A New, Inexpensive Catalyst Speeds the Production of Oxygen from Water

The material could replace rare metals and lead to more economical production of carbon-neutral fuels.

By David L. Chandler, MIT News Office

February 24, 2022 -- An electrochemical reaction that splits apart water molecules to produce oxygen is at the heart of multiple approaches aiming to produce alternative fuels for transportation. But this reaction has to be facilitated by a catalyst material, and today’s versions require the use of rare and expensive elements such as iridium, limiting the potential of such fuel production.

Now, researchers at MIT and elsewhere have developed an entirely new type of catalyst material, called a metal hydroxide-organic framework (MHOF), which is made of inexpensive and abundant components. The family of materials allows engineers to precisely tune the catalyst’s structure and composition to the needs of a particular chemical process, and it can then match or exceed the performance of conventional, more expensive catalysts.

The findings are described today in the journal Nature Materials, in a paper by MIT postdoc Shuai Yuan, graduate student Jiayu Peng, Professor Yang Shao-Horn, Professor Yuriy Román-Leshkov, and nine others.

Oxygen evolution reactions are one of the reactions common to the electrochemical production of fuels, chemicals, and materials. These processes include the generation of hydrogen as a byproduct of the oxygen evolution, which can be used directly as a fuel or undergo chemical reactions to produce other transportation fuels; the manufacture of ammonia, for use as a fertilizer or chemical feedstock; and carbon dioxide reduction in order to control emissions.

But without help, “these reactions are sluggish,” Shao-Horn says. “For a reaction with slow kinetics, you have to sacrifice voltage or energy to promote the reaction rate.” Because of the extra energy input required, “the overall efficiency is low. So that’s why people use catalysts,” she says, as these materials naturally promote reactions by lowering energy input.

But until now, these catalysts “are all relying on expensive materials or late transition metals that are very scarce, for example iridium oxide, and there has been a big effort in the community to find alternatives based on Earth-abundant materials that have the same performance in terms of activity and stability,” Román-Leshkov says. The team says they have found materials that provide exactly that combination of characteristics.

Other teams have explored the use of metal hydroxides, such as nickel-iron hydroxides, Román-Leshkov says. But such materials have been difficult to tailor to the requirements of specific applications. Now, though, “the reason our work is quite exciting and quite relevant is that we’ve found a way of tailoring the properties by nanostructuring these metal hydroxides in a unique way.”

The team borrowed from research that has been done on a related class of compounds known as metal-organic frameworks (MOFs), which are a kind of crystalline structure made of metal oxide nodes linked together with organic linker molecules. By replacing the metal oxide in such materials with certain metal hydroxides, the team found, it became possible to create precisely tunable materials that also had the necessary stability to be potentially useful as catalysts.

“You put these chains of these organic linkers next to each other, and they actually direct the formation of metal hydroxide sheets that are interconnected with these organic linkers, which are then stacked, and have a higher stability,” Román-Leshkov says. This has multiple benefits, he says, by allowing a precise control over the nanostructured patterning, allowing precise control of the electronic properties of the metal, and also providing greater stability, enabling them to stand up to long periods of use.

In testing such materials, the researchers found the catalysts’ performance to be “surprising,” Shao-Horn says. “It is comparable to that of the state-of-the-art oxide materials catalyzing for the oxygen evolution reaction.”

Being composed largely of nickel and iron, these materials should be at least 100 times cheaper than existing catalysts, they say, although the team has not yet done a full economic analysis.

This family of materials “really offers a new space to tune the active sites for catalyzing water splitting to produce hydrogen with reduced energy input,” Shao-Horn says, to meet the exact needs of any given chemical process where such catalysts are needed.

The materials can provide “five times greater tunability” than existing nickel-based catalysts, Peng says, simply by substituting different metals in place of nickel in the compound. “This would potentially offer many relevant avenues for future discoveries.” The materials can also be produced in extremely thin sheets, which could then be coated onto another material, further reducing the material costs of such systems.

So far, the materials have been tested in small-scale laboratory test devices, and the team is now addressing the issues of trying to scale up the process to commercially relevant scales, which could still take a few years. But the idea has great potential, Shao-Horn says, to help catalyze the production of clean, emissions-free hydrogen fuel, so that “we can bring down the cost of hydrogen from this process while not being constrained by the availability of precious metals. This is important, because we need  hydrogen production technologies that can scale.”

The research team included others at MIT, Stockholm University in Sweden, SLAC National Accelerator Laboratory, and Institute of Ion Beam Physics and Materials Research in Dresden, Germany. The work was supported by the Toyota Research Institute.

https://news.mit.edu/2022/metal-hydroxide-organic-framework-oxygen-0224

 

Some Gut Microbes Awaken 'Zombie' Viruses

Gut bacteria brew all sorts of chemicals, but we don't know what most of them do. A new study suggests that one such compound, previously linked to cancer, may serve as a bizarre weapon in microbial skirmishes.

From:  Howard Hughes Medical Institute

February 23, 2022 -- Some gut bacteria have a spooky superpower: they can reanimate dormant viruses lurking within other microbes.

This viral awakening unleashes full-blown infections that destroy the virus-carrying cells, Howard Hughes Medical Institute Investigator Emily Balskus's lab first published as a preprint on bioRxiv and later in the journal Nature on February 23, 2022. A cryptic molecule called colibactin can summon the killer viruses from their slumber, they found.

Microbes often generate noxious compounds to attack one another within the cramped quarters of the gut. But among these chemical weapons, colibactin appears unusual, says Balskus, a chemical biologist at Harvard University. "It doesn't directly kill the target organisms, which is what we normally think of bacterial toxins doing within microbial communities." Instead, colibactin tweaks microbial cells just so, activating latent -- and lethal -- viruses tucked away in some bacteria's genomes.

Humans have long sought out the potent compounds that microbes produce. "We know a lot about their chemical properties, we purify them in the lab, and we use them as medicine, including antibiotics," says Breck Duerkop, who studies bacterial viruses at the University of Colorado School of Medicine.

But why bacteria make these compounds and what effects they have on neighboring organisms are open-ended questions, says Duerkop, who was not involved in this research. He calls Balskus's teams new work "one step in the right direction."

Chemical dark matter

Scientists have known for years that colibactin can wreak havoc on human cells. Research by Balskus and many others has shown that the compound damages DNA, which can lead to colorectal cancer. But establishing a connection between this compound and disease proved particularly formidable.

In 2006, a French team reported that mammalian cells that encountered the gut bacteria E. coli suffered fatal damage to their DNA. The researchers linked this damage to a cluster of E. coli genes encoding machinery for building a complex molecule. Dubbed colibactin, the molecule was extraordinarily difficult to study. After many tries, researchers simply couldn't isolate it from the E. coli making it.

Colibactin is one of many ephemeral compounds that scientists suspect microbes make. Like invisible particles of dark matter in space, this "chemical dark matter" requires creative means to study. As part of her exploration of the gut's microbial chemistry, Balskus uses indirect approaches to examine these elusive molecules.

Over the past 10 years, her team has probed colibactin by studying the microbial machinery that manufactures it. She and her colleagues have pieced together colibactin's structure and determined that it damages DNA by forming errant connections within the double helix.

Building off this work, scientists elsewhere uncovered a definitive link to cancer: the molecule's distinctive fingerprints appear in genes known to drive colorectal tumor growth.

A role for viruses

Balskus's most recent colibactin study got its start with another disease: COVID-19. Like many other labs, hers had to rearrange things to reduce physical contact among researchers. As part of the reshuffling, postdoc Justin Silpe and graduate student Joel Wong ended up working near one another for the first time. Their conversations led them and Balskus to wonder how colibactin affected other microbes in a crowded gut.

Early on, they found that exposing colibactin-producing bacteria to non-producers had little effect, suggesting that, on its own, the molecule isn't particularly deadly. Silpe and Wong weren't sure if colibactin, a large, unstable molecule, could even enter bacterial cells to damage their DNA. They then wondered if a third party -- bacteria-infecting viruses -- might be involved. Hardly more than bits of genetic information, these viruses can slip into bacteria's DNA and lie quietly in wait. Then, once triggered, they cause an infection that blows up the cell like a landmine.

When the researchers grew colibactin producers alongside bacteria carrying such latent viruses, they saw the number of viral particles spike, and the growth of many virus-containing bacteria drop. That suggested the molecule sparked a surge in active, cell-killing infections. Colibactin does indeed enter bacteria and damage DNA, the team showed. That damage sounds a cellular wake-up bell that rouses the viruses.

Many microbes appeared equipped to protect themselves against colibactin. Balskus's lab identified a resistance gene encoding a protein that neutralizes the compound in a wide variety of bacteria.

Though colibactin clearly has a dangerous side, it may serve as more than just a lethal weapon, Balskus says. For example, both DNA damage and awakened viruses can also induce genetic changes, rather than death, in neighboring bacteria, potentially benefiting colibactin producers.

Balskus's team's discoveries suggest that cancer may be collateral damage caused by whatever else colibactin-producing bacteria are doing. "We always suspected that bacteria made this toxin to target other bacteria in some way," she says. "It didn't make sense from an evolutionary perspective that they acquired it to target human cells."

Next, Balskus plans to investigate how the compound alters the community of microbes in the gut -- which ones disappear and which thrive after exposure to the compound. "The key to preventing cancer may be understanding the effects colibactin has on the microbe community and how its production is controlled," she says.

          https://www.sciencedaily.com/releases/2022/02/220223111242.htm

 

2022 Russian Invasion of Ukraine

On 24 February 2022, Russia launched a large-scale invasion of Ukraine, its neighbour to the southwest, marking a dramatic escalation of the Russo-Ukrainian War that began in 2014.

The invasion was preceded by a Russian military build-up that started in early 2021, during which Russian president Vladimir Putin criticized NATO's post-1997 enlargement as a threat to his country's security and demanded that Ukraine be legally prohibited from joining the military alliance; he also expressed irredentist views.  On 21 February 2022, Russia officially recognised the Donetsk People's Republic and the Luhansk People's Republic, two self-proclaimed states in the Donbas region of eastern Ukraine, and sent troops to the territories. The following day, the Russian Federation Council unanimously authorised Putin to use military force outside Russia's borders.

Around 05:00 EET (UTC+2) on 24 February, Putin announced a "special military operation" in eastern Ukraine; minutes later, missiles began to hit locations across Ukraine, including the capital, Kyiv.  The Ukrainian Border Service said that its border posts with Russia and Belarus were attacked.  Two hours later, Russian ground forces entered the country.  Ukrainian president Volodymyr Zelenskyy responded by enacting martial law, severing diplomatic ties with Russia, and ordering general mobilisation.  The invasion received widespread international condemnation, including new sanctions imposed on Russia, while anti-war protests in Russia were met with mass arrests.

The invasion has been described as the largest conventional military attack on European soil since World War II.

Post-Soviet context and Orange Revolution

After the dissolution of the Soviet Union in 1991, Ukraine and Russia maintained close ties.  In 1994, Ukraine agreed to abandon its nuclear arsenal; it signed the Budapest Memorandum on Security Assurances on the condition that Russia, the United Kingdom (UK), and the United States (US) would provide assurances against threats or use of force against the territorial integrity or political independence of Ukraine. Five years later, Russia was one of the signatories of the Charter for European Security, which "reaffirmed the inherent right of each and every participating State to be free to choose or change its security arrangements, including treaties of alliance, as they evolve".

In 2004, Viktor Yanukovych, then prime minister, was declared the winner of the presidential elections, which had been largely rigged, according to a Supreme Court of Ukraine ruling.  The results caused a public outcry in support of the opposition candidate, Viktor Yushchenko, who challenged the outcome. During the tumultuous months of the revolution, candidate Yushchenko suddenly became gravely ill, and was soon found by multiple independent physician groups to have been poisoned by TCDD dioxin.  Yushchenko strongly suspected Russian involvement in his poisoning.  All of this eventually resulted in the peaceful Orange Revolution, bringing Yushchenko and Yulia Tymoshenko to power, while casting Yanukovych in opposition.

In 2008, Russian president Vladimir Putin spoke out against Ukraine's potential accession to NATO.  In 2009, Romanian analyst Iulian Chifu and his co-authors opined that with regard to Ukraine, Russia has pursued an updated version of the Brezhnev Doctrine, a Cold War policy of Soviet intervention in the countries of the Soviet sphere of influence during the late 1980s and early 1990s.  In 2009, Yanukovych announced his intent to again run for president in the 2010 presidential election, which he won.

Ukrainian revolution and the Donbas war

The Euromaidan protests began in 2013 over the Ukrainian government's decision to suspend the signing of the European Union–Ukraine Association Agreement, instead choosing closer ties to Russia and the Eurasian Economic Union. Following weeks of protests, Yanukovych and the leaders of the Ukrainian parliamentary opposition signed a settlement agreement on 21 February 2014 that called for an early election. The following day, Yanukovych fled from Kyiv ahead of an impeachment vote that stripped him of his powers as president.  Leaders of the Russian-speaking eastern regions of Ukraine declared continuing loyalty to Yanukovych, causing the 2014 pro-Russian unrest in Ukraine.  The unrest was followed by the annexation of Crimea by Russia in March 2014 and the War in Donbas, which started in April 2014 with the creation of the Russia-backed quasi-states of the Donetsk and Luhansk People's Republics.

On 14 September 2020, Ukrainian president Volodymyr Zelenskyy approved Ukraine's new National Security Strategy, "which provides for the development of the distinctive partnership with NATO with the aim of membership in NATO."  On 24 March 2021, Zelenskyy signed the Decree No. 117/2021, approving the "strategy of de-occupation and reintegration of the temporarily occupied territory of the Autonomous Republic of Crimea and the city of Sevastopol."

In July 2021, Putin published an essay titled On the Historical Unity of Russians and Ukrainians, in which he re-affirmed his view that Russians and Ukrainians were "one people".  American historian Timothy Snyder described Putin's ideas as imperialism.  British journalist Edward Lucas described it as historical revisionism.  Other observers have described the Russian leadership as having a distorted view of modern Ukraine and its history.

Russia has said that a possible Ukrainian accession to NATO and the NATO enlargement in general threaten its national security.  In turn, Ukraine and other European countries neighbouring Russia accused Putin of attempting Russian irredentism and of pursuing aggressive militaristic policies.

https://en.wikipedia.org/wiki/2022_Russian_invasion_of_Ukraine

 

Pets Affect Human Brain Health

Study Shows Long-Term Pet Ownership Linked to Slower Decline in Cognition Over Time

From:  American Academy of Neurology

Minneapolis – February 23, 2022 -- Owning a pet, like a dog or cat, especially for five years or longer, may be linked to slower cognitive decline in older adults, according to a preliminary study released today, February 23, 2022, that will be presented at the American Academy of Neurology's 74th Annual Meeting being held in person in Seattle, April 2 to 7, 2022 and virtually, April 24 to 26, 2022.

“Prior studies have suggested that the human-animal bond may have health benefits like decreasing blood pressure and stress,” said study author Tiffany Braley, MD, MS, of the University of Michigan Medical Center in Ann Arbor and a member of the American Academy of Neurology. “Our results suggest pet ownership may also be protective against cognitive decline.”

The study looked at cognitive data from 1,369 older adults with an average age of 65 who had normal cognitive skills at the start of the study. A total of 53% owned pets, and 32% were long-term pet owners, defined as those who owned pets for five years or more. Of study participants, 88% were white, 7% were Black, 2% were Hispanic and 3% were of another ethnicity or race.

Researchers used data from the Health and Retirement Study, a large study of Medicare beneficiaries. In that study, people were given multiple cognitive tests. Researchers used those cognitive tests to develop a composite cognitive score for each person, ranging from zero to 27. The composite score included common tests of subtraction, numeric counting and word recall. Researchers then used participants’ composite cognitive scores and estimated the associations between years of pet ownership and cognitive function.

Over six years, cognitive scores decreased at a slower rate in pet owners. This difference was strongest among long-term pet owners. Taking into account other factors known to affect cognitive function, the study showed that long-term pet owners, on average, had a cognitive composite score that was 1.2 points higher at six years compared to non-pet owners. The researchers also found that the cognitive benefits associated with longer pet ownership were stronger for Black adults, college-educated adults and men. Braley says more research is needed to further explore the possible reasons for these associations.

“As stress can negatively affect cognitive function, the potential stress-buffering effects of pet ownership could provide a plausible reason for our findings,” said Braley. “A companion animal can also increase physical activity, which could benefit cognitive health. That said, more research is needed to confirm our results and identify underlying mechanisms for this association.”

A limitation of the study was that length of pet ownership was assessed only at one time point, so information regarding ongoing pet ownership was unavailable.

The study was supported by the National Institutes of Health, the National Heart, Lung, and Blood Institute and the National Institute on Aging.

            https://www.aan.com/PressRoom/Home/PressRelease/4957

A High-Fiber Diet May Reduce Risk of Dementia

Researchers from the University of Tsukuba, Japan, find that higher levels of dietary fiber, particularly soluble fiber, are associated with a lower risk of dementia

February 10, 2022 -- Tsukuba, Japan—We're always hearing that we should eat more fiber. It's known to be vitally important for a healthy digestive system and also has cardiovascular benefits like reduced cholesterol. Now, evidence is emerging that fiber is also important for a healthy brain. In a new study published this month in the journal Nutritional Neuroscience, researchers in Japan have shown that a high-fiber diet is associated with a reduced risk of developing dementia.

"Dementia is a devastating disease that usually requires long-term care," says lead author of the study Professor Kazumasa Yamagishi. "We were interested in some recent research which suggested that dietary fiber may play a preventative role. We investigated this using data that were collected from thousands of adults in Japan for a large study that started in the 1980s."

Participants completed surveys that assessed their dietary intake between 1985 and 1999. They were generally healthy and aged between 40 and 64 years. They were then followed up from 1999 until 2020, and it was noted whether they developed dementia that required care.

The researchers split the data, from a total of 3739 adults, into four groups according to the amount of fiber in their diets. They found that the groups who ate higher levels of fiber had a lower risk of developing dementia.

The team also examined whether there were differences for the two main types of fiber: soluble and insoluble fibers. Soluble fibers, found in foods such as oats and legumes, are important for the beneficial bacteria that live in the gut as well as providing other health benefits. Insoluble fibers, found in whole grains, vegetables, and some other foods, are known to be important for bowel health. The researchers found that the link between fiber intake and dementia was more pronounced for soluble fibers.

The team has some ideas as to what might underlie the link between dietary fiber and the risk of dementia.

"The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain," says Professor Yamagishi. "One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia. It's also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels. The work is still at an early stage, and it's important to confirm the association in other populations."

In many countries today, such as the US and Australia, many people consume less fiber than is recommended by nutritionists. By encouraging healthy eating habits with high dietary fiber, it might be possible to reduce the incidence of dementia.

https://www.tsukuba.ac.jp/en/research-news/20220210140000.html

 

How Venus Fly Trap plants Snap Shut

The mechanosensitive ion channel is related to channels found in a variety of other organisms

From:  Scripps Research Institute

February 17, 2022 -- Scientists at Scripps Research have revealed the three-dimensional structure of Flycatcher1, an aptly named protein channel that may enable Venus fly trap plants to snap shut in response to prey. The structure of Flycatcher1, published February 14 in Nature Communications, helps shed light on longstanding questions about the remarkably sensitive touch response of Venus fly traps. The structure also gives the researchers a better understanding of how similar proteins in organisms including plants and bacteria, as well as proteins in the human body with similar functions (called mechanosensitive ion channels), might operate.

"Despite how different Venus fly traps are from humans, studying the structure and function of these mechanosensitive channels gives us a broader framework for understanding the ways that cells and organisms respond to touch and pressure," says co-senior author and Scripps Research professor Andrew Ward, PhD.

"Every new mechanosensitive channel that we study helps us make progress in understanding how these proteins can sense force and translate that to action and ultimately reveal more about human biology and health," adds co-senior author Ardem Patapoutian, PhD, a Scripps Research professor who won the Nobel Prize in Physiology or Medicine for research on the mechanosensitive channels that allow the body to sense touch and temperature.

Mechanosensitive ion channels are like tunnels that span the membranes of cells. When jostled by movement, the channels open, letting charged molecules rush across. In response, cells then alter their behavior -- a neuron might signal its neighbor, for instance. The ability for cells to sense pressure and movement is important for people's senses of touch and hearing, but also for many internal body processes -- from the ability of the bladder to sense that it's full to the ability of lungs to sense how much air is being breathed.

Previously, scientists had homed in on three ion channels in Venus fly traps thought to be related to the ability of the carnivorous plant to snap its leaves shut when its sensitive trigger hairs get touched. One, Flycatcher1, caught researchers' attention because its genetic sequence looked similar to a family of mechanosensitive channels, MscS, found in bacteria.

"The fact that variants of this channel are found throughout evolution tells us that it must have some fundamental, important functions that have been maintained in different types of organisms," says co-first author Sebastian Jojoa-Cruz, a graduate student at Scripps Research.

In the new study, the researchers used cryo-electron microscopy -- a cutting-edge technique that reveals the locations of atoms within a frozen protein sample -- to analyze the precise arrangement of molecules that form the Flycatcher1 protein channel in Venus fly trap plants. They found that Flycatcher1 is, in many ways, similar to bacterial MscS proteins -- seven groups of identical helices surrounding a central channel. But, unlike other MscS channels, Flycatcher1 has an unusual linker region extending outward from each group of helices. Like a switch, each linker can be flipped up or down. When the team determined the structure of Flycatcher1, they found six linkers in the down position, and just one flipped up.

"The architecture of Flycatcher1's channel core was similar to other channels that have been studied for years, but these linker regions were surprising," says Kei Saotome, PhD, a former postdoctoral research associate at Scripps Research and co-first author of the new paper.

To help elucidate the function of these switches, the researchers altered the linker to disrupt the up position. Flycatcher1, they found, no longer functioned as usual in response to pressure; the channel remained open for a longer duration when it would normally close upon removal of pressure.

"The profound effect of this mutation tells us that the conformations of these seven linkers is likely relevant for how the channel works," says co-senior author Swetha Murthy, PhD, of Vollum Institute at Oregon Health and Science University, a former postdoctoral research associate at Scripps Research.

Now that they solved the molecular structure, the research team is planning future studies on the function of Flycatcher1 to understand how different conformations affect its function. More work is also needed to determine whether Flycatcher1 is solely responsible for the snapping shut of Venus fly trap leaves, or whether other suspected channels play complementary roles.

In addition to Jojoa-Cruz, Saotome, Murthy, Patapoutian and Ward, authors of the study, "Structural insights into the Venus flytrap mechanosensitive ion channel Flycatcher1," are Che Chun Alex Tsui and Wen-Hsin Lee of Scripps Research, and Mark Sansom of University of Oxford.

https://www.sciencedaily.com/releases/2022/02/220217141334.htm

  

Diamonds Aren't Forever (And Neither is Your Love)

Quillette published a four-alarm summary about diamonds, marriage and sex on February 17, 2022.  Written by Rob Brooks, it is a thoughtful and well assembled discussion about the selling of diamonds and the genuine passions of modern marriages. 

See  https://quillette.com/2022/02/17/diamonds-arent-forever-and-neither-is-your-love/ 

Key Gastroenterology Discoveries

Scientists Map Entire Human Gut at Single Cell Resolution

From: UNC School of Medicine at Chapel Hill

February 17, 2022 -- UNC School of Medicine scientists led by Scott Magness, PhD, sequenced the genes expressed in individual single cells from human digestive tracts to discover new cell-type characteristics and gain insights into important cell functions such as nutrient absorption and immune defense.

 If you get nervous, you might feel it in your gut. If you eat chili, your gut might revolt, but your friend can eat anything and feel great. You can pop ibuprofen like candy with no ill effects, but your friend’s belly might bleed and she might get no pain relief. Why is this? The quick answer is because we’re all different. The next questions are how different exactly, and what do these differences mean for health and disease? Answering these is much more difficult, but the UNC School of Medicine lab of Scott Magness, PhD, is revealing some interesting scientific answers.

For the first time, the Magness lab used entire human GI tracts from three organ donors to show how cell types differ across all regions of the intestines, to shed light on cellular functions, and to show gene expression differences between these cells and between individuals.

This work, published in Cellular and Molecular Gastroenterology and Hepatology, opens the door to exploring the many facets of gut health in a much more precise manner at greater resolution than ever before.

“Our lab showed it’s possible to learn about each cell type’s function in important processes, such as nutrient absorption, protection from parasites, and the production of mucus and hormones that regulate eating behavior and gut motility,” said Magness, associate professor in the Joint UNC-NC State Department of Biomedical Engineering and senior author of the paper. “We also learned how the gut lining might interact with the environment through receptors and sensors, and how drugs could interact with different cell types.”

The Sensitive Gut

Think of a typical pharmaceutical commercial voiceover when the voice actor pleasantly recites possible side effects, such as diarrhea, vomiting, intestinal bleeding, and other unpleasant collateral damage. Well, the Magness lab is attempting to understand why those side effects happen, down to the level of individual cells, their functions, their locations, and their genes.

For this research, the Magness lab focused on the epithelium: the single-cell thick layer separating the inside of the intestines and colon from everything else. Like other cell populations and the microbiota, the epithelium is incredibly important to human health, and for years scientists have been exploring it. But until now, researchers could only take tiny biopsies the size of grains of rice from a few parts of the digestive tract, usually from the colon or limited regions of the small intestine.

“Such exploration would be like looking at the United States from space but only investigating what’s going on in Massachusetts, Oklahoma, and California,” Magness said. “To really learn about the country, we’d want to see everything.”

Magness leaned on co-first authors, postdoctoral fellow Joseph Burclaff, PhD, and graduate student, Jarrett Bliton, both trainees in the Magness lab.

“Not only do we want to identify where the cells are located, but we want to know exactly which cell types do what, and why,” Burclaff said. “So, staying with the map analogy, we don’t want to just say, ‘oh, there’s North Carolina’. We want to know where to get the best barbecue. We want a ground level view to know as much as possible.”

In the past, researchers would mash up those rice-sized biopsies to identify all epithelial cell types and learn some general features of these cells. Magness’s approach was to sample thousands of individual cells from every part of the lower digestive tract (small intestine and colon) to create an atlas and then study the potential roles of these cells through the genes that each cell expresses. Knowing all of this would deepen scientific knowledge about the gut epithelium and hopefully encourage other scientists to explore each cell’s function in biology, in disease, and in the unfortunate scenario of pharmaceutical side effects.

To do such a deep individual cell dive, Magness needed two things: better technology and the entire digestive tracts of humans.

The Biology of Data

UNC-Chapel Hill acquired state-of-the-art RNA sequencing technology several years ago for the creation of the Advanced Analytics Core Facility through the UNC Center for Gastrointestinal Disease and Biology, which developed the scientific and intellectual heft – research faculty, staff, postdocs, and students – to use state-of-the-art equipment.

The Magness Group acquired human digestive tracts through a research agreement with organ donor services at HonorBridge. When intestines are harvested for transplant and if they are not claimed by higher-priority groups, HonorBridge staff coordinates with the Magness Group to donate the transplant-grade organs for research.

Six to eight hours after harvest, the Magness lab receives intact intestinal tracts, each about 15 to 30 feet long. They remove the epithelial layer, which is one long connected piece of tissue despite being only one cell thick. Then the researchers use enzymes to break down the epithelium into individual cells. For this study, they repeated this for organs from three separate donors.

Using sequencing technology to characterize gene expression, the Magness group first extracts RNA from each cell while keeping each cell separate, and then they run single-cell sequencing, which takes a snapshot of which genes each intestinal cell is expressing and how much.

“The picture we get from each cell is a mosaic of all the different types of genes the cells make and this complement of genes creates a ‘signature’ to tell us what kind of cell it is and potentially what it is doing,” Magness said. “Is it a stem cell or a mucous cell or a hormone-producing cell or an immune-signaling cell?

Burclaff added, “We were able to see the differences in cell types throughout the entire digestive tracts, and we can see different gene expression levels in the same cell types from three different people. We can see the different sets of genes turned on or off in individual cells. This is how, for instance, we might begin to understand why some people form toxicity to certain foods or drugs and some people don’t.”

A major problem with this kind of research is the sheer amount of data produced. The single cell sequencing picks up about 11,000 ‘reads’, or individual samples of gene products in just one cell, and in many thousands of individual cells, each with different combinations of the 20,000-plus human genes that are turned on or off. This creates almost 140,000,000 data points for all the 12,590 cells in the study that have to be put into a “visual” format so that scientists can make sense of the vast amount of information.

“The human brain can only comprehend two dimensions, three is challenging,” Magness said. “Add time, and it’s even trickier to comprehend what a single cell is up to. The amount of data our experiments produced was basically millions of dimensions all at once.”

Bliton devised computational techniques to filter the data to produce a manageable data set that included cell populations from all portions of the GI tract. Then, based on what Magness and other researchers had already learned of each cell type, Bliton could computationally identify each cell type from each region. He then plotted these data in a manner that humans can understand and interpret.

Reining in the immense data allowed the scientists to learn a lot about each cell type. Consider the tuft cell, discovered 40 years ago and so named because they look as if they have tufts of hair on their surface. Turns out these tuft cells express similar genes as those on taste buds on the tongue. Other researchers discovered that these tuft cells sensed worm infections and sent signals to the immune system to begin waging war. The Magness lab showed that tuft cells exhibit a set of genes thought to be important for sensing and “tasting” other kinds of intestinal content so it can signal the immune system if need be. This would represent a much broader function than sensing if there’s a parasite in your gut or not.

“Not only did we describe every single cell type and every single gene they express individually, but we also looked at potential functions,” Burclaff said. “If you look at intestinal mucus, which is a complex mixture that protects the cells, we show which cells express various mucin proteins, how much, and in which regions of the digestive tract. We looked at where specific enzymes that digest food are expressed. We looked at cells with anti-inflammatory gene expression and synapse genes where the gut is probably connected to nerves so it can talk to the rest of the body. We looked at aquaporins, proteins involved in transferring water through the intestinal membrane.”

What the Magness group found was a whole new level of variation in potential functions that had not previously been appreciated through mashing up biopsy samples.

The researchers explored all epithelial receptors – the cell surface proteins used to communicate with other cells and molecules and with the environment of the gut. Magness and colleagues could see which receptors were expressed the most and in which cell types, painting a new picture of how cells might interact with gut contents such as nutrients, microbes, toxins, and drugs.

“As far as we know, we’re the first to do this kind of analysis across the length of the human gut from three full donors,” Bliton said. “We can look at each cell type and predict which pharmaceuticals might affect which cell type individually.”

For instance, there’s a class of drugs to treat inflammatory bowel disease; they’re designed to hit specific targets, certain immune cells that trigger inflammation. But the Magness lab learned that some epithelial cells express the same genes as those in the immune cells that are intended to be the target. This finding indicates there could be “off-target” effects in epithelial cells that are not intended and could lead to side-effects.

“This was not known,” Burclaff said. “Lots of drugs have bad GI side effects. And it could be because the drugs are affecting individual cells along the entire length of the GI tract. We show where these receptors are most expressed and in which cell types.”

This kind of knowledge is just one outcome from the Magness lab’s initial study.

“We want the scientific, medical, and pharmaceutical community to use what we’ve found,” Magness said. “We adopted an analytic approach to methodically address each cell type, produce easy-to-read and accessible spreadsheets for most scientists, and show several examples of what we can be discovered with this kind of high resolution, precision approach.”

Funding for this research came from the National Institutes of Health, the Katherine E. Bullard Charitable Trust, the Crohn’s and Colitis Foundation, and the University Cancer Research Fund at UNC-Chapel Hill.

Aside from the aforementioned researchers, other authors are Keith Breau, Meryem Ok, Ismael Gomez-Martinez, Jolene Ranek, Aadra Bhatt, Jeremy Purvis, and John Woosley, all at UNC-Chapel Hill.

https://news.unchealthcare.org/2022/02/scientists-map-entire-human-gut-at-single-cell-resolution/

  

Phonograph Records

Phonograph Records

A phonograph disc record (also known as a gramophone disc record, especially in British English), or simply a phonograph record, gramophone record, disc record, long-playing record, or record, is an analog  sound  storage medium in the form of a flat disc with an inscribed, modulated spiral  groove. The groove usually starts near the periphery and ends near the center of the disc. At first, the discs were commonly made from shellac, with earlier records having a fine abrasive filler mixed in. Starting in the 1940s polyvinyl chloride became common, hence the name "vinyl". In the mid-2000s, gradually, records made of any material began to be called vinyl disc records, also known as vinyl records or vinyl for short.

The phonograph disc record was the primary medium used for music reproduction throughout the 20th century. It had co-existed with the phonograph cylinder  from the late 1880s and had effectively superseded it by around 1912. Records retained the largest market share even when new formats such as the compact cassette were mass-marketed. By the 1980s, digital media, in the form of the  compact disc, had gained a larger market share, and the record left the mainstream in 1991.  Since the 1990s, records continue to be manufactured and sold on a smaller scale, and during the 1990s and early 2000s were commonly used by disc jockeys  (DJs), especially in dance music genres. They were also listened to by a growing number of audiophiles.”  The phonograph record has made a niche resurgence as a format for rock music in the early 21st century—9.2 million records were sold in the US in 2014, a 260% increase since 2009.  Likewise, sales in the UK increased five-fold from 2009 to 2014.

As of 2017, 48 record pressing facilities remain worldwide, 18 in the US and 30 in other countries. The increased popularity of the record has led to the investment in new and modern record-pressing machines.  Only two producers of lacquers (acetate discs or master discs) remain: Apollo Masters in California, and MDC in Japan.  On February 6, 2020, a fire destroyed the Apollo Masters plant. According to the Apollo Masters website, their future is still uncertain.

Phonograph records are generally described by their diameter in inches (12-inch, 10-inch, 7-inch) (although they were designed in millimeters), the rotational speed in revolutions per minute (rpm) at which they are played (8+¹⁄₃, 16+²⁄₃, 33+¹⁄₃, 45, 78), and their time capacity, determined by their diameter and speed (LP [long playing], 12-inch disc, 33+¹⁄₃ rpm; SP [single], 10-inch disc, 78 rpm, or 7-inch disc, 45 rpm; EP [extended play], 12-inch disc or 7-inch disc, 33+¹⁄₃ or 45 rpm); their reproductive quality, or level of “fidelity (high-fidelity, orthophonic, full-range, etc.); and the number of audio channels (mono, stereo, quad, etc.).

The phrase broken record refers to a malfunction when the needle skips/jumps back to the previous groove and plays the same section over and over again indefinitely.

The large cover (and inner sleeves) are valued by collectors and artists for the space given for visual expression, especially in the case of 12-inch discs.

            https://en.wikipedia.org/wiki/Phonograph_record

  

Accurately Predicting and Preparing for the Impact of Approaching Storms

Climate experts and engineers have created a new model to predict the damage caused by adverse weather. This new framework for 'consequence forecasting' enables first responders to effectively target resources prior to an extreme weather event, such as Storm Eunice.

From:  Newcastle University

February 18, 2022 -- Climate experts and engineers have created a new model to predict the damage caused by adverse weather. This new framework for 'consequence forecasting' enables first responders to effectively target resources prior to an extreme weather event, such as Storm Eunice.

The pre-event decision-making model works by first developing relationships between wind speed and faults on the electricity network. The relationships are then used to estimate faults of electricity networks and potential customer interruptions. This model can be used as early as 24 hours before extreme weather events.

Published in the journal Climate Risk Management, the study findings can enable effective first response to manage infrastructure systems impacted by hazardous weather. Having the forecasting tools to predict and prepare for storm damage will reduce the societal consequences of extreme weather, including power loss for customers and fines for electrical distribution companies.

The study was led by Dr Sean Wilkinson of Newcastle University's School of Engineering, and involved experts from the Met Office and EPFL, Lausanne, Switzerland. The team used an advanced weather numerical model to develop the prediction system.

The framework presented in the paper applies to an electricity distribution network threatened by approaching windstorms. However, it could equally be applied to other infrastructure systems or elements of the built environment, or any type of weather event.

Dr Wilkinson said: "Our model has the potential to change the way we manage weather and climate risks to our infrastructure networks. While electricity network operators already prepare extra resources when a storm approaches, predicting how many power lines may be blown down and where these are likely to be located will allow them to better target the necessary resources to more quickly repair any damage. This is likely to become even more important in the future as our changed climate is predicted to produce more frequent and more intense storms and some of these may be beyond the experience of the people tasked to deal with them."

Study co-author, Professor Hayley Fowler, of Newcastle University's School of Engineering, added: "This consequence forecasting is so important for planning emergency response in fast-evolving storms like Eunice. Our model could be used to regularly update energy companies and other infrastructure operators on the potential consequences of approaching storms, as forecasts are updated in real-time. This is particularly relevant since the first very high-resolution climate models, which are also used for today's weather forecasts, predict a significantly greater increase in the frequency of severe winter storms in Europe with climate change."

      https://www.sciencedaily.com/releases/2022/02/220218110721.htm

 

Flies Have Sophisticated Cognitive Abilities

Common flies feature more advanced cognitive abilities than previously believed. Using a custom-built immersive virtual reality arena, neurogenetics and real-time brain activity imaging, researchers found attention, working memory and conscious awareness-like capabilities in fruit flies.

From:  University of California San Diego

February 17, 2022 -- As they annoyingly buzz around a batch of bananas in our kitchens, fruit flies appear to have little in common with mammals. But as a model species for science, researchers are discovering increasing similarities between us and the miniscule fruit-loving insects.

In a new study, researchers at the University of California San Diego's Kavli Institute for Brain and Mind (KIBM) have found that fruit flies (Drosophila melanogaster) have more advanced cognitive abilities than previously believed. Using a custom-built immersive virtual reality environment, neurogenetic manipulations and in vivo real-time brain-activity imaging, the scientists present new evidence Feb. 16 in the journal Nature of the remarkable links between the cognitive abilities of flies and mammals.

The multi-tiered approach of their investigations found attention, working memory and conscious awareness-like capabilities in fruit flies, cognitive abilities typically only tested in mammals. The researchers were able to watch the formation, distractibility and eventual fading of a memory trace in their tiny brains.

"Despite a lack of obvious anatomical similarity, this research speaks to our everyday cognitive functioning -- what we pay attention to and how we do it," said study senior author Ralph Greenspan, a professor in the UC San Diego Division of Biological Sciences and associate director of KIBM. "Since all brains evolved from a common ancestor, we can draw correspondences between fly and mammalian brain regions based on molecular characteristics and how we store our memories."

To arrive at the heart of their new findings the researchers created an immersive virtual reality environment to test the fly's behavior via visual stimulation and coupled the displayed imagery with an infra-red laser as an averse heat stimulus. The near 360-degree panoramic arena allowed Drosophila to flap their wings freely while remaining tethered, and with the virtual reality constantly updating based on their wing movement (analyzed in real-time using high-speed machine-vision cameras) it gave the flies the illusion of flying freely in the world. This gave researchers the ability to train and test flies for conditioning tasks by allowing the insect to orient away from an image associated with the negative heat stimulus and towards a second image not associated with heat.

They tested two variants of conditioning, one in which flies were given visual stimulation overlapping in time with the heat (delay conditioning), both ending together, or a second, trace conditioning, by waiting 5 to 20 seconds to deliver the heat after showing and removing the visual stimulation. The intervening time is considered the "trace" interval during which the fly retains a "trace" of the visual stimulus in its brain, a feature indicative of attention, working memory and conscious awareness in mammals.

The researchers also imaged the brain to track calcium activity in real-time using a fluorescent molecule they genetically engineered into their brain cells. This allowed the researchers to record the formation and duration of the fly's living memory since they saw the trace blinking on and off while being held in the fly's short-term (working) memory. They also found that a distraction introduced during training -- a gentle puff of air -- made the visual memory fade more quickly, marking the first time researchers have been able to prove such distractedness in flies and implicating an attentional requirement in memory formation in Drosophila.

"This work demonstrates not only that flies are capable of this higher form of trace conditioning, and that the learning is distractible just like in mammals and humans, but the neural activity underlying these attentional and working memory processes in the fly show remarkable similarity to those in mammals," said Dhruv Grover, a UC San Diego KIBM research faculty member and lead author of the new study. "This work demonstrates that fruit flies could serve as a powerful model for the study of higher cognitive functions. Simply put, the fly continues to amaze in how smart it really is."

The scientists also identified the area of the fly's brain where the memory formed and faded -- an area known as the ellipsoid body of the fly's central complex, a location that corresponds to the cerebral cortex in the human brain.

Further, the research team discovered that the neurochemical dopamine is required for such learning and higher cognitive functions. The data revealed that dopamine reactions increasingly occurred earlier in the learning process, eventually anticipating the coming heat stimulus.

The researchers are now investigating details of how attention is physiologically encoded in the brain. Grover believes the lessons learned from this model system are likely to directly inform our understanding of human cognition strategies and neural disorders that disrupt them, but also contribute to new engineering approaches that lead to performance breakthroughs in artificial intelligence designs.

The coauthors of the study include Dhruv Grover, Jen-Yung Chen, Jiayun Xie, Jinfang Li, Jean-Pierre Changeux and Ralph Greenspan (all affiliated with the UC San Diego Kavli Institute for Brain and Mind, and J.-P. Changeux also a member of the Collège de France).

      https://www.sciencedaily.com/releases/2022/02/220217141245.htm

  

Ultraprecise Atomic Clock Has Been Developed

Expected Use:  new studies in physics

From: University of Wisconsin--Madison

By Sarah Perdue

February 16, 2022 – University of Wisconsin–Madison physicists have made one of the highest performance atomic clocks ever, they announced Feb. 16 in the journal Nature.

Their instrument, known as an optical lattice atomic clock, can measure differences in time to a precision equivalent to losing just one second every 300 billion years and is the first example of a “multiplexed” optical clock, where six separate clocks can exist in the same environment. Its design allows the team to test ways to search for gravitational waves, attempt to detect dark matter, and discover new physics with clocks.

“Optical lattice clocks are already the best clocks in the world, and here we get this level of performance that no one has seen before,” says Shimon Kolkowitz, a UW–Madison physics professor and senior author of the study. “We’re working to both improve their performance and to develop emerging applications that are enabled by this improved performance.”

Atomic clocks are so precise because they take advantage of a fundamental property of atoms: when an electron changes energy levels, it absorbs or emits light with a frequency that is identical for all atoms of a particular element. Optical atomic clocks keep time by using a laser that is tuned to precisely match this frequency, and they require some of the world’s most sophisticated lasers to keep accurate time.

By comparison, Kolkowitz’s group has “a relatively lousy laser,” he says, so they knew that any clock they built would not be the most accurate or precise on its own. But they also knew that many downstream applications of optical clocks will require portable, commercially available lasers like theirs. Designing a clock that could use average lasers would be a boon.

In their new study, they created a multiplexed clock, where strontium atoms can be separated into multiple clocks arranged in a line in the same vacuum chamber. Using just one atomic clock, the team found that their laser was only reliably able to excite electrons in the same number of atoms for one-tenth of a second.

However, when they shined the laser on two clocks in the chamber at the same time and compared them, the number of atoms with excited electrons stayed the same between the two clocks for up to 26 seconds. Their results meant they could run meaningful experiments for much longer than their laser would allow in a normal optical clock.

“Normally, our laser would limit the performance of these clocks,” Kolkowitz says. “But because the clocks are in the same environment and experience the exact same laser light, the effect of the laser drops out completely.”

The group next asked how precisely they could measure differences between the clocks. Two groups of atoms that are in slightly different environments will tick at slightly different rates, depending on gravity, magnetic fields, or other conditions.

They ran their experiment over a thousand times, measuring the difference in the ticking frequency of their two clocks for a total of around three hours. As expected, because the clocks were in two slightly different locations, the ticking was slightly different. The team demonstrated that as they took more and more measurements, they were better able to measure those differences.

Ultimately, the researchers could detect a difference in ticking rate between the two clocks that would correspond to them disagreeing with each other by only one second every 300 billion years — a measurement of precision timekeeping that sets a world record for two spatially separated clocks.

It would have also been a world record for the overall most precise frequency difference if not for another paper, published in the same issue of Nature. That study was led by a group at JILA, a research institute in Colorado. The JILA group detected a frequency difference between the top and bottom of a dispersed cloud of atoms about 10 times better than the UW–Madison group.

Their results, obtained at one millimeter separation, also represent the shortest distance to date at which Einstein’s theory of general relativity has been tested with clocks. Kolkowitz’s group expects to perform a similar test soon.

“The amazing thing is that we demonstrated similar performance as the JILA group despite the fact that we’re using an orders of magnitude worse laser,” Kolkowitz says. “That’s really significant for a lot of real-world applications, where our laser looks a lot more like what you would take out into the field.”

To demonstrate the potential applications of their clocks, Kolkowitz’s team compared the frequency changes between each pair of six multiplexed clocks in a loop. They found that the differences add up to zero when they return to the first clock in the loop, confirming the consistency of their measurements and setting up the possibility that they could detect tiny frequency changes within that network.

“Imagine a cloud of dark matter passes through a network of clocks — are there ways that I can see that dark matter in these comparisons?” Kolkowitz asks. “That’s an experiment we can do now that you just couldn’t do in any previous experimental system.”

This work was supported in part by the NIST Precision Measurements Grants program, the Northwestern University Center for Fundamental Physics and the John Templeton Foundation through a Fundamental Physics grant, the Wisconsin Alumni Research Foundation, the Army Research Office (W911NF-21-1-0012), and a Packard Fellowship for Science and Engineering.

https://news.wisc.edu/ultraprecise-atomic-clock-poised-for-new-physics-discoveries/

  

Dog Domestication Theory May Be Wrong

”Domestication simply may have made dogs less fearful and more subservient”

Ross Pomeroy of Real Clear Science has a piece in Big Think questioning the notion that wolves were domesticated to be smarter and more gentle than their wolfish ancestors.  See

The traditional story of dog domestication might be all wrong - Big Think

The Most Extreme 'Rogue Wave' on Record

Confirmed in the North Pacific off the coast of British Columbia

From: Science Alert

By Carly Cassella

February 14, 2022 -- In November of 2020, a freak wave came out of the blue, lifting a lonesome buoy off the coast of British Columbia 17.6 meters high (58 feet).

The four-story wall of water has now been confirmed as the most extreme rogue wave ever recorded.

Such an exceptional event is thought to occur only once every 1,300 years. And unless the buoy had been taken for a ride, we might never have known it even happened.

For centuries, rogue waves were considered nothing but nautical folklore. It wasn't until 1995 that myth became fact. On the first day of the new year, a nearly 26-meter-high wave (85 feet) suddenly struck an oil-drilling platform roughly 160 kilometers (100 miles) off the coast of Norway.

At the time, the so-called Draupner wave defied all previous models scientists had put together.

Since then, dozens more rogue waves have been recorded (some even in lakes), and while the one that surfaced near Ucluelet, Vancouver Island was not the tallest, its relative size compared to the waves around it was unprecedented.

Scientists define a rogue wave as any wave more than twice the height of the waves surrounding it. The Draupner wave, for instance, was 25.6 meters tall, while its neighbors were only 12 meters tall.

In comparison, the Ucluelet wave was nearly three times the size of its peers.

"Proportionally, the Ucluelet wave is likely the most extreme rogue wave ever recorded," says physicist Johannes Gemmrich from the University of Victoria. 

"Only a few rogue waves in high sea states have been observed directly, and nothing of this magnitude."

Today, researchers are still trying to figure out how rogue waves are formed so we can better predict when they will arise. This includes measuring rogue waves in real time and also running models on the way they get whipped up by the wind.

The buoy that picked up the Ucluelet wave was placed offshore along with dozens of others by a research institute called MarineLabs in an attempt to learn more about hazards out in the deep.

Even when freak waves occur far offshore, they can still destroy marine operations, wind farms, or oil rigs. If they are big enough, they can even put the lives of beachgoers at risk.

Luckily, neither Ucluelet nor Draupner caused any severe damage or took any lives, but other rogue waves have.

Some ships that went missing in the 1970s, for instance, are now thought to have been sunk by sudden, looming waves. The leftover floating wreckage looks like the work of an immense white cap.

Unfortunately, a recent study predicts wave heights in the North Pacific are going to increase with climate change, which suggests the Ucluelet wave may not hold its record for as long as our current predictions suggest. 

"We are aiming to improve safety and decision-making for marine operations and coastal communities through widespread measurement of the world's coastlines," says MarineLabs CEO Scott Beatty. 

"Capturing this once-in-a-millennium wave, right in our backyard, is a thrilling indicator of the power of coastal intelligence to transform marine safety."

The study was published in Scientific Reports. 

https://www.sciencealert.com/a-rogue-wave-four-stories-high-is-the-largest-on-record