sequence it’s trying to replicate.”

It’s well-known that Taq rejects any wrong items that land into its proverbial shopping cart — that rejection is the key, after all, to successfully duplicating a DNA sequence. What’s surprising in the new work is just how frequently Taq rejects correct bases. “It’s the equivalent of a shopper grabbing half a dozen identical cans of tomatoes, putting them in the cart, and testing all of them when only one can is needed.”

The take-home message: Taq is much, much less efficient at doing its job than it could be.

The find is a leap toward revolutionizing medical care, explained Philip Collins, a professor in the UCI Department of Physics & Astronomy who’s a co-corresponding author of the new research. That’s because if scientists understand how Taq functions, then they can better understand just how accurate a person’s sequenced genome truly is.

“Every single person has a slightly different genome,” said Collins, “with different mutations in different places. Some of those are responsible for diseases, and others are responsible for absolutely nothing. To really get at whether these differences are important or healthcare — for properly prescribing medicines — you need to know the differences accurately.”

“Scientists don’t know how these enzymes achieve their accuracy,” said Collins, whose lab created the nano-scale devices for studying Taq’s behavior. “How do you guarantee to a patient that you’ve accurately sequenced their DNA when it’s different from the accepted human genome? Does the patient really have a rare mutation,” asks Collins, “or did the enzyme simply make a mistake?”

“This work could be used to develop improved versions of Taq that waste less time while making copies of DNA,” Weiss said.

The impacts of the work don’t stop at medicine; every scientific field that relies on accurate DNA sequencing stands to benefit from a better understanding of how Taq works. In interpreting evolutionary histories using ancient DNA, for example, scientists rely on assumptions about how DNA changes over time, and those assumptions rely on accurate genetic sequencing.

“We’ve entered the century of genomic data,” said Collins. “At the beginning of the century we unraveled the human genome for the very first time, and we’re starting to understand organisms and species and human history with this newfound information from genomics, but that genomic information is only useful if it’s accurate.”

Co-authors on this study include Mackenzie Turvey, Ph.D., a former UCI graduate student in physics & astronomy, and Kristin Gabriel, Ph.D., a former UCI graduate student in molecular biology & biochemistry. This research was funded by the National Human Genome Research Institute of the NIH.

Video: https://youtu.be/96VfOrbGkcw

The two are only between 200 AU and 2,000 AU apart (one AU is the distance from the Earth to the sun), at least 10 times closer than the only other known supermassive binary black hole system.

The close separation is significant because such systems are expected to merge eventually. That event will release a massive amount of energy in the form of gravitational waves, causing ripples in space in every direction (and oscillations in matter) as the waves pass through.

Finding systems like this is also important for understanding the processes by which galaxies formed and how they ended up with massive black holes at their centers.

Methods

Researchers serendipitously discovered the system when they noticed a repeating sinusoidal pattern in its radio brightness emission variations over time, based on data taken after 2008. A subsequent search of historical data revealed that the system also was varying in the same manner in the late 1970s to early 1980s. That type of variation is exactly what researchers would expect if the jetted emission from one black hole is affected by the Doppler effect due to its orbital motion as it swings around the other black hole.

Matthew Lister in the College of Science at Purdue University and his team imaged the system from 2002 to 2012, but the team’s radio telescope lacks the resolution to resolve the individual black holes at such a large distance. His imaging data supports the binary black hole scenario and also provides the orientation angle of the jetted outflow, which is a critical component in the paper’s model for the Doppler-induced variations.

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Tuberculosis (TB) infects more than 10 million people a year, killing more than 1 million a year. The Bacillus Calmette-Guérin (BCG) vaccine is widely used to inoculate children against TB, but its effectiveness wanes over time. Researchers around the world are hunting for more effective vaccines and treatments.

“We are very excited that we can reverse BCG’s waning effectiveness by combining it with a host-directed therapy into one dose, which makes it very practical for the clinic,” says Joanne Turner, PhD, Texas Biomed’s Executive Vice President, Research, and senior paper author.

Decades of research

Turner emphasized the finding builds on more than 20 years of research. Throughout her career, she has been investigating the role of a molecule, interleukin-10 (IL-10) on TB. IL-10 typically helps dampen excessive inflammation during infection, but through numerous studies, Turner and her colleagues have found IL-10 does more harm than good in TB, definitively showing it drives TB infection.

In previous studies, Turner and her colleagues blocked IL-10 at different times during infection — late into infection, the first three weeks during infection — and have knocked out IL-10 completely. All signs pointed to improved TB control and longer survival. In the current study, the team looked at what happens if they temporarily block IL-10 before infection occurs, at the same time as giving the BCG vaccine.

Host-directed therapy + vaccine

The researchers combined the BCG vaccine with an antibody that blocks IL-10 activity for about one week. Since the antibody targets the host, not the pathogen, that makes it a “host-directed therapy.” They gave the mixture to mice in one shot, waited six weeks to ensure the IL-10 blocker was no longer present and the BCG protection had been generated, and then exposed the mice to TB. Those mice controlled TB infection for nearly a year, which is significant for mice with normal lifespans of about two years. In contrast, mice given only the BCG vaccine lost control of TB infection within two months and had significant inflammation and damage in the lungs. Notably, the mice given the vaccine/IL-10 blocker had higher levels of various long-term memory immune cells, which are critical for ongoing TB control.

“This shows that the early development of an immune response is key for controlling TB infection in the long run, and that IL-10 inhibits the development of that long-term immunity,” Turner says. “But by briefly blocking IL-10 at the same time as giving the vaccine, it allows the vaccine and immune system to do their jobs, creating those long-lasting memory immune cells.”

Collaborators at Texas Biomed plan to investigate if the combination is safe and effective in nonhuman primates. If those results are also promising then the combination could move into human clinical trials. The team is optimistic, especially since the BCG vaccine is already in widespread use and the IL-10 blocker is being tested against other diseases.

Models matter

Experimentally, IL-10 had been somewhat dismissed as playing a significant role in TB, even though it was detected in humans with TB. But that conclusion was made in the most common strain of research mouse, which is fairly resistant to TB and don’t produce much IL-10.

Turner began investigating a different mouse strain, called CBA/J, which is much more susceptible to TB. Working with these mice, she and colleagues began to piece together IL-10’s role and what happens when it is blocked. To definitively show a molecule’s function, researchers often knock out the gene that codes for the molecule. Turner bred the CBA/J IL-10 knock-out mice, which required several years of effort, and since 2011 the mice have been instrumental in proving IL-10 drives TB. These mice can even form human-like granulomas, which are cellular aggregates that form around the bacteria to prevent it from spreading.

“We only saw that because we were working in a different mouse strain than the standard laboratory mouse strain,” Turner says. “It is gratifying that those knock-out mice we developed are available for other researchers to work with. Diversity in animal models is important to understand the commonalities across species that help us better understand human diseases.”

But cleaning solar panels currently is estimated to use about 10 billion gallons of water per year — enough to supply drinking water for up to 2 million people. Attempts at waterless cleaning are labor intensive and tend to cause irreversible scratching of the surfaces, which also reduces efficiency. Now, a team of researchers at MIT has devised a way of automatically cleaning solar panels, or the mirrors of solar thermal plants, in a waterless, no-contact system that could significantly reduce the dust problem, they say.

The new system uses electrostatic repulsion to cause dust particles to detach and virtually leap off the panel’s surface, without the need for water or brushes. To activate the system, a simple electrode passes just above the solar panel’s surface, imparting an electrical charge to the dust particles, which are then repelled by a charge applied to the panel itself. The system can be operated automatically using a simple electric motor and guide rails along the side of the panel. The research is described in the journal Science Advances, in a paper by MIT graduate student Sreedath Panat and professor of mechanical engineering Kripa Varanasi.

Despite concerted efforts worldwide to develop ever more efficient solar panels, Varanasi says, “a mundane problem like dust can actually put a serious dent in the whole thing.” Lab tests conducted by Panat and Varanasi showed that the dropoff of energy output from the panels happens steeply at the very beginning of the process of dust accumulation and can easily reach 30 percent reduction after just one month without cleaning. Even a 1 percent reduction in power, for a 150-megawatt solar installation, they calculated, could result in a $200,000 loss in annual revenue. The researchers say that globally, a 3 to 4 percent reduction in power output from solar plants would amount to a loss of between $3.3 billion and $5.5 billion.

“There is so much work going on in solar materials,” Varanasi says. “They’re pushing the boundaries, trying to gain a few percent here and there in improving the efficiency, and here you have something that can obliterate all of that right away.”

Many of the largest solar power installations in the world, including ones in China, India, the U.A.E., and the U.S., are located in desert regions. The water used for cleaning these solar panels using pressurized water jets has to be trucked in from a distance, and it has to be very pure to avoid leaving behind deposits on the surfaces. Dry scrubbing is sometimes used but is less effective at cleaning the surfaces and can cause permanent scratching that also reduces light transmission.

Water cleaning makes up about 10 percent of the operating costs of solar installations. The new system could potentially reduce these costs while improving the overall power output by allowing for more frequent automated cleanings, the researchers say.

“The water footprint of the solar industry is mind boggling,” Varanasi says, and it will be increasing as these installations continue to expand worldwide. “So, the industry has to be very careful and thoughtful about how to make this a sustainable solution.”

Other groups have tried to develop electrostatic based solutions, but these have relied on a layer called an electrodynamic screen, using interdigitated electrodes. These screens can have defects that allow moisture in and cause them to fail, Varanasi says. While they might be useful on a place like Mars, he says, where moisture is not an issue, even in desert environments on Earth this can be a serious problem.

The new system they developed only requires an electrode, which can be a simple metal bar, to pass over the panel, producing an electric field that imparts a charge to the dust particles as it goes. An opposite charge applied to a transparent conductive layer just a few nanometers thick deposited on the glass covering of the the solar panel then repels the particles, and by calculating the right voltage to apply, the researchers were able to find a voltage range sufficient to overcome the pull of gravity and adhesion forces, and cause the dust to lift away.

Using specially prepared laboratory samples of dust with a range of particle sizes, experiments proved that the process works effectively on a laboratory-scale test installation, Panat says. The tests showed that humidity in the air provided a thin coating of water on the particles, which turned out to be crucial to making the effect work. “We performed experiments at varying humidities from 5 percent to 95 percent,” Panat says. “As long as the ambient humidity is greater than 30 percent, you can remove almost all of the particles from the surface, but as humidity decreases, it becomes harder.”

Varanasi says that “the good news is that when you get to 30 percent humidity, most deserts actually fall in this regime.” And even those that are typically drier than that tend to have higher humidity in the early morning hours, leading to dew formation, so the cleaning could be timed accordingly.

“Moreover, unlike some of the prior work on electrodynamic screens, which actually do not work at high or even moderate humidity, our system can work at humidity even as high as 95 percent, indefinitely,” Panat says.

In practice, at scale, each solar panel could be fitted with railings on each side, with an electrode spanning across the panel. A small electric motor, perhaps using a tiny portion of the output from the panel itself, would drive a belt system to move the electrode from one end of the panel to the other, causing all the dust to fall away. The whole process could be automated or controlled remotely. Alternatively, thin strips of conductive transparent material could be permanently arranged above the panel, eliminating the need for moving parts.

By eliminating the dependency on trucked-in water, by eliminating the buildup of dust that can contain corrosive compounds, and by lowering the overall operational costs, such systems have the potential to significantly improve the overall efficiency and reliability of solar installations, Varanasi says.

The research was supported by Italian energy firm Eni. S.p.A. through the MIT Energy Initiative.

Developing new strategies and vaccine technologies is critical for controlling the pandemic and preparing for future outbreaks as the coronavirus continues to evolve and mutate, say the researchers.

The new method, described in the journal PLOS ONE, is an entirely unique approach to vaccination. Red blood-cell membranes are embedded with SARS-CoV-2 spike proteins, which then form virus-like particles.

“We take red blood cells and remove everything from the inside. We then attach spike proteins to their outside to mimic a corona virus,” explains graduate student Isabella Passos-Gastaldo, a lead author on the paper.

The particles, shown to activate the immune system and produce antibodies in mice, are completely harmless.

“Current vaccine delivery methods often cause drastic immune system reactions and have short-lived responses,” says Maikel Rheinstadter, a senior supervisor on the paper and a professor in the Department of Physics & Astronomy at McMaster.

“Some of the vaccines that have been developed have shown side effects. This delivery platform opens new possibilities for vaccines and therapeutics,” he says.

The researchers found cells can be loaded with a large dose of viral proteins, yet likely produce few side effects, making the new method more tolerable and effective than other vaccine options.

“We have developed a method where we can trigger an immune response without the use of genetic material and yet we are able to synthesize these particles in a very short amount of time,” says Sebastian Himbert, lead author on the study and a recent graduate student in the Department of Physics & Astronomy at McMaster.

The technology can be quickly adapted to develop vaccines for variants or new viruses that may emerge in future.

“This is the kind of creative, interdisciplinary research that McMaster is known for. It was exhilarating working with physicists, structural biologists and immunologists to design a radically different vaccine platform,” says Dawn Bowdish, Professor of Medicine at McMaster and Canada Research Chair in Aging & Immunity and co-author of the paper.

The researchers first reported this technique in 2020, when they modified red blood cells to deliver drugs throughout the body, which could then target infections or treat catastrophic diseases such as cancer or Alzheimer’s.

“This platform makes our own blood cells smart in many different ways,” explains Rheinstadter. “In this case it’s a vaccine. We are using our own cells much like nano robots inside of our bodies and whenever they see a disease, they can fight it.”

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In a study published this month in Science Advances, a team led by the University of Tsukuba found that D-serine serves as a chemical signal that allows tissue migration in marine sea squirts when they lose their tails on transforming from tadpoles into their mature form. Their findings offer a broader understanding of the chemical signals that occur during the organism’s transformation.

In mammals, D-serine binds to an ion channel found in neurons called the N-methyl-D-aspartate type glutamate receptor (NMDAR) to regulate the transmission of messages in the brain. D-serine also plays a functional role in mammalian skin tissue. However, its role in non-mammals is less understood, something the researchers at the University of Tsukuba aimed to address.

“D-serine has been detected in organisms such as insects, nematodes, and molluscs,” says lead author of the study, Professor Yasunori Sasakura. “Its global presence in metazoans is reflective of the conserved presence of a protein that converts L-serine to its D-form, called a serine racemase.”

The team’s previous results implicated a serine racemase in the tail regression of tadpoles of the marine sea squirt Ciona. In this study, they sought to clarify the role of D-serine in this process and found that D-serine is responsible for forming a pocket in the Ciona epidermis that allows the tail to regress into the main body. This pocket was formed by D-serine binding to NMDAR in the epidermis, causing the release of fluid-filled vesicles.

“The results were striking,” explains Professor Sasakura. “We found that the epidermal vesicle release in Ciona is quite similar to a process occurring in mammalian skin, involving a flux of cations mediated through NMDARs.”

To evaluate what happened when D-serine was absent during Ciona tail regression, the research team created a mutation that omitted the protein responsible for making D-serine from L-serine. Ciona organisms lacking this protein failed to complete tail regression, whereas regular Ciona organisms were able to successfully complete the process.

“Our findings provide insight into how epidermal homeostasis is maintained in animals, contributing toward further evolutionary perspectives of D-amino acid function among metazoans,” says Sasakura.

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Authors of the study believe their breakthrough modelling on ‘active matter’ could mark a turning point in the design of robots. With further development of the concept, it may be possible to determine the shape, movement and behaviour of a soft solid not by its natural elasticity but by human-controlled activity on its surface.

The surface of an ordinary soft material always shrinks into a sphere. Think of the way water beads into droplets: the beading occurs because the surface of liquids and other soft material naturally contracts into the smallest surface area possible — i.e. a sphere. But active matter can be designed to work against this tendency. An example of this in action would be a rubber ball that’s wrapped in a layer of nano-robots, where the robots are programmed to work in unison to distort the ball into a new, pre-determined shape (say, a star).

It is hoped that active matter will lead to a new generation of machines whose function will come from the bottom up. So, instead of being governed by a central controller (the way today’s robotic arms are controlled in factories), these new machines would be made from many individual active units that cooperate to determine the machine’s movement and function. This is akin to the workings of our own biological tissues, such as the fibres in heart muscle.

Using this idea, scientists could design soft machines with arms made of flexible materials powered by robots embedded in their surface. They could also tailor the size and shape of drug delivery capsules, by coating the surface of nanoparticles in a responsive, active material.. This in turn could have a dramatic effect on how a drug interacts with cells in the body.

Work on active matter challenges the assumption that the energetic cost of the surface of a liquid or soft solid must always be positive because a certain amount of energy is always necessary to create a surface.

Dr Jack Binysh, study first author, said: “Active matter makes us look at the familiar rules of nature — rules like the fact that surface tension has to be positive — in a new light. Seeing what happens if we break these rules, and how we can harness the results, is an exciting place to be doing research.”

Corresponding author Dr Anton Souslov added: “This study is an important proof of concept and has many useful implications. For instance, future technology could produce soft robots that are far squishier and better at picking up and manipulating delicate materials.”

For the study, the researchers developed theory and simulations that described a 3D soft solid whose surface experiences active stresses. They found that these active stresses expand the surface of the material, pulling the solid underneath along with it, and causing a global shape change. The researchers found that the precise shape adopted by the solid could then be tailored by altering the elastic properties of the material.

In the next phase of this work — which has already begun — the researchers will apply this general principle to design specific robots, such as soft arms or self-swimming materials. They will also look at collective behaviour — for example, what happens when you have many active solids, all packed together.

This work was a collaboration between the Universities of Bath and Birmingham. It was funded by the Engineering and Physical Sciences Research Council (EPSRC) through New Investigator Award no. EP/T000961/1.

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“I’m aware of no other documented case in which the invasion rate of a large aquatic system has been suppressed through a management intervention,”said Ricciardi. “This layer of protection is clearly beneficial. There are many highly invasive freshwater species in Europe, for example, that could be delivered in ballast water and would almost certainly proliferate in the Great Lakes. The regulation is likely preventing their introduction.”

The world’s most invaded freshwater ecosystem

No other freshwater ecosystem on Earth has been invaded as much, or as frequently, as the Great Lakes basin. Nearly 190 non-native species of fish, invertebrates, plants, plankton, and microbes have established populations in the basin over past two centuries. Nearly 65% of invaders recorded since the opening of the St Lawrence seaway in 1959 were transported to the Great Lakes in the ballast tanks of ships from overseas ports. These include notorious stowaways such as the zebra mussel, the quagga mussel, the spiny water flea, and the round goby — each among the most ecologically and economically damaging invaders in the basin.

Between 1959 and the mid-2000s, one new invader was discovered established in the Great Lakes every 6-7 months.

This onslaught prompted a move by Canada and the USA to harmonize regulations and mandate flushing saltwater through ballast tanks of all ships while they were still in open ocean, before entering the St Lawrence seaway bound for the Great Lakes. Saltwater flushing has been shown in experiments to cause a massive reduction in the abundance and variety of freshwater organisms carried in ballast tanks.

Empirical evidence of an abrupt reduction in invasion risk

The true test of such a regulation is its effect on the observed rate of species invasion. Since 2008, invasions reported in the Great Lakes basin have declined by 85% and are now at their lowest rate in two centuries. Other factors could have contributed to the abrupt decline in the invasion rate, but empirical evidence points to ballast water regulation as the overwhelming primary cause.

Although the Great Lakes remain vulnerable to invasions from poorly regulated sources, such as trade in living organisms (e.g. aquarium pets, live bait, ornamental garden plants, food markets), this study highlights the potential benefit of an internationally coordinated, evidence-based control strategy.

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