Their findings were published in the Federation of European Biochemical Societies journal on October 26.

Being allergic to dogs is a common malady and one that is growing worldwide. Over the years, scientists have been able to identify seven different dog allergens — molecules or molecular structures that bind to an antibody and produce an unusually strong immune response that would normally be harmless.

These seven are named Canis familiaris allergens 1 to 7 (Can f 1-7). But while there are seven, just one, Can f 1, is responsible for the majority (50-75 percent) of reactions in people allergic to dogs. It is found in dogs’ tongue tissue, salivary glands, and their skin.

Researchers have yet to identify Can f 1’s IgE epitopes — those specific parts of the antigens that are recognized by the immune system and stimulate or ‘determine’ an immune response (which is why epitopes are also called antigen determinants). More specifically, epitopes are short amino acid sequences making up part of a protein that induces the immune response.

Epitopes bind to a specific antigen receptor on the surface of immune system antibodies, B cells, or T Cells, much like how the shape of a jigsaw puzzle piece fits the specific shape of another puzzle piece. (The part of the receptor that binds to the epitope is in turn called a paratope). Antibodies, also known as immunoglobulin, come in five different classes or isotypes: IgA (for immunoglobulin A), IgD, IgE, IgG, or IgM. The IgE isotype (only found in mammals) plays a key role in allergies and allergic diseases. There is also an IgE epitope that is the puzzle piece that fits the IgE isotype’s paratope.

In recent years, there has been extensive effort at developing epitope-focused vaccines — in this case, a vaccine against dog allergies.

“We want to be able to present small doses of these epitopes to the immune system to train it to deal with them, similar to the principle behind any vaccine,” said Takashi Inui, a specialist in allergy research, professor at Osaka Prefecture University and a lead author of the study. “But we can’t do this without first identifying the Can f 1’s IgE epitope.”

So the researchers used X-ray crystallography (in which the diffraction of x-rays through a material is analyzed to identify its ‘crystal’ structure) to determine the structure of the Can f 1 protein as a whole — the first time this had ever been done.

They found that the protein’s folding pattern is at first glance extremely similar to three other Can f allergens. However, the locations of surface electrical charges were quite different, which in turn suggest a series of ‘residues’ that are good candidates for the IgE epitope.

Using this basic data, further experimental work needs to be performed to narrow the candidates down, but the findings suggest the development of a hypoallergenic vaccine against Can f 1 — a dog-allergy vaccine — is within our grasp.

The production of a ‘hypoallergenic vaccine’ by use of such epitopes would not just be a world-first with respect to dog allergies but is rare with respect to any allergic reaction. If the researchers’ work is indeed used to develop a dog allergy vaccine, the principles behind it could be used much more widely against various allergies.

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Materials provided by Osaka Prefecture University. Note: Content may be edited for style and length.

“Iodine, the same chemical added as a nutrient to table salt, is eating up ozone in dusty air high in the atmosphere,” said Rainer Volkamer, a CIRES Fellow and professor of chemistry at CU Boulder. Volkamer led the team that made precision atmospheric measurements by aircraft over the eastern Pacific Ocean several years ago. The new finding, he said, has implications for not only air quality, but climate, too — iodine chemistry can make greenhouse gases stick around longer and should give us pause to re-think geoengineering schemes involving dust.

“Our understanding of the iodine cycle is incomplete,” Volkamer said. “There are land-based sources and chemistry we didn’t know about, which we must now consider.”

Atmospheric researchers have long been interested in the observation that dusty layers of air are often very low in the air pollutant ozone, which, when concentrated, can damage people’s lungs and even crops. It seemed that some kind of dust-surface chemistry was eating up ozone, but no one had been able to show that happening in laboratory experiments. Others have speculated about this, but there’s been a lot of doubt, said Volkamer. By contrast, lab experiments have long shown that a gaseous form of iodine can gobble up ozone — but there were only hints of a connection between dust and iodine.

There were other tantalizing hints about the process in a dataset from 2012, from a series of aircraft flights offshore Chile and Costa Rica. Dust seen blowing offshore from South America had striking levels of gaseous iodine. Volkamer handed the data to then-CU Boulder graduate student Theodore Koenig, lead author on this study. Koenig describes those data as one in a set of blurry photographs shared by atmospheric chemists around the world. In one image, for example, “iodine seemed to correlate with dust … but not absolutely clearly,” he said. Everywhere, dust seemed to destroy ozone, but why? “Iodine and ozone clearly connect, but there weren’t any ‘photos’ of both with dust,” said Koenig, who is now an air pollution researcher at Peking University in China.

The data from TORERO (the “Tropical Ocean Troposphere Exchange of Reactive Halogens and Oxygenated Hydrocarbons,” a field campaign funded by the National Science Foundation) captured those three characters together, finally, in one image he said, and it was clear that where desert dust contained significant levels of iodine — like dust from the Atacama and Sechura deserts in Chile and Peru — the iodine was quickly transformed into a gaseous form and ozone dropped to very low levels. But how did that dust-based iodine transform? “The mechanism still remains elusive,” Volkamer said. “That’s future work.”

So the picture is another blurry one, Koenig said, but still, the science is sharper than it was. “I have more questions at the end of the project than at the start,” he said. “But they’re better, more specific questions.”

They’re also very important, for anyone interested in the future of the atmosphere, Volkamer said. Iodine’s reactions in the atmosphere are known to play a role in reducing levels of OH, for example, which can increase the lifetime of methane and other greenhouse gases. Perhaps more importantly, various geoengineering ideas involve injecting dust particles high into Earth’s atmosphere, to reflect incoming solar radiation. There, in the stratosphere, ozone is not a pollutant; rather, it forms a critical “ozone layer” that helps shield the planet from incoming radiation.

If iodine from dust was chemically transformed into an ozone-depleting form in the stratosphere, Volkamer said, “well, that’d not be good, as it could delay the recovery of the ozone layer. Let’s avoid adding anthropogenic iodine into the stratosphere!”

But how do cells fold themselves so precisely into such complicated configurations during development? What are the fundamental forces driving this process?

Now, researchers at Harvard Medical School have discovered a mechanical process by which sheets of cells morph into the delicate, looping semicircular canals of the inner ear.

Published Dec. 22 in Cell, the research, done in zebrafish, reveals that the process involves a combination of hyaluronic acid, produced by cells, that swells with water, and thin connectors between cells that direct the force of this swelling to shape the tissue.

Although conducted in zebrafish, the work reveals a basic mechanism for how tissues take on shapes — one that is likely to be conserved across vertebrates, the researchers say, and may also have implications for bioengineering.

A Model of Transparency

Study senior author Sean Megason, professor of systems biology in the Blavatnik Institute at HMS, and his team study how cells develop into complex, three-dimensional structures. To address this question, they turned to a classic — and ideal — model organism: zebrafish.

“They’re transparent, so we just stick them under a microscope and look at this entire process from a single cell to a larva that can swim and has all its parts,” explained study first author Akankshi Munjal, who conducted the research as a postdoctoral researcher at HMS and is now an assistant professor of cell biology at Duke University.

These parts include the semicircular canals, three fluid-filled tubes in the inner ear that are needed for balance and orienting in space. Little is known about how the semicircular canals form, in part because in many species they are obscured by the middle and outer ear. In zebrafish, however, the canals sit close to the surface, allowing researchers to watch them develop under a microscope.

“This was an exciting opportunity for us to look at how a three-dimensional organ forms from a simple sheet of cells,” Munjal said. “We could look at the inner ear in the embryo with complete accessibility.”

“The inner ear is a model for how cells work together to make complex structures that are needed for organisms to function,” Megason added. “We went into it thinking it was a beautiful structure, but not knowing what we would find.”

What they did find surprised them.

The conventional thinking is that the proteins actin and myosin act as tiny motors inside cells, pushing and pulling them in different directions to fold a tissue into a specific shape. However, the researchers discovered that zebrafish semicircular canals form through a markedly different process. During development, the cells produce hyaluronic acid, which is perhaps most well known as an antiwrinkle agent in beauty products. Once in the extracellular matrix the acid swells up, not unlike a diaper in a swimming pool. This swelling creates enough force to physically move nearby cells, but since the pressure is the same in all directions, the researchers wondered how the tissue ends up stretching in one direction and not another to form an elongated shape. The team found that this is accomplished by thin connectors between cells — dubbed cytocinches — that constrain the force.

“It’s like if you were to put a corset on a water balloon and deform it into an oblong structure,” Munjal said. This combination of swelling and cinching progressively shapes an initially flat sheet of cells into tubes.

“Our work shows a new way of doing things,” Megason said, adding that he hopes it will encourage people to consider additional mechanisms that may be involved in shaping tissues. “Cells have to use many different forces in order to accomplish what they need to, and time will tell exactly what the balance is between the molecular approaches of actin and myosin and the more physical approaches of pressure.”

Their discovery likely has broader implications, Megason and Munjal added.

The genes that control hyaluronic acid production in zebrafish semicircular canals are also present in the semicircular canals of mammals, suggesting that a similar process may be occurring. Moreover, hyaluronic acid is found in multiple parts of the human body, including skin and joints, indicating that it may play a role in shaping many tissues and organs — an avenue for future research.

If that does turn out to be the case, then studying the genes involved in hyaluronic acid production could help researchers understand congenital defects in organs where hyaluronic acid drives development.

“This is likely to be a widespread, conserved mechanism across species and organs,” Munjal said.

The mechanism could also be applied to bioengineering, where researchers are attempting to prod stem cells into forming buds, tubes, and other complicated shapes, with the ultimate goal of culturing organs in the lab.

Lab-grown organs are still a work in progress, Megason noted, but a key step will be parsing how organs form inside an organism. “We’re trying to dissect the steps of how a complex organ such as the inner ear is made in vivo, and then quantitatively understand those steps,” Megason said. “We hope this will set the foundational groundwork for having cells grow into whatever pattern and shape we want.”

This work was supported by the National Institutes of Health (R01DC015478), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K99HD098918), and a Human Frontier Science Program Long-Term Fellowship.

The researchers found an evolutionary tweak in feather nanostructure that has more than doubled the range of iridescent colors birds can display. This insight could help researchers understand how and when brilliant iridescence first evolved in birds, as well as inspire the engineering of new materials that can capture or manipulate light.

As iridescent birds move, nanoscale structures within their feathers’ tiny branch-like filaments — known as barbules — interact with light to amplify certain wavelengths depending on the viewing angle. This iridescence is known as structural coloration, wherein crystal-like nanostructures manipulate light.

“If you take a single barbule from an iridescent feather, cross-section it and put it under an electron microscope, you’ll see an ordered structure with black dots, or sometimes black rings or platelets, within a gray substrate,” said first author Klara Nordén, a Ph.D. student in the lab of senior author Mary Caswell Stoddard, associate professor of ecology and evolutionary biology at Princeton and associated faculty in Princeton’s High Meadows Environmental Institute (HMEI). “The black dots are pigment-filled sacs called melanosomes, and the gray surrounding them is feather keratin. I find these nanoscale structures just as beautiful as the colors they produce.”

Curiously, the melanosome structures come in variety of shapes. They can be rod-shaped or platelet-shaped, solid or hollow. Hummingbirds, for example, tend to have hollow, platelet-shaped melanosomes, while peacocks have rod-shaped melanosomes. But why birds evolved iridescent nanostructures with so many different types of melanosomes has been a mystery, with scientists unsure if some melanosome types are better than others at producing a broad range of vibrant colors.

To answer this question, the researchers combined evolutionary analysis, optical modeling and plumage measurements — all of which allowed them to uncover general design principles behind iridescent feather nanostructures.

Nordén and Stoddard worked with co-author Chad Eliason, a postdoctoral fellow at The Field Museum, to first survey the literature and compile a database of all described iridescent feather nanostructures in birds, which included more than 300 species. They then used a family tree of birds to illustrate which groups evolved the different melanosome types.

There are five primary types of melanosomes in iridescent feather nanostructures: thick rods, thin rods, hollow rods, platelets and hollow platelets. Except for thick rods, all of these melanosome types are found in brilliantly colored plumage. Because the ancestral melanosome type is rod-shaped, previous work focused on the two obvious features unique to iridescent structures: platelet shape and hollow interior.

However, when the researchers evaluated the results of their survey, they realized that there was a third melanosome feature that has been overlooked — thin melanin layers. All four melanosome types in iridescent feathers — thin rods, hollow rods, platelets and hollow platelets — create thin melanin layers, much thinner than a structure built with thick rods. This is important because the size of the layers in the structures is key to producing vibrant colors, Nordén said.

“Theory predicts that there is a kind of Goldilocks zone in which the melanin layers are just the right thickness to produce really intense colors in the bird-visible spectrum,” she said. “We suspected that thin rods, platelets or hollow forms may be alternative ways to reach that ideal thickness from the much larger ancestral melanosome size — the thick rods.”

The researchers tested their idea on bird specimens at the American Museum of Natural History in New York City by measuring the color of iridescent bird plumage that results from nanostructures with different melanosome types. They also used optical modeling to simulate the colors that would be possible to produce with different types of melanosomes. From these data, they determined which feature — thin melanin layers, platelet shape or hollowness — has the greatest influence on the range and intensity of color. Combining the results of the optical modeling and plumage analyses, the researchers determined that thin melanin layers — no matter the shape of the melanosomes — nearly doubled the range of colors an iridescent feather could produce.

“This key evolutionary breakthrough — that melanosomes could be arranged in thin melanin layers — unlocked new color-producing possibilities for birds,” Stoddard said. “The diverse melanosome types are like a flexible nanostructural toolkit, offering different routes to the same end: brilliant iridescent colors produced by thin melanin layers.”

This may explain why there exists such a great diversity of melanosome types in iridescent nanostructures. Iridescent nanostructures likely evolved many times in different groups of birds, but, by chance, thin melanin layers evolved from a thick rod in different ways. Some groups evolved thin melanin layers by flattening the melanosomes (producing platelets), others by hollowing out the interior of the melanosome (producing hollow forms), and yet others by shrinking the size of the rod (producing thin rods).

The findings of the study could be used to reconstruct brilliant iridescence in prehistoric animals, Nordén said. Melanosomes can be preserved in fossil feathers for millions of years, which means that paleontologists can infer original feather color — even iridescence — in birds and dinosaurs by measuring the size of fossilized melanosomes.

“Based on the thick solid rods that have been described in the plumage of Microraptor, for example, we can say that this feathered theropod likely had iridescent plumage much more like that of a starling than that of a peacock,” Nordén said.

The composition of melanosomes and keratin in bird feathers could hold clues for engineering advanced iridescent nanostructures that can efficiently capture or manipulate light, or be used to produce eco-friendly paints that do not require dyes or pigments. Super-black coatings such as Vantablack similarly use nanostructures that absorb and disperse rather than reflect light, similar to the black plumage of species in the birds-of-paradise (Paradisaeidae) family.

Iridescent feathers also could lead to a richer understanding of multifunctional materials, Nordén said. Unlike human-made materials, which are often developed for a single function, natural materials are inherently multipurpose. Melanin not only helps produce iridescence; it also protects birds from dangerous ultraviolet radiation, strengthens feathers and inhibits microbial growth.

“What if the different types of melanosomes initially evolved for some reason unrelated to the iridescent color — such as for making the feather mechanically stronger, or more resistant to microbial attack,” Nordén said. “These are some of the questions we are excited to tackle next.”