biology (68)

LNPs...

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Cancer cells are one of the main targets for expanded mRNA-LNP use. Credit: Iliescu Catalin / Alamy

Topics: Biology, Biotechnology, Cancer, COVID-19, Nanotechnology

Note: This is an advertisement on Nature Portfolio discussing that there may be a silver lining in the pandemic we've all experienced.

Lipid nanoparticles (LNPs) transport small molecules into the body. The most well-known LNP cargo is mRNA, the key constituent of some of the early vaccines against COVID-19. But that is just one application: LNPs can carry many different types of payload and have applications beyond vaccines.

Barbara Mui has been working on LNPs (and their predecessors, liposomes) since she was a Ph.D. student in Pieter Cullis’s group in the 1990s. “In those days, LNPs encapsulated anti-cancer drugs,” says Mui, who is currently a senior scientist at Acuitas. This company developed the LNPs used in the Pfizer-BioNTech mRNA vaccine against SARS-CoV-2. She says it soon became clear that LNPs worked even better as carriers of polynucleotides. “The first one that worked really well was encapsulating small RNAs,” Mui recalls.

But it was mRNA where LNPs proved most effective, primarily because LNPs are comprised of positively charged lipid nanoparticles that encapsulate negatively charged mRNA. Once in the body, LNPs enter cells via endocytosis into endosomes and are released into the cytoplasm. “Without the specially designed chemistry, the LNP and mRNA would be degraded in the endosome,” says Kathryn Whitehead, professor in the departments of chemical engineering and biomedical engineering at Carnegie Mellon University.

LNPs are an ideal delivery system for mRNA. “COVID accelerated the acceptance of LNPs, and people are more interested in them,” says Mui. LNP-mRNA vaccines for other infectious diseases, such as HIV or malaria, or for non-communicable diseases, such as cancer, could be next. And the potential doesn’t end with mRNA; there is even more scope to adapt LNPs to carry different types of cargo. But to realize these potential benefits, researchers first need to overcome challenges and decrease toxicity, increase their ability to escape from the endosomes, increase their thermostability, and work out how to effectively target LNPs to organs across the body.

Another potential application for LNPs is immunotherapy. Genetically modifying lymphocytes such as T cells or NK cells with chimeric antibody receptors (CARs) has proven useful in blood cancers. Often this process involves extracting lymphocytes from the blood of the person receiving the treatment, editing the cells in culture to express CARs, and then reintroducing them into the blood. However, LNPs could make it possible to express the desired CAR in vivo by shuttling CAR mRNA to the target lymphocytes. Mui has been involved in vivo studies showing this process works in mouse T cells (Rurik, J.G. et al. Science 375, 91-96, 2022). And Vita Golubovskaya, VP of research and development at ProMab Biotechnologies, presented preliminary data (available here) at the CAR-TCR Summit in September 2022 regarding LNPs that direct CAR-mRNA to NK cells, which can then kill target cells. “The RNA-LNP is a very exciting and novel technology that can be used for delivering CAR and bi-specific antibodies against cancer,” she says.

Beyond COVID vaccines: what’s next for lipid nanoparticles? Nature Portfolio

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Like Mushrooms for Plastics...

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Credit: VTT Technical Research Centre of Finland

Topics: Biology, Biotechnology, Chemistry, Materials Science, Mechanical Engineering

A research group from VTT Technical Research Center of Finland has unlocked the secret behind the extraordinary mechanical properties and ultra-light weight of certain fungi. The complex architectural design of mushrooms could be mimicked and used to create new materials to replace plastics. The research results were published on February 22, 2023, in Science Advances.

VTT's research shows for the first time the complex structural, chemical, and mechanical features adapted throughout the course of evolution by Hoof mushroom (Fomes fomentarius). These features interplay synergistically to create a completely new class of high-performance materials.

Research findings can be used as a source of inspiration to grow from the bottom up the next generation of mechanically robust and lightweight, sustainable materials for various applications under laboratory conditions. These include impact-resistant implants, sports equipment, body armor, and exoskeletons for aircraft, electronics, or windshield surface coatings.

Mushrooms could help replace plastics in new high-performance ultra-light materials, VTT Technical Research Centre of Finland, Phys.org.

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Wonderful...

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Image Source: MedPage Today

Topics: Biology, Biotechnology, Civilization, COVID-19, DNA, Epidemiology

Currently authorized bivalent COVID-19 boosters demonstrated similar protection against symptomatic illness from the XBB/XBB.1.5 Omicron subvariants as from BA.5-related subvariants, according to a CDC study.

From December 2022 to January 2023, the bivalent boosters' vaccine effectiveness (VE) against symptomatic infection was a similar 48% versus XBB/XBB.1.5-related strains and 52% versus BA.5-related sublineages, reported Ruth Link-Gelles, Ph.D., of the CDC's National Center for Immunization and Respiratory Diseases, and colleagues in Morbidity and Mortality Weekly Report (MMWR).

Meanwhile, Pfizer's updated booster demonstrated superior neutralizing antibody activity compared with the company's original product against all the latest Omicron subvariants, including XBB.1, according to Kena Swanson, Ph.D., of Pfizer Vaccine Research and Development in Pearl River, New York and colleagues, writing in the New England Journal of Medicine. Their findings contradict earlier research from other labs that found no significant difference in neutralizing activity with the bivalent over the monovalent vaccine.

According to the latest estimates from the CDC, XBB.1.5 is responsible for 49.1% of new COVID-19 cases in the U.S., while XBB is responsible for another 3.3%.

CDC: Bivalent COVID Vaccines Stop Illness From XBB.1.5

— And Pfizer lab data show better neutralization against the latest variants with the bivalent shot, Ingrid Hein, Staff Writer, MedPage Today

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Life Detector...

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An Orbitrap cell. Credit: Ricardo Arevalo

Topics: Astrobiology, Astronautics, Biology, Laser, NASA, Planetary Science, Space Exploration

As space missions delve deeper into the outer solar system, the need for more compact, resource-conserving, and accurate analytical tools have become increasingly critical—especially as the hunt for extraterrestrial life and habitable planets or moons continues.

A University of Maryland–led team developed a new instrument specifically tailored to the needs of NASA space missions. Their mini laser-sourced analyzer is significantly smaller and more resource efficient than its predecessors—all without compromising the quality of its ability to analyze planetary material samples and potential biological activity onsite. The team's paper on this new device was published in the journal Nature Astronomy on January 16, 2023.

Weighing only about 17 pounds, the instrument is a physically scaled-down combination of two important tools for detecting signs of life and identifying compositions of materials: a pulsed ultraviolet laser that removes small amounts of material from a planetary sample and an Orbitrap analyzer that delivers high-resolution data about the chemistry of the examined materials.

"The Orbitrap was originally built for commercial use," explained Ricardo Arevalo, lead author of the paper and an associate professor of geology at UMD. "You can find them in the labs of pharmaceutical, medical and proteomic industries. The one in my own lab is just under 400 pounds, so they're quite large, and it took us eight years to make a prototype that could be used efficiently in space—significantly smaller and less resource-intensive but still capable of cutting-edge science."

The team's new gadget shrinks down the original Orbitrap while pairing it with laser desorption mass spectrometry (LDMS)—techniques that have yet to be applied in an extraterrestrial planetary environment. The new device boasts the same benefits as its larger predecessors but is streamlined for space exploration and onsite planetary material analysis, according to Arevalo.

Small laser device can help detect signs of life on other planets, University of Maryland, Phys.org.

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Permafrost Zombies...

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(Credit: Tatiana Gasich/Shutterstock)

Topics: Biology, Biosecurity, Climate Change

Thirteen viruses from tens of thousands of years ago have been recovered and reactivated, according to a preprint paper published in BioRxiv. These threats had been idling in the Siberian tundra for approximately 30,000 to 50,000 years before being brought back.

Thanks to climate change, the thawing of the frozen terrain could revive an assortment of ancient pathogens, creating a potential threat that these viral “zombies” could pose.

“Zombie” Viruses

Permafrost — the frigid terrain that stays frozen throughout the year — comprises over 10 percent of our planet’s surface and substantial swaths of the Arctic, a circumpolar area containing Alaska, Scandinavia, and Siberia. But the Arctic’s temperatures are warming almost four times faster than the average worldwide, and the permafrost there is fading fast, freeing all sorts of frozen organisms, including microbes and viruses from thousands of years ago.

An abundance of research has delved into the diversity of microbes that the thawing of the permafrost has freed, but far fewer researchers have described the viruses. In fact, though these threats can sometimes resume their activity following their thaw, scientists have studied this process of viral recovery and reactivation only two other times, in 2014 and in 2015.

'Zombie' Viruses, Up to 50,000 Years Old, Are Awakening, Sam Walters, Discovery Magazine

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The Apogee of Evil...

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Credit: Erik English.

Topics: Biology, Biosecurity, Civilization, COVID-19, Democracy, Existentialism

Weaponizing a pathogen sounds like something out of an archetype Bond villain, minus the wrapped-up plot twists by the time the credits roll, and the obligatory fawning of a stereotypical bikinied woman over the intrepid MI-6 spy. Real life doesn't conclude so cleanly. Before every student became accustomed to active shooter drills, my generation ducked under wooden desks to shield themselves from nuclear fallout. Life has always been precarious, as we have always had a segment of society that would "go there."

On that high note, I will see you on the 29th of November. Happy Thanksgiving!

Pandemics can begin in many ways. A wild animal could infect a hunter, or a farm animal might spread a pathogen to a market worker. Researchers in a lab or in the field could be exposed to viruses and unwittingly pass them to others. Natural spillovers and accidents have been responsible for every historical plague, each of which spread from a single individual to afflict much of humanity. But the devastation from past outbreaks pales in comparison to the catastrophic harm that could be inflicted by malicious individuals intent on causing new pandemics.

Thousands of people can now assemble infectious viruses from a genome sequence and commercially available synthetic DNA, and numerous projects aim to find and publicly identify new viruses that could cause pandemics by characterizing their growth, transmission, and immune evasion capabilities in the laboratory. Once these projects succeed, the world will face a significant new threat: If a single terrorist with the necessary skills were to release a new virus equivalent to SARS-CoV-2, which has claimed 20 million lives worldwide, that person would have killed more people than if they were to detonate a nuclear warhead in a dense city. If they were to release numerous such viruses across multiple travel hubs, the resulting pandemics could not plausibly be contained and would spread much faster than even the most rapidly produced biomedical countermeasures. And if one of those viruses spread as easily as the omicron variant—which rapidly infected millions of people within weeks of being identified—but had the lethality of smallpox, which killed about 30 percent of those infected, the subsequent loss of essential workers could trigger the collapse of food, water, and power distribution networks—and with them, societies.

To avoid this future, societies need to rethink how they can delay pandemic proliferation, detect all exponentially growing biological threats, and defend humanity by preventing infections. A comprehensive set of directions detailing how we can build a world free from catastrophic biological threats is required. That roadmap now exists.

How a deliberate pandemic could crush societies and what to do about it, Kevin Esvelt, Bulletin of the Atomic Scientists

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Syncing Fireflies...


Some fireflies have a mystifying gift for flashing their abdomens in sync. New observations are overturning long-accepted explanations for how the synchronization occurs, at least for some species.

Topics: Biology, Biomimetics, Biotechnology, Computer Modeling, Mathematics

In Japanese folk traditions, they symbolize departing souls or silent, ardent love. Some Indigenous cultures in the Peruvian Andes view them as the eyes of ghosts. And across various Western cultures, fireflies, glow-worms, and other bioluminescent beetles have been linked to a dazzling and at times contradictory array of metaphoric associations: “childhood, crop, doom, elves, fear, habitat change, idyll, love, luck, mortality, prostitution, solstice, stars and fleetingness of words and cognition,” as one 2016 review noted.

Physicists revere fireflies for reasons that might seem every bit as mystical: Of the roughly 2,200 species scattered around the world, a handful has the documented ability to flash in synchrony. In Malaysia and Thailand, firefly-studded mangrove trees can blink on the beat as if strung up with Christmas lights; every summer in Appalachia, waves of eerie concordance ripple across fields and forests. The fireflies’ light shows lure mates and crowds of human sightseers, but they have also helped spark some of the most fundamental attempts to explain synchronization, the alchemy by which elaborate coordination emerges from even very simple individual parts.

Orit Peleg remembers when she first encountered the mystery of synchronous fireflies as an undergraduate studying physics and computer science. The fireflies were presented as an example of how simple systems achieve synchrony in Nonlinear Dynamics and Chaos, a textbook by the mathematician Steven Strogatz that her class was using. Peleg had never even seen a firefly, as they are uncommon in Israel, where she grew up.

“It’s just so beautiful that it somehow stuck in my head for many, many years,” she said. But by the time Peleg began her own lab, applying computational approaches to biology at the University of Colorado and at the Santa Fe Institute, she had learned that although fireflies had inspired a lot of math, quantitative data describing what the insects were actually doing was scant.

How Do Fireflies Flash in Sync? Studies Suggest a New Answer. Joshua Sokol, Quanta Magazine

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Cellulose Shoes...

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Credit: Tom Mannion

Topics: Additive Manufacturing, Biology, Biotechnology, Environment, Genetics, Nanotechnology

For Hermes, the Greek god of speed, these bacterial sneakers would have been just the ticket. Modern Synthesis co-founders Jen Keane, CEO, and Ben Reeve, CTO, are now setting out to make them available to mere mortals, raising a $4.1 million investment to scale up production. Keane, a graduate from Central Saint Martins School of Art and Design in London, and synthetic biologist Reeve, then at Imperial College London, set up Modern Synthesis in 2020 to pursue ‘microbial weaving’.

Their goal is to produce a new class of material, a hybrid/composite that will replace animal- and petrochemical-made sneakers with a biodegradable, yet durable, alternative. The shoe's upper is made by bacteria that naturally produce nanocellulose—Komagataeibacter rhaeticus—and can be further genetically engineered to also self-dye by producing melanin for color.

The process begins with a two-dimensional yarn scaffold shaped by robotics, which the scientists submerge in a fermentation medium containing the cellulose-producing bacteria. The K. rhaeticus ‘weave’ the sneaker upper by depositing the biomaterial on the scaffold. Once the sheets emerge from their microbial baths, they are shaped on shoe lasts following traditional footwear techniques. “It’s more than the sum of its parts,” Reeves says of the biocomposite. “Initially the scaffold helps the bacteria grow, then the microbial yarn reinforces the material: it holds the scaffold together.” Once the shoe is made, it is sterilized and the bacteria are washed out.

Cellulose shoes made by bacteria, Lisa Melton, Nature Biotechnology

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Nucleocapsid Rhapsody...

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Fig. 1. SARS-CoV-2 N is expressed on the surface of live cells early during infection.
(A) Maximum intensity projections of laser confocal microscopy z-stack images of infected Vero cells with wt SARS-CoV-2 (top) or SARS-CoV-2_eGFP, stained live at 24 hpi (MOI = 1). Scale bars, 20 μm. Images are representative of at least three independent experiments with similar results. DAPI, 4′,6-diamidino-2-phenylindole. (B) Flow cytometry analyses of Vero cells inoculated with wt (top) or eGFP-expressing (bottom) SARS-CoV-2 (MOI = 1), stained live at 24 hpi against SARS-CoV-2 S and N proteins. Representative dot plots of flow cytometry analyses showing double staining of surface S, N, and eGFP proteins, indicating the percentage of the gated cell population for each quadrant of the double staining. Data are representative of at least three independent experiments, each performed with triplicate samples. (C and D) Time course of surface S, N, and eGFP protein expression in live infected Vero cells with wt (C) and eGFP reporter (D) SARS-CoV-2 at 8 and 12 hpi (MOI = 1). Representative histogram overlays of surface S, N, and intracellular eGFP proteins of flow cytometry analyses. Data are representative of one experiment of at least two independent experiments performed in triplicate.

Topics: Biology, COVID-19, Research

Abstract

SARS-CoV-2 nucleocapsid protein (N) induces strong antibody (Ab) and T cell responses. Although considered to be localized in the cytosol, we readily detect N on the surface of live cells. N released by SARS-CoV-2–infected cells or N-expressing transfected cells binds to neighboring cells by electrostatic high-affinity binding to heparan sulfate and heparin, but not other sulfated glycosaminoglycans. N binds with high affinity to 11 human chemokines, including CXCL12β, whose chemotaxis of leukocytes is inhibited by N from SARS-CoV-2, SARS-CoV-1, and MERS-CoV. Anti-N Abs bound to the surface of N-expressing cells activate Fc receptor-expressing cells. Our findings indicate that cell surface N manipulates innate immunity by sequestering chemokines and can be targeted by Fc-expressing innate immune cells. This, in combination with its conserved antigenicity among human CoVs, advances its candidacy for vaccines that induce cross-reactive B and T cell immunity to SARS-CoV-2 variants and other human CoVs, including novel zoonotic strains.

Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity, Alberto Domingo Lopez-Munoz, Ivan Kosik, Jaroslav Holly, Jonathan W. Yewdell, Science Advances

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Soap-Like Properties...

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1 Soap, shampoo, and worm-like micelles Soaps and shampoos are made from amphiphilic molecules with water-loving (red) and water-hating (blue) parts that arrange themselves to form long tubes known as “worm-like micelles”. Entanglements between the tubes give these materials their pleasant, sticky feel. b The micelles can, however, disentangle themselves, just as entangled long-chain polymer molecules can slide apart too. In polymers, this process can be modeled by imagining the molecule sliding, like a snake, out of an imaginary tube formed by the surrounding spatial constraints. c Worm-like micelles can also morph their architecture by performing reconnections (left), breakages (down), and fusions (right). These operations occur randomly along the backbone, are in thermal equilibrium, and are reversible. (Courtesy: Davide Michieletto)

Topics: Biology, Biotechnology, DNA, Molecules

DNA molecules are not fixed objects – they are constantly getting broken up and glued back together to adopt new shapes. Davide Michieletto explains how this process can be harnessed to create a new generation of “topologically active” materials.

Call me naive, but until a few years ago I had never realized you can actually buy DNA. As a physicist, I’d been familiar with DNA as the “molecule of life” – something that carries genetic information and allows complex organisms, such as you and me, to be created. But I was surprised to find that biotech firms purify DNA from viruses and will ship concentrated solutions in the post. In fact, you can just go online and order DNA, which is exactly what I did. Only there was another surprise in store.

When the DNA solution arrived at my lab in Edinburgh, it came in a tube with about half a milligram of DNA per centimeter cube of water. Keen to experiment with it, I tried to pipette some of the solutions out, but they didn’t run freely into my plastic tube. Instead, it was all gloopy and resisted the suction of my pipette. I rushed over to a colleague in my lab, eagerly announcing my amazing “discovery”. They just looked at me like I was an idiot. Of course, solutions of DNA are gloopy.

I should have known better. It’s easy to idealize DNA as some kind of magic material, but it’s essentially just a long-chain double-helical polymer consisting of four different types of monomers – the nucleotides A, T, C, and G, which stack together into base pairs. And like all polymers at high concentrations, the DNA chains can get entangled. In fact, they get so tied up that a single human cell can have up to 2 m of DNA crammed into an object just 10 μm in size. Scaled up, it’s like storing 20 km of hair-thin wire in a box no bigger than your mobile phone.

Make or break: building soft materials with DNA, Davide Michieletto is a Royal Society university research fellow in the School of Physics and Astronomy, University of Edinburgh, UK

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Zombie Apocalypse...

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A nurse prepares a COVID-19 vaccine in Guwahati, India, on 10 April. A new subvariant named BA.2.75 that was first detected in India has surfaced in many other countries. ANUPAM NATH/AP IMAGES

Topics: Biology, COVID-19, DNA, Economics, Environment, Evolution, Existentialism

Ed Rybicki, a virologist at the University of Cape Town in South Africa, concentrated his article in Scientific American on the viruses dominating the news cycle in the early 2000s: Ebola, Marburg, and HIV. Not comforting, but he said, "HIV, which is thought to have first emerged in humans in the 1930s, is another kind of virus, known as a retrovirus." Not mentioned, but the H1N1 comes from the 1918 Flu Pandemic, and a friend in Texas lost his girlfriend to it also in the early 2000s. Retro means "a process that reverses the normal flow of information in cells" and relates to a bridge between the first forms of life on this planet. In an e-brief, I wrote my first year at JSNN, an article in Nature: Education posits that viruses are not ‘alive’ because they don’t have metabolic processes, one of the four criteria for life (“organized, metabolism, genetic code, and reproduction”). The last part is important: they cannot reproduce asexually (unicellular division), or sexually with genders, spermatozoa, and an incubation period before birthing a copy. In other words, they aren't "alive," but they aren't dead either. They manage to replicate themselves by invading a host. Usually us.

It DOES mention three possible mechanisms as to origins: The Progressive Hypothesis, i.e., “bits and pieces” of a genome gained the ability to move in and out of cells (retroviruses like HIV given as an example); The Regressive Hypothesis, meaning the viruses evolved from some common ancestor to their current state (reductio ad absurdum), lastly The Virus-First Hypothesis, which puts any anthropocentric notions away and their hypothesis that viruses existed before mortals as “self-replicating units.”

I am as ready for this pandemic to be over as anyone else. However, this read from AAAS didn't give me hope that a societal "all-clear" will be uttered, or that we'll overcome our shared arrogance and stupidity:

In the short history of the COVID-19 pandemic, 2021 was the year of the new variants. Alpha, Beta, Gamma, and Delta each had a couple of months in the Sun.

But this was the year of Omicron, which swept the globe late in 2021 and has continued to dominate, with subvariants—given more prosaic names such as BA.1, BA.2, and BA.2.12.1—appearing in rapid succession. Two closely related subvariants named BA.4 and BA.5 are now driving infections around the world, but new candidates, including one named BA.2.75, are knocking on the door.

Omicron’s lasting dominance has evolutionary biologists wondering what comes next. Some think it’s a sign that SARS-CoV-2’s initial frenzy of evolution is over and it, like other coronaviruses that have been with humanity much longer, is settling into a pattern of gradual evolution. “I think a good guess is that either BA.2 or BA.5 will spawn additional descendants with more mutations and that one or more of those subvariants will spread and will be the next thing,” says Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center.

But others believe a new variant different enough from Omicron and all other variants to deserve the next Greek letter designation, Pi, may already be developing, perhaps in a chronically infected patient. And even if Omicron is not replaced, its dominance is no cause for complacency, says Maria Van Kerkhove, technical lead for COVID-19 at the World Health Organization. “It’s bad enough as it is,” she says. “If we can’t get people to act [without] a new Greek name, that’s a problem.”

As Omicron rages on, scientists have no idea what comes next, Kai Kupferschmidt, American Association for the Advancement of Science

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Microbots and Chemo..

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Credit: Gao Wang

Topics: Biology, Cancer, Chemotherapy, Robotics

Chemotherapy disrupts cancer cells’ ability to reproduce by frustrating cell division and damaging the cells’ DNA. In response to the pharmaceutical onslaught, cancer cells acquire mutations that reduce the therapy’s effectiveness. Compounding the challenge of fighting cancer: Under chemical and other stresses, mutation rates increase.

A team led by Princeton University’s Robert Austin and Chongqing University’s Liyu Liu has developed a novel approach to study—and potentially thwart—cancer cells’ adaptation to chemotherapy. Their cancer cell analogs are wheeled, cylindrical robots about 65 mm in diameter and 60 mm in height (see photo above). Fifty of the robots roll independently of each other over a square table, whose 4.2 × 4.2 m2 surface is covered by 2.7 million LEDs (see photo below). Light from the LEDs serves as the robots’ food. Once a robot has “eaten” the light beneath it, the corresponding LEDs are dimmed until they recover a fixed time later.

The bottom surface of each robot is equipped with four semiconductor-based sensors that can detect the intensities and spatial gradients of the three colors of light emitted by the light table: red, green, and blue (RGB). Each robot’s six-byte genome analog determines how sensitive it is to the three colors. The sensitivity, in turn, determines how readily the robot moves in response to the colors’ intensities and spatial gradients.

Evolving robots could optimize chemotherapy, Charles Day, Physics Today

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Breadbaskets and War...

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Image Source: Hub Pages

Topics: Biology, Civics, Civil Rights, Climate Change, Democracy, Existentialism, Politics

The cornucopia’s history lies in Greek mythology. There are a lot of different stories it might have originated from, but the most common one tells the story of the lightning god, Zeus. As an infant, Zeus was in great danger from his father, Cronus. Zeus was taken to the island of Crete and cared for and nursed by a goat named Amalthea. One day, he accidentally broke off one of her horns, and in order to repay her, he used his powers to ensure that the horn would be a symbol of eternal nourishment, which is where we get the idea that the cornucopia represents abundance.

The History Behind the “Horn of Plenty”, Winnie Lam, Daily Nexus

*****

Russia’s war highlights the fragility of the global food supply — sustained investment is needed to feed the world in a changing climate.

Six boxes of wheat seed sit in our cold store. This is the first time in a decade that my team has not been able to send to Ukraine the improved germplasm we’ve developed as part of the Global Wheat Program at the International Maize and Wheat Improvement Center in Texcoco, Mexico. International postal and courier services are suspended. The seed had boosted productivity year on year in the country, which is now being devastated by war.

Our work builds on the legacy of Norman Borlaug, who catalyzed the Green Revolution and staved off famine in South Asia in the 1970s. Thanks to him, I see how a grain of wheat can affect the world.

Among the horrifying humanitarian consequences of Russia’s invasion of Ukraine are deeply troubling short-, medium- and long-term disruptions to the global food supply. Ukraine and Russia contribute nearly one-third of all wheat exports (as well as almost one-third of the world’s barley and one-fifth of its corn, providing an estimated 11% of the world’s calories). Lebanon, for instance, gets 80% of its wheat from Ukraine alone.

Broken bread — avert global wheat crisis caused by invasion of Ukraine, Alison Bentley, Nature

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Fantastic Plastic...

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Plastic fantastic: this perovskite-based device can be reconfigured and could play an important role in artificial intelligence systems. (Courtesy: Purdue University/Rebecca McElhoe)

Topics: Artificial Intelligence, Biology, Computer Science, Materials Science

Researchers in the US have developed a perovskite-based device that could be used to create a high-plasticity architecture for artificial intelligence. The team, led by Shriram Ramanathan at Purdue University, has shown that the material’s electronic properties can be easily reconfigured, allowing the devices to function like artificial neurons and other components. Their results could lead to more flexible artificial-intelligence hardware that could learn much like the brain.

Artificial intelligence systems can be trained to perform a task such as voice recognition using real-world data. Today this is usually done in software, which can adapt when additional training data are provided. However, machine learning systems that are based on hardware are much more efficient and researchers have already created electronic circuits that behave like artificial neurons and synapses.

However, unlike the circuits in our brains, these electronics are not able to reconfigure themselves when presented with new training information. What is needed is a system with high plasticity, which can alter its architecture to respond efficiently to new information.

Device can transform into four components for artificial intelligence systems, Sam Jarman, Physics World

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RNA and Covid-19...

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NIST researcher Megan Cleveland uses a PCR machine to amplify DNA sequences by copying them numerous times through a series of chemical reactions.
Credit: M. Cleveland/NIST

Topics: Biology, Biotechnology, COVID-19, Diversity in Science, NIST, Research, Women in Science

Scientists track and monitor the circulation of SARS-CoV-2, the virus that causes COVID-19, using methods based on a laboratory technique called polymerase chain reaction (PCR). Also used as the “gold standard” test to diagnose COVID-19 in individuals, PCR amplifies pieces of DNA by copying them numerous times through a series of chemical reactions. The number of cycles it takes to amplify DNA sequences of interest so that they are detectable by the PCR machine, known as the cycle threshold (Ct), is what researchers and medical professionals look at to detect the virus.

However, not all labs get the same Ct values (sometimes also called “Cq” values). In efforts to make the results more comparable between labs, the National Institute of Standards and Technology (NIST) contributed to a multiorganizational study that looked at anchoring these Ct values to a reference sample with known amounts of the virus.

Researchers published their findings in the journal PLOS One.

SARS-CoV-2 is an RNA virus: Its genetic material is single-stranded instead of double-stranded like DNA and contains some different molecular building blocks, namely uracil in place of thymine. But the PCR test only works with DNA, and labs first must convert the RNA to DNA to screen for COVID-19. For the test, RNA is isolated from a patient’s sample and combined with other ingredients, including short DNA sequences are known as primers, to transform the RNA into DNA.

RNA Reference Materials Are Useful for Standardizing COVID-19 Tests, Study Shows, NIST

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Tardigrades and Qubits...

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(Credit: Giovanni Cancemi/Shutterstock) 

Topics: Biology, Condensed Matter Physics, Modern Physics, Quantum Mechanics

Note: After presenting my research proposal and acceptance by my committee, I've been taking a well-needed break from blogging. I'll post on and off until the New Year, which isn't too far off. Happy holidays!

In recent years, evidence has emerged that quantum physics seems to play a role in some of life’s fundamental processes. But just how it might do this is something of a mystery.

On the one hand, quantum phenomena are generally so delicate that they can only be observed when all other influences are damped – in other words in carefully controlled systems at temperatures close to absolute zero. By contrast, the conditions for life are generally complex, warm, and damp. Understanding this seemingly contradictory state of affairs is an important goal.

So physicists and biologists are keen to explore the boundaries of these very different regimes—life and quantum mechanics—to better understand where they might overlap.

Now Rainer Dumke at the Nanyang Technological University in Singapore and colleagues have created an exotic quantum state called entanglement using a superconducting qubit and a microscopic animal called a tardigrade. Along the way, the team has created the most extreme form of suspended animation ever recorded. “The tardigrade itself is shown to be entangled with the remaining subsystems,” they say.

To perform their entanglement experiment, Dumke and co cooled their tardigrade to below 10 millikelvins, almost to absolute zero, while reducing the pressure to a millionth of that in the atmosphere. In these conditions, no chemical reaction can occur so the tardigrade’s metabolism must have entirely halted stopped and the processes of life halted.

“This is to date the most extreme exposure to low temperatures and pressures that a tardigrade has been recorded to survive, clearly demonstrating that the state of cryptobiosis ultimately involves a suspension of all metabolic processes given that all chemical reactions would be prohibited with all its constituent molecules cooled to their ground states,” say the researchers.

In this condition, the tardigrade can be thought of as a purely dielectric element. Indeed, the researchers simulated their experiment by treating the tardigrade as a dielectric cube.

The experimental setup consisted of two superconducting capacitors, which when cooled can exist in a superposition of states called a qubit. They placed the tardigrade between the capacitor plates of one qubit so that it became an integral part of the capacitor. The team was then able to measure the effect of the tardigrade on the qubit’s properties.

How a Tardigrade "Micro Animal" Became Quantum Entangled with Superconducting Qubit, The Physics AriXiv Blog, Discovery Magazine

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ACE2 Gum and Covid...

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Visual Abstract

Topics: Biology, Biotechnology, COVID-19, Research

To advance a novel concept of debulking virus in the oral cavity, the primary site of viral replication, virus-trapping proteins CTB-ACE2 were expressed in chloroplasts and clinical-grade plant material was developed to meet FDA requirements. Chewing gum (2 g) containing plant cells expressed CTB-ACE2 up to 17.2 mg ACE2/g dry weight (11.7% leaf protein), have physical characteristics and taste/flavor like conventional gums, and no protein was lost during gum compression. CTB-ACE2 gum efficiently (>95%) inhibited entry of lentivirus spike or VSV-spike pseudovirus into Vero/CHO cells when quantified by luciferase or red fluorescence. Incubation of CTB-ACE2 microparticles reduced SARS-CoV-2 virus count in COVID-19 swab/saliva samples by >95% when evaluated by microbubbles (femtomolar concentration) or qPCR, demonstrating both virus trapping and blocking of cellular entry. COVID-19 saliva samples showed low or undetectable ACE2 activity when compared with healthy individuals (2,582 versus 50,126 ΔRFU; 27 versus 225 enzyme units), confirming greater susceptibility of infected patients for viral entry. CTB-ACE2 activity was completely inhibited by pre-incubation with SARS-CoV-2 receptor-binding domain, offering an explanation for reduced saliva ACE2 activity among COVID-19 patients. Chewing gum with virus-trapping proteins offers a generally affordable strategy to protect patients from most oral virus re-infections through debulking or minimizing transmission to others.

Debulking SARS-CoV-2 in saliva using angiotensin-converting enzyme 2 in chewing gum to decrease oral virus transmission and infection, Molecular Therapy: Cell.com

Henry Daniell, Smruti K. Nair, Nardana Esmaeili, Geetanjali Wakade, Naila Shahid, Prem Kumar Ganesan, Md Reyazul Islam, Ariel Shepley-McTaggart, Sheng Feng, Ebony N. Gary, Ali R. Ali, Manunya Nuth, Selene Nunez Cruz, Jevon Graham-Wooten, Stephen J. Streatfield, Ruben Montoya-Lopez, Paul Kaznica, Margaret Mawson, Brian J. Green, Robert Ricciardi, Michael Milone, Ronald N. Harty, Ping Wang, David B. Weiner, Kenneth B. Margulies, Ronald G. Collman

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Your Brain on Covid...

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Credit: Getty Images

Topics: Biology, COVID-19, DNA, Research

Note: I have friends who thankfully survived infection now affected by this phenomenon. The article thus grabbed my attention.

SARS-CoV-2 appears to travel widely across the cerebral cortex

“Brain fog” is not a formal medical descriptor. But it aptly describes an inability to think clearly that can turn up in multiple sclerosis, cancer, or chronic fatigue. Recently, the condition has grabbed headlines because of reports that it afflicts those recovering from COVID-19.

COVID’s brain-related symptoms go beyond mere mental fuzziness. They range across a spectrum that encompasses headaches, anxiety, depression, hallucinations, and vivid dreams, not to mention well-known smell and taste anomalies. Strokes and seizures are also on the list. One study showed that more than 80 percent of COVID patients encountered neurological complications.

The mystery of how the virus enters and then inhabits the brain’s protected no-fly zone is under intensive investigation. At the 50th annual meeting of the Society for Neuroscience, or SFN (held in virtual form this month after a pandemic hiatus in 2020), a set of yet-to-be-published research reports chronicle aspects of the COVID-causing SARS-COV-2 virus’s full trek in the brain—from cell penetration to dispersion among brain regions, to disruption of neural functioning.

How COVID Might Sow Chaos in the Brain, Gary Stix, Scientific American

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Foxes, Minks, Racoon Dogs...

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Topics: Biology, COVID-19, Education, Research

During the first year of the COVID-19 pandemic, the “[lab] leak” theory gained little traction. Sure, U.S. President Donald Trump suggested SARS-CoV-2 originated in a laboratory in Wuhan, China—and called it “the China virus”—but he never presented evidence, and few in the scientific community took him seriously. In fact, early in the pandemic, a group of prominent researchers dismissed lab-origin notions as “conspiracy theories” in a letter in The Lancet. A report from a World Health Organization (WHO) “joint mission,” which sent a scientific team to China in January to explore possible origins with Chinese colleagues, described a lab accident as “extremely unlikely.”

But this spring, views began to shift. Suddenly it seemed that the lab-leak hypothesis had been too blithely dismissed. In a widely read piece, fueled by a “smoking gun” quote from a Nobel laureate, a veteran science journalist accused scientists and the mainstream media of ignoring “substantial evidence” for the scenario. The head of WHO openly pushed back against the joint mission’s conclusion, and U.S. President Joe Biden ordered the intelligence community to reassess the lab-leak possibility. Eighteen scientists, including leaders in virology and evolutionary biology, signed a letter published in Science in May that called for a more balanced appraisal of the “laboratory incident” hypothesis.

Yet behind the clamor, little had changed. No breakthrough studies have been published. The highly anticipated U.S. intelligence review, delivered to Biden on 24 August, reached no firm conclusions but leaned toward the theory that the virus has a natural origin.

Fresh evidence that would resolve the question may not emerge anytime soon. China remains the best place to hunt for clues, but its relative openness to collaboration during the joint mission seems to have evaporated. Chinese officials have scoffed at calls from Biden and WHO Director-General Tedros Adhanom Ghebreyesus for an independent audit of key Wuhan labs, which some say should include an investigation of notebooks, computers, and freezers. Chinese vice health minister Zeng Yixin said such demands show “disrespect toward common sense and arrogance toward science.” In response to the increasing pressure, China has also blocked the “phase 2” studies outlined in the joint mission’s March report, which could reveal a natural jump between species.

Despite the impasse, many scientists say the existing evidence—including early epidemiological patterns, SARS-CoV-2’s genomic makeup, and a recent paper about animal markets in Wuhan—makes it far more probable that the virus, like many emerging pathogens, made a natural “zoonotic” jump from animals to humans.

Virologist Robert Garry of Tulane University finds it improbable that a Wuhan lab worker picked up SARS-CoV-2 from a bat and then brought it back to the city, sparking the pandemic. As the WIV study of people living near bat caves shows, the transmission of related bat coronaviruses occurs routinely. “Why would the virus first have infected a few dozen lab researchers?” he asks. The virus may also have moved from bats into other species before jumping to humans, as happened with SARS. But again, why would it have infected a lab worker first? “There are hundreds of millions of people who come in contact with wildlife.”

The earliest official announcement about the pandemic came on 31 December 2019, when Wuhan’s Municipal Health Commission reported a cluster of unexplained pneumonia cases linked to the city’s Huanan seafood market. The WHO report devotes much attention to details about Huanan and other Wuhan markets but also cautions that their role remains “unclear” because several early cases had no link to any market. But after reading the report, Andersen became more convinced that the Huanan market played a critical role.

One specific finding bolsters that case, Wang says. The report describes how scientists took many samples from floors, walls, and other surfaces at Wuhan markets and were able to culture two viruses isolated from Huanan. That shows the market was bursting with a virus, Wang says: “In my career, I have never been able to isolate a coronavirus from an environmental sample.”

The report also contained a major error: It claimed there were “no verified reports of live mammals being sold around 2019” at Huanan and other markets linked to early cases. A surprising study published in June by Zhou Zhao-Min of China West Normal University and colleagues challenged that view. It found nearly 50,000 animals from 38 species, most alive, for sale at 17 shops at Huanan and three other Wuhan markets between May 2017 and November 2019. (The researchers had surveyed the markets as part of a study of a tick-borne disease afflicting animals.)

Live animals can more easily transmit a respiratory virus than meat from a butchered one, and the animals included masked palm civets, the main species that transmitted SARS-CoV to humans, and raccoon dogs, which also naturally harbored that virus and have been infected with SARS-CoV-2 in lab experiments. Minks—a species farmed for fur that has acquired SARS-CoV-2 infections from humans in many countries— were also abundant. “None of the 17 shops posted an origin certificate or quarantine certificate, so all wildlife trade was fundamentally illegal,” Zhou and his colleagues wrote in their paper. (Zhou did not respond to emails from Science.)

Call of the Wild: Why many scientists say it’s unlikely that SARS-CoV-2 originated from a “lab leak,” Jon Cohen, Science Magazine

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Interstellar Cellular Membranes...

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Topics: Astrobiology, Biology, Chemistry, Cosmology

The origin of life is one of the great unanswered questions in science. One piece of this puzzle is that life started on Earth 4.5 billion years ago, just a few hundred million years after the formation of the Solar System, and involved numerous critical molecular components. How did all these components come to be available so quickly?

One potential explanation is that the Earth was seeded from space with the building blocks for life. The idea is that space is filled with clouds of gas and dust that contain all the organic molecules necessary for life.

Indeed, astronomers have observed these buildings blocks in interstellar gas clouds. They can see amino acids, the precursors of proteins, and the machinery of life. They can also see the precursors of ribonucleotides, molecules that can store information in the form of DNA.

But there is another crucial component for life – molecules that can form membranes capable of encapsulating and protecting the molecules of life in compartments called protocells. On Earth, the membranes of all cells are made of molecules called phospholipids. But these have never been observed in space. Until now.

First evidence of cell membrane molecules in space, Physics arXiv blog, Astronomy

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