One of the most common limb malformation in humans, syndactyly was thought to be caused by insufficient removal of the connective tissue between the developing digits. In a study, published today in Developmental Cell, researchers reveal that the overlying skin also plays an active role and is required for sculpting of the digits, and that a layer of non-adhesive cells on the skin’s surface is required to prevent the fusion of adjacent digits.

“Our study identifies epidermal developmental processes required for digit separation that expand beyond the insufficient removal of connective tissue. These additional factors play an integral role in syndactyly and may be implicated in other complex syndromes, including Van der Woude syndrome,” said Ghaidaa Kashgari, PhD, a post-doctoral researcher in the UCI School of Medicine Department of Biological Chemistry, and first author on the paper titled, “Epithelial migration and non-adhesive periderm are required for digit separation during mammalian development.”

Van der Woude syndrome is characterized by cleft lip and/or cleft palate. In addition, seven to eight percent of Van der Woude patients have limb defects, most commonly soft tissue syndactyly which suggests there is a shared developmental mechanism in oral-clefting and digit separation.

“Our research shows that the GRHL3 gene is required for normal digit separation. When this gene is mutated, it can affect the function of the non-adhesive cells on the skin’s surface causing conditions such as Van der Woude syndrome associated with syndactyly as well as cleft lip and palate,” said Bogi Andersen, MD, a professor of medicine and biological chemistry in the UCI School of Medicine, and director of the UCI Skin Biology Resource-based Center.

Story Source:

Materials provided by University of California – Irvine. Note: Content may be edited for style and length.

Results published in the Journal of the American Chemical Society provide new insights on the way molecules pack and order themselves into “tunable” interfaces, monolayer thick surfaces with structures that can be modified for specific functionalities.

“Understanding the design rules of the chemistry happening at the liquid-liquid interface ultimately informs how we can make new materials with custom properties,” said Benjamin Doughty of ORNL’s Chemical Sciences Division.

The study expands interest in using soft materials to mimic lipid bilayers — selective membranes with important biological functions, such as processing signals across the brain’s neural network and transporting ions, proteins, and other molecules across cells.

Co-authors previously designed biomimetic membranes using lipid-coated water droplets in oil and demonstrated their potential as sensory components for neuromorphic, or brain-like, computers with natural information processing, learning and memory.

“Because lipids are inherently fragile and decay, we are interested in developing polymer-based counterparts that offer stability and can also give us a range of natural functionalities,” said Pat Collier of ORNL’s Center for Nanophase Materials Sciences, a DOE Office of Science User Facility.

Without the knowledge of interfacial chemistry, however, creating functional bilayers from natural or synthetic molecules involves a certain degree of mystery. Chemical species interacting in a beaker of solution may or may not form analogous membranes with selective properties, such as the capability to store or filter sensory impulses that make up the nondigital language of neuromorphic computing.

“To be able to train molecules for specific purposes and unlock new functionalities, we need to understand what is happening on a molecular level during self-assembly,” Collier said.

For the experiment, researchers chose an oligomer, a small polymer variant with a similar structure to natural lipids, and used surface spectroscopy methods to probe the molecular monolayer — one side of a bilayer — formed between water and oil.

The ORNL team is one of only a few groups that has probed the liquid-liquid interface, an important area of research, but understudied because of technical challenges.

“Our goal was to investigate how the asymmetry at the oil-water interface causes species to adsorb differently, to pack and order into a functional design,” Doughty said.

The studied oligomer is an amphiphilic molecule, meaning parts of its structure are hydrophobic while others are hydrophilic. When samples stabilized in oil are introduced into a water-based solution, the molecules self-assemble in response to their mixed attraction and repulsion to water.

Like goes to like — the oligomers’ slightly charged polar heads want to be in the water phase, which is also polar, and the nonpolar tails want to be in the oil phase, which is not.

“Being able to observe in real time how these molecules arrange at a varied interface is a broadly applicable fundamental scientific accomplishment,” Doughty said.

As shown in the animation, the charged oligomer heads home in on the water phase; but the flexible tails coil up in the oil when they have room to spare, or tighten to accommodate neighbors as the interface becomes crowded.

“We discovered that adjusting the ions, or charged particles, in the water phase aided in the formation of well-defined interfaces, with oligomers taking on more tightly coiled structures,” Doughty said.

Too few ions and the tails spread out loosely, leaving gaps; too many, and they squeeze in, ballooning from the surface.

“The findings point to approaches for modifying the size and shape of monolayers, and — at the next stage — enabling bilayers with asymmetrical designs, just like natural lipids,” Collier said. “The work brings us a step closer to unlocking new potentials in biomaterials.”

Tailoring surfaces on a molecular level to design new materials opens possibilities not only for biocomputing but also broadly for chemical separations, sensing and detection.

“Observing the liquid-liquid interface helps us understand the chemistry that drives all of these technologies,” said Doughty.

The wildfire, driven by strong winds and explosive growth, was unprecedented in how it burned the landscape, destroying more than 300 homes in Washington’s Methow Valley. But “megafires” like the Carlton Complex are becoming more common in western U.S. forests as the climate warms and forests are crowded with trees after years of fire exclusion.

In the first major study following the devastating Carlton Complex fire, researchers from the University of Washington and U.S. Forest Service found that previous tree thinning and prescribed burns helped forests survive the fire. The study, published Feb. 22 in the journal Ecological Applications, shows that even in extreme wildfires, reducing built-up fuels such as small trees and shrubs pays off.

“Our study suggests that the fuel treatments were worth the investment, yielding a more desirable post-fire outcome than if they hadn’t been implemented,” said lead author Susan Prichard, a research scientist at the UW School of Environmental and Forest Sciences. “There are a lot of benefits to creating more resilient landscapes, and this study suggests that even in the worst-case scenario wildfires, it can be worth it.”

On July 17, 2014, sustained winds of 35 mph raced through the Methow Valley, blasting oxygen into several fires that had started earlier that week. Before long, the fires joined and spread. A column of smoke stretched 30,000 feet high, dropping embers and igniting dry grasses, trees and other fuels on the ground over thousands of acres.

Propelled by the fast-moving column of smoke and wind, the flames traveled all the way to the Columbia River.

“It was the kind of fire that even experts who have studied them for decades had not seen before,” said Prichard, who lives in the Methow Valley. “It was a devastating fire for our community. I truly thought people would be killed by that fire, and it still feels miraculous that everyone survived.”

In the aftermath, Prichard and collaborators wondered if actions such as controlled burns and thinning were helpful in the case of a megafire like the Carlton Complex. State and federal agencies sink ample resources into these efforts to increase the resiliency of forests to wildfires by removing small- and medium-sized trees, leaving larger, mature trees that are more likely to survive future drought and wildfires.

After a forest is thinned, prescribed burning is used to reduce leftover woody debris on logging sites or across landscapes that have built up downed trees, pine needles, grasses and shrubs.

The Carlton Complex fire burned across hundreds of sites that were previously thinned or burned, offering a testbed for the researchers to analyze whether the work helped reduce fire impacts in those areas during the megafire. The researchers used satellite images of burn severity to examine how past fuel treatments performed in the context of this extreme wildfire event.

They found that even during the first explosive days of the Carlton Complex, areas that were thinned and prescribed burned had more trees survive than areas that didn’t receive those fuel treatments.

“Some of the treatments measurably reduced fire impacts even under very hot, dry and windy conditions,” said co-author David W. Peterson, a research scientist at U.S. Forest Service Wenatchee Forestry Sciences Lab. “Our results suggest that as we increase our ‘restoration footprint’ — the proportion of forest area treated to reduce fuels — forests may become increasingly resilient to wildfires under a broad range of conditions.”

They also found that thinning and burning on slopes that were protected from prevailing winds was more effective in reducing the wildfire’s impacts on the landscape than similar treatments in areas directly exposed to the wind. Because winds often move through the Methow Valley in a predictable pattern, fire managers could thin and burn strategically in areas where these activities would be most effective.

Those efforts helped mature, naturally fire-resistant ponderosa pines survive. These mature trees, in turn, will provide seeds that produce younger trees across the landscape.

While this study focused on the Carlton Complex fire, its results have broader implications for forests around the world that are prone to wildfires. This work adds to the growing library of studies showing how thinning trees and controlled burns can reduce the severity of the next fire on the landscape.

“I’m hopeful our study will encourage policymakers as well as managers to invest in restoration,” Prichard said. “It’s our best hope for protecting our streams, rivers and landscapes from catastrophic fires.”

This research was funded by the U.S. Forest Service’s Western Wildland Environmental Threat Assessment Center, the Joint Fire Science Program and the National Fire Plan.