Culture

SAN ANTONIO (June 17, 2021) -- Middle-aged people with depressive symptoms who carry a genetic variation called apolipoprotein (APOE) ε4 may be more at risk to develop tau protein accumulations in the brain's emotion- and memory-controlling regions, a new study by researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) and collaborating institutions suggests.

The Journal of Alzheimer's Disease published the findings in its June 2021 print issue. The research is based on depression assessments and positron emission tomography (PET) imaging conducted among 201 participants in the multigenerational Framingham Heart Study. The mean age of these participants was 53.

Decades before diagnosis

PET scans typically are conducted in older adults, so the Framingham PET studies in middle-aged persons are unique, said Mitzi M. Gonzales, PhD, lead author of the study and a neuropsychologist with the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, which is part of UT Health San Antonio.

"This gives us an interesting opportunity to study people at midlife and get a sense of factors that might be associated with protein accumulations in individuals who are cognitively normal," Dr. Gonzales said. "These persons are likely decades before any type of dementia diagnosis, if they are to develop dementia in the future."

No associations found with amyloid beta

Amyloid beta (amyloid-β) and tau are proteins that aggregate in the brains of people with Alzheimer's disease and also typically increase to a milder extent with normal aging. The study found no associations of depressive symptoms and depression with amyloid-β. The only association was with tau, and only in APOE ε4 variant carriers. About one-fourth of the participants (47 of 201) were ε4 carriers, by virtue of having at least one copy of the ε4 allele.

Having one copy of APOE ε4 increases the risk of developing Alzheimer's by as much as two- to threefold, but some people with this variant live into their 80s and 90s and never develop the disease. "It's important to keep in mind that just because a person is identified as carrying the APOE ε4 allele does not mean that he will develop dementia in the future," Dr. Gonzales said. "It just means that the risk is higher."

Depressive symptoms (and depression if symptoms were severe enough to reach that diagnostic threshold) were evaluated with the Center for Epidemiological Studies Depression Scale at the time of PET imaging, as well as eight years prior. Associations between depressive symptoms and depression with PET outcomes at both time points were evaluated, adjusting for age and sex.

Centers of emotion and cognition

The study showed associations between depressive symptoms and increased tau in two brain regions, the entorhinal cortex and amygdala. "These associations do not infer that the tau accumulation causes the depressive symptoms, or vice versa," Dr. Gonzales said. "We only note that both are present in the ε4 carriers."

The entorhinal cortex is important for memory consolidation and tends to be an area where protein deposition occurs early on, she noted. The amygdala, meanwhile, is considered the emotion center of the brain.

"Longitudinal studies are needed to further understand what is happening, but it is intriguing to think about the clinical significance of our findings in terms of cognition as well as emotional regulation," Dr. Gonzales said.

Nanodecoys made from human lung spheroid cells (LSCs) can bind to and neutralize SARS-CoV-2, promoting viral clearance and reducing lung injury in a macaque model of COVID-19. By mimicking the receptor that the virus binds to rather than targeting the virus itself, nanodecoy therapy could remain effective against emerging variants of the virus.

SARS-CoV-2 enters a cell when its spike protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell's surface. LSCs - a natural mixture of lung epithelial stem cells and mesenchymal cells - also express ACE2, making them a perfect vehicle for tricking the virus.

"If you think of the spike protein as a key and the cell's ACE2 receptor as a lock, then what we are doing with the nanodecoys is overwhelming the virus with fake locks so that it cannot find the ones that let it enter lung cells," says Ke Cheng, corresponding author of the research. "The fake locks bind and trap the virus, preventing it from infecting cells and replicating, and the body's immune system takes care of the rest."

Cheng is the Randall B. Terry Jr. Distinguished Professor in Regenerative Medicine at North Carolina State University and a professor in the NC State/UNC-Chapel Hill Joint Department of Biomedical Engineering.

Cheng and colleagues from NC State and UNC-CH converted individual LSCs into nanovesicles, or tiny cell membrane bubbles with ACE2 receptors and other lung cell-specific proteins on the surface.

They confirmed that the spike protein did bind to the ACE2 receptors on the decoys in vitro, then used a fabricated SARS-Co-V-2 mimic virus for in vivo testing in a mouse model. The decoys were delivered via inhalation therapy. In mice, the nanodecoys remained in the lungs for 72 hours after one dose and accelerated clearance of the mimic virus.

Finally, a contract research organization conducted a pilot study in a macaque model and found that inhalation therapy with the nanodecoys accelerated viral clearance, and reduced inflammation and fibrosis in the lungs. Although no toxicity was noted in either the mouse or macaque study, further study will be necessary to translate this therapy for human testing and determine exactly how the nanodecoys are cleared by the body.

"These nanodecoys are essentially cell 'ghosts,' and one LSC can generate around 11,000 of them," Cheng says. "Deploying millions of these decoys exponentially increases the surface area of fake binding sites for trapping the virus, and their small size basically turns them into little bite-sized snacks for macrophages, so they are cleared very efficiently."

The researchers point out three other benefits of the LSC nanodecoys. First, they can be delivered non-invasively to the lungs via inhalation therapy. Second, since the nanodecoys are acellular - there's nothing living inside - they can be easily preserved and remain stable longer, enabling off-the-shelf use. Finally, LSCs are already in use in other clinical trials, so there is an increased likelihood of being able to use them in the near future.

"By focusing on the body's defenses rather than a virus that will keep mutating we have the potential to create a therapy that will be useful long-term," Cheng says. "As long as the virus needs to enter the lung cell, we can keep tricking it."

The research appears in Nature Nanotechnology and was supported by the National Institutes of Health and the American Heart Association. Dr. Jason Lobo, pulmonologist at UNC-CH, is co-author of the paper.

TROY, N.Y. -- Optoelectronic materials that are capable of converting the energy of light into electricity, and electricity into light, have promising applications as light-emitting, energy-harvesting, and sensing technologies. However, devices made of these materials are often plagued by inefficiency, losing significant useful energy as heat. To break the current limits of efficiency, new principles of light-electricity conversion are needed.

For instance, many materials that exhibit efficient optoelectronic properties are constrained by inversion symmetry, a physical property that limits engineers' control of electrons in the material and their options for designing novel or efficient devices. In research published today in Nature Nanotechnology, a team of materials scientists and engineers, led by Jian Shi, an associate professor of materials science and engineering at Rensselaer Polytechnic Institute, used a strain gradient in order to break that inversion symmetry, creating a novel optoelectronic phenomenon in the promising material molybdenum disulfide (MoS2) -- for the first time.

To break the inversion symmetry, the team placed a vanadium oxide (VO2) wire underneath a sheet of MoS2. Molybdenum disulfide is a flexible material, Shi said, so it deformed its original shape to follow the curve of the VO2 wire, creating a gradient within its crystal lattice. Imagine what would happen if you placed a piece of paper over a pencil that was sitting on a table. The varied tension created in the paper is like the strain gradient formed in the MoS2 lattice.

That gradient, Shi said, breaks the material's inversion symmetry and allows electrons traveling within the crystal to be manipulated. The unique photo-response observed near the strain gradient allows a current to flow through the material. It's known as the flexo-photovoltaic effect, and it could be harnessed to design novel and/or high-efficiency optoelectronics.

"This is the first demonstration of such an effect in this material," Shi said. "If we have a solution that does not create heat during photon-electricity conversion, then the electronic devices or circuits could be improved."

Vanadium oxide is very sensitive to temperature, so the team was also able to demonstrate that the flexo-photovoltaic effect brought about temperature dependence at the site where the MoS2 and VO2 materials meet -- changing the lattice's gradient accordingly.

"This discovery suggests a novel principle that could be used for remote thermal sensing," said Jie Jiang, a postdoctoral research fellow in Shi's lab and the first author on this paper.

What the team was able to demonstrate here, Shi said, not only shows great promise for this material, but also suggests the potential of using such an approach in engineering other materials with favorable optoelectronic properties that are plagued by inversion symmetry.

The article 'The RNA Atlas expands the catalog of human non-coding RNAs', published today in Nature Biotechnology, is the result of more than five years of hard work to further unravel the complexity of the human transcriptome. Never before such a comprehensive effort was undertaken to characterize all RNA-molecules in human cells and tissues.

RNAs in all shapes and sizes

Our transcriptome is - analogous to our genome - the sum of all RNA molecules that are transcribed from the DNA strands that make up our genome. However, there's no 1-on-1 relationship with the latter. Firstly, each cell and tissue hasve a unique transcriptomes, with varying RNA production and compositions, including tissue-specific RNAs. Secondly, not all RNAs are transcribed from typical - protein coding - genes that eventually produce proteins. Many of our RNA molecules are not used as a template to build proteins, but originate from what once was called junk DNA: long sequences of DNA with unknown functions.

These non-coding RNAs (ncRNAs) come in all kinds of shapes and sizes: short, long, and even circular RNAs. Many of them even lack the tail of adenine-molecules that is typical for protein-coding RNAs.

300 human cell and tissue types and three sequencing methods

"There have been other projects to catalogue our transcriptome but the RNA-Atlas project is unique because of the applied sequencing methods," says prof. Pieter Mestdagh from the Center for Medical Genetics at Ghent University. "Not only did we look at the transcriptome of as many as 300 human cell and tissue types, but most importantly, we did so with three complementary sequencing technologies, one aimed at small RNAs, one aimed at polyadenylated (polyA) RNAs and a technique called total RNA sequencing."

This last sequencing technology led to the discovery of thousands of novel non-coding RNA genes, including a novel class of non-polyadenylated single exon genes and many new circular RNAs. By combining and comparing the results of the different sequencing methods the researchers were able to define for every measured RNA transcript, the abundance in the different cells and tissues, whether it has a polyA-tail or not (it appears that for some genes this can differ from cell type to cell type), and whether it is linear of circular. Moreover, the consortium searched and found important clues in determining the function of some of the ncRNAs. By looking at the abundancy of different RNA's in different cell types they found correlations that indicate regulatory functions, and could determine whether this regulation happens on the transcription level (by preventing or stimulating transcription of protein coding genes) or post-transcriptional (e.g. by breaking down RNAs).

An invaluable resource for biomedical science

All data, analyses and results (equivalent to a few libraries of information) are available for download and interrogation in the R2 web portal, enabling the community to implement this resource as a tool for exploration of non-coding RNA biology and function.

Prof. Pavel Sumazin of the Baylor College of Medicine: "By combining all data in one comprehensive catalogue, we have created a new valuable resource for biomedical scientists around the world studying disease processes. A better understanding of the complexity of the transcriptome is indeed essential to better understand disease processes and uncover novel genes that may serve as therapeutic targets or biomarkers. The age of RNA therapeutics is swiftly rising - we've all witnessed the impressive creation of RNA vaccines, and already the first medicines that target RNA are used in the clinic. I'm sure we'll see lots more of these therapies in the next years and decades."

Additive manufacturing offers an unprecedented level of design flexibility and expanded functionality, but the quality and process can drastically differ across production machines, according to Hui Yang, a professor of industrial engineering at Penn State. With applications in aerospace, health care and automotive industries with potential for mass customization, additive manufacturing needs quality management.

To address this concern, Yang and a team of researchers from Penn State, University of Nebraska--Lincoln and the National Institute of Standards and Technology (NIST) proposed the design, development and implementation of a new data-driven methodology for quality control in additive manufacturing. They published their work in the Proceedings of Institute of Electrical and Electronics Engineers (IEEE).

"Like an ecosystem, we have people working in isolated efforts in different areas of additive manufacturing, and systems engineers can help connect the dots to provide a framework for quality management," Yang said. "Quality is indispensable, and if we design a system-level framework of quality management from the start, then we have higher quality and better productivity at less cost. Ultimately, everyone wants to do high-precision, high-end manufacturing, but if quality suffers at any step during production, you lose the competitive advantage needed for the global market. Leveraging data to control and ensure high quality products helps keep that advantage."

The team worked together to analyze various academic papers to deduce a six sigma framework of quality control for additive manufacturing, which lead to their proposed systems engineering approach.

The method hinges on six sigma, a popular approach that uses data-driven tactics to eliminate defects, drive profits and improve quality of products. Through their detailed analysis, the team suggested that this five-step approach of defining, measuring, analyzing, improving and controlling can further the quality management when applied to additive manufacturing.

"Via the research we analyzed, we identified the critical challenges of additive manufacturing and where quality standards are lacking," Yang said. "For each step in the process, you need to identify the sticking points, which is where methods such as machine learning can come into play and help show an engineer or designer how to control the process to avoid defects."

Tim Simpson, Paul Morrow Professor in Engineering Design and Manufacturing and professor of mechanical engineering at Penn State, explained that such defects can become massive liabilities when considered in the context of mass-produced products.

"If your goal is to use additive manufacturing to make parts for a car or a plane, then that part better not fail," Simpson said.

He also noted the cost of failed parts can add up -- a failed metal build, he said, could "easily cost 10 to 20 thousand dollars and require multiple iterations along the way."

By looking for the quality gaps in the standards for mass-produced parts, Simpson said their proposed methodology is critical to ensure quality production with additive manufacturing for both high volume and custom products.

"Quality control processes and methods are established for mass production, where you make hundreds to millions of things," Simpson said. "Additive manufacturing enables customization, and the current quality control methods and accepted practices do not readily apply when you are only making one or a few of an item. We have to think differently to ensure highly quality parts."

Soundar Kumara, Allen E. Pearce and Allen M. Pearce Professor of Industrial Engineering at Penn State, noted that their review represents the state-of-the-art additive manufacturing technologies and can help researchers by providing a comprehensive understanding of the tools and techniques.

CAMBRIDGE, MA--Geothermal energy systems have the potential to power the world and become the leading technology for reducing greenhouse gas emissions if we can drill down far enough into the Earth to access the conditions necessary for economic viability and release the heat beneath our feet. Quaise Inc. is developing a potentially disruptive and completely unique drilling technology to make that happen.

That was the takeaway from a paper presented by Matt Houde of Quaise at the World Geothermal Congress (WGC) on June 15. Houde not only described the company's technology, which was pioneered at MIT, but also presented several calculations and a cost model showing its technical and economic feasibility.

Houde's coauthors are Quaise CEO Carlos Araque, Ken Oglesby of Impact Technologies LLC, and Paul Woskov of the MIT Plasma Science and Fusion Center (PSFC).

Accessing the Mother Lode

The mother lode of geothermal energy is some 2 to 12 miles beneath the Earth's surface where conditions are so extreme (for example, temperatures are over 374 degrees C, or 704 degrees F) that if water could be pumped to the area it would become supercritical, a steam-like phase that most people aren't familiar with. (Familiar phases are liquid water, ice, and the vapor that makes clouds.) Supercritical water, in turn, can carry some 5-10 times more energy than regular hot water, making it an extremely efficient energy source if it could be pumped above ground to turbines that could convert it into electricity.

Today we can't access those conditions except in Iceland and other areas where they are relatively close to the surface. The number one problem: we can't drill down far enough. The drills used by the oil and gas industries can't withstand the formidable temperatures and pressures that are found miles down.

Houde began his talk with a quote from the Department of Energy's 2019 Geovision report, an analysis of the geothermal industry in the United States: "Supercritical resources can be found everywhere on Earth by drilling deep enough...Drilling to this depth is financially prohibitive with existing technology...Economic production of supercritical resources will require the development of entirely new classes of drilling technologies and methods."

Quaise is working to that end. The company's technique replaces the conventional drill bits that mechanically break up the rock with millimeter wave energy (cousins to the microwaves many of us cook with). Those millimeter waves (MMWs) literally melt then vaporize the rock to create ever deeper holes. The title of Houde's WGC talk: "Rewriting the Limits for Deep Geothermal Drilling: Direct Energy Drilling Using Millimeter Wave Technology."

"It sounds like sci-fi technology, but it's not," says Houde. "It is definitely real, and it's feasible and practical. It's just a matter of implementing it and validating it in the lab and in the field."

A Strong Foundation

Houde emphasizes that the Quaise approach is based on technology "that's already mature and commercialized," having been developed over decades for fusion energy research and for the oil and gas industries. Quaise is simply repurposing that technology for a different application.

For example, the MMW energy key to the technology is produced with a gyrotron machine and directed to its target (deep, hot rock) via waveguides. Both were developed over some 50 years of research into nuclear fusion as an energy source. The Quaise technique also takes advantage of conventional drilling technologies such as those developed by the oil and gas industries. Quaise will still use these to drill down through surface layers to bedrock, which was what they were optimized for.

Then the system will switch to the MMW technology. The latter "simplifies everything downhole such that nothing is particularly sensitive to the high temperatures and pressures. That allows us to mitigate many of the issues we have with conventional mechanical rigs at these depths," Houde says.

Running the Numbers

Houde presented several calculations showing the technical feasibility of the Quaise approach. For example, he showed that the drilling rate even several miles into the Earth should be roughly the same as that for conventional geothermal drilling. Further: the Quaise MMW technology automatically melts the rock to create a strong glass "liner" that prevents the hole from collapsing and protects the waveguide. About six miles down, that would replace the cement casings currently used to protect the boreholes associated with conventional, mechanical drilling nearer the surface. This, in turn, actually solves additional problems like the downtime associated with removing broken drill bits.

Houde also presented calculations regarding the removal of the vaporized rock, which is done using existing compressor technology to pump a purge gas down into the hole along with the MMW energy. Think of the general setup as a straw within a larger straw. The energy and gas travel downhole through the inner straw where they eventually reach and vaporize the rock at the bottom. Then the gas carrying the vaporized rock, or particulate, travels back up to the surface through the space between the two straws. "Our calculations show that the particulate can be conveyed uphole with downhole pressures and flow rates that fall within bounds of existing compressors," Houde says.

A cost model of the economic feasibility of the Quaise approach is also promising. Houde notes that few geothermal wells have been drilled past ten kilometers (~six miles), but to get that far using conventional technology costs more than $5,000 per meter. The cost model indicates that MMW drilling could reach twice that depth at drilling costs of around $1,000 per meter.

What's Next?

Although experiments at MIT have shown the general feasibility of drilling with MMW energy, the technique must still be proved in the field. Quaise aims to do just that over the next few years out in the western United States, working in collaboration with Altarock, MIT's PSFC, Oak Ridge National Laboratory, Impact Technologies, and General Atomics.

Investors in the company are the Advanced Research Projects Agency-Energy (Houde is project manager for the ARPA-E grant), The Engine at MIT, Vinod Khosla, and Collaborative Fund, among others.

A video about Quaise can be seen here.

In the realm of social media, anti-science views about COVID-19 align so closely with political ideology -- especially among conservatives -- that its predictability offers a strategy to help protect public health, a new USC study shows.

Resistance to science, including the efficacy of masks and vaccines, poses a challenge to conquering the coronavirus crisis. The goal of achieving herd immunity won't happen until society achieves consensus about science-based solutions.

The USC study's machine-learning assisted analysis of social media communications offers policymakers and public health officials new tools to anticipate shifts in attitudes and proactively respond.

"We show that anti-science views are aligned with political ideology, specifically conservatism," said Kristina Lerman, lead author of the study and a professor at the USC Viterbi School of Engineering. "While that's not necessarily brand new, we discovered this entirely from social media data that gives detailed clues about where COVID-19 is likely to spread so we can take preventive measures."

The study was published in the Journal of Medical Internet Research.

Previous surveys and polls have shown a partisan gulf in views about COVID-19 as well as the costs and benefits of remedies. By contrast, the USC study examined public health attitudes based on Twitter tweets from Jan. 21, 2020, and May 1, 2020.

They sorted people into three groups -- liberal versus conservative, pro-science versus anti-science, and hardline versus moderate -- then trained machine-learning algorithms to sort all the other people. They used geographical data to pare 115 million tweets worldwide down to 27 million tweets by 2.4 million users in the United States.

The researchers further parsed the data by demographics and geography and tracked it over the three-month study period. This approach allowed for near real-time monitoring of partisan and pseudo-science attitudes that could be refined in high detail aided by advanced computing techniques.

Assessing anti-science views can assist in tailoring comms strategies, bracing for outbreaks

What emerged is the ability to track public discourse around COVID-19 and compare it with epidemiological outcomes. For example, the researchers found that anti-science attitudes posted between January and April 2020 were high in some Mountain West and Southern states that were later hit with deadly COVID-19 surges.

In addition, the researchers were able to probe specific topics important to each group: anti-science conservatives were focused on political topics, including former President Trump's reelection campaigns and QAnon conspiracies, while pro-science conservatives paid attention to global outbreaks of the virus and focused more on preventive measures to "flatten the curve." Researchers were able to track attitudes across time and geography to see how they changed. For example, to their surprise, they found that polarization on the topic of science went down over time.

Perhaps most encouraging, they discovered that, even in a highly polarized population, "the number of pro-science, politically moderate users dwarfs other ideological groups, especially anti-science groups." They said their results suggest most people are ready to accept scientific evidence and trust scientists.

The findings can also help policymakers and public health officials. If they see anti-science sentiment growing in one region of the country, they can tailor messages to mitigate distrust of science while also preparing for a potential disease outbreak.

"Now we can use social media data for science, to create spatial and temporal maps of public opinions along ideological lines, pro- and anti-science lines," said Lerman, a computer scientist and expert in mining social media for clues about human behavior at USC's Information Sciences Institute. "We can also see what topics are important to these segments of society, and we can plan proactively to prevent disease outbreaks from happening."

A rare parasitic infection imported from Europe continues to take root in Alberta, Canada. The province is now the North American hotspot for human alveolar echinococcosis (AE), which takes the form of a growth in the liver, causing serious and potentially deadly health complications.

A recently published review of known AE cases in Alberta found 17 instances of human AE diagnosed in the province between 2013 and 2020. Before the recent surge, only two cases of human AE had been previously confirmed in North America--one in Manitoba in 1928 and another in the U.S. state of Minnesota in 1977.

"This parasite has now become very widely established in the wild in the Prairies. It's been found in Saskatchewan and in B.C., but Alberta has had most of the cases of human disease," said University of Alberta infectious diseases expert Stan Houston, who helped lead the study.

"We have been having on average more cases every year. There's been a lull since COVID-19, but I'm suspicious it reflects a slowdown in testing during the pandemic and that we may soon see a surge again."

According to Houston, the strain of AE found in the Alberta cases has been identified by scientists at the Faculty of Veterinary Medicine in Calgary as having originally come from Europe, likely in dogs brought to the area.

The parasite takes the form of a tiny tapeworm in canines--typically foxes and coyotes, but potentially pet dogs--and is considered to be relatively harmless to them. When a rodent ingests parasite eggs from canine feces, it gets a different form of the disease and develops a tumour, or parasitic growth, in the liver, which kills it. When the rodent is eaten by a canine, the parasite takes the tapeworm form again.

"We humans are taking the place of the rodent in the life cycle when we accidentally consume microscopic parasite eggs--maybe in strawberries or lettuce from a garden where a coyote passed through, or possibly a dog if it is carrying the parasite," said Houston, also noting that a human could become infected by petting a dog that has microscopic traces of canine feces in its hair and then touching food or their mouth, accidentally ingesting the parasite's eggs.

The European strain of AE has been notably successful in Alberta, quickly spreading in the wild. Increased human contact with coyotes as they have become urbanized, along with the increasing numbers of people with diseases or therapies that weaken the immune system, are likely to contribute to the number of humans developing the disease.

"In coyotes in Calgary and in Edmonton, more than half have been found to be carrying this parasite. So the new strain seems to not only be more virulent when it affects humans, but it seems to be super-effective in wild hosts," said Houston.

"Diseases from animals have always been important to keep an eye on," he added. "The COVID-19 pandemic has again elevated awareness of the number and importance of human diseases that are transmitted from animals."

Of the 17 cases found in Alberta, 11 patients lived in rural areas, 14 of them owned dogs and six were immunocompromised individuals--of special interest as the disease progresses faster in patients whose immune systems have been suppressed.

The symptoms of AE can be difficult to spot. The infection typically has an incubation period of several years before a patient begins showing signs of illness. Almost half of the cases in Alberta were found accidentally when the patient was getting tested for a different illness. It's often found after an ultrasound shows abnormalities in the liver, followed by an investigative biopsy. When symptoms occur, they can include unspecified pain, jaundice, weakness and weight loss--many of the same conditions that could be expected from a cancerous tumour in the liver.

"In the majority of cases that was the people's first thought when they saw the imaging, that it was cancer," said Houston. "The symptoms would be indistinguishable from many other diseases in the liver, hence the need for a biopsy diagnosis."

If found early enough, treatment can involve surgery to remove the mass from the liver. Because the parasite is initially symptomless, it is often able to slowly grow and by the time it is found, about two-thirds of patients will be inoperable. In those cases, lifelong antiparasitic drugs are the only option. The drugs won't kill the parasite but will prevent it from growing further. If left untreated, the parasite could kill its human host within 10 to 15 years.

Currently the most useful drug for controlling AE is not licensed in Canada (although widely available in most of the rest of the world) and only available through a special physician application process to both the government and manufacturer.

Avoiding the parasite comes down to good hygiene practices and taking simple precautions. Houston said it's a good idea to wash your hands after handling your dog, especially if you suspect it's eaten a rodent or spent time in a dog park or area where coyotes frequent. Also recommended is thoroughly washing produce that comes from the ground or close to the ground, such as lettuce or mushrooms.

The researchers are now working on a new study examining samples of liver biopsies from patients in Alberta where cancer wasn't found, to look for possible previously unrecognized cases of AE.

"That would give us a better picture of what's going on, but more importantly, would give us a chance to give those patients appropriate therapy," said Houston.

"We should be paying attention, but it's still a very rare disease," he added. "People should keep that in perspective, adopt health behaviours and not obsess about this."

PHILADELPHIA - Sour taste does not have the nearly universal appeal that sweet taste does. Slightly sour foods or drinks such as yogurt and lemon juice are yummy to many, but such highly sour foods as spoiled milk are yucky, even dangerous. Like humans, many other animals, including insects, prefer slightly acidic over very acidic foods.

Evolutionary biologists surmise that the need for sour detection to be finely tuned is a two-sided coin: slightly acidic foods can enhance digestion and stimulate saliva production; relative sour-to-sweet taste can signal optimal ripeness of fruit; and extremely sour food, as with bitter taste, is a warning to what not to ingest. However, despite this usefulness, how do animals discern different concentrations of acid to produce contrasting feeding behaviors using the same sour-taste system?

A research group led by Yali Zhang, PhD, Principal Investigator at the Monell Chemical Senses Center, has recently addressed this long-standing question. Their work was recently published in Nature Communications.

Using the fruit fly as a research model, Zhang and his team set out to elucidate how animals tell the difference between low and high concentrations of acid. "We chose flies because they not only help us identify the genetic components involved in taste transduction, they also exhibit pronounced and distinct taste responses to a range of concentrations of acid compared to other animal models," said Zhang.

His team, including authors Tingwei Mi, John Mack, and Christopher Lee from the Monell Center and University of Pennsylvania, found that flies use two distinct types of gustatory (taste) receptor neurons (GRNs), which are analogous to taste receptor cells in mammals, to discriminate slightly from highly sour foods. One group of GRNs are maximally activated by low acidity, while the other group displayed its best responses to high acidity. When tasting an acidic food, the fly's brain evaluates the activation of both neuron populations and decides whether to choose or reject the acidic food, based on which type of neurons win.

"We were thrilled to discover that a fly's acid-taste behavior is dictated by a 'tug-of-war' between low- and high-acid-sensitive taste receptor cells," said Zhang. This binary sour-taste system can explain why many animals, including humans, are attracted to low but repulsed by high concentrations of acids.

In addition, Zhang's group identified a fly protein called Otopetrin-like (OtopLa), which has an analogous counterpart in humans, as a long sought-after sour taste receptor. OtopLa forms a proton-selective ion channel that is specifically required for attractive sour taste response. Remarkably, mutant flies lacking OtopLa are averse to low concentrations of acid as well as repulsed by higher concentrations.

"To my knowledge, OtopLa is the first taste receptor to be identified that is evolutionarily conserved between insects and mammals," said Zhang. This work overturns the established view that insects and mammals make use of different classes of taste receptors.

"I believe our research on fly acid sensation can greatly advance our understanding of sour taste coding in other animals, including humans," said Zhang.

The brain presents different states depending on the communication between billions of neurons, and this network is the basis of all our perceptions, memories, and behaviours. It is often considered a "black box", with difficult access for clinicians and researchers, as few limited tools are available to perform accurate and spaciotemporal studies on brain neuronal behaviour. Now, researchers from the Institute for Bioengineering of Catalonia (IBEC) in collaboration with August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and have added some light to the subject: they succeeded for the first time in controlling neuronal activity in the brain using a molecule responsive to light.

The study included participants from the Autonomous University of Barcelona (UAB) and was carried out in the frame of the Human Brain Project of the EU. It describes the first way to directly photomodulate brain state transitions in vivo.

The work, led by ICREA Research Professors Pau Gorostiza (IBEC-CERCA, BIST, CIBER-BBN) and Mavi Sanchez-Vives (IDIBAPS) and has been recently published in the journal Advanced Science. Results show that this new molecule, named PAI (for Phthalimide-Azo-Iper) can specifically and locally control the muscarinic cholinergic receptors, that is, the acetylcholine receptors, a brain neurotransmitter very important in several processes as learning attention or memory.

Control of brain states transitions with light

Transitions between brain states, such as going from being asleep to awake, or waking up from a coma, are based on the transmission of chemical and electrical signals among groups of neurons involved in different functions. Current techniques to modulate neuronal activity as transcranial-magnetic or ultrasound stimulation have limitations in spatiotemporal and spectral performance. Another technique with high precision that also uses light to control the neurons in the optogenetics, but it depends on genetic manipulation, making difficult its translation to humans due to safety reasons.

Here, researchers applied photopharmacology to tackle these problems. To do so they used a molecule previously developed at IBEC, PAI, that is light responsive and allows a spatiotemporally controlled modulation of brain neurons, binding and controlling the activity of muscarinic cholinergic receptors, key receptors on neuronal interaction and communication. By using this approach, the cholinergic-innervation dependent brain state transitions can be controlled by light using drugs chemically designed to be photosensitive.

"The control of neuronal activity in the brain is key to perform both basic and applied research, and to develop safe and accurate techniques to perform therapeutic brain interventions in clinical neurology" , explains Fabio Riefolo (IBEC), co-first author of the study.

Changes in brain states

Different brain states and transitions among them are associated with brain function. They are closely linked to changes in brain activation patterns, which in turn reflect the activity and parameters of specific neuronal networks. Thus, manipulation of neurons with a spatiotemporal control is fundamental to determine the relation among brain states and behaviour and to study the influence of neuronal circuits on specific behaviours. In addition, PAI is pharmacologically specific for a muscarinic receptor subtype, M2, which offers exciting prospects to study the pharmacology of brain waves.

When applying PAI to the intact brain, and subsequently white light, researchers could modulate the spontaneous emerging slow oscillations in neuronal circuits and reversibly manipulate the brain oscillatory frequency. This new chemically-engineered tool allowed to induce and investigate in detail, in a controlled and non-invasive way, the transitions of brain from sleep- to awake-like states using direct illumination.

In our brain, neuronal activity is driven by molecules known as neuromodulators, for example acetylcholine (ACh), through their binding to cholinergic receptors. However, it is not completely understood the contribution of the different cells expressing ACh receptors in the global brain behaviour. The use of selective and photoswitchable cholinergic drugs as PAI to achieve a spatiotemporal precise modulation of brain activity opens the way to perform accurate basic neuroscience research and to develop future brain therapies and stimulation.

"The photocontrol of endogenous receptors and their functions in the central nervous system, such as the transition between different brain states, is an achievement for neuromodulation technologies", explains Dr. Almudena Barbero-Castillo (IDIBAPS), co-first author of the study.

MADISON - In early January 2021, travelers returning to Tokyo, Japan, from Amazonas, Brazil, were screened for COVID-19 at the airport. A few days later, the National Institute of Infectious Disease of Japan announced that the travelers had returned with a new variant of the SARS-CoV-2 virus.

That variant, known as gamma, or P.1, led to a deadly surge in COVID-19 cases in Brazil this spring, and has now spread across the world. More than 200 cases have been detected in Wisconsin. Whether current vaccines are as effective against the gamma variant remains unknown.

In a new study using variant virus recovered from one of the original travelers, researchers in the U.S. and Japan have found that vaccination with an mRNA vaccine induces antibody responses that would protect humans from infection with the gamma/P.1 variant. Hamsters previously infected with the virus strains first circulating in early 2020 were also protected from infection with the gamma variant nine months later.

The findings, the researchers say, suggest that previous SARS-CoV-2 infection and vaccines that are based on earlier strains of the virus still provide protection against infection with gamma. The study published in the Proceedings of the National Academy of Sciences on June 17, 2021.

"The animals were quite protected," says study lead Yoshihiro Kawaoka, a professor of virology at the University of Wisconsin-Madison School of Veterinary Medicine and the University of Tokyo. "There may be people who get infected with this variant even though they are vaccinated or were previously infected, but they shouldn't get severe disease."

However, he says, "that is not consistent with what has been happening in Brazil," where there have been reports of people reinfected with the gamma variant after recovering from infection with an earlier strain. It's possible, Kawaoka says, that COVID-19 immunity lasts longer in hamsters than in humans, or that cases documented as reinfections are actually first infections.

Kawaoka's research team established the Syrian hamster model for COVID-19 last year, after demonstrating that hamsters are highly susceptible to the SARS-CoV-2 virus and develop disease similar to humans, like ground glass opacity in their lungs. They also develop lasting antibodies that protect against reinfection.

"Animal models are great because (they allow us to) test vaccines, test drugs, test monoclonal antibodies and even do pathogenesis (studies)," says Kawaoka.

In fact, his team studied the gamma variant in hamsters because, while previous studies suggested P.1 might bind better to cells and resist antibodies created by previous infections or vaccination, little is known about the variant's ability to replicate in the body, how much illness or pathogenesis it causes, or how well immune responses react to the virus.

The researchers infected hamsters with either the P.1/gamma variant isolated from the traveler, or with one of two earlier strains of the virus from human samples -- one isolated from a patient in February 2020, and the other from a patient with a non-variant globally predominant strain. Each of the strains replicated similarly in the nose and lungs of hamsters and caused similar illness affecting the lungs.

Next, Kawaoka's team looked at whether antibodies in convalescent sera from 35 recovered COVID-19 patients or from people who'd received the Pfizer-BioNTech mRNA vaccine could neutralize each of the three viral strains.

Following a natural infection or vaccination, the body produces antibodies that learn to recognize the spike protein of the SARS-CoV-2 virus, which is responsible for binding to cells. Should people encounter the virus again, antibodies recognize the spike protein and subsequently fight off or limit the extent of infection.

Earlier studies have shown that a spike protein mutation -- E484K, found in gamma variants -- can change the spike protein's identity just enough that the variant can slip past these defenses. However, antibodies in the blood of vaccinated individuals reacted to all three strains, including gamma.

Antibodies in the blood of recovered COVID-19 patients were also effective at neutralizing each of the strains. However, of the 35 patients, one had been infected with gamma and the antibodies from this individual were less reactive to the non-variant strains.

The researchers say these findings suggest there are some important differences in the spike protein of gamma that might influence immunity, warranting further monitoring. Additionally, Kawaoka's group found that gamma, but not other strains of SARS-CoV-2, can infect and replicate in mice, suggesting that the spike protein interacts differently with cells than earlier strains.

The researchers also found that hamsters that had recovered from infection with either of the earlier strains of SARS-CoV-2 were protected against viral replication in their lungs if reinfected with either the same strain or the gamma variant, three weeks and nine months later.

However, gamma was recovered in the nasal passages of reinfected animals in both groups. The amount of virus in the nasal passages of reinfected animals was 1,000-fold lower than animals infected for the first time.

Finally, the researchers studied whether convalescent plasma from three patients infected with SARS-CoV-2 in early 2020 could protect against viral replication in the nose and lungs of hamsters. They found that convalescent plasma, but not plasma from patients who did not have COVID-19, limited virus replication in the lungs of hamsters infected with the prevailing non-variant strain and with gamma/P.1. Virus was found in their nasal passages.

Vaccination, Kawaoka says, is the best way to seek protection from SARS-CoV-2 and emerging variants, including the delta variant, also known as B.1.617.2. The Centers for Disease Control and Prevention recently designated the delta version as a variant of concern due to evidence that it transmits more readily.

Peter Halfmann, research associate professor at UW-Madison and co-leader of the study, added that the gamma and delta variants are circulating in Madison and other parts of the U.S., highlighting the importance of vaccination.

"The difference between the original strain and (delta) and the original strain and (gamma) is similar," Kawaoka adds, noting: "The (delta) variant may become prevalent but it shouldn't be extremely concerning as long as you are vaccinated."

With SARS-CoV-2 changing as it spreads, some versions of the virus will disappear as new variants emerge, as happened with a European variant in early 2020 that quickly eclipsed the original virus first found in China.

"At least in the vast majority of the population, we don't have good immunity to SARS-CoV-2, so the selective pressure on the virus at the moment is transmissibility," Kawaoka says, explaining why new variants that successfully spread tend to be more transmissible than those that came before. "But it will change. We should expect to see the selective pressure become immunity."

This is why vaccines will likely need to be modified in the coming years, he explains, in order to protect against a virus that will evolve to evade the protections we devise so long as spread of the virus remains high, or if our immune systems don't maintain defenses for long enough to prevent reinfections.

"We don't know which one is going to be the case ... it's too early to say how long immunity to this virus lasts," he says. "Hamsters look different from humans, anyway. It's difficult to predict."

Peter Halfmann, a research associate professor at UW-Madison, and Masaki Imai in the Division of Virology at the University of Tokyo, co-led the study.

It was supported by a Research Program on Emerging and Re-emerging Infectious Diseases (JP19fk0108113, JP19fk0108166, JP20fk0108412, and JP21fk0108104;, a Project Promoting Support for Drug Discovery (JP20nk0101612, JP20nk0101614, and JP20nk0101603); the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) (JP19fm0108006); the Japan Program for Infectious Diseases Research and Infrastructure (JP20wm0125002 and 20fk0108272) from the Japan Agency for Medical Research and Development (AMED); the National Institutes of Allergy and Infectious Diseases funded Center for Research on Influenza Pathogenesis (CRIP; HHSN272201400008C); the Wisconsin National Primate Research Center (P51?OD011106), and the Collaborative Influenza Vaccine Innovation Center (CIVIC; 75N93019C00051).

Researchers at the University of Texas Medical Branch have observed that SARS-CoV-2, the virus that causes COVID-19, can infect the testes of infected hamsters. The findings, published in the journal Microorganisms, could help explain symptoms some men with COVID-19 have reported and have important implications for men's health.

As the pandemic goes on, clinicians continue to report their findings that COVID-19 affects more than just the lungs. Some patients have reported testicular pain and some reports have shown decreases in testosterone, a key hormone produced in the testes. Autopsies have also shown significant disruption of the testes at the cellular level, including the presence of immune cells.

"Given the magnitude of the COVID-19 pandemic, it is critical to investigate how this disease can impact the testes, and the potential consequences for disease severity, reproductive health, and sexual transmission," said Dr. Rafael Kroon Campos, the study's lead author and postdoctoral fellow in the laboratory of Dr. Shannan Rossi at UTMB.

The Rossi lab has been studying Zika virus infection in the testes for years and wondered if SARS-CoV-2 could cause a similar disease. Hamsters are commonly used to model COVID-19 in humans since they develop similar signs of disease. Virus was detected in the testes of all infected hamsters during the first week but tapered off. The authors think this may represent what could occur in men with mild to moderate COVID-19 disease.

"These findings are the first step in understanding how COVID-19 impacts the male genital tract and potentially men's reproductive health," said Rossi, an associate professor in the Departments of Pathology and Microbiology & Immunology. "We have much more to do before we have the full picture. Moving forward, we will investigate ways to blunt this impact, including using antivirals, antibody therapies and vaccines."

Future studies also include modeling conditions associated with severe COVID-19, such as pre-existing conditions like obesity and diabetes and SARS-CoV-2 variants of concern, the study authors said.

As demand for electricity rises and climate change brings more frequent and extreme storms, residents in rural and suburban communities must have access to the minimal electricity they need to survive a large, long-duration (LLD) power outage.

A new study in the journal Risk Analysis compared strategies for providing emergency power to residents in two hypothetical New England communities during such an event. The results suggest that cooperative strategies like sharing a higher capacity generator among multiple homes cost 10 to 40 times less than if each household used its own generator.

"Our findings provide impetus for utilities, regulators, and policy makers to make collective options readily accessible to communities," says co-author M. Granger Morgan, Hamerschlag University Professor of Engineering at Carnegie Mellon University and co-director of the National Science Foundation's Center for Climate and Energy Decision Making.

LLD-outages are defined as blackouts that extend over multiple service areas or states and last several days or longer. Over the last decade, severe storms have caused LLD-outages affecting millions of people. In 2012, Superstorm Sandy disrupted power in 21 states, affecting over 8 million customers with approximately 800,000 customers still without power after 10 days. And in 2017, Hurricane Maria devastated electrical service across Puerto Rico for months.

In their study, the researchers focused on power resilience among often-overlooked residential customers in rural and suburban communities. "Rural and suburban communities tend to be more vulnerable in long-duration outages," says Angelena Bohman, lead author and a Ph.D. candidate in Engineering and Public Policy at Carnegie Mellon University.

Most rural and suburban areas have overhead power lines, which can be taken down by high wind events like hurricanes and tornadoes. Ice storms can also weigh down and snap overhead lines. "The more spread out communities are, the harder it is for residents to access support in an emergency due to destroyed or blocked roads and limited fuel access," says Bohman. "They are also likely to have to wait longer for power to be restored as other critical infrastructures and urban communities typically get priority."

The team's analysis focuses on two hypothetical communities in New Hampshire, a region that has experienced both hurricanes and ice storms and where there is a risk of frozen pipes during a winter outage that could result in serious water damage. One of the hypothetical communities relies on a fuel mix for heating; the other uses piped natural gas. The study compares individual and cooperative strategies for providing limited amounts of power to residential customers in both communities during an LLD-outage.

To estimate how much power is needed by each household, the researchers considered only the energy needed for basic survival. In freezing temperatures, households need enough heat to prevent hypothermia and frozen pipes (a thermostat setting of 50° F). They need enough power to support minimal lighting at night and to charge mobile devices. A refrigerator is necessary during summer, but not winter. Air conditioning was not considered a necessity.

The analysis suggests that most houses require roughly 600 running watts during an outage to meet their emergency demand, regardless of the season. This "emergency load" comprises about 10 percent of normal household load.

The researchers analyzed the cost and performance of these four different strategies for providing emergency power during an LLD-outage:

Individual houses each purchase and use their own emergency generator fueled with gasoline, propane, or diesel or have installed a PV + battery system.

A 10-house "neighborhood" operates as a microgrid served by a small, single-phase generator fueled with propane, diesel, or natural gas

A 100-house "community" operates as a microgrid using a three-phase generator fueled by propane, diesel, or natural gas

A single, large, three-phase generator or microturbine capable of serving the entire feeder for a community is located at the substation.

They considered each strategy's performance during outages that lasted five, 10, and 20 days in duration. Compared to the cost of running an individual generator at each home, the results showed that the three cooperative solutions cost 10 to 40 times less per household.

Providing a gas-powered generator to each home would be problematic if an outage lasted more than a few days. A 5.5kW portable generator would require 300 gallons of gasoline during a 20-day outage as well as four to five oil changes. Keeping it running that long would only be plausible if the town made prior arrangements to keep filling stations operating and reached agreements about fuel supply priorities with emergency responders and others.

Co-author Ahmed Abdulla, assistant professor in the department of mechanical and aerospace engineering at Carleton University, points out that while collective strategies are significantly cheaper than individual strategies, they also require prior arrangements between customers and with the local township, local utility, third party suppliers, and regulators such as the state's Public Utility Commission (PUC).

All of this may be worth it to a state like Texas, which suffered devastating rolling blackouts during severe winter storms last February. More than 4.5 million homes and businesses were without power, some for more than three days. "If customers on distribution feeders in Texas had implemented any of the strategies outlined in our paper they would have had access to enough power to avoid frozen pipes, modestly heat their home, keep a few lights on, and cycle through other small loads to make the situation much more bearable," says Bohman.

Finding cost-efficient solutions to mitigate the impacts of climate change is more important than ever, adds Granger. "Unfortunately, the risk of LLD-outages is growing as climate change brings more frequent and extreme weather events. We are developing a set of strategies to assess how resilient a power system is likely to be as it strives to balance decarbonizing the power grid while also protecting it against these extreme events - two goals that are not always easily aligned."

New UMD study suggests that everywhere tyrannosaurs rose to dominance, their juveniles took over the ecological role of medium-sized carnivores

A new study shows that medium-sized predators all but disappeared late in dinosaur history wherever Tyrannosaurus rex and its close relatives rose to dominance. In those areas--lands that eventually became central Asia and Western North America--juvenile tyrannosaurs stepped in to fill the missing ecological niche previously held by other carnivores.

The research conducted by Thomas Holtz, a principal lecturer in the University of Maryland's Department of Geology, verified previous anecdotal reports of a dramatic drop-off in diversity of medium-sized predator species in communities dominated by tyrannosaurs. Diversity of prey species, on the other hand, did not decline. This suggests that medium-sized predators did not disappear because of a drop off in their prey, and that something else--likely young tyrannosaurs--stepped in to fill their ecological role. The study was published online on June 17, 2021, in the Canadian Journal of Earth Sciences.

"Earlier in the history of dinosaurs, in most communities you'd have a bunch of different types of carnivores of various size ranges from small fox-sized all the way up to the occasional giants," Holtz said. "Then something happens between 95 and 80 million years ago, where we see a shift. The really big carnivores, larger than an elephant, like tyrannosaurs and their kin, become the apex predators, and the middle-sized predators, say leopard to buffalo-sized carnivores, are either missing or very rare."

Typically, such a dramatic change in predators would coincide with some change in their prey. Either the prey species would increase dramatically in the absence of predators, or the prey species would also drop off, perhaps indicating why the predators disappeared. But the fact that Holtz found no shift in prey species diversity indicates that something continued to fill the ecological role of the missing middle-sized predators.

Previous work by Holtz and others provides evidence that young tyrannosaurs were faster and more agile than their parents and likely hunted prey more similar to that eaten by the faster, more agile medium-sized dinosaurs.

It is possible that as tyrannosaurs evolved and grew to dominance, their juveniles outcompeted other carnivorous dinosaurs in the middle-size range. But it is also possible that something else eliminated the other carnivores and tyrannosaurs simply stepped in to fill the gap. The shift to tyrannosaur dominance and the disappearance of middle-sized predators happened during a long gap in the fossil record, so scientists can't say exactly what occurred.

"Ultimately resolving that is going to rely on the most basic first-level aspect of paleontology, which is boots on the ground and picks in the sediments," Holtz said. "We need more sampling sites from this interval between about 95 and 80 million years ago."

To conduct the study, Holtz surveyed the existing record of 60 dinosaur communities--assemblages of animals living in the same area at the same time--from the Jurassic and Cretaceous periods (201 to 66 million years ago). First, he counted the number of carnivorous species and sorted them into size categories, with medium-sized dinosaurs weighing in at 50 to 1,000 kilograms and large dinosaurs exceeding 1,000 kilograms.

His analysis revealed that in 31 communities tyrannosaurs were not the largest predators, and there was a wide range of predators in the 50 to 1,000 kilogram category. In Asia and North America, those communities existed from the Jurassic through the early part of the late Cretaceous period (201 to 80 million years ago). Outside of Asia and North America, they continued to exist through the end of the late Cretaceous period (80 to 66 million years ago).

In the other 29 dinosaur communities Holtz surveyed, tyrannosaurs were the largest, and presumably dominant, predator weighing in at over 1,000 kilograms. In those communities, which were all found in Asia and North America, predators ranging from 50 to 1,000 kilograms were rare or absent during the latter half of the late Cretaceous period (80 to 66 million years ago).

Next, Holtz analyzed the same communities looking for shifts in the number of prey species. He found no statistical difference in prey species diversity between the tyrannosaur-dominated and non-tyrannosaur-dominated communities.

"So, what does this mean?" Holtz asked. "In those communities where middle-sized predators are gone but the prey species are just as diverse, can we say that no one is preying upon these middle-sized prey? No. That's almost certainly not the case. It is quite likely juvenile tyrannosaurs took over the ecological role of the missing middle-sized carnivores."

Future studies will drill deeper into the composition of prey species communities to see if there were changes in prey size during the shift to tyrannosaur domination. Holtz also plans to survey the size distribution of carnivores during the Triassic period from 251 to 201 million years ago. Understanding changes in size distribution and species diversity may help paleontologists understand the influences that affect different types of predator and prey communities.

"These interactions are important for understanding what life was like during the time of the dinosaurs," Holtz said. "But in the broader sense, having more understanding of changing ecosystems, and in this case, looking at the predator and prey components of an ecosystem, gives us a better and more diverse view of how the interactions of life work in the world, even today.

Like the movie version of Spider-Man who shoots spider webs from holes in his wrists, a little alpine plant has been found to eject cobweb-like threads from tiny holes in specialised cells on its leaves. It's these tiny holes that have taken plant scientists by surprise because puncturing the surface of a plant cell would normally cause it to explode like a water balloon.

The small perennial cushion-shaped plant with bright yellow flowers, Dionysia tapetodes, is in the primula family and naturally occurs in Turkmenistan and north-eastern Iran, and through the mountains of Afghanistan to the border of Pakistan. What makes it unusual is its leaves, which are covered in long silky fibres that resemble fine cobwebs called 'woolly farina'.

Quite a few of its primula relatives have leaves coated with a fine powder consisting almost entirely from flavone, which is a class of flavonoid. Flavonoids are small specialised molecules involved in plant metabolism and are recognised for their anti-inflammatory and antioxidant properties. But this Dionysia species does not have flavone powder on its leaves, instead it has very fine wool just 1-2 microns thick - far thinner than a human hair, which is about 75 microns.

As part of an ongoing collaboration between the University of Cambridge's plant science research institute Sainsbury Laboratory Cambridge University (SLCU) and Cambridge University Botanic Garden (CUBG), Dionysia was selected from the Botanic Garden's living collection of 8,000 cultivated plant species to be analysed at SLCU's Microscopy Core Facilities.

"The woolly farina threads seem to cover the entire leaf surface with long threads even connecting leaf-to-leaf," said Paul Aston, who is the Botanic Garden Alpine and Woodland Supervisor. "Nobody knew what this wool was or how it was made and so we thought that this would be an interesting specimen to study. There are many things that plants make that we do not yet know about - this is especially true for alpine plants where we see many unusual adaptations to the harsh high altitude environments they live in."

Samples were analysed using advanced light and electron microscopes, which revealed the micron-diameter wool had distinct parallel grooves running along their length. But the most surprising observation was how the wool was emerging from the leaves.

"The leaves are covered in tiny hairs called trichomes. Each trichome has a spherical shaped glandular cell at the end - like a stalk with a single round cell at the tip - and we could see the threads emerging straight out of the glandular cell," said Dr Raymond Wightman, who is the Microscopy Core Facility Manager in the University of Cambridge's Sainsbury Laboratory. "But we know that plant cells are surrounded by a cell wall that protects and retains pressure within the cell. Poking holes through the cell membrane and cell wall would cause the cell to burst - like puncturing a water balloon."

So how were the threads getting out without exploding the cell?

Using a powerful electron microscope at the Cambridge Advanced Imaging Centre (CAIC), they sectioned the glandular cells and when they zoomed in could see tiny gaps in the cells just large enough to thread a single woolly farina fibre through.

"The plant manufactures the fibre inside the cell and then threads it through the gaps that are just wide enough for it," said Dr Matthieu Bourdon who is a researcher at SLCU and co author of the report published in BMC Plant Biology. "There is a distinct opening in the plasma membrane, cell wall and cuticle creating a hole that forms a tight seal around the fibre - we could even see wax on the cell surface acting like a plug to seal any gaps. We observed multiple fibres being extruded from individual glandular cells at specific spots across its surface. The plant must be concentrating the flavone building blocks within the cells at these specific exit sites to be able to produce the elongating fibre."

Dr Wightman also analysed the chemistry of the fibres to find what they are made from using the Institute's Raman microscope, but the wool's complex structure required further analysis using specialist equipment and skills from the University's Yusuf Hamied Department of Chemistry.

"The analysis of the woolly farina sample was challenging because of the small size of the sample and the similarity of the chemicals that it was made up of, said Dr Josephine Gaynord, PhD graduate from the University of Cambridge's Department of Chemistry and who undertook the further analysis using advanced chromatography, mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy techniques. "It helped that we knew the majority of the sample was flavone, a chemical that we could buy and compare to the woolly farina sample. Thanks to some excellent support from the NMR team in the Department of Chemistry we were able to run bespoke analysis and provide possible structures for the modified flavones that were present. It would be very interesting to follow this work up in the future."

Wightman said they were expecting the fibres to be made up of flavonoids similar to the powdery coating on the leaves of some other primula species, but were intrigued by how this species was able to turn flavones into such stable wool-like fibres. "We found the wool produced by Dionysia tapetodes has a special chemical structure that is a mix of flavone and flavone derivatives that may use hydrogen bonding between molecules to form the elongated fibres. This means inside the cell these flavones need to be mixed precisely while being added to the end of the fibre so that they exit the gap as one continuous thread - like squeezing a continuous line of toothpaste from a tube."

"While it is not known what purpose the woolly farina serves, it is thought it could be a protective measure offering tolerance to freezing, drought and/or blocking high UV," said Simon Wallis, Alpine and Woodland Assistant at CUBG. "This latter theory is supported by observations that we have made from our alpine collection, comparing the wool-producing Dionysia tapetodes with a subset of Dionysia tapetodes that do not have woolly farina and are more susceptible to sun scorching."

The team is interested in further exploring the properties of these fibres to determine if they might be a useful biomaterial.