The Illuminating Geometry of Viruses

Mathematical insights into how RNA helps viruses pull together their protein shells could guide future studies of viral behavior and function.

In icosahedral RNA viruses, the genomic material inside their protein shells plays a much more active role in viral assembly than researchers once believed.

In icosahedral RNA viruses, the genomic material inside their protein shells plays a much more active role in viral assembly than researchers once believed.

More than a quarter billion people today are infected with the hepatitis B virus (HBV), the World Health Organization estimates, and more than 850,000 of them die every year as a result. Although an effective and inexpensive vaccine can prevent infections, the virus, a major culprit in liver disease, is still easily passed from infected mothers to their newborns at birth, and the medical community remains strongly interested in finding better ways to combat HBV and its chronic effects. It was therefore notable last month when Reidun Twarock, a mathematician at the University of York in England, together with Peter Stockley, a professor of biological chemistry at the University of Leeds, and their respective colleagues, published their insights into how HBV assembles itself. That knowledge, they hoped, might eventually be turned against the virus.

Their accomplishment has gained further attention because only this past February the teams also announced a similar discovery about the self-assembly of a virus related to the common cold. In fact, in recent years, Twarock, Stockley and other mathematicians have helped reveal the assembly secrets of a variety of viruses, even though that problem had seemed forbiddingly difficult not long before.

Their success represents a triumph in applying mathematical principles to the understanding of biological entities. It may also eventually help to revolutionize the prevention and treatment of viral diseases in general by opening up a new, potentially safer way to develop vaccines and antivirals.

A Geodesic Insight

In 1962, the biologist-chemist duo Donald Caspar and Aaron Klug published a seminal paper on the structural organization of viruses. Among a series of sketches, models and X-ray diffraction patterns that the paper featured was a photograph of a building designed by Richard Buckminster Fuller, the inventor and architect: It was a geodesic dome, the design for which Fuller would become famous. And it was, in part, the lattice structure of the geodesic dome, a convex polyhedron assembled from hexagons and pentagons, themselves divided into triangles, that would inspire Caspar and Klug’s theory.

At the same time that Fuller was promoting the advantages of his domes — namely, that their structure made them more stable and efficient than other shapes — Caspar and Klug were trying to solve a structural problem in virology that had already attracted some of the field’s greats, not least among them James Watson, Francis Crick and Rosalind Franklin. Viruses consist of a short string of DNA or RNA packaged in a protein shell called a capsid, which protects the genomic material and facilitates its insertion into a host cell. Of course, the genomic material has to encode for the formation of such a capsid, and longer strands of DNA or RNA require larger capsids to shield them. It didn’t seem possible that strands as short as those found in viruses could achieve this.

Then, in 1956, three years after their work on DNA’s double helix, Watson and Crick came up with a plausible explanation. A viral genome could include instructions for only a limited number of distinct capsid proteins, which meant that in all likelihood viral capsids were symmetric: The genomic material needed to describe only some small subsection of the capsid and then give orders for it to be repeated in a symmetric pattern. Experiments using X-ray diffraction and electron microscopes revealed that this was indeed the case, making it apparent that viruses were predominantly either helical or icosahedral in shape. The former were rod-shaped structures that resembled an ear of corn, the latter polyhedra that approximated the sphere, consisting of 20 triangular faces glued together.

This 20-sided shape, one of the Platonic solids, can be rotated in 60 different ways without seeming to change in appearance. It also allows for the placement of 60 identical subunits, three on each triangular face, that are equally related to the symmetry axes — a setup that works perfectly for smaller viruses with capsids that consist of 60 proteins.

Reidun Twarock, a mathematician at the University of York, uses her expertise in geometry and symmetry to develop a better understanding of viral structure, infection and evolution.

Reidun Twarock, a mathematician at the University of York, uses her expertise in geometry and symmetry to develop a better understanding of viral structure, infection and evolution.

Christine Cockett

But most icosahedral viral capsids comprise a much larger number of subunits, and placing the proteins in this way never allows for more than 60. Clearly, a new theory was necessary to model larger viral capsids. That’s where Caspar and Klug entered the picture. Having recently read about Buckminster Fuller’s architectural creations, the pair realized it might have relevance to the structures of the viruses they were studying, which in turn sparked an idea. Dividing the icosahedron further into triangles (or, more formally, applying a hexagonal lattice to the icosahedron and then replacing each hexagon with six triangles) and positioning proteins in the corners of those triangles provided a more general and accurate picture of what these kinds of viruses looked like. This partitioning allowed for “quasi-equivalence,” in which subunits differ minimally in how they bond with their neighbors, forming either five-fold or six-fold positions on the lattice.

Such microscopic geodesic domes quickly became the standard way to represent icosahedral viruses, and, for a while, it seemed that Caspar and Klug had solved the problem. A handful of experiments conducted in the 1980s and ’90s, however, revealed some exceptions to the rule, most notably among groups of cancer-causing viruses called polyomaviridae and papillomaviridae.

It became necessary once more for an outside approach — made possible by theories in pure mathematics — to provide insights into the biology of viruses.

Following in Caspar and Klug’s Footsteps

About 15 years ago, Twarock came across a lecture about the different ways in which viruses realize their symmetrical structures. She thought she might be able to extend to these viruses some of the symmetry techniques she had been working on with spheres. “That snowballed,” Twarock said. She and her colleagues realized that with knowledge of structures, “we could make an impact on understanding how viruses function, how they assemble, how they infect, how they evolve.” She didn’t look back: She has spent her time since then working as a mathematical biologist, using tools from group theory and discrete math to continue where Caspar and Klug left off. “We really developed this integrative, interdisciplinary approach,” she said, “where the math drives the biology and the biology drives the math.”

Twarock first wanted to generalize the lattices that could be used so she could identify the positions of capsid subunits that Caspar and Klug’s work failed to explain. The proteins of the human papilloma viruses, for instance, were arranged in five-fold pentagonal structures, rather than hexagonal ones. Unlike hexagons, however, regular pentagons cannot be built from equilateral triangles, nor can they tessellate a plane: When slid next to each other to tile a surface, gaps and overlaps inevitably arise.

So Twarock turned to Penrose tilings, a mathematical technique developed in the 1970s to tile a plane with five-fold symmetry by fitting together four-sided figures called kites and darts. The patterns generated by Penrose tilings do not repeat periodically, making it possible to piece together its two component shapes without leaving any gaps. Twarock applied this concept by importing symmetry from a higher-dimensional space — in this case, from a lattice in six dimensions — into a three-dimensional subspace. This projection does not retain the periodicity of the lattice, but it does produce long-range order, like a Penrose tiling. It also encompasses the surface lattices used by Caspar and Klug. Twarock’s tilings therefore applied to a wider range of viruses, including the polyomaviruses and papillomaviruses that had evaded Caspar and Klug’s classification.

Moreover, Twarock’s constructions not only informed the locations and orientations of the capsid’s protein subunits, but they also provided a framework for how the subunits interacted with each other and with the genomic material inside. “I think this is where we made a very big contribution,” Twarock said. “By knowing about the symmetry of the container, you can understand better determinants of the asymmetric organization of the genomic material [and] constraints on how it must be organized. We were the first to actually float the idea that there should be order, or remnants of that order, in the genome.”

Twarock has been pursuing that line of research ever since.

The Role of Viral Genomes in Capsid Formation

Caspar and Klug’s theory applied only to the surfaces of capsids, not to their interiors. To know what was happening there, researchers had to turn to cryo-electron microscopy and other imaging techniques. Not so for Twarock’s tiling model, she said. She and her team set out hunting for combinatorial constraints on viral assembly pathways, this time using graph theory. In the process, they showed that in RNA viruses, the genomic material played a much more active role in the formation of the capsid than previously thought.

Specific positions along the RNA strand, called packaging signals, make contact with the capsid from inside its walls and help it form. Locating these signals with bioinformatics alone proves an incredibly difficult task, but Twarock realized she could simplify it by applying a classification based on a type of graph called a Hamiltonian path. Imagine the packaging signals as sticky pieces along the RNA string. One of them is stickier than the others; a protein will adhere to it first. From there, new proteins come into contact with other sticky pieces, forming an ordered pathway that never doubles back on itself. In other words, a Hamiltonian path.

The genomic RNA of the MS2 virus, when close to the capsid shell, arranges itself as a polyhedral cage (at left). In the planar representation at right, the relative positions of the RNA packaging signals (black points) in contact with the capsid’s protein building blocks are shown. Twarock uses Hamiltonian paths along segments of the RNA (yellow) to help determine the virus’s assembly mechanism.

The genomic RNA of the MS2 virus, when close to the capsid shell, arranges itself as a polyhedral cage (at left). In the planar representation at right, the relative positions of the RNA packaging signals (black points) in contact with the capsid’s protein building blocks are shown. Twarock uses Hamiltonian paths along segments of the RNA (yellow) to help determine the virus’s assembly mechanism.

Geraets JA, Dykeman EC, Stockley PG, Ranson NA, Twarock R, adapted by Lucy Reading-Ikkanda/Quanta Magazine

Coupled with the geometry of the capsid, which places certain constraints on the local configurations in which the RNA can contact neighboring RNA-capsid binding sites, Twarock and her team mapped subsets of Hamiltonian paths to describe potential positions of the packaging signals. Weeding out the unpromising ones, Twarock said, was “a matter of taking care of dead ends.” Placements that would be both plausible and efficient, enabling effective and rapid assembly, were more limited than expected. The researchers concluded that a number of RNA-capsid binding sites must occur in every viral particle and are probably conserved features of genome organization. If so, the sites might be good novel targets for antiviral therapies.

Twarock and her colleagues, in collaboration with Stockley’s team in Leeds, have employed this model to delineate the packaging mechanism for several different viruses, starting with the bacteriophage MS2 and the satellite tobacco mosaic virus. They predicted the presence of packaging signals in MS2 in 2013 using Twarock’s mathematical tools, then provided experimental evidenceto back up those claims in 2015. This past February, the researchers identified sequence-specific packaging signals in the human parechovirus, part of the picornavirus family, which includes the common cold. And last month, they published their insights into the assembly of the hepatitis B virus. They plan on doing similar work on several other types of viruses, including alphaviruses, and hope to apply their findings to gain a better understanding of how such viruses evolve.

Going Beyond the Geometry

When Twarock’s team announced their finding on the parechovirus in February, headlines claimed they were closing in on a cure for the common cold. That’s not quite right, but it is a goal they’ve kept in mind in their partnership with Stockley.

Peter Stockley, a professor of biological chemistry at the University of Leeds, studies viral assembly mechanisms to help inform antiviral and vaccine strategies.

Peter Stockley, a professor of biological chemistry at the University of Leeds, studies viral assembly mechanisms to help inform antiviral and vaccine strategies.

Courtesy of Peter Stockley

The most immediate application would be to find a way to disrupt these packaging signals, creating antivirals that interfere with capsid formation and leave the virus vulnerable. But Stockley hopes to go a different route, focusing on prevention before treatment. Vaccine development has come a long way, he acknowledged, but the number of available vaccines pales in comparison to the number of infections that pose threats. “We’d like to vaccinate people against several hundred infections,” Stockley said, whereas only dozens of vaccines have been approved. Creating a stable, noninfectious immunogen to prepare the immune system for the real thing has its limitations. Right now, approved strategies for vaccines rely on either chemically inactivated viruses (killed viruses that the immune system can still recognize) or attenuated live viruses (live viruses that have been made to lose much of their potency). The former often provide only short-lived immunity, while the latter carry the risk of being converted from attenuated viruses to virulent forms. Stockley wants to open up a third route. “Why not make something that can sort of replicate but doesn’t have pathological features to it?” he asked.

In a poster presented at the Microbiology Society Annual Conference in April, Stockley, Twarock and other researchers describe one of their current areas of focus: using the research on packaging signals and self-assembly to probe a world of synthetic viruses. By understanding capsid formation, it may be possible to engineer viruslike particles (VLPs) with synthetic RNA. These particles would not be able to replicate, but they would allow the immune system to recognize viral protein structures. Theoretically, VLPs could be safer than attenuated live viruses and might provide greater protection for longer periods than do chemically inactivated viruses.

Twarock’s mathematical work also has applications beyond viruses. Govind Menon, a mathematician at Brown University, is exploring self-assembling micro- and nanotechnologies. “The mathematical literature on synthetic self-assembly is quite thin,” Menon said. “However, there were many models to study the self-assembly of viruses. I began to study these models to see if they were flexible enough to model synthetic self-assembly. I soon found that models rooted in discrete geometry were better suited to [our research]. Reidun’s work is in this vein.”

Miranda Holmes-Cerfon, a mathematician at the Courant Institute of Mathematical Sciences at New York University, sees connections between Twarock’s virus studies and her own research into how tiny particles floating in solutions can self-organize. That relevance speaks to what she regards as one of the valuable aspects of Twarock’s investigations: the mathematician’s ability to apply her expertise to problems in biology.

“If you talk to biologists,” Holmes-Cerfon said, “the language they use is so different than the language they use in physics and math. The questions are different, too.” The challenge for mathematicians is tied to their willingness to seek out questions with answers that inform the biology. One of Twarock’s real talents, she said, “is doing that interdisciplinary work.”


Watched chimps change their hunting habits

Chimpanzees in Uganda may have changed their hunting strategy in response to being watched by scientists.

While studying the animals, researchers documented very different hunting habits of two closely neighbouring chimp “tribes”.

“Sonso” chimps hunt in small groups for colobus monkeys, while those from the “Waibira” troop hunt solo and catch “whatever they can get their hands on”.

The findings show how sensitive chimp society is to human presence.

They are published in the journal PLoS One,

Biologists who have followed and studied these animals for years think that work may have disturbed the group hunting that seems key to chasing and catching colobus monkeys.

Lead researcher Dr Catherine Hobaiter, from the University of St Andrews, said the Waibira group’s behaviour might have changed to a more “opportunistic” strategy because those chimps were much less used to the presence of human scientists.

Speaking to BBC News from Budongo Forest, in Uganda, where she studies both of these chimpanzee groups, Dr Hobaiter said Sonso and Waibira chimps “shared territorial borders”, so she would expect their food sources and prey to be the same.

“The main thing that’s different about them right now is how used to having humans follow them around the forest they are,” Dr Hobaiter said.

“For Sonso – most of the current generation of adults were born with us being there, so they’re really incredibly relaxed about our presence.

“But [for] Waibira – some of the young ones have started to grow up and become very comfortable with us, but some of the adults would be 30-40 years old when we started, and five years of us following them round is a fraction of their lifetime.

“It just takes time with chimpanzees.”

At other sites where researchers had begun a similar habituation and close observation of wild chimp groups, Dr Hobaiter said, a similar “pattern” had emerged.

“They hunt for lots of different species, then later they seem to switch and settle in to hunting colobus.”

Key to this could be the natural tendency of chimpanzees’ groups to be territorial and wary of newcomers.

“I think that makes it that much harder for them to accept our presence as being a part of their lives,” said Dr Hobaiter.

Following our cousins

“Long-term research with wild chimpanzees brings real conservation benefits, but we have to remember that our presence can affect their behaviour.”

Dr Hobaiter said that – as well as conserving endangered primates and the forests they lived in – directly observing and recording chimpanzee behaviour was the best way to understand the origins of human language and social structure.

“But we need to ask – should we be going in there [to follow the chimps]?

“We can do amazing things with camera traps, remote microphones and drones – it’s getting much easier to get good quality data.

“Part of our work is to understand what our impact is and to try to minimise it.”

Stem Cells Of Type 1 Diabetes Patients Transformed Into Insulin-Secreting Beta Cells; Research May Lead To New Therapy

For those living with Type 1 diabetes, the condition is a part of daily life. Insulin shots, blood sugar monitoring, and carb counting become routine, and patients expect them to stay so for the rest of their lives. This form of diabetes currently has no cure, something researchers have been diligently trying to change.The most recent attempt to take down diabetes comes from researchers at Washington University School of Medicine in St. Louis and Harvard University, who have managed to change stem cells derived from diabetes patients into insulin–secreting cells.


cellsStem cell-derived beta cells (blue) are capable of producing insulin (green) when they come into contact with glucose. 

Patients with Type 1 diabetes lack the ability to create their own insulin, meaning they rely on regular injections of the hormone to control blood sugar. The study hints at a possible new therapy for patients that relies on a personalized approach — using the patients’ own cells to create new ones capable of manufacturing the insulin they need. The research, published in Nature Communications, details new cells that produce insulin when they encounter sugar in both culture and mouse trials.

“In theory, if we could replace the damaged cells in these individuals with new pancreatic beta cells — whose primary function is to store and release insulin to control blood glucose — patients with type 1 diabetes wouldn’t need insulin shots anymore,” said Dr. Jeffery R. Millman, an assistant professor of medicine and biomedical engineering at Washington university and first author of the study, in a press release. “The cells we manufactured sense the presence of glucose and secrete insulin in response. And beta cells do a much better job controlling blood sugar than diabetic patients can.”

Millman had conducted previous studies involving the creation of beta cells derived from people who did not suffer from diabetes. In the new experiment, however, the stem cells used come from the skin of Type 1 diabetes patients.

“There had been questions about whether we could make these cells from people with type 1 diabetes,” MIllman said. “Some scientists thought that because the tissue would be coming from diabetes patients, there might be defects to prevent us from helping stem cells differentiate into beta cells. It turns out that’s not the case.”

The idea of replacing beta cells is actually more than two decades old, originating with Washington university researchers Dr. Paul E. Lacy and David W. Sharp, who began transplanting such cells into Type 1 diabetes patients. Today, there has been some success with beta cell transplants, but these cells come from pancreas tissue provided by organ donors. As with all donated types of tissues, cells, and organs, the supply falls short of the demand. The new technique would solve this problem, but Millman said scientists need to conduct more research to make sure the new cells don’t cause tumor development — a problem that has cropped up in many types of stem cell research. There has been no evidence of tumors so far in the mice, though, even up to a year after cell implantation.

Millman predicts the stem cell-derived beta cells could be ready for testing in humans in three to five years. This process would consist of implanting the cells under the skin of diabetes patients, a minimally invasive procedure that would give the cells access to a the patient’s blood supply.

“What we’re envisioning is an outpatient procedure in which some sort of device filled with the cells would be placed just beneath the skin,” he said.

Millman said that the technique could, in the future, even be used to help those with Type 2 diabetes, neonatal diabetes, and Wolfram syndrome.

Source: Millman J, Xie C, Van Dervort A, Gurtler M, Pagliuca F, Melton D. Generation of Stem Cell-derived B-cells from Patients with Type 1 Diabetes. Nature Communications. May 10, 2016.

The Thousands of Serengeti Wildebeest That Drown Each Year Serve a Greater Purpose

It’s the largest, most spectacular animal migration on our planet. Every year, some 1.2 million wildebeest trample through the Serengeti and the perilous Mara River crossings where thousands of them succumb to the river rapids.

Ecologists know that animal migration, especially on grand scales, affects land ecosystems. But now for the first time they have measured the ecological contribution of mass drownings in the iconic Kenyan river. What they have found is an astonishing example of the circle of life that sustains the natural world.

When immense numbers of wildebeest embark on their annual migration across the savannas of East Africa, the stream of animals takes some 200,000 zebra and antelope along for the trip.

You have probably seen a natural documentary depiction of this epic pilgrimage, especially its most dramatic part around the Mara River where the animals have to make several crossings. Most of them brave the waters with success, but unlucky ones are often shown drowning or being eaten by crocodiles.

All those carcasses eventually pile up in the river, and are slowly consumed by the various creatures that inhabit the ecosystem, both in the river, on land and in the skies.

A team lead by ecologist Amanda Subalusky from the Cary Institute of Ecosystem Studies wondered about the crazy amount of biomass these drownings must represent.

“We used historical reports from 2001 to 2010 and field surveys from 2011 to 2015 to quantify the frequency and size of wildebeest mass drownings in the Kenyan portion of the Mara River,” the team writes in the paper.

Armed with data from field surveys and biochemical analysis, they calculated the fate of an animal carcass as it drowns and enters the river ecosystem.

The researchers found that, on average, 6,200 wildebeest drown each year in the Kenyan portion of Mara River, amounting to 1,100 tons of biomass.

“To put this in perspective, it’s the equivalent of adding ten blue whale carcasses to the moderately-sized Mara River each year. This dramatic subsidy delivers terrestrial nitrogen, phosphorus, and carbon to the river’s food web,” says one of the team, ecologist Emma Rosi.

The team used cameras to track scavenger birds, and a common aquatic ecosystem nutrient tracking method, stable isotope analysis, which allowed them to trace the nutrients from the drowned animals all the way down the food chain.

It turns out that each mass drowning represents a massive boon to the local river ecosystem, feeding everyone in the river. Only a small proportion – some 2 percent – of the wildebeest feast is eaten by crocs.

On land, up to 9 percent of the corpses are devoured by several vulture species. But the biggest winners are the various species of common fish in the river. When carcasses are abundant, they will make up half of the diet for these fish.

And once the drowned bodies have been picked clean, the bones end up leaching even more nutrients into the waters, continuing to feed the ecosystem for years to come.

As dramatic as it is to have thousands of animals go down in the turbulent waters every year, ultimately the gain for the ecosystem is much greater than the loss to the herd.

“These mass drownings have little impact on the wildebeest herd, comprising only 0.5 percent of the total herd size, but they provide huge short-term and long-term sources of nutrients to the Mara River,” write the researchers.

As humans have encroached on animal habitats, mass migration routes have altered. The researchers point out that loss of widespread drownings could be responsible for fundamentally altering river ecosystems.

But each year, the wildebeest still travel across the Serengeti plains, with unlucky ones still drowning in troves, providing sustenance to myriad river creatures long after their death.

“What is happening there is a window into the past, when large migratory herds were free to roam the landscape, and drownings likely played an important role in rivers throughout the world,” says Subalusky.

Source: PNAS.

Mammoths, sabre-tooth tigers and other megafauna went extinct because of ancient climate change

‘We should be quite worried about the warming that is going on now and … about whether again we are going to see a suite of extinctions’

Mammoths, sabre-tooth tigers, giant sloths and other ‘megafauna’ died out across most of the world at the end of the last Ice Age because the changing climate became too wet, according to a new study.

By studying the bones of the long-dead animals, researchers were able to work out levels of water in the environment.

And they found a link between the time large grassland animals and their predators became extinct in different parts of the world over a period of 15,000 to 11,000 years ago and a sudden increase in moisture.

This changed the environment from one dominated by grass to one more suited to trees, bogs and peatlands at the same time as human hunters moved in – creating a lethal “double whammy” that proved too much for many species.

The researchers warned that this process showed how vulnerable today’s large grassland animals could be to climate change, which will result in an increase in rainfall in some places.

One of the researchers, Professor Alan Cooper, of the Australian Centre for Ancient DNA at Adelaide University, said in a video: “What we have found by looking into the actual bones themselves is a signal of sudden environmental change just before they became extinct.

“We see water, moisture, everywhere, which we think is changing the vegetation patterns away from grass, which is what they want, towards trees. What we are really seeing is a double whammy, where the environment is suddenly shifting, the populations are in major trouble, and humans are turning up and hunting is taking off.”

It had long been a “big mystery” why Africa’s megafauna had remained when populations in the rest of the world died out, he said.

“The idea has been that they evolved with humans and were somehow used to them,” said Professor Cooper.

“What we see instead is, because there were no glaciers and large amounts of water to melt, grasslands were always present in Africa, so the animals never had the stress they had elsewhere.

“So it had nothing to do with being use to humans.”

He said the timing of the extinctions around the world, which hit South America first, then North America and then Europe, correlated with the increase in water.

“What it shows is climate change can have some quite large impacts across landscape-sized environments and that we should be quite worried about the warming that is going on now, the changes in water production, and about whether again we are going to see a suite of extinctions,” he said.

Elephants, rhinos and giraffes could all be at risk. “With added rainfall in these areas, we could actually see some quite major impacts on these populations, relatively quickly,” Professor Cooper said.

The international team of researchers, from the US, Russia and Canada as well as Australia, looked at levels of nitrogen isotopes from bone collagen that had been radiocarbon dated. This gave an indication of levels of moisture in the landscape, they said in a paper about the research in the journal Nature Ecology and Evolution.

“Grassland megafauna were critical to the food chains. They acted like giant pumps that shifted nutrients around the landscape,” said Dr Tim Rabanus-Wallace, also of Adelaide University.

“When the moisture influx pushed forests and tundras to replace the grasslands, the ecosystem collapsed and took many of the megafauna with it.”

Plants can ‘hear’ themselves being eaten, say researchers

Researchers have found that plants can identify sounds nearby, such as the sound of eating. 

Most people don’t give a second thought when tucking into a plate of salad.

But perhaps we should be a bit more considerate when chomping on lettuce, as scientists have found that plants actually respond defensively to the sounds of themselves being eaten.

The researchers at the University of Missouri (MU) found that plants can identify sounds nearby, such as the sound of eating, and then react to the threats in their environment, reports Daily Mail.

“Previous research has investigated how plants respond to acoustic energy, including music,” said Heidi Appel, senior research scientist in the Division of Plant Sciences in the College of Agriculture, Food and Natural Resources and the Bond Life Sciences Center at MU.

“However, our work is the first example of how plants respond to an ecologically relevant vibration.

“We found that ‘feeding vibrations’ signal changes in the plant cells’ metabolism, creating more defensive chemicals that can repel attacks from caterpillars.”

Appel collaborated with Rex Cocroft, professor in the Division of Biological Sciences at MU.

In the study, caterpillars were placed on Arabidopsis, a small flowering plant related to cabbage and mustard.

Using a laser and a tiny piece of reflective material on the leaf of the plant, Cocroft was able to measure the movement of the leaf in response to the chewing caterpillar.

Cocroft and Appel then played back recordings of caterpillar feeding vibrations to one set of plants, but played back only silence to the other set of plants.

When caterpillars later fed on both sets of plants, the researchers found that the plants previously exposed to feeding vibrations produced more mustard oils, a chemical that is unappealing to many caterpillars.

“What is remarkable is that the plants exposed to different vibrations, including those made by a gentle wind or different insect sounds that share some acoustic features with caterpillar feeding vibrations did not increase their chemical defenses,” Cocroft said.

“This indicates that the plants are able to distinguish feeding vibrations from other common sources of environmental vibration.”

Appel and Cocroft say future research will focus on how vibrations are sensed by the plants, what features of the complex vibrational signal are important, and how the mechanical vibrations interact with other forms of plant information to generate protective responses to pests.

“Plants have many ways to detect insect attack, but feeding vibrations are likely the fastest way for distant parts of the plant to perceive the attack and begin to increase their defenses,” Cocroft said.

“Caterpillars react to this chemical defense by crawling away, so using vibrations to enhance plant defenses could be useful to agriculture,” Appel said.

“This research also opens the window of plant behavior a little wider, showing that plants have many of the same responses to outside influences that animals do, even though the responses look different.”

The study, “Plants respond to leaf vibrations caused by insect herbivore chewing,” was funded in part by the National Science Foundation and was published in Oecologia.

Plants can ‘talk’ too…

Researchers in Bonn, Germany, found plants give off a gas when under “attack”.

Super-sensitive microphones picked up a “bubbling” sound from a healthy plant.

But this rose to a piercing screech when it was under threat.

Even a tiny insect bite could have an effect.

“The more a plant is subjected to stress, the louder the signal,” said Dr Frank Kühnemann.

Plants do not actually scream in pain. But different sounds are heard when the gas they emit, ethylene, is bombarded with lasers.

The research could help to work out which pieces of fruit and vegetables are likely to stay fresh longer, as a cucumber which is starting to go off produces a squealing sound.

It could then be separated from the fresher ones.

Brain Cells We Thought Were Just Fillers Might Actually Be the Key to Our Body Clocks

Neurons aren’t everything.

Scientists have discovered that brain cells that were once considered to be simple place-holders for neurons could actually play an important role in helping to regulate our circadian behaviour.

Astrocytes are a kind of glial cell – the support cells that are often called the glue of the nervous system, as they provide structure and protection for neurons. But a new study shows that astrocytes aren’t just gap-fillers, and may be crucial for keeping time in our inner body clock.

 Scientific consensus has long regarded our internal clock as being controlled by the suprachiasmatic nuclei (SCN), a brain region in the hypothalamus made up of around 20,000 neurons. But there’s about 6,000 star-shaped astrocyte cells in the same area, the exact function of which has never been fully explained.

Now, a team from Washington University in St. Louis has figured out how to independently control astrocytes in mice – and by altering the astrocytes, the scientists were able to slow down the animals’ sense of time.

“We had no idea they would be that influential,” says one of the researchers, Matt Tso.

It was once thought the suprachiasmatic nuclei was the only part of the brain that regulated circadian rhythms, but scientists now understand that cells throughout the body all have their own circadian clocks – including the cells that make up our lungs, heart, liver, and everything else.

In 2005, one of the team, neuroscientist Erik Herzog, helped figure out that astrocytes also include these clock genes.

By isolating the brain cells from rats and coupling them with a bioluminescent protein, Herzog’s team showed that they glowed rhythmically – evidence that they were capable of keeping time like other cells.

 It took more than a decade for the researchers to figure out how to measure the same astrocyte behaviour in a living specimen, by using CRISPR-Cas9 gene-editing to delete a clock gene called Bmal1 in the astrocytes of mice.

Left to their own devices, mice have circadian clocks that last for approximately 23.7 hours. We know this because mice in constant darkness will start running on a wheel every 23.7 hours, and usually don’t miss their time slot by more than 10 minutes.

Humans also miss the 24-hour mark slightly – a Harvard University study in 1999 found that our internal clocks run a tad overlong, on a daily cycle of 24 hours, 11 minutes.

But even though Herzog had demonstrated in 2005 that astrocytes were involved in keeping time, the team didn’t necessarily expect mice without Bmal1 to be affected, because most research surrounding the suprachiasmatic nuclei has demonstrated the controlling effect of neurons, not astrocytes.

“When we deleted the gene in the astrocytes, we had good reason to predict the rhythm would remain unchanged,” says Tso.

“When people deleted this clock gene in neurons, the animals completely lost rhythm, which suggests that the neurons are necessary to sustain a daily rhythm.”

But, to the researchers’ surprise, deleting the clock gene in the astrocytes saw the mouse internal clocks run slower – beginning their daily run about 1 hour later than usual.

In another experiment, the team studied mice with a mutation that caused their circadian clocks to run fast. By repairing this gene in the animals’ astrocytes – but not fixing the defect in their neurons – they weren’t sure what the affect would be.

“We expected the SCN to follow the neurons’ pace,” says Tso. “There are 10 times more neurons in the SCN than astrocytes. Why would the behaviour follow the astrocytes?”

With the mutation fixed in the animals’ astrocytes, the mouse began their running routine 2 hours later than mice that hadn’t had the mutation repaired (in either astrocytes or neurons).

“[These results] suggests that the astrocytes are somehow talking to the neurons to dictate rhythms in the brain, and in behaviour,” Herzog told Diana Kwon at The Scientist.

While the researchers acknowledge that they don’t fully understand the extent to which astrocytes control circadian behaviour, it’s clear something powerful is going on.

Of course, we can’t guarantee yet whether astrocytes in humans are regulating body clocks in the same way, but that’s something that later studies may be able to confirm.

We’ll have to wait to see the results of future research to know more, but until then, one thing’s for sure – these brain cells are definitely there for a lot more than just neuron padding.


The World’s Rarest and Most Ancient Dog Has Just Been Re-Discovered in the Wild

The first sighting in more than half a century.

After decades of fearing that the New Guinea highland wild dog had gone extinct in its native habitat, researchers have finally confirmed the existence of a healthy, viable population, hidden in one of the most remote and inhospitable regions on Earth.

According to DNA analysis, these are the most ancient and primitive canids in existence, and a recent expedition to New Guinea’s remote central mountain spine has resulted in more than 100 photographs of at least 15 wild individuals, including males, females, and pups, thriving in isolation and far from human contact.

 “The discovery and confirmation of the highland wild dog for the first time in over half a century is not only exciting, but an incredible opportunity for science,” says the group behind the discovery, the New Guinea Highland Wild Dog Foundation (NGHWDF).

“The 2016 Expedition was able to locate, observe, gather documentation and biological samples, and confirm through DNA testing that at least some specimens still exist and thrive in the highlands of New Guinea.”

If you’re not familiar with these handsome creatures, until now, New Guinea highland wild dogs were only known from two promising but unconfirmed photographs in recent years – one taken in 2005, and the other in 2012.

They had not been documented with certainty in their native range in over half a century, and experts feared that what was left of the ancient dogs had dwindled to extinction.

But maybe they were just really good at hiding?

Last year, a NGHWDF expedition made it to the Papua province of western New Guinea, which is bordered by Papua New Guinea to the east and the West Papua province to the west.

 Led by zoologist James K McIntyre, the expedition ran into local researchers from the University of Papua, who were also on the trail of the elusive dogs.

A muddy paw print in September 2016 finally gave them what they were looking for – recent signs that something distinctly dog-like was wandering the dense forests of the New Guinea highlands, some 3,460 to 4,400 metres (11,351 to 14,435 feet) above sea level.

Trail cameras were immediately deployed throughout the area, so they could monitor bait sites around the clock. The cameras captured more than 140 images of wild Highland Wild Dog in just two days on Puncak Jaya – the highest summit of Mount Carstensz, and the tallest island peak in the world.

dogPregnant female.

new-guinea-pupsHighland wild dog pups.

The team was also able to observe and document dogs in the area first-hand, and DNA analysis of faecal samples have confirmed their relationship to Australian dingos and New Guinea singing dogs – the captive-bred variants of the New Guinea highland wild dog.

Due to the lack of evidence of the species, it’s been unclear exactly how dingoes, singing dogs, and highland wild dogs actually relate to one another, but that’s a question that will hopefully soon be answered, because these animals truly are our best bet for getting a better understanding of canid evolution.

As the NGHWD explains:

“The fossil record indicates the species established itself on the island at least 6,000 years ago, believed to have arrived with human migrants. However, new evidence suggests they may have migrated independently of humans.

While the taxonomy and phylogenetic relationships with related breeds and Australian dingoes is currently controversial and under review for both New Guinea singing dogs and highland wild dogs, the scientific and historical importance of the highland wild dog remains critical to understanding canid evolution, canid and human co-evolution and migrations, and human ecology and settlement derived from the study of canids and canid evolution.”

As far as dogs go, you’d be hard-pressed to find a more attractive one – their coats are most commonly golden, but there are also black and tan, and cream variants. Their tails are carried high over their backsides in a fish hook shape, like a Shiba Inu.

In all of the dogs observed so far, their ears sit erect and triangular on the top of the head.

dog-variantsSome of the wild dog sightings. 

running-dogA wary observer. 

Though it’s yet to be confirmed, the highland wild dogs could make the same unique vocalisations of their captive-bred counterparts – the New Guinea singing dogs.

According to the NGHWDF, there are roughly 300 New Guinea singing dogs remaining in the world, living in zoos, private facilities, and private homes, and they’re known for their high-pitched howls, which they will perform in chorus with one another, and sometimes for several minutes at a time:

 The research into these amazing dogs is ongoing, and a scientific paper on the discovery is expected to be released in the coming months.

And the good news is the researchers are optimistic of the highland wild dogs’ chances of survival.

Local mining companies have been tasked with taking special environmental stewardship measures to protect the remote area and ecosystem surrounding their facilities, which means they have “inadvertently created a sanctuary in which the HWD could thrive”, says the NGHWDF.

The Amount of Food Spiders Eat Each Year Will Haunt You for the Rest of Your Life

Spiders are already horrifying, with their eight beady little eyes and spindly legs and sticky webs. They also probably eat more meat than your mind can wrap your head around—more meat than humans eat, even.
 Spider meal specialist Martin Nyffeler of the University of Basel, Switzerland decided, hey, let’s try and estimate the total weight of all of the food spiders around the world eat per year. Some data crunching resulted in a number so bafflingly high you’ll either squirm or thank the spiders for keeping us safe from all the other bugs. Maybe both.

That number: The world’s estimated 25 million metric tons of spiders eat between 300 and 800 million metric tons of food per year, according to estimates published today in the very silly-sounding journal The Science of Nature. (That almost feels like calling something the Ferrari of Lamborghinis in academic journal speak). That food consists mainly of insects, little non-insect bugs called springtails, and even small vertebrates. The researchers make several assessments, using the amount of food individual spiders need to eat, the number of insects they catch in their webs, and the number of insects they kill on the hunt.

The 300 to 800 million metric ton figure is pretty close to the mass of meat and fish humans eat per year—around 400 metric tons, according to the paper. It’s also equal to the mass of humans: There are 7.4 billion people on earth, and the average human’s weight is around 130 pounds. Converted to metric tons, that’s a bit over 400 million.

 The idea to do this eye-opening calculation came from a book Nyffeler read 40 years ago, The World of Spiders by arachnologist William Bristowe in 1958, according to a prepared statement he passed along to Gizmodo. “In this book, Bristowe speculated that the weight of insects annually killed by the British spider population would exceed the combined weight of the British human population,” wrote Nyffeler. “This statement fascinated me very much. I decided that I would like to find out if Bristowe was correct with his speculation.”

You might think this means spiders are helping our crops by eating all of the pests, but that doesn’t seem to be the case. “Instead spiders appear to play a significant ecological role as predators of insects in forests and undisturbed grasslands,” Nyffeler wrote. Very generally speaking, spiders don’t seem to eat as many bugs in agricultural areas because these heavily managed systems don’t have as many or as good an assortment of prey.

Our apologies for that horrible image. But hey, at least they aren’t eating you. Yet.

Source:The Science of Nature

A new hypothesis of dinosaur relationships and early dinosaur evolution.