Unlocking the secret strength of marine mussels

How do you create strong, yet quick-release connections between living and non-living tissues? This is a question that continues to puzzle bioengineers who aim to create materials that bond together for advanced biomedical applications.

Looking to nature for inspiration, the McGill-led research zeroed in on the marine mussel byssus, a fibrous holdfast, which these bivalve mollusks use to anchor themselves in seashore habitats. The byssus attaches to rocky surfaces using an underwater glue, but the other end (the byssus stem root) is firmly anchored within the mussel’s soft living tissue. This area of contact between the living tissue and the non-living byssus stem root is known as a biointerface, and is the focus of a study by McGill professor of Chemistry Matthew Harrington.

“Up to this point, it was baffling how the byssus stem root biointerface could be strong enough to resist constant crashing waves but also be suddenly released by the mussel upon demand,” said Harrington. “It seemed as if the mussel could somehow control its strength.”

Surprisingly strong, yet releasable

Following a cross-disciplinary investigation, the team found that the stem root separates into approximately 40-50 sheets known as lamellae that interlock with the living tissue, creating an incredibly strong interface much like interleaving two phone books together.

“The biggest surprise is how this strength can be lowered through the beating movements of billions of tiny hair-like cilia on the surface of the living tissue. Cilia movement is under the control of the neurotransmitters serotonin and dopamine, enabling the quick release of the whole stem root on demand.” says Harrington who holds the Canada Research Chair in Green Chemistry

This finding is particularly relevant for biomedical engineers and materials scientists as they look towards the future of bio-implants, wearable sensors, brain-computer interface design, and more.

“The stem root biointerface is unlike anything seen in human-made materials and could offer important inspiration for the next generation of biointerfaces,” said Harrington. “Since further medical advances will depend on novel biointerface design, these findings could have impact on human health in the future.”

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Researchers have taught an algorithm to ‘taste’

For non-connoisseurs, picking out a bottle of wine can be challenging when scanning an array of unfamiliar labels on the shop shelf. What does it taste like? What was the last one I bought that tasted so good?

Here, wine apps like Vivino, Hello Vino, Wine Searcher and a host of others can help. Apps like these let wine buyers scan bottle labels and get information about a particular wine and read the reviews of others. These apps build upon artificially intelligent algorithms.

Now, scientists from the Technical University of Denmark (DTU), the University of Copenhagen and Caltech have shown that you can add a new parameter to the algorithms that makes it easier to find a precise match for your own taste buds: Namely, people’s impressions of flavour.

“We have demonstrated that, by feeding an algorithm with data consisting of people’s flavour impressions, the algorithm can make more accurate predictions of what kind of wine we individually prefer,” says Thoranna Bender, a graduate student at DTU who conducted the study under the auspices of the Pioneer Centre for AI at the University of Copenhagen.

More accurate predictions of people’s favourite wines

The researchers held wine tastings during which 256 participants were asked to arrange shot-sized cups of different wines on a piece of A3 paper based upon which wines they thought tasted most similarly. The greater the distance between the cups, the greater the difference in their flavour. The method is widely used in consumer tests. The researchers then digitized the points on the sheets of paper by photographing them.

The data collected from the wine tastings was then combined with hundreds of thousands of wine labels and user reviews provided to the researchers by Vivino, a global wine app and marketplace. Next, the researchers developed an algorithm based on the enormous data set.

“The dimension of flavour that we created in the model provides us with information about which wines are similar in taste and which are not. So, for example, I can stand with my favourite bottle of wine and say: I would like to know which wine is most similar to it in taste — or both in taste and price,” says Thoranna Bender.

Professor and co-author Serge Belongie from the Department of Computer Science, who heads the Pioneer Centre for AI at the University of Copenhagen, adds:

“We can see that when the algorithm combines the data from wine labels and reviews with the data from the wine tastings, it makes more accurate predictions of people’s wine preferences than when it only uses the traditional types of data in the form of images and text. So, teaching machines to use human sensory experiences results in better algorithms that benefit the user.”

Can also be used for beer and coffee

According to Serge Belongie, there is a growing trend in machine learning of using so-called multimodal data, which usually consists of a combination of images, text and sound. Using taste or other sensory inputs as data sources is entirely new. And it has great potential — e.g., in the food sector. Belongie states:

“Understanding taste is a key aspect of food science and essential for achieving healthy, sustainable food production. But the use of AI in this context remains very much in its infancy. This project shows the power of using human-based inputs in artificial intelligence, and I predict that the results will spur more research at the intersection of food science and AI.”

Thoranna Bender points out that the researchers’ method can easily be transferred to other types of food and drink as well:

“We’ve chosen wine as a case, but the same method can just as well be applied to beer and coffee. For example, the approach can be used to recommend products and perhaps even food recipes to people. And if we can better understand the taste similarities in food, we can also use it in the healthcare sector to put together meals that meet with the tastes and nutritional needs of patients. It might even be used to develop foods tailored to different taste profiles.”

The researchers have published their data on an open server and can be used for free.

“We hope that someone out there will want to build upon our data. I’ve already fielded requests from people who have additional data that they would like to include in our dataset. I think that’s really cool,” concludes Thoranna Bender.

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Covid inquiry: Earlier lockdown could have kept schools open, says Matt Hancock

The former health secretary says avoiding action in autumn 2020 led to tougher lockdowns later on.

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Strictly Come Dancing: Amy Dowden’s blood clot after chemo

The dancer, 33, says her “nightmare seems to be never ending” after a blood clot on her lung.

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Head teacher says autistic student died despite family’s plea for support

Isaac Uzoegbu was hit by a car when he ran from home. His head teacher says it could have been prevented.

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Scientists build tiny biological robots from human cells

Researchers at Tufts University and Harvard University’s Wyss Institute have created tiny biological robots that they call Anthrobots from human tracheal cells that can move across a surface and have been found to encourage the growth of neurons across a region of damage in a lab dish.

The multicellular robots, ranging in size from the width of a human hair to the point of a sharpened pencil, were made to self-assemble and shown to have a remarkable healing effect on other cells. The discovery is a starting point for the researchers’ vision to use patient-derived biobots as new therapeutic tools for regeneration, healing, and treatment of disease.

The work follows from earlier research in the laboratories of Michael Levin, Vannevar Bush Professor of Biology at Tufts University School of Arts & Sciences, and Josh Bongard at the University of Vermont in which they created multicellular biological robots from frog embryo cells called Xenobots, capable of navigating passageways, collecting material, recording information, healing themselves from injury, and even replicating for a few cycles on their own. At the time, researchers did not know if these capabilities were dependent on their being derived from an amphibian embryo, or if biobots could be constructed from cells of other species.

In the current study, published in Advanced Science, Levin, along with PhD student Gizem Gumuskaya discovered that bots can in fact be created from adult human cells without any genetic modification and they are demonstrating some capabilities beyond what was observed with the Xenobots. The discovery starts to answer a broader question that the lab has posed — what are the rules that govern how cells assemble and work together in the body, and can the cells be taken out of their natural context and recombined into different “body plans” to carry out other functions by design?

In this case, researchers gave human cells, after decades of quiet life in the trachea, a chance to reboot and find ways of creating new structures and tasks. “We wanted to probe what cells can do besides create default features in the body,” said Gumuskaya, who earned a degree in architecture before coming into biology. “By reprogramming interactions between cells, new multicellular structures can be created, analogous to the way stone and brick can be arranged into different structural elements like walls, archways or columns.” The researchers found that not only could the cells create new multicellular shapes, but they could move in different ways over a surface of human neurons grown in a lab dish and encourage new growth to fill in gaps caused by scratching the layer of cells.

Exactly how the Anthrobots encourage growth of neurons is not yet clear, but the researchers confirmed that neurons grew under the area covered by a clustered assembly of Anthrobots, which they called a “superbot.”

“The cellular assemblies we construct in the lab can have capabilities that go beyond what they do in the body,” said Levin, who also serves as the director of the Allen Discovery Center at Tufts and is an associate faculty member of the Wyss Institute. “It is fascinating and completely unexpected that normal patient tracheal cells, without modifying their DNA, can move on their own and encourage neuron growth across a region of damage,” said Levin. “We’re now looking at how the healing mechanism works, and asking what else these constructs can do.”

The advantages of using human cells include the ability to construct bots from a patient’s own cells to perform therapeutic work without the risk of triggering an immune response or requiring immunosuppressants. They only last a few weeks before breaking down, and so can easily be re-absorbed into the body after their work is done.

In addition, outside of the body, Anthrobots can only survive in very specific laboratory conditions, and there is no risk of exposure or unintended spread outside the lab. Likewise, they do not reproduce, and they have no genetic edits, additions or deletions, so there is no risk of their evolving beyond existing safeguards.

How Are Anthrobots Made?

Each Anthrobot starts out as a single cell, derived from an adult donor. The cells come from the surface of the trachea and are covered with hairlike projections called cilia that wave back and forth. The cilia help the tracheal cells push out tiny particles that find their way into air passages of the lung. We all experience the work of ciliated cells when we take the final step of expelling the particles and excess fluid by coughing or clearing our throats. Earlier studies by others had shown that when the cells are grown in the lab, they spontaneously form tiny multicellular spheres called organoids.

The researchers developed growth conditions that encouraged the cilia to face outward on organoids. Within a few days they started moving around, driven by the cilia acting like oars. They noted different shapes and types of movement — the first. important feature observed of the biorobotics platform. Levin says that if other features could be added to the Anthrobots (for example, contributed by different cells), they could be designed to respond to their environment, and travel to and perform functions in the body, or help build engineered tissues in the lab.

The team, with the help of Simon Garnier at the New Jersey Institute of Technology, characterized the different types of Anthrobots that were produced. They observed that bots fell into a few discrete categories of shape and movement, ranging in size from 30 to 500 micrometers (from the thickness of a human hair to the point of a sharpened pencil), filling an important niche between nanotechnology and larger engineered devices.

Some were spherical and fully covered in cilia, and some were irregular or football shaped with more patchy coverage of cilia, or just covered with cilia on one side. They traveled in straight lines, moved in tight circles, combined those movements, or just sat around and wiggled. The spherical ones fully covered with cilia tended to be wigglers. The Anthrobots with cilia distributed unevenly tended to move forward for longer stretches in straight or curved paths. They usually survived about 45-60 days in laboratory conditions before they naturally biodegraded.

“Anthrobots self-assemble in the lab dish,” said Gumuskaya, who created the Anthrobots. “Unlike Xenobots, they don’t require tweezers or scalpels to give them shape, and we can use adult cells — even cells from elderly patients — instead of embryonic cells. It’s fully scalable — we can produce swarms of these bots in parallel, which is a good start for developing a therapeutic tool.”

Little Healers

Because Levin and Gumuskaya ultimately plan to make Anthrobots with therapeutic applications, they created a lab test to see how the bots might heal wounds. The model involved growing a two-dimensional layer of human neurons, and simply by scratching the layer with a thin metal rod, they created an open ‘wound’ devoid of cells.

To ensure the gap would be exposed to a dense concentration of Anthrobots, they created “superbots” a cluster that naturally forms when the Anthrobots are confined to a small space. The superbots were made up primarily of circlers and wigglers, so they would not wander too far away from the open wound.

Although it might be expected that genetic modifications of Anthrobot cells would be needed to help the bots encourage neural growth, surprisingly the unmodified Anthrobots triggered substantial regrowth, creating a bridge of neurons as thick as the rest of the healthy cells on the plate. Neurons did not grow in the wound where Anthrobots were absent. At least in the simplified 2D world of the lab dish, the Anthrobot assemblies encouraged efficient healing of live neural tissue.

According to the researchers, further development of the bots could lead to other applications, including clearing plaque buildup in the arteries of atherosclerosis patients, repairing spinal cord or retinal nerve damage, recognizing bacteria or cancer cells, or delivering drugs to targeted tissues. The Anthrobots could in theory assist in healing tissues, while also laying down pro-regenerative drugs.

Making New Blueprints, Restoring Old Ones

Gumuskaya explained that cells have the innate ability to self-assemble into larger structures in certain fundamental ways. “The cells can form layers, fold, make spheres, sort and separate themselves by type, fuse together, or even move,” Gumuskaya said. “Two important differences from inanimate bricks are that cells can communicate with each other and create these structures dynamically, and each cell is programmed with many functions, like movement, secretion of molecules, detection of signals and more. We are just figuring out how to combine these elements to create new biological body plans and functions — different than those found in nature.”

Taking advantage of the inherently flexible rules of cellular assembly helps the scientists construct the bots, but it can also help them understand how natural body plans assemble, how the genome and environment work together to create tissues, organs, and limbs, and how to restore them with regenerative treatments.

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Study identifies key algae species helping soft corals survive warming oceans

Scleractinian corals, or hard corals, have been disappearing globally over the past four decades, a result of climate change, pollution, unsustainable coastal development and overfishing. However, some Caribbean octocorals, or soft corals, are not meeting the same fate.

During a two-year survey of soft corals in the Florida Keys, Mary Alice Coffroth, professor emerita of geology at the University at Buffalo, along with a small team of UB researchers, identified three species of octocorals that have survived heat waves. While the coral animal itself may be heat tolerant, Coffroth said that her team concluded that the symbiotic algae inside the coral serve as a protector of sorts.

“The resistance and resilience of Caribbean octocorals offers clues for the future of coral reefs,” Coffroth said.

A recent paper outlining their research, “What makes a winner? Symbiont and host dynamics determine Caribbean octocoral resilience to bleaching,” was published on Nov. 22, in Science Advances by the American Association for the Advancement of Science (AAAS).

Coffroth is the lead author on the study she conducted between 2015 and 2017 with graduate student Louis Buccella, undergraduates Katherine Eaton and Alyssa Gooding and technician Harleena Franklin. Howard Lasker, professor emeritus in the departments of Environment and Sustainability and Geology, also contributed to the study.

Algae helps corals survive heat waves

Both hard and soft coral depend on a nutritional symbiosis with single-celled algae living within their tissues. Warmer waters can cause the symbiosis to break down, resulting in a loss of the algal symbionts, which turns the corals white, a phenomenon known as bleaching.

“Bleaching can lead to coral death,” said Coffroth, who has studied coral reefs in the Florida Keys since 1998, including a more recent study in 2020-21. “It’s unclear if the algae leave or are ejected from the coral.

“In this study, we examined possible mechanisms that contribute to the heightened resistance and resilience of three octocoral species in the face of the recurring marine heat waves leading to bleaching events,” Coffroth said, noting that this is the first study that follows both symbiont genetic makeup and density in Caribbean octocorals before, during and after a major heat wave.

By and large, Caribbean octocorals harbor symbionts within the genus Breviolum, she said. And this symbiont is helping to make the octocoral better able to handle the rising heat.

“The Breviolum densities declined during the heatwaves but recovered quickly,” she explained. “Octocoral mortality was low compared to their scleractinian relatives.”

2014 El Niño prompted research

When Coffroth saw bleached corals during the 2014 El Niño and knew that a similar event was predicted for the following summer, she applied for a Rapid Response Research (RAPID) grant from the National Science Foundation. She was awarded $56,305 and with her master’s student, Buccella, conducted the study in the Keys, following the fate of the octocorals and their symbionts for 28 months.

She and other members of the team made trips to the Keys Marine Lab at the Florida Institute of Oceanography to study the octocorals in the spring and fall of 2015 and 2016 and spring and summer of 2017, recording coral coloration and taking samples to study density of the symbionts and their genetic identity.

“We knew it was critical to follow individual colonies across an event with long-term monitoring of both host and symbiont responses,” she said, “and to examine the response at least at the level of symbiont species, if not the genotype, to identify potentially resilient species.”

Climate change moving faster than coral evolution

Although the study began almost a decade ago, Coffroth said the findings are extremely relevant because they mirror what is happening right now, with the continuing warming of ocean waters, increased storms and major bleaching events across the globe.

“There is evidence that corals are withstanding higher temperature now than they did in the 1960s,” she said. “That signals evolution, but the problem is that climate change is moving too fast, faster than evolution.”

In addition to their beautiful aesthetics, coral reefs provide many benefits to the planet and its inhabitants, including barriers to coastal regions that are susceptible to hurricanes and other tropical storms; habitat for large fish such as grouper and snapper; a tourist destination for snorkeling, fishing and diving; and a source for bioactive compounds used in drugs to treat inflammation and certain kinds of cancer.

“If you a see picture of coral reefs when I started diving in the 1970s and compare it with one now, it makes you want to cry,” she said. “The change is just amazing.”

While she noted that this study has some important observations, further study is needed to better understand what is happening to the ecosystem.

“I’m seeing species bleach that have never bleached before but also ones showing more resilience,” she said. “There is a lot of variation within both the animal and symbiont genera. We need to understand the variation.”

The hope is to continue research into coral reef relationships and the durability of the symbiotic algae while also taking steps to halt the damage to the environment by human action, such as overfishing and the burning of fossil fuels.

“We can’t stop global warming,” Coffroth said. “But the hope is that we can slow it down.”

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Genomic study sheds light on how carnivorous Asian pitcher plants acquired signature insect trap

Possessing more than two complete sets of chromosomes can be a hindrance to long-term survival of a plant lineage, yet scientists are also finding evidence it’s likely behind some evolutionary innovation.

Sudden inheritance of whole suites of extra gene copies can add redundancy to an organism’s regular sets of functions, actually permitting some of those copies to evolve and express in entirely new ways.

In the case of the East Asian pitcher plant, this mutational freedom may have even fine-turned its ability to capture prey and satisfy its appetite for “meat.”

That’s just one of the findings in a new study that sequences the genome of Nepenthes gracilis, a species of carnivorous plant related to Venus flytraps, as well as sundews, beets and spinach.

“Our findings not only provide key insights into the adaptive landscape of the Nepenthes genome, but also broaden our understanding of how polyploidy — having multiple sets of chromosomes — can stimulate the evolution of new functions,” says Victor Albert, PhD, Empire Innovation Professor in the University at Buffalo Department of Biological Sciences, within the College of Arts and Sciences.

Albert is the co-senior author of the study, which was published Thursday (Nov. 23) in Nature Plants, along with Kenji Fukushima, PhD, of the University of Würzburg in Germany. Other contributors from UB include Charlotte Lindqvist, PhD, professor of biological sciences, and PhD students Emily Caroll and Michaela Richter.

Albert’s work was supported in part by the National Science Foundation.

Recessive subgenomes are more free to change function

The idea of “man-eating plants” has long captured our macabre imaginations. Pitcher plants, however, require a much smaller meal.

They capture insects using their highly specialized pitcher-shaped leaves. The bottom of their pitchers are filled with digestive fluids that drown and eventually break down prey. This process releases nutrients, such as nitrogen and phosphate, that allow pitcher plants to thrive in nutrient-poor habitats.

“Plant carnivory is something of a hunt for fertilizer,” Albert says.

In a 1992 study, Albert and colleagues discovered that the Asian, Australian and American pitcher plants possess similar features despite having evolved independently. Later research published in 2017 showed that each of these species co-opted many of the same ancient proteins.

In this new study, Albert and Fukushima’s teams discovered that the specialized pitcher trap of the Asian pitcher plant, or Nepenthes, may have been promoted by polyploidy. Nepenthes’ lineage had already evolved carnivory, so the duplicated genomes may have simply tweaked its mode of capture.

The team discovered that Nepenthes has a decaploid genome in its diploid state, a complex structure almost unprecedented in flowering plants that reflects possession of five whole-genome multiples, or “subgenomes.”

The team found that the fifth subgenome is “dominant,” retaining more gene copies and expressing them at higher levels than the other four older, “recessive” subgenomes. Yet it’s the recessive subgenomes — not the dominant one — that may carry more of the key genes for Nepenthes’ specialized carnivory.

“The dominant subgenome exhibits greater influence of natural selection pressure to maintain gene functions,” Fukushima says. “Whereas the recessive subgenomes, impacted less by functional preservation, have become more free to vary over evolutionary time.”

Some of Nepenthes’ duplicate carnivory genes may have originally evolved for defending against what eventually became their prey. The enzymes that help Nepenthes break down insects’ hard exoskeletons, for example, were repurposed from those that originally shielded plants from being eaten by these animals.

“This lineage of Nepenthes didn’t evolve new genes to become carnivorous — they grabbed collections, or toolkits, of genes that were already there,” Albert says.

One hypothesis suggests that polyploidy has a negligible effect on long-term evolution, as species with multiplicated genomes may undergo extinction at rates higher than those like humans, which have just two sets of chromosomes. Yet the study’s findings add to the evidence that ancient polyploidy events can sometimes underlie evolutionary jumps still visible among plants today.

Evidence found for the evolution of separate male and female plants

Nepenthes is part of the just 6% of flowering plant species that are dioecious, meaning each individual plant produces either male or female flowers. In fact, Nepenthes is the only dioecious carnivorous plant.

Albert and Fukushima’s team also identified a male-specific region of the genome containing three genes potentially responsible for controlling these sex differences. One of these, called LEAFY, is a key gene expressed early in flower development that acts as a master regulator.

“LEAFY seems to have had a duplicate form and moved into the Y chromosome region of Nepenthes, thereafter diverging in its function. This use of LEAFY is unprecedented so far in flowering plants,” Albert says. “The LEAFY gene is such a central regulator across flowering plants that, when artificially added or deleted through genetic engineering, it will change a plant’s flowering time.”

“Although we now have bioinformatic evidence pointing toward LEAFY being one of the key genes involved in the sex determination mechanism of Nepenthes, actually proving this is going to require further studies in living plants,” he adds.

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Covid inquiry: Lockdown should have been three weeks earlier – Hancock

The ex-health secretary also said a “toxic culture”, driven by Dominic Cummings, hindered the Covid response.

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Norovirus: Winter vomiting virus cases rising

Hundreds of people are now in hospital with norovirus, the latest NHS England figures show.

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