Atomic structure of antifungal drug confirms unusual mechanism, opens door to less-toxic derivatives

Illinois chemistry professor Martin Burke co-led a team that mapped the unusual aggregate structure of the antifungal drug amphotericin B, illuminating the path to develop less-toxic forms of the drug.  Photo by L. Brian Stauffer

Advanced molecular imaging technology has now mapped the structure of a drug widely used to treat fungal infections but whose workings have mystified researchers and physicians for nearly 70 years.

In a new study, researchers at the University of Illinois Urbana-Champaign, the University of Wisconsin, Madison and the National Institutes of Health described in atomistic detail the structure of the drug amphotericin B, a powerful but toxic antifungal agent.

Seeing the structure provides illumination in the researchers’ quest to formulate less-toxic AmB derivatives, said Dr. Martin D. Burke, a professor of chemistry at Illinois and a member of the Carle Illinois College of Medicine, as well as a medical doctor. Burke co-led the study with Chad Rienstra, a Wisconsin professor of biochemistry, and Taras Pogorelov, an Illinois research professor of chemistry. The researchers reported their findings in the journal Nature Structural & Molecular Biology.

“It’s like we were driving in the dark at night, and all of a sudden we were able to put the lights on. With the clarity of this structure, we can see where we need to go to reach our goal of a less-toxic antifungal drug,” Burke said.

Previously, researchers and physicians thought that AmB killed fungal cells by forming channels in the cell membrane, the outer envelope that encases the cell. However, in 2014, while Rienstra was a professor at Illinois, Burke and Rienstra’s group found that amphotericin primarily kills cells by robbing the membrane of sterol molecules – cholesterol in human cells and ergosterol in fungal cells. Individual amphotericin molecules aggregated into a larger structure that absorbed sterol molecules out of cell membranes like a sponge, causing the cells to die.

Stretchy, washable battery brings wearable devices closer to reality

Dr. Ngoc Tan Nguyen and his colleagues have created a battery that is both flexible and washable. It works even when twisted or stretched to twice its normal length, or after being washed multiple times. Photo credit: Kai Jacobson

UBC researchers have created what could be the first battery that is both flexible and washable. It works even when twisted or stretched to twice its normal length, or after being tossed in the laundry.

“Wearable electronics are a big market and stretchable batteries are essential to their development,” says Dr. Ngoc Tan Nguyen (he/him), a postdoctoral fellow at UBC’s faculty of applied science. “However, up until now, stretchable batteries have not been washable. This is a critical addition if they are to withstand the demands of everyday use.”

The battery developed by Dr. Nguyen and his colleagues offers a number of engineering advances. In normal batteries, the internal layers are hard materials encased in a rigid exterior. The UBC team made the key compounds—in this case, zinc and manganese dioxide—stretchable by grinding them into small pieces and then embedding them in a rubbery plastic, or polymer. The battery comprises several ultra-thin layers of these polymers wrapped inside a casing of the same polymer. This construction creates an airtight, waterproof seal that ensures the integrity of the battery through repeated use.

New State of Matter: Crystalline and Flowing at the Same Time

Cluster crystals consist of a core of organic polymers surrounded by DNA molecules (right). Pressed together (left), they exhibit properties of crystals and liquids at the same time.
© Natasa Adzic, University of Vienna

More than 20 years ago, researchers predicted that with sufficiently high density certain particles of matter would form a new state of matter that features the properties of both crystalline solids and flowing liquids. Scientists from Forschungszentrum Jülich, the University of Siegen, and the University of Vienna have now succeeded in creating this state in a laboratory. Their experimental concept opens up the possibility for further development and could pave the way for further discoveries in the world of complex states of matter.

Through their research efforts, the team was able to finally disprove an intuitive assumption that in order for two particles of matter to merge and form larger units (i.e. aggregates or clusters), they must be attracted to each other. As early as the turn of the century, a team of soft matter physicists headed by Christos Likos of the University of Vienna predicted on the basis of theoretical considerations that this does not necessarily have to be the case. They suggested that purely repulsive particles could also form clusters, provided they are fully overlapping and that their repulsion fulfils certain mathematical criteria.

A new layer-by-layer built inorganic-organic material enables optical switching of magnetic properties

Materials chemists have developed a facile process for piling ultrathin inorganic and organic layers in a pre-designed manner into flexible room-temperature thin-film magnets, whose magnetic properties can be controlled with successive external light illuminations.

In the big data era, photo-controlled room-temperature magnets could open new horizons for high-density information storage, in particular, if these materials could be synthesized from non-critical raw materials and fabricated in device-integrable thin-film form. Now a team of Aalto University researchers from the Department of Chemistry and Material Science and the Department of Applied Physics report such dream-of-the-dream materials.

For the material fabrication, the Aalto researchers utilize the Millennium Prize awarded ALD (atomic layer deposition) technology, which they have modified so that within the ALD-grown ferrimagnetic inorganic layers ultrathin photo-switchable organic layers can be deposited through additional MLD (molecular layer deposition) cycles.

The inorganic component harnessed by the researchers into these thin films is unique itself, as it possesses an extremely high magnetic coercivity field, but is at the same time really simple in its chemical composition, being composed of iron and oxygen only.

Silvopasture could tackle Colombian Amazon’s high deforestation rates

Silvopastoral farming, where trees and forage plants are planted in livestock pasture, may support biodiversity and offer solutions to high deforestation rates, according to a new University of Bristol-led study that investigated the effects of the farming method across farms in Colombia, South America.

A transition to silvopastoral systems (SPS), when implemented in a participatory way where farmers can decide how the system is adopted in their farms and make commitments to conserve remnant forests, could help Colombia meet its greenhouse gas emissions targets for 2030 and protect the country’s Amazonian forests.

Over the last 20 years, Colombia — the second most biodiverse country in the world, has lost more than 4.6million hectares of forest, partly due to the expansion of cattle farming, which in turn is related to complex historical, economic and political reasons. While a range of national and international agri-environmental projects aimed at reducing deforestation levels have been implemented in Colombia, until now their uptake and efficacy was not known.

The BioSmart project, comprising entomologists, economists, geographers, climate modelers and botanists, sought to assess biodiversity value in silvopasture compared with non-SPS conventional pasture sites. The team recorded the number of insects and plant species across 16 SPS farm sites in Caquetá, Colombia. An Amazonian department which experiences particularly high levels of deforestation where 6,883km2 of forest was cleared between 2000-2020, equivalent to 8.5% of the region’s total forest-covered land.

Key surveys overestimate COVID-19 vaccination rates in the USA

Estimates of COVID-19 vaccine uptake in the USA based on large surveys that are used to guide policy-making decisions tend to overestimate the number of vaccinated individuals, research published in Nature suggests.

In the USA, the CDC (Centers for Disease Control and Prevention) compiles data on national vaccine uptake, but reporting can sometimes be delayed. Surveys that measure attitudes and behavior towards COVID-19 vaccines can fill a gap when there is a lag in real-time data, and can inform government responses to the epidemic. However, some surveys diverge substantially in their findings.

The authors of a new paper published in Nature today find that in May 2021, Delphi–Facebook’s COVID-19 symptom tracker (250,000 responses per week) overestimated vaccine uptake by 17 percentage points, and a survey from the US Census Bureau (75,000 responses per wave) overestimated vaccine uptake by 14 percentage points compared to benchmark estimates from the CDC.

These overestimation errors go orders of magnitude beyond the statistical uncertainty provided by the surveys. A survey by Axios–Ipsos also overestimated uptake, but by a smaller amount (4.2 percentage points in May 2021)—despite being the smallest survey (about 1,000 responses per week). These findings indicate that bigger is not always better when it comes to datasets, if we fail to account for data quality.

The authors note that COVID-19 vaccine uptake was not the primary focus of any of the surveys. For example, Delphi-Facebook intends to measure changes in COVID-related behaviors over time. However, the bias in estimates of vaccine uptake in the two large surveys indicates that they are not representative of the US adult population. Lack of statistical representativeness may also be causing bias in other survey outcomes they suggest.

Study finds bio-based cellulose acetate plastic used in consumer goods disintegrates in ocean much faster than assumed

WHOI postdoctoral investigator Michael Mazzotta cuts plastic samples to measure respiration signals of microbial communities respiring cellulose diacetate. A new study led by WHOI researchers finds that cellulose diacetate, a bio-based plastic, degrades in the ocean faster than previously thought.
Image credit: Collin Ward © Woods Hole Oceanographic Institution

Cellulose diacetate (CDA), a bio-based plastic widely used in consumer goods, disintegrates, and degrades in the ocean far quicker than previously assumed, according to a new study published in Environmental Science & Technology Letters.

“These findings challenge the paradigm set by governmental agencies and advocacy groups that CDA-based materials persist in the ocean for decades,” according to the paper, “Rapid Degradation of Cellulose Diacetate by Marine Microbes.” “While no one plastic type will likely meet all of the diverse and growing needs of consumers, these initial findings on the fate of CDA-based materials in the ocean, combined with previous reports in terrestrial and wastewater systems, represent a positive step towards identifying high utility, bio-based plastics with low environmental persistence.”

CDA is largely derived from wood pulp, making it a “bio-based” plastic. It is widely used in consumer goods, including cigarette filters, textiles, coatings, films, food packaging, and other products such as eye glass frames and tool handles.

Scientists Show How Wildfire Smoke Increases Ozone Pollution

Using data gathered from a specially equipped jet that spent a month flying through and studying wildfire plumes, scientists have a better understanding now of how wildfire smoke impacts air quality.

Crucially, they found a mechanism for predicting the production of the pollutant ozone—which, at the ground level, can create poor breathing conditions and also harm ecosystems. Also, the team found that mixing wildfire smoke with urban pollution ramps up the production of ozone, meaning that wildfires upwind of cities are a recipe for air quality problems.

"Of course it is well known that wildfires lower air quality. But it's important to understand the chemical and physical mechanisms by which they do so that we can more effectively forecast how individual fires will impact the communities downwind of them," says Paul O. Wennberg, R. Stanton Avery Professor of Atmospheric Chemistry and Environmental Science and Engineering.

Wennberg is a corresponding author of a paper on the research that was published by Science Advances on December 8.

The paper draws on data collected through the NASA/NOAA FIREX-AQ project, which spent

a month flying missions out of Boise, Idaho, during the summer of 2019. (The project later studied agricultural fires in the Midwest.) Riding a DC-8 that had been converted into a flying laboratory, scientists flew through smoke plumes and gathered information from instruments mounted on the plane. Included in the payload were two instruments from Caltech operated by chemistry graduate students Krystal Vasquez and Hannah Allen, staff scientist John Crounse, and lead author Lu Xu, who completed the work as a staff scientist in Wennberg's lab and is now a research scientist with the Cooperative Institute for Research in Environmental Sciences (CIRES) at the University of Colorado Boulder working in NOAA's Chemical Sciences Laboratory.

Early heat warning system to help save lives in changing climate

A Griffith University-led three-year project to develop an early warning system in homes during extreme heat events has received more than $2 million in funding.

The EtHOs project, was awarded $2.35 million by global charitable foundation Wellcome to help limit the thousands of lives lost each year to heat stress.

Led by Dr Shannon Rutherford, from the School of Medicine and Dentistry, EtHOs is a multidisciplinary research team within the Climate Action research group that includes experts in aged-care nursing, IT, human physiology, engineering, climate science, health economics and environmental epidemiology.

Dr Rutherford said the team recognized that climate change would lead to more extreme and frequent heat episodes and said action must be taken to reduce the risk to older populations who were more vulnerable to heat stress.

“We want to develop an individualized early warning system for older people living at home specific to their home environment and considering different people may be vulnerable to heat for different reasons, and we all have different needs for and levels of access to cooling options,” Dr Rutherford said.

“We would like older people living at home and in the community to have access to a system that helps them, their families and care systems feel safe and confident in their homes as the world experiences more frequent and more intense heat events.”

Burrowing snakes have far worse eyesight than their ancestors

The prong-snouted blind snake (Anilios bituberculatus)
is common across southern Australia.
Credit: Tom Charlton

The ancestor of all living snakes probably had substantially better vision than present-day burrowing snakes, according to new research.

An international team of scientists – led by the Natural History Museum and the University of Plymouth – carried out the first detailed analysis of gene sequence data for any species of the so-called 'blindsnakes' (Scolecophidia), a group of small-eyed burrowers.

They found that seven of the 12 genes associated with bright-light vision in most snakes and lizards species are not present in scolecophidians.

This, they say, demonstrates extensive vision gene loss over tens of millions of years of evolutionary history, similar to that which has also been observed in burrowing mammals with reduced vision.

It also challenges the hypothesis that all snakes living across the world today evolved from extreme burrowers, because the vision genes lost in scolecophidians are present in most other living snakes. The researchers say it would be extremely unlikely for such genetic deficiencies to have been reversed through evolution.

Scolecophidians are dedicated burrowers and form one half of the oldest divergence in the snake tree.

They comprise around 460 of the approximately 3,850 currently recognized living snake species, and likely diverged from their closest living relatives (Alethinophidia, which includes all other living snakes) more than 65 million years ago.