Eye, hair and skin color from a DNA sample of an unidentified individual

New tool will be used when standard forensic profiling is not helpful

An international team has developed a novel tool to accurately predict eye, hair and skin color from human biological material -- even a small DNA sample -- left, for example, at a crime scene or obtained from archeological remains. This all in one pigmentation profile tool provides a physical description of the person in a way that has not previously been possible by generating all three pigment traits together using a freely available web tool.

An international team, led by scientists from the School of Science at IUPUI and Erasmus MC University Medical Center Rotterdam in the Netherlands, has developed a novel tool to accurately predict eye, hair and skin color from human biological material -- even a small DNA sample -- left, for example, at a crime scene or obtained from archeological remains. This all in one pigmentation profile tool provides a physical description of the person in a way that has not previously been possible by generating all three pigment traits together using a freely available web tool.

The tool is designed to be used when standard forensic DNA profiling is not helpful because no reference DNA exists against which to compare the evidence sample.

The HIrisPlex-S DNA test system is capable of simultaneously predicting eye, hair and skin color phenotypes from DNA. Users, such as law enforcement officials or anthropologists, can enter relevant data using a laboratory DNA analysis tool, and the web tool will predict the pigment profile of the DNA donor.

"We have previously provided law enforcement and anthropologists with DNA tools for eye color and for combined eye and hair color, but skin color has been more difficult," said forensic geneticist Susan Walsh from IUPUI, who co-directed the study. "Importantly, we are directly predicting actual skin color divided into five subtypes -- very pale, pale, intermediate, dark and dark to black -- using DNA markers from the genes that determine an individual's skin coloration. This is not the same as identifying genetic ancestry. You might say it's more similar to specifying a paint color in a hardware store rather than denoting race or ethnicity.

"If anyone asks an eyewitness what they saw, the majority of time they mention hair color and skin color. What we are doing is using genetics to take an objective look at what they saw," Walsh said.

The innovative high-probability and high-accuracy complete pigmentation profile webtool is available online without charge.

The study, "HIrisPlex-S System for Eye, Hair and Skin Colour Prediction from DNA: Introduction and Forensic Developmental Validation," is published in the peer-reviewed journal Forensic Science International: Genetics.

"With our new HIrisPlex-S system, for the first time, forensic geneticists and genetic anthropologists are able to simultaneously generate eye, hair and skin color information from a DNA sample, including DNA of the low quality and quantity often found in forensic casework and anthropological studies," said Manfred Kayser of Erasmus MC, co-leader of the study.

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Discovery of episodic memory replay in rats could lead to better treatments for Alzheimer's disease

Researchers have reported the first evidence that non human animals can mentally replay past events from memory. The discovery could help improve the development of drugs to treat Alzheimer's disease by providing a way to study memory in animals that more closely addresses how memory works in people.

The study, led by IU professor Jonathon Crystal, appears today in the journal Current Biology.

"The reason we're interested in animal memory isn't only to understand animals, but rather to develop new models of memory that match up with the types of memory impaired in human diseases such as Alzheimer's disease," said Crystal, a professor in the IU Bloomington College of Arts and Sciences' Department of Psychological and Brain Sciences and director of the IU Bloomington Program in Neuroscience.

Under the current paradigm, Crystal said most preclinical studies on potential new Alzheimer's drugs examine how these compounds affect spatial memory, one of the easiest types of memory to assess in animals. But spatial memory is not the type of memory whose loss causes the most debilitating effects of Alzheimer's disease.

"If your grandmother is suffering from Alzheimer's, one of the most heartbreaking aspects of the disease is that she can't remember what you told her about what's happening in your life the last time you saw her," said Danielle Panoz-Brown, an IU Ph.D. student who is the first author on the study. "We're interested in episodic memory -- and episodic memory replay -- because it declines in Alzheimer's disease, and in aging in general."

Episodic memory is the ability to remember specific events. For example, if a person loses their car keys, they might try to recall every single step -- or "episode" -- in their trip from the car to their current location. The ability to replay these events in order is known as "episodic memory replay." People wouldn't be able to make sense of most scenarios if they couldn't remember the order in which they occurred, Crystal said.

To assess animals' ability to replay past events from memory, Crystal's lab spent nearly a year working with 13 rats, which they trained to memorize a list of up to 12 different odors. The rats were placed inside an "arena" with different odors and rewarded when they identified the second-to-last odor or fourth-to-last odor in the list.

The team changed the number of odors in the list prior to each test to confirm the odors were identified based upon their position in the list, not by scent alone, proving the animals were relying on their ability to recall the whole list in order. Arenas with different patterns were used to communicate to the rats which of the two options was sought.

After their training, Crystal said, the animals successfully completed their task about 87 percent of the time across all trials. The results are strong evidence the animals were employing episodic memory replay.

Additional experiments confirmed the rats' memories were long-lasting and resistant to "interference" from other memories, both hallmarks of episodic memory. They also ran tests that temporarily suppressed activity in the hippocampus -- the site of episodic memory -- to confirm the rats were using this part of their brain to perform their tasks.

Crystal said the need to find reliable ways to test episodic memory replay in rats is urgent since new genetic tools are enabling scientists to create rats with neurological conditions similar to Alzheimer's disease. Until recently, only mice were available with the genetic modifications needed to study the effect of new drugs on these symptoms.

"We're really trying push the boundaries of animal models of memory to something that's increasingly similar to how these memories work in people," he said. "If we want to eliminate Alzheimer's disease, we really need to make sure we're trying to protect the right type of memory."

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Genetic clues reveal origins of the killer fungus behind the 'amphibian plague'

New research has revealed a deadly disease that threatens the survival of the world's frogs originated from East Asia, and global trade was almost certainly responsible for the disease's spread.

The frog chytrid fungus (Batrachochytrium dendrobatidis) has long been identified as a cause of the decline and extinction of species of amphibians across several continents since the 1970s.

It has spread around the world but until now it has remained unclear where killer strains of the pathogen first emerged.

An international team of researchers led by Imperial College London, including four scientists from the One Health Research Group at James Cook University, traced the ancestor of the pathogen to a single strain in East Asia.

Their findings support the idea that rather than dating back thousands of years, as previously thought, the range of the disease expanded greatly between 50 and 120 years ago, coinciding with the rapid global expansion of intercontinental trade.

According to the researchers, human movement of amphibians -- such as through the pet trade -- has directly contributed to spreading the pathogen around the world.

JCU's Dr Lee Skerratt, one of the authors of the paper, said the findings highlight the importance of global biosecurity measures.

"Australia has strict rules and regulations surrounding biosecurity and this finding confirms why regulations are so important," Dr Skerratt said.

"We hope this news will push policy change in countries with less strict biosecurity measures."

The team also uncovered additional strains of the fungus that could cause further species decline, highlighting the importance of strict biosecurity policies.

"If more strains are allowed to spread we could see additional extinctions," Dr Skerratt said.

"Countries need to act now to improve regulations before these additional strains spread."

Chytrid fungus causes a disease called chytridiomycosis that leads to heart failure, and is responsible for the decline or extinction of hundreds of species of frogs.

The paper, Recent Asian origin of chytrid fungi causing global amphibian declines, was published in Science today.

These findings come on the 20th anniversary of Dr Lee Berger's discovery during her PhD that the chytrid fungus is the cause of global amphibian species decline.

Dr Berger led the Australian contribution and was an Australian Research Council Future Fellow and Postdoctoral Fellow at James Cook University from 2004 to 2016.

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Large predators once hunted to near-extinction are showing up in unexpected places

Sightings of alligators and other large predators in places where conventional wisdom says they 'shouldn't be' have increased in recent years, in large part because local populations, once hunted to near-extinction, are rebounding. A new article finds that far from being outliers, these sightings signify the return of highly adaptable predators to prime hunting grounds they occupied long ago -- a trend that opens new opportunities for future conservation.

Alligators on the beach. Killer whales in rivers. Mountain lions miles from the nearest mountain.

In recent years, sightings of large predators in places where conventional wisdom says they "shouldn't be" have increased, in large part because local populations, once hunted to near-extinction, are rebounding -- thanks to conservation.

Many observers have hypothesized that as these populations recover the predators are expanding their ranges and colonizing new habitats in search of food.

A Duke University-led paper published today in the journal Current Biology suggests otherwise.

It finds that, rather than venturing into new and alien habitats for the first time, alligators, sea otters and many other large predators -- marine and terrestrial species alike -- are re-colonizing ecosystems that used to be prime hunting grounds for them before humans decimated their populations and well before scientists started studying them.

"We can no longer chock up a large alligator on a beach or coral reef as an aberrant sighting," said Brian Silliman, Rachel Carson Associate Professor of Marine Conservation Biology at Duke's Nicholas School of the Environment. "It's not an outlier or short-term blip. It's the old norm, the way it used to be before we pushed these species onto their last legs in hard-to-reach refuges. Now, they are returning."

By synthesizing data from recent scientific studies and government reports, Silliman and his colleagues found that alligators, sea otters, river otters, gray whales, gray wolfs, mountain lions, orangutans and bald eagles, among other large predators, may now be as abundant or more abundant in "novel" habitats than in traditional ones.

Their successful return to ecosystems and climatic zones long considered off-limits or too stressful for them upends one of the most widely held paradigms of large animal ecology, Silliman said.

"The assumption, widely reinforced in both the scientific and popular media, is that these animals live where they live because they are habitat specialists. Alligators love swamps; sea otters do best in saltwater kelp forests; orangutans need undisturbed forests; marine mammals prefer polar waters. But this is based on studies and observations made while these populations were in sharp decline. Now that they are rebounding, they're surprising us by demonstrating how adaptable and cosmopolitan they really are," Silliman said.

For instance, marine species such as sting rays, sharks, shrimps, horseshoe crabs and manatees now make up 90 percent of alligators' diet when they're in seagrass or mangrove ecosystems, showing that gators adapt very well to life in a saltwater habitat.

The unanticipated adaptability of these returning species presents exciting new conservation opportunities, Silliman stressed.

"It tells us these species can thrive in a much greater variety of habitats. Sea otters, for instance, can adapt and thrive if we introduce them into estuaries that don't have kelp forests. So even if kelp forests disappear because of climate change, the otters won't," he said. "Maybe they can even live in rivers. We will find out soon enough."

As top predators return, the habitats they re-occupy also see benefits, he said. For instance, introducing sea otters to estuarine seagrass beds helps protect the beds from being smothered by epiphytic algae that feed on excess nutrient runoff from inland farms and cities. The otters do this by eating Dungeness crabs, which otherwise eat too many algae-grazing sea slugs that form the bed's front line of defense.

"It would cost tens of millions of dollars to protect these beds by re-constructing upstream watersheds with proper nutrient buffers," Silliman said, "but sea otters are achieving a similar result on their own, at little or no cost to taxpayers."

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25 years of fossil collecting yields clearest picture of extinct 12-foot aquatic predator

More than two decades of exploration at a Pennsylvania fossil site have given paleontologists their best idea of how a giant, prehistoric predator would have looked and behaved.

After 25 years of collecting fossils at a Pennsylvania site, scientists at the Academy of Natural Sciences of Drexel University now have a much better picture of an ancient, extinct 12-foot fish and the world in which it lived.

Although Hyneria lindae was initially described in 1968, it was done without a lot of fossil material to go on. But since the mid-1990s, dedicated volunteers, students, and paleontologists digging at the Red Hill site in northern Pennsylvania's Clinton County have turned up more -- and better quality -- fossils of the fish's skeleton that have led to new insights.

Academy researchers Ted Daeschler, PhD, and Jason Downs, PhD, who specialize in the Devonian time period (a time before dinosaurs and even land animals) when Hyneria lived, have been able to reconstruct that the predator had a blunt, wide snout, reached 10-12 feet in length, had small eyes and featured a sensory system that allowed it to hunt prey by feeling pressure waves around it.

"Dr. Keith Thomson, the man who first described Hyneria in 1968, did not have enough fossil material to reconstruct the anatomy that we have now been able to document with more extensive collections," explained Daeschler, curator of Vertebrate Zoology at the Academy, as well as a professor in Drexel's College of Arts and Sciences.

Originally, pieces of the fish were collected in the 1950s. Thomson described and officially named Hyneria lindae in 1968, but he had just a few pieces of a crushed skull and some scales to work with.

The new discoveries that Daeschler and Downs (who is an assistant professor at Delaware Valley University) wrote about in the Journal of Vertebrate Paleontology were made possible by years of collecting that turned up, "well-preserved, well-prepared three-dimensional material of almost all of the [bony] parts of the skeleton," according to Downs.

No single complete skeleton exists of this giant, but enough is there to show that Hyneriawould have truly been a monster to the other animals in the subtropical streams of the Devonian Period, roughly 365 million years ago. An apex predator, Hyneria's mouth was bristling with two-inch fangs. For reference, that's bigger than most modern Great White Shark's teeth.

Due to its sheer size, weaponry, and sensory abilities, Hyneria may have preyed upon anything from ancient placoderms (armored fish), to acanthodians (related to sharks) and sarcopterygians (lobe-finned fish, the group Hyneria belongs to) -- including early tetrapods (limbed vertebrates) that are also found at the site.

Since the streams Hyneria lived in were likely murky and not conducive to hunting by eyesight, sensory canals allowed it to detect fish swimming near it and attack them.

"We discovered that the skull roof elements have openings on their surfaces that connect up, forming a network of tubes that would function like the sensory line system in some modern aquatic vertebrates," Daeschler said. "Similarly, we found a network of connected pores on the parts of the scales that would be exposed on the body of Hyneria."

All of the new information gleaned about Hyneria is doubly valuable because it provides more information about the ecosystem -- and time period -- it lived in. The Devonian was a pivotal time in vertebrate evolution, especially since some of Hyneria's fellow lobe-finned fish developed specialized fins that would take them onto land and eventually give rise to all limbed verterbates including reptiles, amphibians and mammals.

"Hyneria lived in a time and place that is of incredible interest to those of us studying the vertebrate fin-to-limb transition," Downs commented. "Each study like this one contributes more to our understanding of these ecosystems and what may have played a part in the successful transition to land."

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Scientists find the first bird beak, right under their noses

Researchers have pieced together the three-dimensional skull of an iconic, toothed bird that represents a pivotal moment in the transition from dinosaurs to modern-day birds.

 Ichthyornis dispar holds a key position in the evolutionary trail that leads from dinosaurian species to today's avians. It lived nearly 100 million years ago in North America, looked something like a toothy seabird, and drew the attention of such famous naturalists as Yale's O.C. Marsh (who first named and described it) and Charles Darwin.
Yet despite the existence of partial specimens of Ichthyornis dispar, there has been no significant new skull material beyond the fragmentary remains first found in the 1870s. Now, a Yale-led team reports on new specimens with three-dimensional cranial remains -- including one example of a complete skull and two previously overlooked cranial elements that were part of the original specimen at Yale -- that reveal new details about one of the most striking transformations in evolutionary history.
"Right under our noses this whole time was an amazing, transitional bird," said Yale paleontologist Bhart-Anjan Bhullar, principal investigator of a study published in the journal Nature. "It has a modern-looking brain along with a remarkably dinosaurian jaw muscle configuration."
Perhaps most interesting of all, Bhullar said, is that Ichthyornis dispar shows us what the bird beak looked like as it first appeared in nature.
"The first beak was a horn-covered pincer tip at the end of the jaw," said Bhullar, who is an assistant professor and assistant curator in geology and geophysics. "The remainder of the jaw was filled with teeth. At its origin, the beak was a precision grasping mechanism that served as a surrogate hand as the hands transformed into wings."
The research team conducted its analysis using CT-scan technology, combined with specimens from the Yale Peabody Museum of Natural History; the Sternberg Museum of Natural History in Fort Hays, Kan.; the Alabama Museum of Natural History; the University of Kansas Biodiversity Institute; and the Black Hills Institute of Geological Research.
Co-lead authors of the new study are Daniel Field of the Milner Centre for Evolution at the University of Bath and Michael Hanson of Yale. Co-authors are David Burnham of the University of Kansas, Laura Wilson and Kristopher Super of Fort Hays State University, Dana Ehret of the Alabama Museum of Natural History, and Jun Ebersole of the McWane Science Center.
"The fossil record provides our only direct evidence of the evolutionary transformations that have given rise to modern forms," said Field. "This extraordinary new specimen reveals the surprisingly late retention of dinosaur-like features in the skull of Ichthyornis -- one of the closest-known relatives of modern birds from the Age of Reptiles."
The researchers said their findings offer new insight into how modern birds' skulls eventually formed. Along with its transitional beak, Ichthyornis dispar had a brain similar to modern birds but a temporal region of the skull that was strikingly like that of a dinosaur -- indicating that during the evolution of birds, the brain transformed first while the remainder of the skull remained more primitive and dinosaur-like.
"Ichthyornis would have looked very similar to today's seabirds, probably very much like a gull or tern," said Hanson. "The teeth probably would not have been visible unless the mouth was open but covered with some sort of lip-like, extra-oral tissue."
In recent years Bhullar's lab has produced a large body of research on various aspects of vertebrate skulls, often zeroing in on the origins of the avian beak. "Each new discovery has reinforced our previous conclusions. The skull of Ichthyornis even substantiates our molecular finding that the beak and palate are patterned by the same genes," Bhullar said. "The story of the evolution of birds, the most species-rich group of vertebrates on land, is one of the most important in all of history. It is, after all, still the age of dinosaurs."

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Hidden secret of immortality enzyme telomeras

 

Can we stay young forever, or even recapture lost youth?

Research has recently uncovered a crucial step in the telomerase enzyme catalytic cycle. This catalytic cycle determines the ability of the human telomerase enzyme to synthesize DNA.

Research from the laboratory of Professor Julian Chen in the School of Molecular Sciences at Arizona State University recently uncovered a crucial step in the telomerase enzyme catalytic cycle. This catalytic cycle determines the ability of the human telomerase enzyme to synthesize DNA "repeats" (specific DNA segments of six nucleotides) onto chromosome ends, and so afford immortality in cells. Understanding the underlying mechanism of telomerase action offers new avenues toward effective anti-aging therapeutics. illustration depicting the enzyme telomerase This figure depicts the enzyme telomerase as well as telomeres relative to a chromosome.
Typical human cells are mortal and cannot forever renew themselves. As demonstrated by Leonard Hayflick a half-century ago, human cells have a limited replicative lifespan, with older cells reaching this limit sooner than younger cells. This "Hayflick limit" of cellular lifespan is directly related to the number of unique DNA repeats found at the ends of the genetic material-bearing chromosomes. These DNA repeats are part of the protective capping structures, termed "telomeres," which safeguard the ends of chromosomes from unwanted and unwarranted DNA rearrangements that destabilize the genome.
Each time the cell divides, the telomeric DNA shrinks and will eventually fail to secure the chromosome ends. This continuous reduction of telomere length functions as a "molecular clock" that counts down to the end of cell growth. The diminished ability for cells to grow is strongly associated with the aging process, with the reduced cell population directly contributing to weakness, illness, and organ failure.
The fountain of youth at molecular level
Counteracting the telomere shrinking process is the enzyme, telomerase, that uniquely holds the key to delaying or even reversing the cellular aging process. Telomerase offsets cellular aging by lengthening the telomeres, adding back lost DNA repeats to add time onto the molecular clock countdown, effectively extending the lifespan of the cell. Telomerase lengthens telomeres by repeatedly synthesizing very short DNA repeats of six nucleotides -- the building blocks of DNA -- with the sequence "GGTTAG" onto the chromosome ends from an RNA template located within the enzyme itself. However, the activity of the telomerase enzyme is insufficient to completely restore the lost telomeric DNA repeats, nor to stop cellular aging.
The gradual shrinking of telomeres negatively affects the replicative capacity of human adult stem cells, the cells that restore damaged tissues and/or replenish aging organs in our bodies. The activity of telomerase in adult stem cells merely slows down the countdown of the molecular clock and does not completely immortalize these cells. Therefore, adult stem cells become exhausted in aged individuals due to telomere length shortening that results in increased healing times and organ tissue degradation from inadequate cell populations.
Tapping the full potential of telomeraseUnderstanding the regulation and limitation of the telomerase enzyme holds the promise of reversing telomere shortening and cellular aging with the potential to extend human lifespan and improve the health and wellness of elderly individuals. Research from the laboratory of Chen and his colleagues, Yinnan Chen, Joshua Podlevsky and Dhenugen Logeswaran, recently uncovered a crucial step in the telomerase catalytic cycle that limits the ability of telomerase to synthesize telomeric DNA repeats onto chromosome ends.
"Telomerase has a built-in braking system to ensure precise synthesis of correct telomeric DNA repeats. This safe-guarding brake, however, also limits the overall activity of the telomerase enzyme," said Professor Chen. "Finding a way to properly release the brakes on the telomerase enzyme has the potential to restore the lost telomere length of adult stem cells and to even reverse cellular aging itself."
This intrinsic brake of telomerase refers to a pause signal, encoded within the RNA template of telomerase itself, for the enzyme to stop DNA synthesis at the end of the sequence 'GGTTAG'. When telomerase restarts DNA synthesis for the next DNA repeat, this pause signal is still active and limits DNA synthesis. Moreover, the revelation of the braking system finally solves the decades-old mystery of why a single, specific nucleotide stimulates telomerase activity. By specifically targeting the pause signal that prevents restarting DNA repeat synthesis, telomerase enzymatic function can be supercharged to better stave off telomere length reduction, with the potential to rejuvenate aging human adult stem cells.
Human diseases that include dyskeratosis congenita, aplastic anemia, and idiopathic pulmonary fibrosis have been genetically linked to mutations that negatively affect telomerase activity and/or accelerate the loss of telomere length. This accelerated telomere shortening closely resembles premature aging with increased organ deterioration and a shortened patient lifespan from critically insufficient cell populations. Increasing telomerase activity is the seemingly most promising means of treating these diseases.
While increased telomerase activity could bring youth to aging cells and cure premature aging-like diseases, too much of a good thing can be damaging for the individual. Just as youthful stem cells use telomerase to offset telomere length loss, cancer cells employ telomerase to maintain their aberrant and destructive growth. Augmenting and regulating telomerase function will have to be performed with precision, walking a narrow line between cell rejuvenation and a heightened risk for cancer development.
Distinct from human stem cells, somatic cells constitute the vast majority of the cells in the human body and lack telomerase activity. The telomerase deficiency of human somatic cells reduces the risk of cancer development, as telomerase fuels uncontrolled cancer cell growth. Therefore, drugs that increase telomerase activity indiscriminately in all cell types are not desired. Toward the goal of precisely augmenting telomerase activity selectively within adult stem cells, this discovery reveals the crucial step in telomerase catalytic cycle as an important new drug target. Small molecule drugs can be screened or designed to increase telomerase activity exclusively within stem cells for disease treatment as well as anti-aging therapies without increasing the risk of cancer.

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