Oldest known fossilized skin is 21 million years older than previous examples

Researchers have identified a 3D fragment of fossilized skin that is at least 21 million years than previously described skin fossils. The skin, which belonged to an early species of Paleozoic reptile, has a pebbled surface and most closely resembles crocodile skin. It's the oldest example of preserved epidermis, the outermost layer of skin in terrestrial reptiles, birds, and mammals, which was an important evolutionary adaptation in the transition to life on land. The fossil is described on January 11 in the journal Current Biology along with several other specimens that were collected from the Richards Spur limestone cave system in Oklahoma.

"Every now and then we get an exceptional opportunity to glimpse back into deep time," says first author Ethan Mooney, a paleontology graduate student at the University of Toronto who worked on the project as an undergraduate with paleontologist Robert Reisz at the University of Toronto.

"These types of discoveries can really enrich our understanding and perception of these pioneering animals."

Skin and other soft tissues are rarely fossilized, but the researchers think that skin preservation was possible in this case because of the cave system's unique features, which included fine clay sediments that slowed decomposition, oil seepage, and a cave environment that was likely an oxygenless environment.

"Animals would have fallen into this cave system during the early Permian and been buried in very fine clay sediments that delayed the decay process," says Mooney.

"But the kicker is that this cave system was also an active oil seepage site during the Permian, and interactions between hydrocarbons in petroleum and tar are likely what allowed this skin to be preserved."

The skin fossil is tiny -- smaller than a fingernail. Microscopic examination undertaken by coauthor Tea Maho of the University of Toronto Mississauga revealed epidermal tissues, a hallmark of the skin of amniotes, the terrestrial vertebrate group that includes reptiles, birds, and mammals and which evolved from amphibian ancestors during the Carboniferous Period.

"We were totally shocked by what we saw because it's completely unlike anything we would have expected," says Mooney.

"Finding such an old skin fossil is an exceptional opportunity to peer into the past and see what the skin of some of these earliest animals may have looked like."

The skin shares features with ancient and extant reptiles, including a pebbled surface similar to crocodile skin, and hinged regions between epidermal scales that resemble skin structures in snakes and worm lizards.

However, because the skin fossil is not associated with a skeleton or any other remains, it is not possible to identify what species of animal or body region the skin belonged to.

The fact that this ancient skin resembles the skin of reptiles alive today shows how important these structures are for survival in terrestrial environments.

"The epidermis was a critical feature for vertebrate survival on land," says Mooney.

"It's a crucial barrier between the internal body processes and the harsh outer environment."

The researchers say that this skin may represent the ancestral skin structure for terrestrial vertebrates in early amniotes that allowed for the eventual evolution of bird feathers and mammalian hair follicles.

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Researchers discover potential microbiome links to skin aging

The effects of aging and external factors like UV exposure on skin are well documented. As people age or spend more time in the sun, their skin tends to become drier and more wrinkled,

Recent findings have identified an exciting potential new link to signs of skin aging -- the skin microbiome, the collection of microorganisms that inhabits our skin. The results come from a collaborative study carried out by researchers at the Center for Microbiome Innovation (CMI) at the University of California San Diego (UC San Diego) and L'Oréal Research and Innovation.

Their work was published in Frontiers in Aging on January 11, 2024, in an article entitled "A multi-study analysis enables identification of potential microbial features associated with skin aging signs." To the best of the team's knowledge, the study is the first to isolate microbes associated specifically with signs of skin aging and skin health, rather than chronological age.

Combining CMI's sophisticated data analysis abilities with L'Oréal's knowledge and expertise in skin health assessment, the study comprehensively examined data collected during 13 studies that L'Oréal had carried out in the past, consisting of 16S rRNA amplicon sequence data and corresponding skin clinical data for over 650 female participants, aged 18 -- 70. While each of the studies included in the analysis had focused on one particular area of interest -- for example, crow's feet wrinkles or moisture loss -- this multi-study analysis collated the data to search for trends related to specific microbes while accounting for other variables, such as age.

"Previous studies have shown that the types of microbes on our skin change fairly predictably with age," said corresponding author Se Jin Song, the CMI Director of Research. "Our skin also changes physiologically with age; for example, we gain wrinkles and our skin gets drier. But there is variation in what this looks like in people -- you've probably noticed that there are some people who have younger or older looking skin than many others their age. Using advanced statistical methods, we were able to tease apart the microbes that are associated with these types of aging signs for skin, like crow's feet wrinkles, from those that are associated with simply age as a chronological number."

Two notable trends emerged from the analysis. First, the team found a positive association between skin microbiome diversity and lateral cantonal lines (crow's feet wrinkles), which are generally viewed as one of the key signs of skin aging. Second, they observed a negative correlation between microbiome diversity and transepidermal water loss, which is the amount of moisture that evaporates through the skin. In further exploring the trends, the researchers identified several potential biomarkers that warrant investigation as microorganisms of interest. It would be premature to infer causation or actionable insights, but the study's results have provided researchers with directions on the next steps to hone in on better understanding microbial associations with skin aging.

"At L'Oréal, our commitment is to create beauty products that meet the unique needs of each individual. Our recent collaboration with the Center for Microbiome Innovation has shed light on the role of the skin microbiome in aging, particularly in how it affects wrinkles and overall skin quality," said co-author Qian Zheng, Head of Advanced Research, North America at L'Oréal. "This research is groundbreaking in identifying new microbial biomarkers linked to visible signs of aging like crow's feet wrinkles. It marks a significant step towards developing technologies for healthier, more youthful skin. We look forward to sharing new results as they become available, furthering the scientific community's understanding and contributing to advancing new skincare solutions."

Future paths of investigation the team has suggested include metabolomics work to discover chemical biomarkers related to skin aging, as well as meta-transcriptomics research into potential targets for genetic engineering. Research into other layers of the skin has also been considered, as many studies focus on the outer skin due to the ease of sample collection.

"While the study's findings represent an advance of our knowledge of the skin microbiome, we view them as just the beginning of a new phase of research," said co-author Rob Knight, the CMI Faculty Director and Professor of Pediatrics, Bioengineering, Computer Science & Engineering and Data Science at UC San Diego. "By confirming a link between the microbiome and skin health, we've laid the groundwork for further studies that discover specific microbiome biomarkers related to skin aging, and, one day, show how to modify them to generate novel and highly targeted recommendations for skin health."

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Scientists 3D-print hair follicles in lab-grown skin

A team led by scientists at Rensselaer Polytechnic Institute has 3D-printed hair follicles in human skin tissue cultured in the lab. This marks the first time researchers have used the technology to generate hair follicles, which play an important role in skin healing and function.

The finding, published in the journal Science Advances, has potential applications in regenerative medicine and drug testing, though engineering skin grafts that grow hair are still several years away.

"Our work is a proof-of-concept that hair follicle structures can be created in a highly precise, reproducible way using 3D-bioprinting. This kind of automated process is needed to make future biomanufacturing of skin possible," said Pankaj Karande, Ph.D., an associate professor of chemical and biological engineering and a member of Rensselaer's Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies, who led the study.

"The reconstruction of hair follicles using human-derived cells has historically been a challenge. Some studies have shown that if these cells are cultured in a three-dimensional environment, they can potentially originate new hair follicles or hair shafts, and our study builds on this work," Karande said.

When it comes to engineering human skin, hair may at first seem superfluous. However, hair follicles are quite important: They produce sweat, helping regulate body temperature, and they contain stem cells that help skin heal.

Hair follicles are also an entry point for topical drugs and cosmetics, making them an important part of dermatological testing. But today, initial safety testing is done on engineered skin tissues that lack hair follicles.

"Right now, contemporary skin models -- the engineered structures that mimic human skin -- are quite simple. Increasing their complexity by adding hair follicles would give us even more information about how skin interacts with topical products," said Carolina Catarino, Ph.D., first author of the study, who earned her doctorate at Rensselaer and is now a researcher developing new skin testing methods at Grupo Boticário, a cosmetics company in her home country of Brazil.

"Dr. Karande's lab is at the forefront of skin tissue engineering. This team has already successfully printed skin with working blood vessels, and this latest research is an exciting next step in developing and testing better treatments for burns and other skin conditions," said Deepak Vashishth, Ph.D., director of the Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies.

"Dr. Karande's work is a great example of advances being made by RPI researchers at the interface of engineering and life sciences with impact on human health," said Shekhar Garde, Ph.D., dean of Rensselaer's School of Engineering. "Bringing multichannel 3-D printing to biological realm is opening exciting opportunities that would have been hard to imagine in the past."

The researchers created their follicle-bearing skin with 3D-printing techniques adapted for printing at the cellular level.

The scientists begin by allowing samples of skin and follicle cells to divide and multiply in the lab until there are enough printable cells. Next, the researchers mix each type of cell with proteins and other materials to create the "bio-ink" used by the printer. Using an extremely thin needle to deposit the bio-ink, the printer builds the skin layer by layer, while also creating channels for depositing the hair cells. Over time, the skin cells migrate to these channels surrounding the hair cells, mirroring the follicle structures present in real skin.

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This fish doesn't just see with its eyes -- it also sees with its skin

A few years ago while on a fishing trip in the Florida Keys, biologist Lori Schweikert came face to face with an unusual quick-change act. She reeled in a pointy-snouted reef fish called a hogfish and threw it onboard. But later when she went to put it in a cooler she noticed something odd: its skin had taken on the same color and pattern as the deck of the boat.

A common fish in the western Atlantic Ocean from North Carolina to Brazil, the hogfish is known for its color-changing skin. The species can morph from white to mottled to reddish-brown in a matter of milliseconds to blend in with corals, sand or rocks.

Still, Schweikert was surprised because this hogfish had continued its camouflage even though it was no longer alive. Which got her wondering: can hogfish detect light using only their skin, independently of their eyes and brain?

"That opened up this whole field for me," Schweikert said.

In the years that followed, Schweikert started researching the physiology of "skin vision" as a postdoctoral fellow at Duke University and Florida International University.

In 2018, Schweikert and Duke biologist Sönke Johnsen published a study showing that hogfish carry a gene for a light-sensitive protein called opsin that is activated in their skin, and that this gene is different from the opsin genes found in their eyes.

Other color-changing animals from octopuses to geckos have been found to make light-sensing opsins in their skin, too. But exactly how they use them to help change color is unclear.

"When we found it in hogfish, I looked at Sönke and said: Why have a light detector in the skin?" said Schweikert, now an assistant professor at the University of North Carolina Wilmington.

One hypothesis is that light-sensing skin helps animals take in their surroundings. But new findings suggest another possibility -- "that they could be using it to view themselves," Schweikert said.

In a study appearing Aug. 22 in the journal Nature Communications, Schweikert, Johnsen and colleagues teamed up to take a closer look at hogfish skin.

The researchers took pieces of skin from different parts of the fish's body and took pictures of them under a microscope.

Up close, a hogfish's skin looks like a pointillist painting. Each dot of color is a specialized cell called a chromatophore containing granules of pigment that can be red, yellow or black.

It's the movement of these pigment granules that changes the skin color. When the granules spread out across the cell, the color appears darker. When they cluster together into a tiny spot that's hard to see, the cell becomes more transparent.

Next, the researchers used a technique called immunolabeling to locate the opsin proteins within the skin. They found that in the hogfish, opsins aren't produced in the color-changing chromatophore cells. Instead, the opsins reside in other cells directly beneath them.

Images taken with a transmission electron microscope revealed a previously unknown cell type, just below the chromatophores, packed with opsin protein.

This means that light striking the skin must pass through the pigment-filled chromatophores first before it reaches the light-sensitive layer, Schweikert said.

The researchers estimate that the opsin molecules in hogfish skin are most sensitive to blue light. This happens to be the wavelength of light that the pigment granules in the fish's chromatophores absorb best.

The findings suggest that fish's light-sensitive opsins act somewhat like internal Polaroid film, capturing changes in the light that is able to filter through the pigment-filled cells above as the pigment granules bunch up or fan out.

"The animals can literally take a photo of their own skin from the inside," Johnsen said. "In a way they can tell the animal what it's skin looks like, since it can't really bend over to look."

"Just to be clear, we're not arguing that hogfish skin functions like an eye," Schweikert added. Eyes do more than merely detect light -- they form images. "We don't have any evidence to suggest that's what's happening in their skin," Schweikert said.

Rather, it's a sensory feedback mechanism that lets the hogfish monitor its own skin as it changes color, and fine-tune it to fit what it sees with its eyes.

"They appear to be watching their own color change," Schweikert said.

The researchers say the work is important because it could pave the way to new sensory feedback techniques for devices such as robotic limbs and self-driving cars that must fine-tune their performance without relying solely on eyesight or camera feeds.

"Sensory feedback is one of the tricks that technology is still trying to figure out," Johnsen said. "This study is a nice dissection of a new sensory feedback system."

"If you didn't have a mirror, and you couldn't bend your neck, how would you know if you're dressed appropriately?" Schweikert said. "For us it may not matter," she added. But for creatures that use their color-changing abilities to hide from predators, warn rivals or woo mates, "it could be life or death."

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Iceman Ötzi: Dark skin, bald head, Anatolian ancestry

A research team has used advanced sequencing technology to analyze Ötzi's genome to obtain a more accurate picture of the Iceman's appearance and genetic origins.

Ötzi's genome was decoded for the first time more than ten years ago. This was also the first time the genome of a mummy had been sequenced. The results provided important insights into the genetic makeup of prehistoric Europeans. Advances in sequencing technology have now enabled a research team from the Max Planck Institute for Evolutionary Anthropology and Eurac Research to reconstruct Ötzi's genome more accurately. The results of this recent analysis refine the Iceman's genetic picture: compared to other contemporary Europeans, Ötzi's genome has an unusually high proportion of genes in common with those of early farmers from Anatolia. And, contrary to previous findings, at the time of his death, Ötzi had advanced hair loss and may have even been bald. Furthermore, his skin was darker than previously thought. Ötzi's genes also show a predisposition to diabetes and obesity.

The genetic makeup of most present-day Europeans has resulted mainly from the admixture of three ancestral groups: western hunter-gatherers gradually merged with early farmers who migrated from Anatolia about 8,000 years ago and who were later on joined by Steppe Herders from Eastern Europe, approximately 4,900 years ago.

The initial analysis of the Iceman's genome revealed genetic traces of these Steppe Herders. However, the refined new results no longer support this finding. The reason for the inaccuracy: the original sample had been contaminated with modern DNA. Since that first study, not only have sequencing technologies advanced enormously, but many more genomes of other prehistoric Europeans have been fully decoded, often from skeletal finds. This has made it possible to compare Ötzi's genetic code with his contemporaries. The result: among the hundreds of early European people who lived at the same time as Ötzi and whose genomes are now available, Ötzi's genome has more ancestry in common with early Anatolian farmers than any of his European counterparts.

Ötzi's ancestry and appearance

The research team concludes that the Iceman came from a relatively isolated population that had very little contact with other European groups. "We were very surprised to find no traces of Eastern European Steppe Herders in the most recent analysis of the Iceman genome; the proportion of hunter-gatherer genes in Ötzi's genome is also very low. Genetically, his ancestors seem to have arrived directly from Anatolia without mixing with hunter gatherer groups," explains Johannes Krause, head of the Department of Archaeogenetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig, and co-author of the study.

The study also yielded new results about Ötzi's appearance. His skin type, already determined in the first genome analysis to be Mediterranean-European, was even darker than previously thought. "It's the darkest skin tone that has been recorded in contemporary European individuals," explains anthropologist Albert Zink, study co-author and head of the Eurac Research Institute for Mummy Studies in Bolzano: "It was previously thought that the mummy's skin had darkened during its preservation in the ice, but presumably what we see now is actually largely Ötzi's original skin color. Knowing this, of course, is also important for the proper conservation of the mummy."

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'Resurrecting' the legendary figure behind Count Dracula

Vlad III, known as Vlad the Impaler, was a 15th century prince and military leader who was so terrifying, he's thought to have inspired the creation of the literary vampire, Count Dracula. Now, a scientific examination of his letters is giving new insights into his health. Researchers now reporting in ACS' Analytical Chemistry, say the results suggest that Vlad probably had skin and respiratory conditions and could have even cried literal tears of blood.

The legendary figure's official title was Vlad III, Voivode of Wallachia, and he lived in the southern region of Romania in the mid-1400s. Of course, there's no evidence that Vlad III was a vampire, but he was feared for his ruthlessness. Some estimates place his death toll at over 80,000 people, many dying by impalement, earning him his nickname. He was also referred to as Vlad Drăculea, translating to "the son of the dragon," which many believe inspired the eponymous character from the novel Dracula.

Though over 500 years have passed since Vlad's reign, some artifacts have remained, including several letters he penned at different points throughout his life. The molecules and proteins present on documents and other relics like these can provide scientists with a unique understanding of the life and times of people from the past. So, Vincenzo Cunsolo and colleagues wanted to, for the first time, investigate these letters to learn more about the health of the infamous Vlad Drăculeaa, as well as the environment he lived in.

To uncover the letters' secrets, the researchers used a specialized plastic film called EVA, or ethylene-vinyl acetate, to extract any proteins or small molecules from the paper without damaging it. These extracts were then analyzed with mass spectrometry, allowing researchers to characterize thousands of different peptides. Of these, the team focused on those with the most advanced deamidation, a form of protein degradation that occurs with age. The most degraded proteins were likely the oldest, and therefore, they are the most likely to be from Vlad compared to newer, less-degraded proteins that could have originated from other people handling the letters more recently. A total of 16 proteins were of human origin, relating to skin, breathing and blood.

The researchers say that the data they acquired, although not exhaustive, suggest that Vlad could have suffered from respiratory issues, and potentially even a condition called hemolacria, which would have caused him to cry tears of blood -- quite fitting for such a spooky character. Other proteins identified by the team indicate that he could have been exposed to certain, plague-related bacteria or even pesky fruit flies. In all, the researchers say that this work helps shed light on some important documents of the past, as well as the people who may have written them.

From Science Daily

Researchers identify 135 new melanin genes responsible for pigmentation

The skin, hair and eye color of more than eight billion humans is determined by the light-absorbing pigment known as melanin. An article recently published in the journal Science features research from Vivek Bajpai, Ph.D., lead author and an assistant professor in the School of Sustainable Chemical, Biological and Materials Engineering at the University of Oklahoma, and collaborators from Stanford University. Their research has identified 135 new genes associated with pigmentation.

Melanin is produced within special structures called melanosomes. Melanosomes are found inside melanin-producing pigment cells called melanocytes. Although all humans have the same number of melanocytes, the amount of melanin they produce differs and gives rise to the variation in human skin color.

"To understand what actually causes different amounts of melanin to be produced, we used a technology called CRISPR-Cas9 to genetically engineer cells," Bajpai said. "Using CRISPR, we systematically removed more than 20,000 genes from hundreds of millions of melanocytes and observed the impact on melanin production."

To identify which genes influence melanin production, cells that lost melanin during the gene removal process needed to be separated from millions of other cells that did not. Using in vitro cell cultures, Bajpai developed a novel method to achieve this goal that detects and quantifies the melanin-producing activity of melanocytes. By passing light through the melanocytes, he could record if the light was either absorbed or scattered by the melanin inside.

"If there are a lot of melanin-producing melanosomes, the light will scatter much more than in cells with little melanin," Bajpai said. "Using a process called side-scatter of flow cytometry, we were able to separate cells with more or less melanin. These separated cells were then analyzed to determine the identity of melanin-modifying genes. We identified both new and previously known genes that play important roles in regulating melanin production in humans."

The researchers found 169 functionally diverse genes that impacted melanin production. Of those, 135 were not previously associated with pigmentation. They further identified the function of two newly discovered genes: KLF6 and COMMD3. The DNA-binding protein KLF6 led to a loss of melanin production in humans and animals, confirming the role KLF6 plays in melanin production in other species as well. The COMMD3 protein regulated melanin synthesis by controlling the acidity of melanosomes.

Historically, darker pigmentation has been needed to protect against ultraviolet radiation in areas closer to the equator and for people who spend hours in direct sunlight. As humans moved into areas with less direct sunlight or fewer hours of daylight overall, less melanin was needed. Over time, this resulted in melanosomes that produced less melanin, thus absorbing more sunlight.

"By understanding what regulates melanin, we can help protect lighter-skinned people from melanoma, or skin cancer," Bajpai said. "By targeting these new melanin genes, we could also develop melanin-modifying drugs for vitiligo and other pigmentation diseases."

The technological processes developed and used by the research team could also be applied to identify genes that regulate melanin production in fungi and bacteria. Melanin production in fungi and bacteria enables them to be more pathogenic to humans or crops. Researchers could develop effective interventions against these microbes and their diseases by discovering and targeting such melanin-producing genes.

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Skin patch shows promise for toddlers with peanut allergy

A global phase 3 clinical trial that included Ann & Robert H. Lurie Children's Hospital of Chicago found that a year-long immunotherapy through a skin patch safely desensitized toddlers with peanut allergy, lowering the risk of a severe allergic reaction from accidental exposure. Results of this randomized, double-blind, placebo-controlled trial for children 1-3 years of age, funded by DBV Technologies, were published in the New England Journal of Medicine.

"We were excited to contribute to this landmark study that carries so much promise for our young patients with peanut allergy," said co-author Melanie Makhija, MD, who was the Principal Investigator of the study at Lurie Children's and is an Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "Children who originally reacted to a small fraction of a peanut were able to tolerate the equivalent of one to four peanuts after completing the treatment course. This means that these children will be well protected from accidental exposure to peanuts. Importantly, we found that the peanut patch was safe, with very low chances of a severe allergic reaction. This is terrific news for families of kids with peanut allergies."

Peanut allergy affects approximately 2 percent of children in the United States, Canada and other westernized countries, and it commonly persists into adulthood. Life-threatening allergic reactions can be triggered by unintentional exposure to minute quantities, including through products manufactured on shared equipment as peanuts. Currently, there are no approved treatments for peanut-allergic children younger than 4 years of age.

Since 2012, the clinical trials program for food allergies at Lurie Children's has enrolled patients on numerous studies of novel treatments, including the oral immunotherapy for peanuts that has been approved by the Food and Drug Administration (FDA). Ongoing trials are available for all age groups, from infancy to young adulthood. The program is led by Principal Investigators Elizabeth Lippner, MD, and Abigail Lang, MD, MSCI.

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Scales or feathers? It all comes down to a few genes

Scales, spines, feathers and hair are examples of vertebrate skin appendages, which constitute a remarkably diverse group of micro-organs. Despite their natural multitude of forms, these appendages share early developmental processes at the embryonic stage. Two researchers from the University of Geneva (UNIGE) have discovered how to permanently transform the scales that normally cover the feet of chickens into feathers, by specifically modifying the expression of certain genes. These results, published in the journal Science Advances, open new perspectives for studying mechanisms that have enabled radical evolutionary transitions in form among species.

The skin of terrestrial vertebrates is adorned with diverse keratinized appendages, such as hair, feathers, and scales. Despite the diversity of forms within and among species, the embryonic development of skin appendages typically begins in a very similar way. Indeed, all of these structures develop from cells that produce a localized thickening on the skin surface and express particular genes. One of these genes, called Sonic hedgehog (Shh), controls a signaling pathway -- a communication system that allows the transmission of messages within and between cells. Shh signalling is involved in the development of diverse structures, including the neural tube, limb buds and skin appendages.

A common ancestor

The laboratory of Michel Milinkovitch, professor in the Department of Genetics and Evolution at the Faculty of Science of the UNIGE, is interested in the physical and biological processes that generate the diversity of skin appendages in vertebrates. In particular, his group has previously demonstrated that hair, feathers and scales are homologous structures inherited from a reptilian common ancestor.

Feathers of the chicken embryo are used by scientists as a model system to understand skin appendage development. While it is known that certain breeds of chickens, such as the 'Brahma' and 'Sablepoot' varieties, exhibit feathered legs and dorsal foot surfaces, the genetic determinism of this trait is not fully understood.

A transient modification for a permanent change

As the signaling pathways responsible for this transformation have not been fully determined, Michel Milinkovitch's group investigated the potential role of the Shh pathway. "We used the classic technique of 'egg candling', in which a powerful torch illuminates blood vessels on the inside of the eggshell. This allowed us to precisely treat chicken embryos with a molecule that specifically activates the Shh pathway, injected directly into the bloodstream,'' explains Rory Cooper, a post-doctoral researcher in Michel Milinkovitch's laboratory and co-author of the study.

The two scientists observed that this single stage-specific treatment is sufficient to trigger the formation of abundant juvenile down-type feathers, in areas that would normally be covered with scales. Remarkably, these experimentally-induced feathers are comparable to those covering the rest of the body, as they are regenerative and are subsequently and autonomously replaced by adult feathers.

After comparison with embryos injected with a 'control' solution (without the active molecule), RNA sequencing analysis showed that the Shh pathway is both immediately and persistently activated following injection of the molecule. This confirms that activation of the Shh pathway underlies the conversion of scales into feathers.

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Skin: An additional tool for the versatile elephant trunk

A new study from Georgia Institute of Technology suggests that an elephant's muscles aren't the only way it stretches its trunk -- its folded skin also plays an important role. The combination of muscle and skin gives the animal the versatility to grab fragile vegetation and rip apart tree trunks.

The research, in collaboration with Zoo Atlanta, finds that an elephant's skin doesn't uniformly stretch. The top of the trunk is more flexible than the bottom, and the two sections begin to diverge when an elephant reaches more than 10%. When stretching for food or objects, the dorsal section of the trunk slides further forward.

The findings could improve robotics, which today are typically built for either great strength or flexibility. Unlike an elephant's trunk, the machines can't do both.

As an example, the study's authors point to soft robotics. Their fluid-filled cavities allow flexible movements but can easily break when forces are applied. The researchers say the elephant findings suggest that wrapping soft robotics with a skin-like structure could give the machines protection and strength while continuing to allow flexibility.

The paper is published in the Proceedings of the National Academy of Sciences (PNAS) by the same Georgia Tech team that authored a study last summer about how elephants use their trunk muscles to inhale food and water.

"When people extend their tongue -- a muscle-filled, boneless tissue similar in composition to an elephant's trunk -- it stretches uniformly. We expected the same when we challenged an elephant to reach for food," said Andrew Schulz, the study's lead author and a Ph.D. student in Georgia Tech's George W. Woodruff School of Mechanical Engineering. He and the team filmed two African savanna elephants reaching for bran cubes and apples at Zoo Atlanta.

"But when we looked at our high-speed camera footage and plotted the trunk's movements, we were surprised. The top and bottom weren't the same at all," Schulz said.

After seeing the video, Schulz stretched the tissue of a dissected elephant to better understand the skin's elasticity. That's when he found that the top of the skin, which is folded, is 15% more flexible than the wrinkled bottom side. It's also when the team realized they weren't just seeing muscle movement on the video. They were also tracking a thick sheet of skin.

"Flexible skin folds are the elephant's innovation," said David Hu, Schulz's advisor and a professor in the Woodruff School and the School of Biological Sciences. "They protect the dorsal section and make it easier for the elephant to reach downward, the most common gripping style when picking up items."

The Georgia Tech study also found that an elephant trunk differs in another way from other boneless, muscle-filled appendages found in nature, such as squid and octopus tentacles. Instead of extending evenly, an elephant telescopically stretches its trunk like an umbrella, gradually lengthening in waves.

An elephant first extends the section that includes the tip of its trunk, then the adjacent section and so on, gradually working its way back toward its body. Schulz says the progressive movement towards the base is intentional.

"Elephants are like people: they're lazy," he said. "The section at the end of the trunk is 1 liter of muscle. The section closest to its mouth is 11-15 liters of muscle. An elephant will first stretch the end of its trunk, then the adjacent section, because they're easier to move. If an elephant doesn't have to work very hard to reach something, it won't."

Schulz said he had to rely on a drawing from 1908 when learning about trunk anatomy because scientists and engineers haven't done much research on the biomechanics of elephants during the last century. Part of his curiosity of elephants is based on helping them; he thinks a better understanding of the animals will lead to better conservation efforts. As a mechanical engineer, Schulz also sees the applications of robotics.

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Rubbery camouflage skin exhibits smart and stretchy behaviors

The skin of cephalopods, such as octopuses, squids and cuttlefish, is stretchy and smart, contributing to these creatures' ability to sense and respond to their surroundings. A Penn State-led collaboration has harnessed these properties to create an artificial skin that mimics both the elasticity and the neurologic functions of cephalopod skin, with potential applications for neurorobotics, skin prosthetics, artificial organs and more.  

Led by Cunjiang Yu, Dorothy Quiggle Career Development Associate Professor of Engineering Science and Mechanics and Biomedical Engineering, the team published its findings on June 1 in the Proceedings of the National Academy of Sciences. 

Cephalopod skin is a soft organ that can endure complex deformations, such as expanding, contracting, bending and twisting. It also possesses cognitive sense-and-respond functions that enable the skin to sense light, react and camouflage its wearer. While artificial skins with either these physical or these cognitive capabilities have existed previously, according to Yu, until now none has simultaneously exhibited both qualities -- the combination needed for advanced, artificially intelligent bioelectronic skin devices.  

"Although several artificial camouflage skin devices have been recently developed, they lack critical noncentralized neuromorphic processing and cognition capabilities, and materials with such capabilities lack robust mechanical properties," Yu said. "Our recently developed soft synaptic devices have achieved brain-inspired computing and artificial nervous systems that are sensitive to touch and light that retain these neuromorphic functions when biaxially stretched."  

To simultaneously achieve both smartness and stretchability, the researchers constructed synaptic transistors entirely from elastomeric materials. These rubbery semiconductors operate in a similar fashion to neural connections, exchanging critical messages for system-wide needs, impervious to physical changes in the system's structure. The key to creating a soft skin device with both cognitive and stretching capabilities, according to Yu, was using elastomeric rubbery materials for every component. This approach resulted in a device that can successfully exhibit and maintain neurological synaptic behaviors, such as image sensing and memorization, even when stretched, twisted and poked 30% beyond a natural resting state.  

"With the recent surge of smart skin devices, implementing neuromorphic functions into these devices opens the door for a future direction toward more powerful biomimetics," Yu said. "This methodology for implementing cognitive functions into smart skin devices could be extrapolated into many other areas, including neuromorphic computing wearables, artificial organs, soft neurorobotics and skin prosthetics for next-generation intelligent systems."

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Electronic skin: Physicist develops multisensory hybrid material

The "smart skin" developed by Anna Maria Coclite is very similar to human skin. It senses pressure, humidity and temperature simultaneously and produces electronic signals. More sensitive robots or more intelligent prostheses are thus conceivable.

The skin is the largest sensory organ and at the same time the protective coat of the human being. It "feels" several sensory inputs at the same time and reports information about humidity, temperature and pressure to the brain. For Anna Maria Coclite, a material with such multisensory properties is "a kind of 'holy grail' in the technology of intelligent artificial materials. In particular, robotics and smart prosthetics would benefit from a better integrated, more precise sensing system similar to human skin." The ERC grant winner and researcher at the Institute of Solid State Physics at TU Graz has succeeded in developing the three-in-one hybrid material "smart skin" for the next generation of artificial, electronic skin using a novel process. The result of this pioneering research has now been published in the journal Advanced Materials Technologies.

As delicate as a fingertip

For almost six years, the team worked on the development of smart skin as part of Coclite's ERC project Smart Core. With 2,000 individual sensors per square millimetre, the hybrid material is even more sensitive than a human fingertip. Each of these sensors consists of a unique combination of materials: an smart polymer in the form of a hydrogel inside and a shell of piezoelectric zinc oxide. Coclite explains: "The hydrogel can absorb water and thus expands upon changes in humidity and temperature. In doing so, it exerts pressure on the piezoelectric zinc oxide, which responds to this and all other mechanical stresses with an electrical signal." The result is a wafer-thin material that reacts simultaneously to force, moisture and temperature with extremely high spatial resolution and emits corresponding electronic signals. "The first artificial skin samples are six micrometres thin, or 0.006 millimetres. But it could be even thinner," says Anna Maria Coclite. In comparison, the human epidermis is 0.03 to 2 millimetres thick. The human skin perceives things from a size of about one square millimetre. The smart skin has a resolution that is a thousand times smaller and can register objects that are too small for human skin (such as microorganisms).

Material processing at the nanoscale

The individual sensor layers are very thin and at the same time equipped with sensor elements covering the entire surface. This was possible in a worldwide unique process for which the researchers combined three known methods from physical chemistry for the first time: a chemical vapour deposition for the hydrogel material, an atomic layer deposition for the zinc oxide and nanoprint lithography for the polymer template. The lithographic preparation of the polymer template was the responsibility of the research group "Hybrid electronics and structuring" headed by Barbara Stadlober. The group is part of Joanneum Research's Materials Institute based in Weiz.

Several fields of application are now opening up for the skin-like hybrid material. In healthcare, for example, the sensor material could independently detect microorganisms and report them accordingly. Also conceivable are prostheses that give the wearer information about temperature or humidity, or robots that can perceive their environment more sensitively. On the path to application,smart skin scores with a decisive advantage: the sensory nanorods -- the "smart core" of the material -- are produced using a vapor-based manufacturing process. This process is already well established in production plants for integrated circuits, for example. The production of smart skin can thus be easily scaled and implemented in existing production lines.

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Sunlight exposure guidelines may need to be revised

Previously published solar exposure guidelines for optimal vitamin D synthesis based on a study of skin samples may need to be revised, according to new research published today in PNAS.

A study by researchers from King's College London, with support from the NIHR Guy's and St Thomas' Biomedical Research Centre, has tested the optimum ultraviolet radiation (UVR) wavelengths for human skin production of vitamin D in sunlight.

UVR from sunlight can cause sunburn and skin cancer, however, it is the most important source of vitamin D that is essential for healthy bone development and maintenance.

Public health advice on sunlight exposure takes both risk and benefits into account. Calculating the potential risks and benefits from sunlight exposure is not simple because the health outcomes from UVR exposure vary considerably with wavelength within the sun's UVR spectrum. For example, the sun's UVR contains less than 5% short wavelength UVB radiation but this is responsible for over 80% of the sunburn response. Each health outcome from solar exposure has its own unique wavelength dependency.

The association between specific UVB wavelengths and vitamin D production was determined more than thirty years ago in skin samples (ex vivo). However, the finding is less well established and there have been doubts about its accuracy. These doubts compromise risk/benefit calculations for optimal solar exposure.

Researchers led by the Professor Antony Young from King's College London measured blood vitamin D levels in 75 healthy young volunteers, before, during, and after partial or full body exposure to five different artificial UVR sources with different amounts of UVB radiation, to weigh the trade-off between the benefits of solar exposure, which include vitamin D synthesis, versus the risks of sunburn and skin cancer.

They then compared their results with those that would be predicted from the old ex vivo vitamin D study and found the previous study is not an accurate predictor of benefit from UVR exposure.

The authors recommend a simple systematic correction of the ex vivo wavelength dependency for vitamin D. The new study means that many risk benefit calculations for solar UVR exposure must be reviewed with a revised version of the wavelength dependency for vitamin D.

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Superficial relationship: Enzymes protect the skin by ignoring microbes and viruses

The human body is constantly exposed to various environmental actors, from viruses to bacteria to fungi, but most of these microbial organisms provoke little or no response from our skin, which is charged with monitoring and protecting from external dangers.

Until now, researchers weren't quite sure how that happened -- and why our skin wasn't constantly alarmed and inflamed.

In a study published May 21, 2021 in Science Immunology, scientists at University of California San Diego School of Medicine identify and describe two enzymes responsible for protecting our skin and body's overall health from countless potential microbial intruders. These enzymes, called histone deacetylases (HDACs), inhibit the body's inflammatory response in the skin.

"We have figured out why we tolerate certain microbes living on our skin, while the same bacteria would make us very sick if exposed elsewhere in the body," said Richard Gallo, MD, PhD, Ima Gigli Distinguished Professor of Dermatology and chair of the Department of Dermatology at UC San Diego School of Medicine. "In our research, we identified enzymes that act on the chromosome of specific skin cells that provide immune tolerance by the skin.

"Without these enzymes telling our cells to ignore certain bacteria, we'd have a constant rash on our skin."

Gallo and colleagues say the potential mechanism for how the environment can interact and alter cell function is through epigenetic control of gene expression. Within the skin cells, proteins called toll-like receptors (TLRs) allow the cells to sense their surroundings and potential dangers.

In most organs, TLRs act as a warning system that triggers an inflammatory response to threats. But in skin cells, the two identified HDAC enzymes, HDAC8 and HDAC9, inhibit the inflammatory response.

"This is one of the first demonstrations of how the microbiome can interact with epigenetic factors in the skin and modulate the skin's behavior through the inflammatory response," said George Sen, PhD, associate professor of dermatology and cellular and molecular medicine at UC San Diego School of Medicine. "Whatever environment we're facing can change a person's specific response to it. Since this epigenetic change is reversible, unlike alterations to our DNA, we can potentially control our skin inflammatory response through targeting of these enzymes."

The research was initially conducted in mouse models in which HDAC8 and HDAC9 had been genetically knocked out. As a result, the mice's skin could not tolerate microbial or viral exposures, resulting in a heightened immune reaction. The team then reproduced the findings with human cells in a culture dish.

Gallo said the work could change how doctors treat certain types of skin inflammation or other dermatologic conditions.

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Skin deep: Aquatic skin adaptations of whales and hippos evolved independently

 A new study shows that the similarly smooth, nearly hairless skin of whales and hippopotamuses evolved independently. The work suggests that their last common ancestor was likely a land-dwelling mammal, uprooting current thinking that the skin came fine-tuned for life in the water from a shared amphibious ancestor. The study is published today in the journal Current Biology and was led by researchers at the American Museum of Natural History; University of California, Irvine; University of California, Riverside; Max Planck Institute of Molecular Cell Biology and Genetics; and the LOEWE-Centre for Translational Biodiversity Genomics (Germany).

"How mammals left terra firma and became fully aquatic is one of the most fascinating evolutionary stories, perhaps rivaled only by how animals traded water for land in the first place or by the evolution of flight," said John Gatesy, a senior research scientist in the American Museum of Natural History's Division of Vertebrate Zoology and a corresponding author on the study. "Our latest findings contradict the current dogma in the field -- that relatives of the amphibious hippo might have been part of the transition as mammals re-entered life in the water."

Despite their contrasting appearances, fully aquatic cetaceans -- the group that includes whales, dolphins, and porpoises -- and semi-aquatic hippopotamuses are each other's closest living relatives and share a common ancestor that lived about 55 million years ago. They also share a number of characteristics that are odd for most mammals: they give birth and nurse underwater, and lack scrotal testes and sebaceous glands (that secrete oily sebum) as well as most of their hair. Since these traits are rarely found in other mammals, one would assume that they were already present in the common ancestor of hippos and cetaceans. But how and when cetacean ancestors became fully aquatic remains a subject of intense debate.

Paleontological studies on transitional extinct cetaceans suggest that entry into water was a gradual process that included amphibious phases. So did hippos and cetaceans develop adaptations for an aquatic lifestyle independently? Or was their common ancestor already amphibious, and from there, cetaceans diverged to become fully aquatic?

"The simplest hypothesis is that the ancestor of whales and hippos was already amphibious, but evolution isn't always the shortest distance between two points," said the study's lead author Mark Springer, a biology professor at the University of California, Riverside.

To help resolve this question, the researchers looked to the animals' skin, which shows profound evolutionary changes in response to aquatic life.

"When a group of animals becomes aquatic, skin becomes much more streamlined and uniform throughout," said Maksim Plikus, a co-corresponding author and a skin biologist from the University of California, Irvine. "Complex derivatives like hairs, nails, or sweat glands are no longer needed, and in fact, can become a hinderance to life under water, so those go away. And it loses the barrier function performed by the outer layer of skin, which in terrestrial mammals, is vital to keeping water from evaporating out of the body and preventing pathogens from getting in."

The researchers compared the anatomy of hippo and cetacean skin based on histology and used genomic screens to compile a comprehensive list of "skin genes" that have been inactivated in both hippos and cetaceans. This was aided by examining -- for the first time -- the genome of the pygmy hippo, Choeropsis liberiensis, one of only two living hippo species.

"When you look at the molecular signatures, there is a striking and clear answer," said study co-corresponding author and evolutionary genomicist Michael Hiller, from the Max Planck Institute of Molecular Cell Biology and Genetics and the LOEWE-Centre for Translational Biodiversity Genomics in Germany. "Our results strongly support the idea that 'aquatic' skin traits found in both hippos and cetaceans evolved independently. And not only that, we can see that the gene losses in the hippo lineage happened much later than in the cetacean lineage."

These gene results are in line with examinations of the skin itself: Unlike whales, hippos actually do have a very specialized kind of sweat gland that produces "blood sweat," an orange-colored substance that is speculated to have natural anti-microbial and sunscreen properties. And while cetaceans only have a few whiskers, hippos are fully whiskered but also have sparse body hairs, most prominent on their ears and the tip of their tail. The latter are used when hippos defecate, during which they quickly spin their tail and the brush-like hairs help to pulverize the feces all around as a way to mark territory. In addition, cetacean skin is much thicker than hippo skin, and hippos are alone in having hooves.

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Scaled, armored or naked: How does the skin of fish evolve?

Usually scaled, the skin of fish can also be naked or made up of bony plates that form an armour, sometimes even covered with teeth. But how has this skin evolved over the ages? To answer this question, researchers at the University of Geneva (UNIGE), Switzerland, have reconstructed the evolution of the protective skin structures in fish, going back to the common ancestor of ray-finned fish, more than 420 million years ago. They found that only fish that had lost their scales were able to develop a bony armour, and that the protective state of their skin influenced their choice of open water or sea floor habitats. This study, published in the journal Evolution Letters, provides a new explanation for the incredible diversity of this lineage of fish, which includes more than 25,000 species.

Ray-finned fish, such as catfish or goldfish, constitute the most diverse lineage of vertebrates on Earth, with no less than 25,000 species, i.e. half of the planet's vertebrates. "Far from being limited to scales, these fish species can also have completely naked skin or a bony armour, sometimes covered with teeth, as is the case with certain catfish," notes Juan Montoya, a researcher in the Department of Genetics and Evolution at the UNIGE Faculty of Science. But how did the protective structure of the skin evolve in these fish?

A family tree that goes back 420 million years

The researchers used an evolutionary tree of fish that lists 11,600 species. "In order to reconstruct the ancestral characteristics of the species, we worked in parallel with a second tree of 304 species, which precisely establishes the links of relationship," explains Alexandre Lemopoulos, a researcher in the Department of Genetics and Evolution at the Faculty of Science of the UNIGE. They asked themselves two questions: What type of protection do the fish have on their skin? And do they live in the open water or on the seabed?

Using mathematical models, they reconstructed the most likely ancestral state and, as they went up the family tree, they reconstructed the transitions between the three skin types and observed whether these had conditioned their habitat. "We were able to go back to the first ancestor of ray-finned fish, more than 420 million years ago, who had scales," enthuses Juan Montoya.

Only naked fish can develop armour

By analysing the transitional stages, the Geneva researchers found several lineages of fish that lost their scales, but at different positions in the tree. "There is therefore no temporal coincidence in this evolution," emphasises Alexandre Lemopoulos. Moreover, once a lineage of fish has lost its scales, it cannot find them again. "On the other hand, some of these naked fish subsequently developed bony plates covering part or all of their body, forming a solid armour," points out Juan Montoya. "We now need to discover the underlying genetic mechanism, which probably no longer allows a return to the scale stage, but makes it possible to build a compensatory external skeleton." Thus, only naked fish were able to build up this armour. "It does not seem possible to go directly from a scaly skin to a cuirassed skin, nor to have a mixture of these two structures," he says.

Skin conditions the place of residence

The researchers also observed that the change in skin condition conditioned the place of habitation. "Several species of fish that have lost their scales have left the open waters in which they lived for the seabed, certainly finding an advantage in this new environment," explains Alexandre Lemopoulos. This is a pre-adaptation: the fish lose their scales, change environment and find advantages. As this sequence was repeated independently in several groups of fish, the researchers deduce that a skin without scales offers a real advantage for living on the bottom. "It should be noted that once a lineage of fish establishes itself on the seabed, it no longer returns to the open water, even if it subsequently develops a bony armour," he continues.

Two hypotheses seem to explain this 'move': respiration and immune defence. "Fish breathe through their gills, but also through their skin. Bare skin improves gas exchange in poorly oxygenated water by increasing the respiratory surface," suggests Alexandre Lemopoulos. Furthermore, recent studies have shown that the immune defence against viruses and bacteria, which are very present in the seabed, was more effective when the skin had no scales.

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Squids: Sophisticated skin

 Squids have long been a source of fascination for humans, providing the stuff of legend, superstition and myth. And it's no wonder -- their odd appearances and strange intelligence, their mastery of the open ocean can inspire awe in those who see them.

Legends aside, squids continue to intrigue people today -- people like UC Santa Barbara professor Daniel Morse -- for much the same, albeit more scientific, reasons. Having evolved for hundreds of millions of years to hunt, communicate, evade predators and mate in the vast, often featureless expanses of open water, squids have developed some of the most sophisticated skin in the animal kingdom.

"For centuries, people have been amazed at the ability of squids to change the color and patterns of their skin -- which they do beautifully -- for camoflage and underwater communication, signaling to one another and to other species to keep away, or as attraction for mating and other kinds of signaling," said Morse, a Distinguished Professor Emeritus of Biochemistry and Molecular Genetics.

Like their cephalopod cousins the octopus and cuttlefish, squids have specialized pigment-filled cells called chromatophores that expand to expose them to light, resulting in various shades of pigmentary color. Of particular interest to Morse, however, is the squids' ability to shimmer and flicker, reflecting different colors and breaking light over their skin. It's an effect that is thought to mimic the dappled light of the upper ocean -- the only feature in an otherwise stark seascape. By understanding how squids manage to fade themselves into even the plainest of backgrounds -- or stand out -- it may be possible to produce materials with the same, light tuning properties for a variety of applications.

Morse has been working to unlock the secret of squid skin for the last decade, and with support from the Army Research Office and research published in the journal Applied Physics Letters, he and co-author Esther Taxon come even closer to unraveling the complex mechanisms that underlie squid skin.

An Elegant Mechanism

"What we've discovered is that not only is the squid able to tune the color of the light that's reflected, but also its brightness," Morse said. Research had thus far has established that certain proteins called reflectins were responsible for iridescence, but the squid's ability to tune the brightness of the reflected light was still something of a mystery, he said.

Previous research by Morse had uncovered structures and mechanisms by which iridocytes -- light-reflecting cells -- in the opalescent inshore squid's (Doryteuthis opalescens) skin can take on virtually every color of the rainbow. It happens with the cell membrane, where it folds into nanoscale accordion-like structures called lamellae, forming tiny, subwavelength-wide exterior grooves.

"Those tiny groove structures are like the ones we see on the engraved side of a compact disc," Morse said. The color reflected depends on the width of the groove, which corresponds to certain light wavelengths (colors). In the squid's iridocytes, these lamellae have the added feature of being able to shapeshift, widening and narrowing those grooves through the actions of a remarkably finely tuned "osmotic motor" driven by reflectin proteins condensing or spreading apart inside the lamellae.

While materials systems containing reflectin proteins were able to approximate the iridescent color changes squid were capable of, attempts to replicate the ability to intensify brightness of these reflections always came up short, according to the researchers, who reasoned that something had to be coupled to the reflectins in squid skin, amplifying their effect.

That something turned out to be the very membrane enclosing the reflectins -- the lamellae, the same structures responsible for the grooves that split light into its constituent colors.

"Evolution has so exquisitely optimized not only the color tuning, but the tuning of the brightness using the same material, the same protein and the same mechanism," Morse said.

Light at the Speed of Thought

It all starts with a signal, a neuronal pulse from the squid's brain.

"Reflectins are normally very strongly positively charged," Morse said of the iridescent proteins, which, when not activated, look like a string of beads. Their same charge means they repel each other.

But that can change when a neural signal causes the reflectins to bind negatively charged phosphate groups that neutralize the positive charge. Without the repulsion keeping the proteins in their disordered state they fold and attract each other, accumulating into fewer, larger aggregations in the lamellae.

These aggregations exert osmotic pressure on the lamellae, a semipermeable membrane built to withstand only so much pressure created by the clumping reflectins before releasing water outside the cell.

"Water gets squished out of the accordion-like structure, and that collapses the accordion so the thickness in spacing between the folds gets reduced, and that's like bringing the grooves of a compact disc closer together," Morse explained. "So the light that's reflected can shift progressively from red to green to blue."

At the same time, the membrane's collapse concentrates the reflectins, causing an increase in their refractive index, amplifying brightness. Osmotic pressure, the motor that drives these tunings of optical properties, couples the lamellae tightly to the reflectins in a highly calibrated relationship that optimizes the output (color and brightness) to the input (neural signal). Wipe away the neural signal and the physics reverses, Morse said.

"It's a very clever, indirect way of changing color and brightness by controlling the physical behavior of what's called a colligative property -- the osmotic pressure, something that's not immediately obvious, but it reveals the intricacy of the evolutionary process, the millennia of mutation and natural selections that have honed and optimized these processes together."

Tunable-Brightness Thin-Films

The presence of a membrane may be the vital link for the development of bioinspired thin films with the optical tuning capacity of the opalescent inshore squid.

"This discovery of the key role the membrane plays in tuning the brightness of reflectance has intriguing implications for the design of future buihybrid materials and coatings with tunable optical properties that could protect soldiers and their equipment," said Stephanie McElhinny, a program manager at the the Army Research Office, an element of the U.S. Army Combat Capabilities Development Command's Army Research Laboratory.

According to the researchers, "This evolutionarily honed, efficient coupling of reflectin of its osmotic amplifier is closely analogous to the impedance matched coupling of activator-transducer-amplifier networks in well-engineered electronic, magnetic, mechanical and acoustic systems." In this case the activator would be the neuronal signal, while the reflectins acts as transducers and the osmotically controlled membranes serve as the amplifiers.

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Novel treatment using patient's own cells opens new possibilities to treat Parkinson's disease

Reprogramming a patient's own skin cells to replace cells in the brain that are progressively lost during Parkinson's disease (PD) has been shown to be technically feasible, reports a team of investigators from McLean Hospital and Massachusetts General Hospital (MGH) in the most recent issue of the New England Journal of Medicine.

PD is the second most common degenerative disease of the brain, and millions of people world-wide experience its symptoms, which include tremor, stiffness, and difficulty with speech and walking. The progressive loss of brain cells called dopaminergic neurons plays a major role in the disease's development. As described in the current report, the use of a patient's own reprogrammed cells is an advance that overcomes barriers associated with the use of cells from another individual.

"Because the cells come from the patient, they are readily available and can be reprogrammed in such a way that they are not rejected on implantation. This represents a milestone in 'personalized medicine' for Parkinson's," says senior author Kwang-Soo Kim, PhD, director of the Molecular Neurobiology Laboratory at McLean Hospital, the largest clinical neuroscience and psychiatric affiliate of Harvard Medical School.

The McLean-MGH team reprogrammed a 69-year-old patient's skin cells to embryo-like pluripotent stem cells (called induced pluripotent stem cells) and then differentiated them to take on the character-istics of dopaminergic neurons, which are lost in Parkinson's. After extensive testing of the cells, Kim ap-plied to the FDA for a single-patient, Investigational New Drug (IND) application and also received the approval of the hospital human subjects ethical review board to implant the cells into the patient's brain.

Bob Carter, MD, PhD, chief of Neurosurgery at MGH and co-senior author, says: "This strategy highlights the emerging power of using one's own cells to try and reverse a condition -- Parkinson's disease -- that has been very challenging to treat. I am very pleased by the extensive collaboration across multiple institutions, scientists, physicians, and surgeons that came together to make this a possibility."

In a series of two separate surgeries in 2017 and 2018 at Weill Cornell Medical Center and MGH, the patient underwent transplantation of the replacement dopamine neurons. Lead author Jeffrey Schweitzer, MD, PhD, a Parkinson's specialized neurosurgeon and director of the Neurosurgical Neurodegenerative Cell Therapy program at MGH, designed a novel minimally invasive neurosurgical implantation procedure to deliver the cells, working in collaboration with Carter at MGH and Michael G. Kaplitt, MD, PhD, a neurosurgeon at Weill Cornell.

Two years later, imaging tests indicate that the transplanted cells are alive and functioning correctly as dopaminergic neurons in the brain. Because the implanted cells originated from the patient, they did not trigger an immune response and were not rejected without the use of an immunosuppressant drug. Kim also noted, "We have shown for the first time in this study that these reprogrammed cells are still recognized as self by the patient's immune system and won't be rejected." These results indicate that this personalized cell-replacement strategy was a technical success, with the cells surviving and functioning in the intended manner. The patient has not developed any side effects, and there are no signs that the cells have caused any unwanted growth or tumors.

As for how the patient feels, in the time that has passed since surgery, the patient has enjoyed improvements in his day-to-day activities and reports an improvement in his quality of life. Routine activities, such as tying his shoes, walking with an improved stride, and speaking with a clearer voice, have become possible again. Some activities -- such as swimming, skiing, and biking, which he had given up years ago -- are now back on his agenda. While it is too early to know whether this treatment approach is viable based on a single patient, the authors have the goal of continuing to test the treatment in formal clinical trials.

"Current drugs and surgical treatments for Parkinson's disease are intended to address symptoms that result from the loss of dopaminergic neurons, but our strategy attempts to go further by directly replacing those neurons," says Kim.

"As a neurologist, my goal is to make state-of-the-art treatments available to patients with Parkinson's," says Todd Herrington, MD, PhD, lead study neurologist at the MGH and Parkinson's expert. "This is a first step in developing this therapy. Parkinson's patients should understand that this therapy is not cur-rently available and there is a lot of work still required to prove this is an effective treatment."

While there is optimism about the future of Parkinson's disease treatments because of their work, Schweitzer cautions against declaring victory against the disease. "These results reflect the experience of one individual patient and a formal clinical trial will be required to determine if the therapy is effec-tive," says Schweitzer.

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Rapamycin may slow skin aging

The search for youthfulness typically turns to lotions, supplements, serums and diets, but there may soon be a new option joining the fray. Rapamycin, a FDA-approved drug normally used to prevent organ rejection after transplant surgery, may also slow aging in human skin, according to a study from Drexel University College of Medicine researchers published in Geroscience.

Basic science studies have previously used the drug to slow aging in mice, flies, and worms, but the current study is the first to show an effect on aging in human tissue, specifically skin -- in which signs of aging were reduced. Changes include decreases in wrinkles, reduced sagging and more even skin tone -- when delivered topically to humans.

"As researchers continue to seek out the elusive 'fountain of youth' and ways to live longer, we're seeing growing potential for use of this drug," said senior author Christian Sell, PhD, an associate professor of Biochemistry and Molecular Biology at the College of Medicine. "So, we said, let's try skin. It's a complex organism with immune, nerve cells, stem cells -- you can learn a lot about the biology of a drug and the aging process by looking at skin."

In the current Drexel-led study, 13 participants over age 40 applied rapamycin cream every 1-2 days to one hand and a placebo to the other hand for eight months. The researchers checked on subjects after two, four, six and eight months, including conducting a blood test and a biopsy at the six- or eight-month mark.

After eight months, the majority of the rapamycin hands showed increases in collagen protein, and statistically significant lower levels of p16 protein, a key marker of skin cell aging. Skin that has lower levels of p16 has fewer senescent cells, which are associated with skin wrinkles. Beyond cosmetic effects, higher levels of p16 can lead to dermal atrophy, a common condition in seniors, which is associated with fragile skin that tears easily, slow healing after cuts and increased risk of infection or complications after an injury.

So how does rapamycin work? Rapamycin blocks the appropriately named "target of rapamycin" (TOR), a protein that acts as a mediator in metabolism, growth and aging of human cells. The capability for rapamycin to improve human health beyond outward appearance is further illuminated when looking deeper at p16 protein, which is a stress response that human cells undergo when damaged, but is also a way of preventing cancer. When cells have a mutation that would have otherwise created a tumor, this response helps prevent the tumor by slowing the cell cycle process. Instead of creating a tumor, it contributes to the aging process.

"When cells age, they become detrimental and create inflammation," said Sell. "That's part of aging. These cells that have undergone stress are now pumping out inflammatory markers."

In addition to its current use to prevent organ rejection, rapamycin is currently prescribed (in higher doses than used in the current study) for the rare lung disease lymphangioleiomyomatosis, and as an anti-cancer drug. The current Drexel study shows a second life for the drug in low doses, including new applications for studying rapamycin to increase human lifespan or improve human performance.

Rapamycin -- first discovered in the 1970s in bacteria found in the soil of Easter Island -- also reduces stress in the cell by attacking cancer-causing free radicals in the mitochondria.

In previous studies, the team used rapamycin in cell cultures, which reportedly improved cell function and slowed aging.

In 1996, a study in Cell of yeast cultures which used rapamycin to block TOR proteins in yeast, made the yeast cells smaller, but increased their lifespan.

"If you ramp the pathway down you get a smaller phenotype," said Sell. "When you slow growth, you seem to extend lifespan and help the body repair itself -- at least in mice. This is similar to what is seen in calorie restriction."

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Living skin can now be 3D-printed with blood vessels included

Researchers at Rensselaer Polytechnic Institute have developed a way to 3D print living skin, complete with blood vessels. The advancement, published online today in Tissue Engineering Part A, is a significant step toward creating grafts that are more like the skin our bodies produce naturally.

"Right now, whatever is available as a clinical product is more like a fancy Band-Aid," said Pankaj Karande, an associate professor of chemical and biological engineering and member of the Center for Biotechnology and Interdisciplinary Studies (CBIS), who led this research at Rensselaer. "It provides some accelerated wound healing, but eventually it just falls off; it never really integrates with the host cells."

A significant barrier to that integration has been the absence of a functioning vascular system in the skin grafts.

Karande has been working on this challenge for several years, previously publishing one of the first papers showing that researchers could take two types of living human cells, make them into "bio-inks," and print them into a skin-like structure. Since then, he and his team have been working with researchers from Yale School of Medicine to incorporate vasculature.

In this paper, the researchers show that if they add key elements -- including human endothelial cells, which line the inside of blood vessels, and human pericyte cells, which wrap around the endothelial cells -- with animal collagen and other structural cells typically found in a skin graft, the cells start communicating and forming a biologically relevant vascular structure within the span of a few weeks. You can watch Karande explain this development here.

"As engineers working to recreate biology, we've always appreciated and been aware of the fact that biology is far more complex than the simple systems we make in the lab," Karande said. "We were pleasantly surprised to find that, once we start approaching that complexity, biology takes over and starts getting closer and closer to what exists in nature."

Once the Yale team grafted it onto a special type of mouse, the vessels from the skin printed by the Rensselaer team began to communicate and connect with the mouse's own vessels.

"That's extremely important, because we know there is actually a transfer of blood and nutrients to the graft which is keeping the graft alive," Karande said.

In order to make this usable at a clinical level, researchers need to be able to edit the donor cells using something like the CRISPR technology, so that the vessels can integrate and be accepted by the patient's body.

"We are still not at that step, but we are one step closer," Karande said.

"This significant development highlights the vast potential of 3D bioprinting in precision medicine, where solutions can be tailored to specific situations and eventually to individuals," said Deepak Vashishth, the director CBIS. "This is a perfect example of how engineers at Rensselaer are solving challenges related to human health."

Karande said more work will need to be done to address the challenges associated with burn patients, which include the loss of nerve and vascular endings. But the grafts his team has created bring researchers closer to helping people with more discrete issues, like diabetic or pressure ulcers.

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