Culture

In the darkest parts of the world where light fails to block out the unfathomable bounty of the stars, look up. There are still fewer specks illuminating the universe than there are bacteria in the world, hidden from sight, a whole universe inside just one human gut.

Many species are known, like E. coli, but many more, sometimes referred to as "microbial dark matter," remain elusive. "We know it's there," said Doug Kenny, a Ph.D. candidate in the Graduate School of Arts and Sciences, "because of how it affects things around it." Kenny is co-first author on a new study in Cell Host and Microbe that illuminates a bit of that microbial dark matter: a species of gut bacteria that can affect cholesterol levels in humans.

"The metabolism of cholesterol by these microbes may play an important role in reducing both intestinal and blood serum cholesterol concentrations, directly impacting human health," said Emily Balskus, professor of chemistry and chemical biology at Harvard University and co-senior author with Ramnik Xavier, , core member at the Broad, co-director of the Center for informatics and therapeutics at MIT and investigator at Massachusetts General Hospital. The newly discovered bacteria could one day help people manage their cholesterol levels through diet, probiotics, or novel treatments based on individual microbiomes.

According to the Centers for Disease Control and Prevention (CDC), in 2016, over 12 percent of adults in the United States age 20 and older had high cholesterol levels, a risk factor for the country's number one cause of death: heart disease. Only half of that group take medications like statins to manage their cholesterol levels; while such drugs are a valuable tool, they don't work for all patients and, though rare, can have concerning side effects.

"We're not looking for the silver bullet to solve cardiovascular disease," Kenny said, "but there's this other organ, the microbiome, another system at play that could be regulating cholesterol levels that we haven't thought about yet."

The hog sewage lagoon

Since the late 1800s, scientists knew that something was happening to cholesterol in the gut. Over decades, work inched closer to an answer. One study even found evidence of cholesterol-consuming bacteria living in a hog sewage lagoon. But those microbes preferred to live in hogs, not humans.

Prior studies are like a case file of clues (one 1977 lab even isolated the telltale microbe but the samples were lost). One huge clue is coprostanol, the byproduct of cholesterol metabolism in the gut. "Because the hog sewage lagoon microbe also formed coprostanol," said Balskus, "we decided to identify the genes responsible for this activity, hoping we might find similar genes in the human gut."

Meanwhile, Damian Plichta, a computational scientist at the Broad Institute and co-first author with Kenny, searched for clues in human data sets. Hundreds of species of bacteria, viruses and fungi that live in the human gut have yet to be isolated and described, he said. But so-called metagenomics can help researchers bypass a step: Instead of locating a species of bacteria first and then figuring out what it can do, they can analyze the wealth of genetic material found in human microbiomes to determine what capabilities those genes encode.

Plichta cross-referenced massive microbiome genome data with human stool samples to find which genes corresponded with high levels of coprostanol. "From this massive amount of correlations," he said, "we zoomed in on a few potentially interesting genes that we could then follow up on." Meanwhile, after Balskus and Kenny sequenced the entire genome of the cholesterol-consuming hog bacterium, they mined the data and discovered similar genes: A signal that they were getting closer.

The human connection

Then Kenny narrowed their search further. In the lab, he inserted each potential gene into bacteria and tested which made enzymes to break down cholesterol into coprostanol. Eventually, he found the best candidate, which the team named the Intestinal Steroid Metabolism A (IsmA) gene.

"We could now correlate the presence or absence of potential bacteria that have these enzymes with blood cholesterol levels collected from the same individuals," said Xavier. Using human microbiome data sets from China, Netherlands and the United States, they discovered that people who carry the IsmA gene in their microbiome had 55 to 75 percent less cholesterol in their stool than those without.

"Those who have this enzyme activity basically have lower cholesterol," Xavier said.

The discovery, Xavier said, could lead to new therapeutics--like a "biotic cocktail" or direct enzyme delivery to the gut--to help people manage their blood cholesterol levels. But there's a lot of work to do first: The team may have identified the crucial enzyme, but they still need to isolate the microbe responsible. They need to prove not just correlation but causation--that the microbe and its enzyme are directly responsible for lowering cholesterol in humans. And, they need to analyze what effect coprostanol, the reaction byproduct, has on human health.

"It doesn't mean that we're going to have answers tomorrow, but we have an outline of how to go about it," Xavier said.

On June 15, 2020, a citizen scientist spotted a never-before-seen comet in data from the Solar and Heliospheric Observatory, or SOHO -- the 4,000th comet discovery in the spacecraft's 25-year history.

The comet is nicknamed SOHO-4000, pending its official designation from the Minor Planet Center. Like most other SOHO-discovered comets, SOHO-4000 is part of the Kreutz family of sungrazers. The Kreutz family of comets all follow the same general trajectory, one that carries them skimming through the outer atmosphere of the Sun. SOHO-4000 is on the small side, with a diameter in the range of 15-30 feet, and it was extremely faint and close to the Sun when discovered -- meaning SOHO is the only observatory that has spotted the comet, as it's impossible to see from Earth with or without a telescope.

"I feel very fortunate to have found SOHO's 4,000th comet. Although I knew that SOHO was nearing its 4,000th comet discovery, I did not initially think that this sungrazer would be it," said Trygve Prestgard, who first spotted the comet in SOHO's data. "It was only after discussing with other SOHO comet hunters, and counting through the most recent sungrazer discoveries, that the idea sunk in. I am honored to be part of such an amazing collaborative effort."

SOHO is a joint mission of the European Space Agency (ESA) and NASA. Launched in 1995, SOHO studies the Sun from its interior to its outer atmosphere, with an uninterrupted view from its vantage point between the Sun and Earth, about a million miles from our planet. But over the past two and half decades, SOHO has also become the greatest comet finder in human history.

SOHO's comet-hunting prowess comes from a combination of its long lifespan, its sensitive instruments focused on the solar corona, and the tireless work of citizen scientists who scour SOHO's data for previously-undiscovered comets, which are clumps of frozen gases, rock and dust that orbit the Sun.

"Not only has SOHO rewritten the history books in terms of solar physics, but, unexpectedly, it's rewritten the books in terms of comets as well," said Karl Battams, a space scientist at the U.S. Naval Research Lab in Washington, D.C., who works on SOHO and manages its comet-finding program.

The vast majority of comets found in SOHO's data are from its coronagraph instrument, called LASCO, short for Large Angle and Spectrometric Coronagraph. Like other coronagraphs, LASCO uses a solid object -- in this case, a metal disk -- to block out the Sun's bright face, allowing its cameras to focus on the relatively faint outer atmosphere, the corona. The corona is critical to understanding how the Sun's changes propagate out into the solar system, making LASCO a key part of SOHO's scientific quest to understand the Sun and its influence.

But focusing on this faint region also means LASCO can do something other telescopes can't -- it can see comets flying extremely close to the Sun, called sungrazers, which are otherwise blotted out by the Sun's intense light and impossible to see. This is why nearly all of SOHO's 4,000 comet discoveries have come from LASCO's data.

Like most who have discovered comets in SOHO's data, Prestgard is a citizen scientist, searching for comets in his free time with the Sungrazer Project. The Sungrazer Project is a NASA-funded citizen science project, managed by Battams, which grew out of comet discoveries by citizen scientists early into SOHO's mission.

"I have been actively involved in the Sungrazer Project for about eight years. My work with sungrazers is what solidified my long-term interest in planetary science," said Prestgard, who recently completed a master's degree in geophysics from Université Grenoble Alpes in France. "I enjoy the feeling of discovering something previously unknown, whether this is a nice "real time" comet or a "long-gone" overlooked one in the archives."

In total, Prestgard has discovered around 120 previously-unknown comets using data from SOHO and NASA's STEREO mission.

Copious comets

This 4,000th comet discovery came earlier than scientists initially expected -- a byproduct of SOHO's teamwork with the Parker Solar Probe mission. In coordination with Parker Solar Probe's fifth flyby of the Sun, the SOHO team ran a special observation campaign in early June, increasing the frequency with which the LASCO instrument takes images of the Sun's corona, as well as doubling the exposure time for each image. These changes in LASCO's imaging were designed to help the instrument pick up faint structures that would later pass over Parker Solar Probe.

"Since Parker Solar Probe was crossing the plane of the sky as seen from Earth, the structures that we see from SOHO's coronagraphs will be in the path of Parker Solar Probe," said Angelos Vourlidas, an astrophysicist at the Johns Hopkins University Applied Physics Lab, in Laurel, Maryland, who works on the Parker Solar Probe and SOHO missions. "It's the optimal configuration to do this type of imaging."

These more-sensitive images also revealed a number of comets that, based on their brightness, would have been too faint to see in SOHO's regular, shorter-exposure images. SOHO typically sees an uptick in comet discoveries each June, because Earth's position in space places SOHO at a good angle to see sunlight reflecting off of comets following the Kreutz path, a family of comets that accounts for about 85% of the comets discovered by SOHO. But this June saw 17 comets discovered in the first nine days of the month, around double the normal rate of discoveries.

"Our exposure time is twice as long, so we're gathering way more light, and seeing comets that are otherwise too faint for us to see -- it's just like any long-exposure photography," said Battams. "It's possible that if we doubled exposure time again, we'd see even more comets."

SOHO is a cooperative effort between ESA and NASA. Mission control is based at NASA's Goddard Space Flight Center in Greenbelt, Maryland. SOHO's Large Angle and Spectrometric Coronagraph Experiment, or LASCO, which is the instrument that provides most of the comet imagery, was built by an international consortium, led by the U.S. Naval Research Lab.

In a series of experiments using human cancer cell lines, scientists at Johns Hopkins Medicine say they have successfully used light as a trigger to make precise cuts in genomic material rapidly, using a molecular scalpel known as CRISPR, and observe how specialized cell proteins repair the exact spot where the gene was cut.

Results of the experiments, published June 11 in Science, not only reveal new details about the DNA repair process, but also are likely, the researchers say, to speed up and aid understanding of the DNA activity that typically causes aging and many cancers.

"Our new system of gene editing allows for targeted DNA cutting within seconds after activation. With previous technologies, gene editing could take much longer -- even hours," says postdoctoral fellow Yang Liu, Ph.D., a member of the Johns Hopkins Medicine research team.

The powerful CRISPR tool has, in recent years, enabled scientists to easily change, or "edit," DNA sequences and alter gene functions to speed the pace of research on gene-linked conditions.

Adapted from a naturally occurring gene editing system found in bacteria, CRISPR uses small sequences of genetic material called RNA as a kind of guide that is coded to match and bind to a specific sequence of genomic DNA within a cell. The CRISPR molecule also contains an enzyme called Cas9, which acts as the scalpel to cut out the DNA sequence. Then, the cell uses its own enzymes and proteins to repair the sliced DNA, often adding DNA sequences that scientists slip into the cell.

Liu says that studying the DNA repair process has been hampered by an inability to damage the DNA, such as by using CRISPR, in a way that's fast, precise and "on demand."

For the new experiments, the scientists modified the CRISPR-Cas9 complex by engineering a light-sensitive RNA molecule that allows the CRISPR complex to cut genomic DNA in living cells only when exposed to a particular wavelength of light.

"The advantage of our technique is that researchers can get the CRISPR machinery to find its target without prematurely cutting the gene, holding back its action until exposed to light," says Johns Hopkins M.D.-Ph.D. candidate Roger Zou, also a member of the research team. "This allows researchers to have far more control over exactly where and when the DNA is cut," he adds.

Other research teams have experimented with both drugs and light activation to control CRISPR timing, says Taekjip Ha, Ph.D., Bloomberg Distinguished Professor of Biophysics and Biophysical Chemistry, Biophysics and Biomedical Engineering at Johns Hopkins University, and a Howard Hughes Medical Institute investigator. His team's experiments differ by improving the precise timing of CRISPR cuts and examining how quickly proteins repair the DNA damage.

For the current study, the Johns Hopkins team, led by Ha and Bin Wu, Ph.D., assistant professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine, delivered an electric pulse to cultures of human embryonic kidney cells and bone cancer cells, which opened pores in the cell membrane and allowed the CRISPR complex with the light-activated RNA molecule to slide into the cells. Then, the scientists waited 12 hours for the CRISPR complex to bind to a targeted spot on the genomic DNA.

When they shined a light on the cells, they tracked the amount of time it took for the CRISPR complex to make the cut.

The team found that within 30 seconds of shining the light on the cells, the CRISPR complex had cut more than 50 percent of its targets.

To further examine the timing of DNA repair, the Johns Hopkins scientists tracked when proteins involved in DNA repair latched on to the DNA cuts. They determined that repair proteins started their work within two minutes of the CRISPR activation, and the repair was completed as early as 15 minutes later.

"We have shown that light-activated gene cutting is very fast, and it has potentially wide applications in biomedical research." says Ha. "Revealing the timing of CRISPR gene cuts allows us to see biological processes far more precisely." Ha and the Johns Hopkins team have dubbed the technique "very fast CRISPR on demand."

Ha also noted that light-activation offers better location control than drugs that can diffuse widely in the cell.

The Johns Hopkins team also used high-resolution microscopes to "see" how repair proteins interact with the CRISPR cut site in living cells.

They used these microscopes and a focused beam of light to show that they could activate CRISPR cutting of one of two gene copies that are normally found in human cells. This capability, they say, offers opportunities for using CRISPR to study and eventually treat conditions linked to only one abnormal gene copy, such as Huntington's disease.

"There is a big research community interested in studying DNA damage and its impact," says Ha. "The technology we developed is well suited to study that."

Ha notes that scientists typically use ionizing radiation or chemicals to study DNA damage. While those methods can also be fast, he says, they are not specific to a certain genomic location.

The team has filed a provisional patent on the CRISPR technology described in this research.

A team of astronomers, including researchers at MIT, has picked up on a curious, repeating rhythm of fast radio bursts emanating from an unknown source outside our galaxy, 500 million light years away.

Fast radio bursts, or FRBs, are short, intense flashes of radio waves that are thought to be the product of small, distant, extremely dense objects, though exactly what those objects might be is a longstanding mystery in astrophysics. FRBs typically last a few milliseconds, during which time they can outshine entire galaxies.

Since the first FRB was observed in 2007, astronomers have catalogued over 100 fast radio bursts from distant sources scattered across the universe, outside our own galaxy. For the most part, these detections were one-offs, flashing briefly before disappearing entirely. In a handful of instances, astronomers observed fast radio bursts multiple times from the same source, though with no discernible pattern.

This new FRB source, which the team has catalogued as FRB 180916.J0158+65, is the first to produce a periodic, or cyclical pattern of fast radio bursts. The pattern begins with a noisy, four-day window, during which the source emits random bursts of radio waves, followed by a 12-day period of radio silence.

The astronomers observed that this 16-day pattern of fast radio bursts reoccurred consistently over 500 days of observations.
"This FRB we're reporting now is like clockwork," says Kiyoshi Masui, assistant professor of physics in MIT's Kavli Institute for Astrophysics and Space Research. "It's the most definitive pattern we've seen from one of these sources. And it's a big clue that we can use to start hunting down the physics of what's causing these bright flashes, which nobody really understands."

Masui is a member of the CHIME/FRB collaboration, a group of more than 50 scientists led by the University of British Columbia, McGill University, University of Toronto, and the National Research Council of Canada, that operates and analyzes the data from the Canadian Hydrogen Intensity Mapping Experiment, or CHIME, a radio telescope in British Columbia that was the first to pick up signals of the new periodic FRB source.

The CHIME/FRB Collaboration has published the details of the new observation today in the journal Nature.

A radio view

In 2017, CHIME was erected at the Dominion Radio Astrophysical Observatory in British Columbia, where it quickly began detecting fast radio bursts from galaxies across the universe, billions of light years from Earth.

CHIME consists of four large antennas, each about the size and shape of a snowboarding half-pipe, and is designed with no moving parts. Rather than swiveling to focus on different parts of the sky, CHIME stares fixedly at the entire sky, using digital signal processing to pinpoint the region of space where incoming radio waves are originating.

From September 2018 to February 2020, CHIME picked out 38 fast radio bursts from a single source, FRB 180916.J0158+65, which the astronomers traced to a star-churning region on the outskirts of a massive spiral galaxy, 500 million light years from Earth. The source is the most active FRB source that CHIME has yet detected, and until recently it was the closest FRB source to Earth.

As the researchers plotted each of the 38 bursts over time, a pattern began to emerge: One or two bursts would occur over four days, followed by a 12-day period without any bursts, after which the pattern would repeat. This 16-day cycle occurred again and again over the 500 days that they observed the source.

"These periodic bursts are something that we've never seen before, and it's a new phenomenon in astrophysics," Masui says.

Circling scenarios

Exactly what phenomenon is behind this new extragalactic rhythm is a big unknown, although the team explores some ideas in their new paper. One possibility is that the periodic bursts may be coming from a single compact object, such as a neutron star, that is both spinning and wobbling -- an astrophysical phenomenon known as precession. Assuming that the radio waves are emanating from a fixed location on the object, if the object is spinning along an axis and that axis is only pointed toward the direction of Earth every four out of 16 days, then we would observe the radio waves as periodic bursts.

Another possibility involves a binary system, such as a neutron star orbiting another neutron star or black hole. If the first neutron star emits radio waves, and is on an eccentric orbit that briefly brings it close to the second object, the tides between the two objects could be strong enough to cause the first neutron star to deform and burst briefly before it swings away. This pattern would repeat when the neutron star swings back along its orbit.

The researchers considered a third scenario, involving a radio-emitting source that circles a central star. If the star emits a wind, or cloud of gas, then every time the source passes through the cloud, the gas from the cloud could periodically magnify the source's radio emissions.

"Maybe the source is always giving off these bursts, but we only see them when it's going through these clouds, because the clouds act as a lens," Masui says.

Perhaps the most exciting possibility is the idea that this new FRB, and even those that are not periodic or even repeating, may originate from magnetars -- a type of neutron star that is thought to have an extremely powerful magnetic field. The particulars of magnetars are still a bit of a mystery, but astronomers have observed that they do occasionally release massive amounts of radiation across the electromagnetic spectrum, including energy in the radio band.

"People have been working on how to make these magnetars emit fast radio bursts, and this periodicity we've observed has since been worked into these models to figure out how this all fits together," Masui says.

Very recently, the same group made a new observation that supports the idea that magnetars may in fact be a viable source for fast radio bursts. In late April, CHIME picked up a signal that looked like a fast radio burst, coming from a flaring magnetar, some 30,000 light years from Earth. If the signal is confirmed, this would be the first FRB detected within our own galaxy, as well as the most compelling evidence of magnetars as a source of these mysterious cosmic sparks.

Aspergillus fumigatus is a species of fungus that can cause serious illnesses in immunocompromised individuals such as those who are undergoing transplantation or cancer chemotherapy. Every year, about 500,000 new Aspergillus cases are reported, and even with antifungal agents in place, the mortality rate remains over 50%. Infections caused by A. fumigatus are difficult to treat because during an infection, the fungus aggregates into small communities called "biofilms." These biofilms not only protect the pathogens from antifungal agents, but also help the fungus evade the immune system. Researchers around the world have been trying to understand how biofilms are produced and how they can be disrupted, as this knowledge will be crucial for developing effective therapeutics.

In a recent paper published in Nature Communications, GlycoNet researchers Dr. Lynne Howell from The Hospital for Sick Children and Dr. Don Sheppard from McGill University solved the structure of a key enzyme called Agd3, which is critical for biofilm formation in A. fumigatus.

For over six years, Howell and Sheppard have been working together to find the vulnerabilities in the biofilm produced by different pathogens. More specifically, they are investigating a group of carbohydrate polymers produced by different enzymes in the pathogens. These carbohydrate polymers serve as a strong 'glue' to hold biofilm together.

"We want to know how these carbohydrates are synthesized and which enzymes are making them," says Sheppard. "If we know how it (biofilm) is made, we know how to take it apart."

The team first found that when this enzyme was missing, the biofilm did not form, and the fungus was weakened. After locating the enzyme in the fungal genome, the team took a deeper dive into the 3D-structure of the enzyme to understand the mechanism by which Agd3 functions in biofilm formation.

"With structural studies, we were able to visualize where and how the enzyme binds the carbohydrate polymers and modifies them to help form the biofilm," says Howell. "Furthermore, we found that this enzyme is composed of several different domains. The architecture of these domains and how they piece together to form the enzyme have never been seen before." Howell says the structural analysis also helped the team define a new family of carbohydrate-processing enzymes that has not been previously characterized.

Resistance of A. fumigatus to antifungal reagents continues to be a health threat worldwide. Sheppard believes gaining structural knowledge of Agd3 will be helpful to develop strategies addressing this concern. In fact, the team is already onto the next step.

"We are now designing antibodies that can inhibit the function of Agd3 based on structural information we gathered," says Sheppard. In collaboration with Howell lab, the team hopes to use structural data of how the antibodies binding to Agd3 to further the development of antibody therapeutics for infections caused by A. fumigatus.

To learn more about the story behind the paper from conception to publications, as well as the highs and lows, read the blog written by first author and former GlycoNet trainee Dr. Natalie Bamford on Nature Microbiology Community here.

Gut bacteria are tiny but may play an outsized role not only in the host animal's digestive health, but in their overall well-being. According to a new study in Nature, specific gut bacteria in the worm may modify the animal's behavior, directing its dining decisions. The research was funded in part by the National Institutes of Health.

"We keep finding surprising roles for gut bacteria that go beyond the stomach," said Robert Riddle, Ph.D., program director at the NIH's National Institute of Neurological Disorders and Stroke (NINDS), which supported the study. "Here, the gut bacteria are influencing how the animal senses its environment and causing it to move toward an external source of the same bacteria. The gut bacteria are literally making their species tastier to the animal."

Researchers at Brandeis University, Waltham, Massachusetts, led by Michael O'Donnell, Ph.D., postdoctoral fellow and first author of the paper, and Piali Sengupta, Ph.D., professor of biology and senior author of the study, were interested in seeing whether it was possible for gut bacteria to control a host animal's behavior. The group investigated the effects of gut bacteria on how worms, called C. elegans, sniff out and choose their next meal.

Bacteria are the worms' primary food. In this study, the researchers measured how worms fed different strains of bacteria reacted to octanol, a large alcohol molecule secreted by some bacteria, which worms normally avoid when it is present at high concentrations.

Dr. O'Donnell and his colleagues discovered that worms grown on Providencia alcalifaciens (JUb39) were less likely to avoid octanol compared to animals grown on other bacteria. Curiously, they found that live JUb39 bacteria were present in the gut of the worms that moved toward octanol, suggesting that the behavior may be determined in part by a substance produced by these bacteria.

Next, the researchers wanted to know how the bacteria exerted control over the worms.

"We were able to connect the dots, all the way from microbe to behavior, and determine the entire pathway that could be involved in this process," said Dr. O'Donnell.

The brain chemical tyramine may play an important role in this response. In the worms, tyramine is transformed into the chemical octopamine, which targets a receptor on sensory neurons that controls avoidance behavior. The results of this study suggested that tyramine produced by bacteria increased levels of octopamine, which made the worms more tolerant of octanol by suppressing the avoidance of octanol that is driven by these neurons.

Using other behavioral tests, the researchers found that genetically engineering worms so that they did not produce tyramine did not affect suppression of octanol avoidance when the worms were grown on JUb39. This suggests that tyramine made by the bacteria may be able to compensate for the endogenous tyramine missing in those animals.

Additional experiments indicated that worms grown on JUb39 preferred eating that type of bacteria over other bacterial food sources. Tyramine produced by the bacteria was also found to be required for this decision.

"In this way, the bacteria can take control over the host animal's sensory decision-making process, which affects their responses to odors and may influence food choices" said Dr. Sengupta.

Future studies will identify additional brain chemicals produced by bacteria that may be involved in changing other worm behaviors. In addition, it is unknown whether specific combinations of bacterial strains present in the gut will result in different responses to environmental cues. Although worms and mammals share many of the same genes and biochemical processes, it is not known whether similar pathways and outcomes exist in higher order animals.

Consumer demand is rising for all things avocado, including oil made from the fruit. Avocado oil is a great source of vitamins, minerals and the type of fats associated with reducing the risk of heart disease, stroke and diabetes. But according to new research from food science experts at the University of California, Davis, the vast majority of avocado oil sold in the U.S. is of poor quality, mislabeled or adulterated with other oils.

In the country's first extensive study of commercial avocado oil quality and purity, UC Davis researchers report that at least 82 percent of test samples were either stale before expiration date or mixed with other oils. In three cases, bottles labeled as "pure" or "extra virgin" avocado oil contained near 100 percent soybean oil, an oil commonly used in processed foods that's much less expensive to produce.

"I was surprised some of the samples didn't contain any avocado oil," said Selina Wang, Cooperative Extension specialist in the Department of Food Science and Technology, who led the study recently published in the journal Food Control. "Most people who buy avocado oil are interested in the health benefits, as well as the mild, fresh flavor, and are willing to pay more for the product. But because there are no standards to determine if an avocado oil is of the quality and purity advertised, no one is regulating false or misleading labels. These findings highlight the urgent need for standards to protect consumers and establish a level playing field to support the continuing growth of the avocado oil industry."

TESTING DOMESTIC AND IMPORTED BRANDS

Wang and Hilary Green, a Ph.D. candidate in Wang's lab, analyzed various chemical parameters of 22 domestic and imported avocado oil samples, which included all the brands they could find in local stores and online. Wang and Green received a $25,000 grant from Dipasa USA, part of the Dipasa Group, a sesame-seed and avocado-oil processor and supplier based in Mexico.

"In addition to testing commercial brands, we also bought avocados and extracted our own oil in the lab, so we would know, chemically, what pure avocado oil looks like," Wang said.

Test samples included oils of various prices, some labeled extra virgin or refined. Virgin oil is supposed to be extracted from fresh fruit using only mechanical means, and refined oil is processed with heat or chemicals to remove any flaws.

Fifteen of the samples were oxidized before the expiration date. Oil loses its flavor and health benefits when it oxidizes, which happens over time and when exposed to too much light, heat or air. Six samples were mixed with large amounts of other oils, including sunflower, safflower and soybean oil.

Only two brands produced samples that were pure and nonoxidized. Those were Chosen Foods and Marianne's Avocado Oil, both refined avocado oils made in Mexico. Among the virgin grades, CalPure produced in California was pure and fresher than the other samples in the same grade.

A PUSH FOR STANDARDS

Ensuring quality is important for consumers, retailers, producers and people throughout the avocado oil industry. Retailers want to sell quality products, shoppers want to get their money's worth and honest producers want to keep fraudulent and low-quality oil out of the marketplace.

But since avocado oil is relatively new on the scene, the Food and Drug Administration has not yet adopted "standards of identity," which are basic food standards designed to protect consumers from being cheated by inferior products or confused by misleading labels. Over the last 80 years, the FDA has issued standards of identity for hundreds of products, like whiskey, chocolate, juices and mayonnaise. Without standards, the FDA has no means to regulate avocado oil quality and authenticity.

Avocado oil isn't the only product without enforceable standards. Honey, spices and ground coffee are other common examples. Foods that fetch a higher price are especially ripe for manipulating, especially when adulterations can be too subtle to detect outside a lab.

Wang is working to develop faster, better and cheaper chemical methods to detect adulteration so bulk buyers can test avocado oil before selling it. She is also evaluating more samples, performing shelf-life studies to see how time and storage affect quality, and encouraging FDA officials to establish reasonable standards for avocado oil.

Wang has experience collaborating with industry and the FDA. Ten years ago, she analyzed the quality and purity of extra virgin olive oil and discovered that most of what was being sold in the U.S. was actually a much lower grade. Her research sparked a cascade of responses that led California to establish one of the world's most stringent standards for different grades of olive oil. The FDA is working with importers and domestic producers to develop standards of identity for olive oil.

"Consumers seeking the health benefits of avocado oil deserve to get what they think they are buying," Wang said. "Working together with the industry, we can establish standards and make sure customers are getting high-quality, authentic avocado oil and the companies are competing on a level playing field."

TIPS FOR CONSUMERS

-The flavor of virgin avocado oil can differ by varieties and region. In general, authentic, fresh, virgin avocado oil tastes grassy, buttery and a little bit like mushrooms.

-Virgin avocado oil should be green in color, whereas refined avocado oil is light yellow and almost clear due to pigments removed during refining.

-Even good oil becomes rancid with time. It's important to purchase a reasonable size that can be finished before the oil oxidizes. Store the oil away from light and heat. A cool, dark cabinet is a good choice, rather than next to the stove.

-How do you know if the oil is rancid? It starts to smell stale, sort of like play dough.

-When possible, choose an oil that's closest to the harvest/production time to ensure maximum freshness. The "best before date" is not always a reliable indicator of quality.

Researchers at the GSK Center for Optical Molecular Imaging have developed a new microscope that looks at the different parameters that change during wound healing. They hope to use this technique to understand how skin disorders, such as foot ulcers in diabetic patients and psoriasis, can be treated.

“Nobody really understands how topical drugs affect the skin because they can’t see below the skin,” said Marina Marjanovic, an associate professor of bioengineering and associate director of the center, which is located at the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign. 

“We need this technique to understand whether the available treatments are curing the underlying condition or just the symptoms,” said Marjanovic, who also is a member of Beckman’s Biophotonics Imaging Lab.

The new microscope can look at different aspects of wound healing simultaneously. The researchers used it to get images of the wound, track collagen that helps in wound healing, and visualize the blood vessel distribution around the wound. Additionally, they also have measured various chemicals in the tissue that indicate how much inflammation is occurring.

The paper “Non-invasive monitoring of pharmacodynamics during the skin wound healing process using multimodal optical microscopy” was published in BMJ Open Diabetes Research & Care.

“This is a continuation of a previous study we did where we made a wound on the ears of mice,” said Aneesh Alex, a visiting scholar at the Beckman Institute and a scientist at GlaxoSmithKline. “In this study, we added more visualization capabilities and studied the wound healing process on the backs of the mice, which is a more accurate model.”

The researchers studied the healing process for a month. They looked at four groups of mice: mice with untreated wounds, mice which had placebo treatments, and mice with two different concentrations of the treatment drug.

“One of the main limitations of optical imaging techniques is its shallow penetration depth in biological tissues,” said Eric Chaney, a research scientist in the Biophotonics Imaging Lab and at the center. The limitation is due to the scattering of light, which makes it difficult for the researchers to look at deeper tissue structures.

“The major advantages of this technique are that we do not use any labels in our imaging and it is completely noninvasive,” Marjanovic said. “We have also done follow-up studies in humans and we have been able to look at the changes in the skin of healthy volunteers and patients with skin conditions.”

The researchers hope to further refine the technique so it can be used for routine studies of skin disorders and their treatments.

“Our Center for Optical Molecular Imaging at the Beckman Institute has been a unique and productive academic-industry partnership with GlaxoSmithKline,” said Dr. Stephen Boppart, Abel Bliss Professor of Engineering and a professor of electrical and computer engineering and of bioengineering, who also is a medical doctor. “By combining our state-of-the-art optical imaging technologies, we have the ability to not only visualize and understand the molecular interactions that occur, but also how these processes may affect drug action and efficacy.”

The work was done in collaboration with GlaxoSmithKline. The data analysis was done with the help of Salma Musaad, a research biostatistician at the Interdisciplinary Health Sciences Institute.

The paper “Non-invasive monitoring of pharmacodynamics during the skin wound healing process using multimodal optical microscopy” can be found at http://dx.doi.org/10.1136/bmjdrc-2019-000974.

Journal

BMJ Open Diabetes Research & Care

DOI

10.1136/bmjdrc-2019-000974.

WASHINGTON -- Researchers have shown that a detection technology borrowed from quantum optics can be used to perform optical coherence tomography (OCT) with much lower light power than previously possible. This could greatly improve the imaging quality available from OCT used for medical imaging applications.

OCT uses light to provide high-resolution 3D images in a non-invasive manner. Although it is commonly used for ophthalmology applications, OCT can also be used to image many other parts of the body such as the skin and inside the ears, mouth, arteries and gastrointestinal tract.

"For clinical applications, being able to perform OCT with low light power is crucial because safety standards limit the light intensity levels that can be used," said research team leader Sylwia Kolenderska from The University of Auckland in New Zealand. "In some cases, these power levels are not high enough to achieve good image quality."

In The Optical Society (OSA) journal Optics Letters, the researchers describe how they replaced standard OCT detectors with superconducting single-photon detectors (SSPDs), a technology used in quantum optics to distinguish individual photons. This setup allowed them to achieve good image quality with power levels up to 1 million times lower than those currently used in OCT instruments.

"In the future, if single-photon detection technology could be made much smaller and less expensive, a line of portable diagnostic machines based on light-based imaging might be created for safe self-diagnosis purposes in the comfort of one's home," said Kolenderska.

Capturing single photons

The researchers came up with the new detection scheme while developing an OCT method based on quantum light for which SSPDs were central. They soon realized that SSPDs could also be used in a standard OCT arrangement to enhance sensitivity.

"Because SSPDs can detect single photons, an OCT instrument using them requires only a tiny amount of light compared to what is currently used in modern OCT machines," said Kolenderska. "Yet, it still produces high-detail images that are comparable with existing OCT systems."

Incorporating SSPDs into a standard OCT system required some changes to the typical optical setup. Modern OCT instruments work by discerning the colors, or wavelengths, of light reflected from an object. This wavelength discrimination can be performed by using a single pixel detector while the light source produces one wavelength at a time or it can be done with a diffraction grating that splits the light into different wavelengths like a prism and a camera that detects these wavelengths.

The researchers used a fiber instead of a grating to separate different colors, which each travel at different speeds down the fiber. At the fiber's output end, they used the SSPD to capture the different colors as they arrive at different times. This allowed the light spectrum to be acquired for reconstructing OCT images.

Low-power light yields high-quality images

To demonstrate the new detection scheme, the researchers acquired OCT images of a stack of three types of glass and a piece of onion, which represented a biological sample. They obtained good-quality images of both samples at light intensity levels at least five orders of magnitude lower than those set by safety standards.

"Our results show that the new detection approach could allow quality OCT imaging of different parts of the body, especially sensitive organs such as the eyes, without worrying about going above the safety levels in terms of light power," said Kolenderska. "In fact, the SSPD would be damaged beyond repair long before even 1% of the safety level is reached."

The researchers did, however, observe artifacts -- elements that do not correspond to the structure of the sample -- in the OCT images they acquired. These appear because the detection system detects all kinds of interactions between photons, not just the ones needed to reconstruct an actual image. They are experimenting to find the best way to prevent these artifacts without compromising imaging speed, which would be important to maintain for clinical applications.

All efforts to replicate in tokamak fusion facilities the fusion energy that powers the sun and stars must cope with a constant problem -- transient heat bursts that can halt fusion reactions and damage the doughnut-shaped tokamaks. These bursts, called edge localized modes (ELMs), occur at the edge of hot, charged plasma gas when it kicks into high gear to fuel fusion reactions.

To prevent such bursts researchers at the DIII-D National Fusion Facility, which General Atomics (GA) operates for the U.S. Department of Energy (DOE), previously pioneered an approach that injects small ripples of magnetic fields into the plasma to cause heat to leak out controllably. Now scientists at the DOE's Princeton Plasma Physics Laboratory (PPPL) have developed a control scheme to optimize the levels of these fields for maximum performance without ELMs.

Path to suppressing ELMs

The research, led by PPPL physicist Florian Laggner and funded by the DOE Office of Science, developed the scheme at DIII-D in San Diego. Laggner said the method, put together with researchers from GA and other collaborating institutions, reveals a path to suppressing ELMs and maximizing fusion power on ITER, the international tokamak under construction in France that is designed to demonstrate the practicality of fusion energy. "We show a path forward, a way that it can be done," said Laggner, lead author of a paper reporting the findings in Nuclear Fusion.

Fusion powers the sun and stars by combining light elements in the form of plasma -- the hot, charged state of matter composed of free electrons and atomic nuclei that makes up 99 percent of the visible universe -- to generate massive amounts of energy. Scientists around the world are seeking to harness fusion for a virtually inexhaustible supply of safe and clean power to generate electricity.

The demonstrated technique uses the expanded capacity of the DIII-D plasma control system to address the inherent conflict between optimizing fusion energy and controlling ELMs. The scheme focuses on the "pedestal," the thin, dense layer of plasma near the edge of the tokamak that increases the pressure of the plasma and thus fusion power. However, if the pedestal grows too high it can create ELM heat bursts by suddenly collapsing.

So the key is controlling the height of the pedestal to maximize fusion power while preventing the layer from becoming so high that it triggers ELMs. The combination calls for real-time control of the process. "You can't just preprogram some constant scheme beforehand, since the plasma and wall conditions may evolve," said Egemen Kolemen, an assistant professor of Mechanical and Aerospace Engineering at Princeton University and a PPPL physicist who oversaw the project. "The control must provide adjustments in real time."

Stable ELM suppression

The developed system created ELM suppression at the minimum amplitude, or size, of the magnetic disturbance. It further reduced the amplitude to allow partial recovery of the confinement lost during the process, thereby achieving both stable ELM suppression and high fusion performance.

"Laggner and colleagues have assembled an impressive suite of control tools to regulate core and edge plasma stability in real-time," said GA physicist Carlos Paz-Soldan, a coauthor of the paper. "Some kind of adaptive control like the techniques pioneered in this work will likely be necessary to regulate the plasma edge stability in ITER."

While the international facility will not simply apply the control system developed by PPPL and GA, it must create its own method for coping with ELMs. Indeed, "active control schemes will enable safe operation at maximized [fusion] gain in future devices such as ITER," the authors said. Moreover, they added, implementation of such a scheme on DIII-D provides proof of principle and "guides future development."

PPPL, on Princeton University's Forrestal Campus in Plainsboro, N.J., is devoted to creating new knowledge about the physics of plasmas -- ultra-hot, charged gases -- and to developing practical solutions for the creation of fusion energy. The Laboratory is managed by the University for the U.S. Department of Energy's Office of Science, which is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit energy.gov/science (link is external).

Spokane, Wash. - When it comes to living to the ripe old age of 100, good genes help but don't tell the full story. Where you live has a significant impact on the likelihood that you will reach centenarian age, suggests a new study conducted by scientists at Washington State University's Elson S. Floyd College of Medicine.

Published in the International Journal of Environmental Research and Public Health and based on Washington State mortality data, the research team's findings suggest that Washingtonians who live in highly walkable, mixed-age communities may be more likely to live to their 100th birthday. They also found socioeconomic status to be correlated, and an additional analysis showed that geographic clusters where the probability of reaching centenarian age is high are located in urban areas and smaller towns with higher socioeconomic status, including the Seattle area and the region around Pullman, Wash.

"Our study adds to the growing body of evidence that social and environmental factors contribute significantly to longevity, said study author Rajan Bhardwaj, a second-year WSU medical student who took an interest in the topic after serving as a home care aide to his aging grandfather. Earlier research, he said, has estimated that heritable factors only explain about 20 to 35% of an individual's chances of reaching centenarian age.

"We know from previous research that you can modify, through behavior, your susceptibility to different diseases based on your genetics," explained Ofer Amram, the study's senior author and an assistant professor who runs WSU's Community Health and Spatial Epidemiology (CHaSE) lab.

In other words, when you live in an environment that supports healthy aging, this likely impacts your ability to successfully beat your genetic odds through lifestyle changes. However, there was a gap in knowledge as to the exact environmental and social factors that make for an environment that best supports living to centenarian age, which this study helped to address.

In collaboration with co-authors Solmaz Amiri and Dedra Buchwald, Bhardwaj and Amram looked at state-provided data about the deaths of nearly 145,000 Washingtonians who died at age 75 or older between 2011 and 2015. The data included information on each person's age and place of residence at the time of death, as well as their sex, race, education level and marital status.

Based on where the person lived, the researchers used data from the American Community Survey, Environmental Protection Agency, and other sources to assign a value or score to different environmental variables for their neighborhood. The variables they looked at included poverty level, access to transit and primary care, walkability, percentage of working age population, rural-urban status, air pollution, and green space exposure. Subsequently, they conducted a survival analysis to determine which neighborhood and demographic factors were tied to a lower probability of dying before centenarian age.

They found that neighborhood walkability, higher socioeconomic status, and a high percentage of working age population (a measure of age diversity) were positively correlated with reaching centenarian status.

"These findings indicate that mixed-age communities are very beneficial for everyone involved," said Bhardwaj. "They also support the big push in growing urban centers toward making streets more walkable, which makes exercise more accessible to older adults and makes it easier for them to access medical care and grocery stores."
Amram added that neighborhoods that offer more age diversity tend to be in urban areas, where older adults are likely to experience less isolation and more community support.

Meanwhile, Bhardwaj said their findings also highlight the importance of continuing efforts to address health disparities experienced by racial minorities, such as African Americans and Native Americans. Consistent with previous research findings, for example, the data shows being white is correlated with living to 100. Looking at gender, the researchers also found that women were more likely to reach centenarian age.

Finally, the researchers wanted to see in which areas of the state people had a higher probability of reaching centenarian age. For each neighborhood, they calculated the years of potential life lost, or the average number of years deceased individuals would have had to continue living to reach age 100. Neighborhoods with lower values for years of potential life lost were considered to have a higher likelihood of reaching centenarian age, and vice versa.

When they mapped the years of potential life lost for all neighborhoods across the state, they saw clusters with high likelihood of living to centenarian age in higher socioeconomic areas in urban centers and small towns across the state, including the greater Seattle area and the Pullman region.

While more research is needed to expand upon their findings, the researchers said the study findings could eventually be used to create healthier communities that promote longevity in older adults.

Annapolis, MD; June 17, 2020--While the prevalence of Lyme disease and other illnesses spread by ticks has steadily increased in the United States over the past 20 years, a new study of the state of American tick surveillance and control reveals an inconsistent and often under-supported patchwork of programs across the country.

Annually reported cases of tickborne disease more than doubled between 2004 and 2018, according to the U.S. Centers for Disease Control and Prevention (CDC), while seven new tickborne germs were discovered in that same timeframe. But a clear gap exists in our public health infrastructure, say researchers who have conducted the first-ever survey of the nation's tick management programs.

The survey showed that less than half of public health and vector-control agencies engage in active tick surveillance, and only 12 percent directly conduct or otherwise support tick-control efforts. These and other findings from the survey, conducted by university researchers at the CDC's five Vector-Borne Disease Regional Centers of Excellence, are published today in the Journal of Medical Entomology.

"Ticks are responsible for the majority of our vector-borne illnesses in the U.S., and our programming does not adequately meet the need in its current form, for both surveillance and control," says Emily M. Mader, MPH MPP, lead author on the study and program manager at the Northeast Regional Center for Excellence in Vector-Borne Diseases, housed at Cornell University.

Mader and colleagues surveyed 140 vector-borne disease professionals working at state, county, and local agencies in the fall of 2018 to learn about their program objectives and capabilities for tick surveillance and control, testing ticks for disease-causing germs, and barriers to success. Reaching even that many respondents proved challenging, as no central database of tick-management programs or contacts was available.

Highlights from the survey of tick-management programs include:

Less than half of tick-management programs proactively collect ticks in their area. While about two-thirds of respondents (65 percent) said their programs engage in passive tick surveillance, such as accepting tick samples submitted by the public, only 46 percent said their programs engage in routine active tick surveillance, such as focused collection of tick samples within their community.

Only a quarter of tick-management programs test ticks for disease-causing germs. Just 26 percent of survey respondents said their jurisdiction conducts or financially supports testing of tick samples for disease-causing pathogens. And only 7 percent said their programs work to evaluate the presence of such pathogens in the animal hosts (such as mice and other rodents) from which ticks acquire those pathogens in their area.

"Pathogen testing is an essential component of surveillance and is needed in order to understand tickborne disease risk to communities," says Mader. "There appears to be a significant barrier for many tick-surveillance programs across the country to access pathogen-testing services."

Capacity for public tick-control efforts is low. Only 12 percent of respondents said that their jurisdiction conducts or financially supports tick control, with those efforts primarily focused reducing tick presence on animal hosts (such as deer and rodents).

Mader says limited resources mean tick-management programs need reliable, proven control methods. "They are not going to invest in a strategy unless it has been investigated and shown to make a difference in reducing the burden of ticks and tickborne diseases," she says. "Right now, supporting this research is a major need. These kinds of evaluations often take at least three years to complete and require a significant investment."

Tick surveillance and control happen in a range of sectors. The most common employment sectors among respondents being public health, mosquito control, cooperative extension, and agriculture. And more than half of respondents (57 percent) said their programs work with academic partners to conduct tick surveillance.

"The world of ticks reaches entomologists, veterinarians, medical doctors, public health, natural resource managers, farmers, pet owners, scientists, and anyone that enjoys the outdoors," says Nohra Mateus-Pinilla, Ph.D., co-author on the study and director of the Veterinary Epidemiology Laboratory at the University of Illinois's Illinois Natural History Survey. "The partnerships stand out because broad, collaborative networks are paramount to a positive and productive path for the advancement of this field."

Info and data sharing on ticks and public health is lagging. Less than a quarter of respondents said their tick-management programs disseminate information to local health departments (23 percent) or report data to the CDC (14 percent).

Greater support for tick-management programs is critical. To improve tick-management programs, respondents commonly cited the need for stable funding, training for personnel, and standardized, research-based guidance and protocols.

In December 2019, the Kay Hagan Tick Act was signed into federal law, authorizing $150 million to strengthen various aspects of the nation's efforts to vector-borne disease, including reauthorization of the CDC's Vector-Borne Disease Regional Centers of Excellence for an additional five years, through 2026. The CDC also issued guidance documents in late 2018 and early 2020 to provide tick-management programs with best practices for surveillance of blacklegged tick species (Ixodes scapularis and Ixodes pacificus) and other hard tick species across the U.S.

These steps address needs revealed in the survey of tick-management programs, and Mader and Mateus-Pinilla say the survey will serve as an important baseline from which to measure future progress and improvement.

"Overall, tick-work demands a long-term commitment. Ticks can take years to complete their life cycle, use different hosts to move around, and take advantage of weather and habitat changes," says Mateus-Pinilla. "As such, research on these vectors requires long-term and sustained commitment to research, surveillance, and partnerships across a broad range of disciplines, health professionals, and the public."

With the global spread of coronavirus infections, personal protective equipments especially hygeine face masks are receiving much attention. Masks are essential items for the primary protection of the respiratory tract from viruses and bacteria that are transmitted through the air as droplets.

N95 masks are currently difficult to obtain, so there is an urgent need for a safe method of prolonging their usability through disinfection and reuse with minimal loss of the performance and integrity. Particulate filtration and air permeability are key factors in determining performance while cleaning and disinfecting N95 certified masks. This is crucial in preventing infections. Shinshu University has a track record of conducting research on production methods and applications of "nanofiber non-woven fabric" since before the coronavirus outbreak.

With this current social backdrop, a research team led by Professor Ick Soo Kim of Shinshu University's Institute for Fiber Engineering (IFES) with Ph.D. students Sana Ullah and Azeem Ullah and Professor Cha Hyung Joon of POSTECH (specially invited professor of IFES) with Ph.D. students Jaeyun Lee and Yeonsu Jeong looked into the effectiveness of sterilizing N95 masks. They looked at commercially available melt-blown nonwoven fabric N95 masks and nonwoven nanofiber masks with N95 filters. They examined the filtration efficiency, comfort of the wearer, and filter shape change after washing and disinfecting. The methods of disinfection test were directly spraying 75% ethanol on the mask filter and air drying, and soaking the mask filter in 75% ethanol solution for 5 minutes to 24 hours and leaving it to air dry naturally.

Filtration efficiency of both of the filters (melt-blown filter and the nanofiber filter) was 95% or more before use, which indicates that the respiratory organs of the wearer can be effectively protected. The tests also clarified that the inside of the filter can be effectively sterilized by spraying ethanol 3 times or more or immersing it in an ethanol solution for more than 5 minutes. However, when the mask was reused after the ethanol disinfection, the filtration efficiency of the melt-blown filter decreased to 64%. On the other hand, the nanofiber filter did not deteriorate in filter performance even after 10 or more uses.

Melt-blown filter works on the principle of electrostatic charge for removal of particulate matter, as in the result of ethanol spraying or dipping the electrostatic charge on the surface of melt-blown filter was lost, so efficiency of melt-blown filter was significantly decreased. On the other hand, filtration mechanism of nanofiber filter is independent of static charge and fully dependent on pore diameter, pore distribution, and morphology of nanofibers. As in the result of disinfection, morphology of nanofibers was not affected, thus it also maintained it's filtration as optimum as it was before use.

In addition, the nanofiber filter has higher heat emission and carbon dioxide emission performance than the melt-blown filter, and exhibits excellent breathability. Similarly, it was confirmed that the nanofiber filter had lower cytotoxicity than the melt-blown filter when a safety experiment using human skin and vascular cells was performed.

As stated above, both mask filters have similar filtering performance at the time of first use, but after disinfecting and reusing, the nanofiber filter does not exhibit performance deterioration. In other words, nanofiber filters can be easily sterilized with ethanol at home and reused multiple times.

"This research is an experimental verification of the biological safety of nanofiber masks and the maintenance of filtration efficiency after washing, which has recently become a problem," Professor Cha Hyung Joon states, who co-presided the research. Professor Ick Soo Kim hopes that nanofiber masks will serve as a means of prevention in the second and third wave of coronavirus infections.

Molecular containers that remove drugs, toxins, or malodorous substances from the environment are called sequestering agents. Scientists have developed a class of molecular containers that specifically sequester neurotransmitter antagonists. The barrel-shaped molecules called Pillar[n]MaxQ bind neuromuscular blocking chemicals 100,000-fold more tightly than established macrocyclic detoxification agents, the researchers report in the journal Angewandte Chemie.

Molecular containers of the cyclodextrin type sequester their targets by complexation. The ring- or barrel-shaped molecules recognize the molecular features of the target molecules and pull them into the central cavity using hydrophobic forces. Once the target molecule is inside this molecular container, it is neutralized. This host-guest complexation is the mechanism by which cyclodextrins, which are large, ring-shaped sugar molecules, eliminate unpleasant odors.

However, cyclodextrins are not very specific and fail for most alkaloids--a class of nitrogen-containing chemicals, including neurotransmitters and many illicit drugs. For these compounds, a class of molecular containers called pillararenes appear to be useful. They keep the alkaloids tightly bound in their pillararene cavity by wrapping a ring wall of aromatic benzene units around the hydrocarbon-rich molecular body.

Lyle Isaacs and his research team from the University of Maryland have further advanced the structure of the pillararenes to make the host-guest interactions stronger and more specific. "We envisioned to create a higher negative charge density around the mouth of the cavity by introducing acidic sulfate functional groups," the authors wrote. The negatively charged sulfate groups attract and bind quaternary ammonium ions, which are a hallmark of several clinically important neuromuscular blocking agents. The sulfate groups also stiffened the molecular structure of the barrels, the researchers found, so that the drug guest was smoothly pulled into the cavity by hydrophobic forces.

The researchers dubbed the molecular containers Pillar[n]MaxQ, where n indicates a target-size-dependent diameter that is variable. They observed that this class of sequestering agents binds the neuromuscular blockers up to 100,000-fold more tightly than the cyclodextrin container Sugammadex, which is in clinical use. Moreover, the sequestering agent discriminated against acetyl choline, a natural transmitter substance of nerve impulses within the central and peripheral nervous systems, which should not be sequestered.

The authors measured the host-guest complexation activities of Pillar[n]MaxQ by titration studies involving calorimetry and nuclear magnetic resonance of the guest molecules. As pillararenes have also been shown to reverse the effects of neuromuscular agents in rats, the researchers are aiming to study the new Pillar[n]MaxQ sequestering actions in animal models. Because of the high binding and the specificity of the chemically tailored molecular containers, they are confident that they will observe positive results.

WASHINGTON--Mild thyroid abnormalities affect up to one in five women with a history of miscarriage or subfertility which is a prolonged time span of trying to become pregnant, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Thyroid disorders are common in women of reproductive age. Although the prevalence of thyroid disorders in pregnancy are well understood, little is known about how common these disorders are in women prior to pregnancy. Detecting thyroid disorders before a woman becomes pregnant is essential because thyroid abnormalities can have negative effects such as reduced fertility, miscarriage and pre-term birth.

"This study has found that mild thyroid abnormalities affect up to one in five women who have a history of miscarriage or subfertility and are trying for a pregnancy," said Rima Dhillon-Smith, M.B.Ch.B., Ph.D., of the University of Birmingham and the Birmingham Women's and Children's NHS Foundation Trust in Birmingham, U.K. "It is important to establish whether treatment of mild thyroid abnormalities can improve pregnancy outcomes, given the high proportion of women who could potentially be affected."

This study was conducted across 49 hospitals in the U.K. over five years. The researchers studied over 19,000 women with a history of miscarriage or subfertility who were tested for thyroid function. They found up to one in five women had mild thyroid dysfunction, especially those with an elevated BMI and of Asian ethnicity, but overt thyroid disease was rare. Women who suffered multiple miscarriages were no more likely to have thyroid abnormalities compared to women who have conceived naturally with a history of one miscarriage.