Earth

Genetic tracing 'barcode' is rapidly revealing COVID-19's journey and evolution

image: Researchers from Drexel University are using a new technique for spotting patterns in the genetic sequence of the SARS-CoV-2 coronavirus that can help scientists trace the path of its transmission and how it has mutated.

Image: 
PLOS

Drexel University researchers have reported a method to quickly identify and label mutated versions of the virus that causes COVID-19. Their analysis, using information from a global database of genetic information gleaned from coronavirus testing, suggests that there are at least 8 to 14 slightly different versions of the virus infecting people in America, some of which are either the same as, or have subsequently evolved from, strains directly from Asia, while others are the same as those found in Europe.

First developed as a way of parsing genetic samples to get a snapshot of the mix of bacteria, the genetic analysis tool teases out patterns from volumes of genetic information and can identify whether a virus has genetically changed. They can then use the pattern to categorize viruses with small genetic differences using tags called Informative Subtype Markers (ISM).

Applying the same method to process viral genetic data can quickly detect and categorize slight genetic variations in the SARS-CoV-2, the novel coronavirus that causes COVID-19, the group reported in a paper recently published in the journal, PLoS Computational Biology. The genetic analysis tool, designed by Drexel graduate researcher Zhengqiao Zhao, that generates these labels is publicly available for COVID-19 researchers on GitHub.

"The types of SARS-CoV-2 viruses that we see in tests from Asia and Europe is different than the types we're seeing in America," said Gail Rosen, PhD, a professor in Drexel's College of Engineering, who led the development of the tool. "Identifying the variations allows us to see how the virus has changed as it has traveled from population to population. It can also show us the areas where social distancing has been successful at isolating COVID-19."

The ISM tool is particularly useful because it does not require analysis of the full genetic sequence of the virus to identify its mutations. In the case of SARS-CoV-2, this means reducing the 30,000-base-long genetic code of the virus to a subtype label 20 bases long.

The ISM tool also identified certain positions in the virus's genetic sequence that changed together as the virus spread. The researchers found that from early April to the end of the summer, three positions in the SARS-CoV-2 sequence mutated at the same time. Those positions are in different parts of the genetic sequence. One part is thought to be associated with cellular signaling and replication. Another portion is associated with formation of the protein spike - the part of the virus that enables its entry into healthy cells - changed in tandem with a third portion of code, which doesn't translate to protein.

While more investigation is needed on how these simultaneous mutations impact the transmission and severity of the virus, sites that change together can be used to consolidate the subtype label into 11 bases, which could make downstream analysis more efficient, according to the researchers.

"It's the equivalent of scanning a barcode instead of typing in the full product code number," Rosen said. "And right now, we're all trying to get through the grocery store a bit faster. For scientists this means being able to move to higher-level analysis much faster. For example, it can be a faster process in studying which virus versions could be affecting health outcomes. Or, public health officials can track whether new cases are the result of local transmission or coming from other regions of the United States or parts of the world."

While these genetic differences might not be enough to delineate a new strain of virus, Rosen's group suggests understanding these genetically significant "subtypes," where they're being found and how prevalent they are in these areas is data granular enough to be useful.

"This allows us to see the very specific fingerprint of COVID-19 from each region around the world, and to look closely at smaller regions to see how it is different," Rosen said. "Our preliminary analysis, using publicly available data from across the world, is showing that the combination of subtypes of virus found in New York is most similar to those found in Austria, France and Central Europe, but not Italy. And the subtype from Asia, that was detected here early in the pandemic has not spread very much, instead we are seeing a new subtype that only exists in America as the one most prevalent in Washington state and on the west coast."

In addition to helping scientists understand how the virus is changing and spreading, this method can also reveal the portion of its genetic code that appears to remain resistant to mutations - a discovery that could be exploited by treatments to combat the virus.

"We're seeing that the spike protein and the part of the virus responsible for packaging its genetic material have developed a few major mutations, but otherwise they are changing at a slower rate," said Bahrad Sokhansanj, PhD, a visiting scholar at Drexel. "Importantly, both are key targets for understanding the body's immune response, identifying antiviral therapeutics, and designing vaccines.

Rosen's Ecological and Evolutionary Signal-Processing and Informatics Laboratory will continue to analyze COVID-19 data as it is collected and to support public health researchers using the ISM process.

Credit: 
Drexel University

Forsyth researchers demonstrate how changing the stem cell response to inflammation may reverse periodontal disease

image: For the study, Dr. Alpdogan Kantarci, his PhD student Dr. Emmanuel Albuquerque, and their team removed stem cells from previously extracted wisdom teeth and placed the stem cells onto petri dishes. The researchers then created a simulated inflammatory periodontal disease environment in the petri dishes. Next, they added two specific types of synthetic molecules called Maresin-1 and Resolvin-E1, both specialized pro-resolving lipid mediators from omega-3 fatty acids. The scientists found that Mar1 and RvE1 stimulated the stem cells to regenerate even under the inflammatory conditions.

Image: 
Photo by Matthew Modoono

Periodontal disease, also known as gum disease, is a serious infection that affects nearly 50 percent of Americans aged 30 years and older. If left unchecked, periodontal disease can destroy the jawbone and lead to tooth loss. The disease is also associated with higher risk of diabetes and cardiovascular disease.

The current treatment for periodontal disease involves opening the infected gum flaps and adding bone grafts to strengthen the teeth. But in new research published recently in the journal Frontiers in Immunology, Forsyth Institute scientists have discovered that a specific type of molecule may stimulate stem cells to regenerate, reversing the inflammation caused by periodontal disease. This finding could lead to the development of new therapeutics to treat a variety of systemic diseases that are characterized by inflammation in the body.

For the study, Dr. Alpdogan Kantarci, his PhD student Dr. Emmanuel Albuquerque, and their team removed stem cells from previously extracted wisdom teeth and placed the stem cells onto petri dishes. The researchers then created a simulated inflammatory periodontal disease environment in the petri dishes. Next, they added two specific types of synthetic molecules called Maresin-1 and Resolvin-E1, both specialized pro-resolving lipid mediators from omega-3 fatty acids. The scientists found that Mar1 and RvE1 stimulated the stem cells to regenerate even under the inflammatory conditions.

"Both Maresin-1 and Resolvin-1 reprogrammed the cellular phenotype of the human stem cells, showing that even in response to inflammation, it is possible to boost capacity of the stem cells so they can become regenerative," said Dr. Kantarci, Associate Member of Staff at the Forsyth Institute.

This finding is important because it allows scientists to identify the specific protein pathways involved in inflammation. Those same protein pathways are consistent across many systemic diseases, including periodontal disease, diabetes, heart disease, dementia, and obesity.

"Now that we understand how these molecules stimulate the differentiation of stem cells in different tissues and reverse inflammation at a critical point in time, the mechanism we identified could one day be used for building complex organs" said Dr. Kantarci. "There is exciting potential for reprogramming stem cells to focus on building tissues."

Credit: 
Forsyth Institute

Future climate changes in nature reserves

image: In the Cotopaxi National Park, Ecuador.

Image: 
Photo: Samuel Hoffmann.

The Earth's nature reserves are the basis for the preservation of global biodiversity. They are set to be affected by future climate change in very different ways. Detailed local knowledge of climate change impacts can therefore make a significant contribution to the management of protected areas and the preservation of their ecological function. A biogeographic study by the University of Bayreuth in the journal "Diversity and Distributions" draws attention to this fact. It is based on climate forecasts for more than 130,000 nature reserves worldwide.

For their new study, Prof. Dr. Carl Beierkuhnlein and Dr. Samuel Hoffmann of the Biogeography research group examined a total of 137,735 nature reserves on six continents. Their focus was on the question of what deviations from current climate conditions these areas will be exposed to over the next five decades, and how this will impact local plant and animal species. "Blanket forecasts on climate change are not specific enough to assist in counteracting the threat of further loss of biodiversity. This can only succeed if we know exactly what local climate change - for example in nature reserves - will be caused by global trends. As our study impressively demonstrates, these local effects can be very different, even in neighbouring areas," says Beierkuhnlein.

Particularly severe local climate changes are expected by 2070, especially in protected areas of tropical countries. Today, these are of great importance for the conservation of globally endangered plant and animal species, and are under great pressure because, at the same time, they are being used intensively by humans. These protected areas are located in mountains high above sea level. In mountains, temperatures are expected to rise noticeably as a result of climate change. Consequently, some endangered species will probably try to migrate to higher and therefore cooler mountain regions. Here, the threat to individual species could increase rapidly because fewer resources are available at higher altitudes. "For migratory species, higher mountain regions could prove to be a dead end", Hoffmann explains.

However, the new study also shows that protected areas in which future climate conditions will differ especially from the present have some characteristics that could have a beneficial effect on the conservation of species. They are often very large, have very different landscape profiles, and therefore offer diverse environmental conditions which are little affected by direct human intervention or fragmented by traffic routes. These circumstances favour the adaptation of species, for example through genetic exchange and greater availability of resources. In addition, some species that are forced to leave their current habitats due to climate change may find new habitats in their very neighbourhood thanks to this diversity of landscape. Hence, management that is well informed about local climate changes can help to mitigate the effects of climate change in nature reserves.

Forecasts of global climate change are always fraught with uncertainty. This is why the Bayreuth researchers worked with ten different global models of climate change in their study of nature reserves. In addition, they included two significantly different scenarios of global greenhouse gas emissions in their assessments. In each of the nature reserves studied, small square areas measuring around one square kilometre were examined. Characteristic properties of these "cells" were then put into relation with climatic change to be expected on a global scale by 2070. These characteristics include, for example, height above sea level, landscape profile, precipitation and temperature, local flora and fauna, and human intervention. With these investigations, the Bayreuth researchers have succeeded in estimating local climate change effects for very small areas worldwide.

Credit: 
Universität Bayreuth

Babies' random choices become their preferences

image: The act of making a choice changes how we feel about our options.

Image: 
Will Kirk/Johns Hopkins University

When a baby reaches for one stuffed animal in a room filled with others just like it, that seemingly random choice is very bad news for those unpicked toys: the baby has likely just decided she doesn't like what she didn't choose.

Though researchers have long known that adults build unconscious biases over a lifetime of making choices between things that are essentially the same, the new Johns Hopkins University finding that even babies engage in this phenomenon demonstrates that this way of justifying choice is intuitive and somehow fundamental to the human experience.

"The act of making a choice changes how we feel about our options," said co-author Alex Silver, a former Johns Hopkins undergraduate who's now a graduate student in cognitive psychology at the University of Pittsburgh. "Even infants who are really just at the start of making choices for themselves have this bias."

The findings are published today in the journal Psychological Science.

People assume they choose things that they like. But research suggests that's sometimes backwards: We like things because we choose them. And, we dislike things that we don't choose.

"I chose this, so I must like it. I didn't choose this other thing, so it must not be so good. Adults make these inferences unconsciously," said co-author Lisa Feigenson, a Johns Hopkins cognitive scientist specializing in child development. "We justify our choice after the fact."

This makes sense for adults in a consumer culture who must make arbitrary choices every day, between everything from toothpaste brands to makes of cars to styles of jeans. The question, for Feigenson and Silver, was when exactly people start doing this. So they turned to babies, who don't get many choices so, as Feigenson puts it, are "a perfect window into the origin of this tendency."

The team brought 10- to 20-month-old babies into the lab and gave them a choice of objects to play with: two equally bright and colorful soft blocks.

They set each block far apart, so the babies had to crawl to one or the other - a random choice.

After the baby chose one of the toys, the researchers took it away and came back with a new option. The babies could then pick from the toy they didn't play with the first time, or a brand new toy.

"The babies reliably chose to play with the new object rather than the one they had previously not chosen, as if they were saying, 'Hmm, I didn't choose that object last time, I guess I didn't like it very much,' " Feigenson said. "That is the core phenomenon. Adults will like less the thing they didn't choose, even if they had no real preference in the first place. And babies, just the same, dis-prefer the unchosen object."

In follow-up experiments, when the researchers instead chose which toy the baby would play with, the phenomenon disappeared entirely. If you take the element of choice away, Feigenson said, the phenomenon goes away.

"They are really not choosing based on novelty or intrinsic preference," Silver said. "I think it's really surprising. We wouldn't expect infants to be making such methodical choices."

To continue studying the evolution of choice in babies, the lab will next look at the idea of "choice overload." For adults, choice is good, but too many choices can be a problem, so the lab will try to determine if that is also true for babies.

Credit: 
Johns Hopkins University

Cheating birds mimic host nestlings to deceive foster parents

video: Pin-tailed Whydah nestling mimics the movements of host nestlings

Image: 
Gabriel Jamie

The common cuckoo is known for its deceitful nesting behaviour - by laying eggs in the nests of other bird species, it fools host parents into rearing cuckoo chicks alongside their own. While common cuckoos mimic their host's eggs, new research has revealed that a group of parasitic finch species in Africa have evolved to mimic their host's chicks - and with astonishing accuracy. The study is published in the journal Evolution.

Working in the savannahs of Zambia, a team of international researchers collected images, sounds and videos over four years to reveal a striking and highly specialised form of mimicry. They focused on a group of finches occurring across much of Africa called the indigobirds and whydahs, of the genus Vidua.

Like cuckoos, the 19 different species within this group of finches forego their parental duties and instead lay their eggs in the nests of other birds. Each species of indigobird and whydah chooses to lay its eggs in the nests of a particular species of grassfinch. Their hosts then incubate the foreign eggs, and feed the young alongside their own when they hatch.

Grassfinches are unusual in having brightly coloured and distinctively patterned nestlings, and nestlings of different grassfinch species have their own unique appearance, begging calls and begging movements. Vidua finches are extremely specialised parasites, with each species mostly exploiting a single host species.

Nestlings of these 'brood-parasitic' Vidua finches were found to mimic the appearance, sounds and movements of their grassfinch host's chicks, right down to the same elaborately colourful patterns on the inside of their mouths.

"The mimicry is astounding in its intricacy and is highly species-specific," said Dr Gabriel Jamie, lead author on the paper and a research scientist in the University of Cambridge's Department of Zoology, and at the FitzPatrick Institute of African Ornithology, University of Cape Town.

He added: "We were able to test for mimicry using statistical models that approximate the vision of birds. Birds process colour and pattern differently to humans so it is important to analyse the mimicry from their perspective rather than just relying on human assessments."

While the mimicry is very precise, the researchers did find some minor imperfections. These may exist due to insufficient time for more precise mimicry to evolve, or because current levels of mimicry are already good enough to fool the host parents. The researchers think that some imperfections might actually be enhanced versions of the hosts' signal, forcing it to feed the parasite chick even more than it would its own.

The mimetic adaptations to different hosts identified in the study may also be critical in the formation of new species, and in preventing species collapse through hybridisation.

"The mimicry is not only amazing in its own right but may also have important implications for how new species of parasitic finches evolve," added Professor Claire Spottiswoode, an author of the paper and a research scientist at both the University of Cambridge and Cape Town.

Vidua nestlings imprint on their hosts, altering their mating and host preferences based on early life experiences. These preferences strongly influence the host environment in which their offspring grow up, and therefore the evolutionary selection pressures they experience from foster parents. When maintained over multiple generations, these selection pressures generate the astounding host-specific mimetic adaptations observed in the study.

Credit: 
University of Cambridge

A factor limiting recovery from bleaching in corals

image: Fluorescent photographs of Aiptasia polyps 3 days after culturing with symbiont cells in different treatments, neither symbionts nor polyps exposed to high temperature (32?°C) for 3 days (left), only symbionts exposed to high temperature (right).

Image: 
NIBB

Increases in seawater temperature can cause coral bleaching through the loss of symbiotic algae. Corals can recover from bleaching by recruiting algae into host cells from the residual symbiont population or from the external environment. However, the high coral mortality that often follows mass-bleaching events suggests that recovery is limited in the wild.

A joint research team from the National Institute for Basic Biology (NIBB), Tohoku University in Japan, and James Cook University in Australia has examined the effect of pre-exposure to heat stress on the capacity of symbiotic algae to infect cnidarian hosts using the Aiptasia (sea-anemone)-zooxanthellae (algae) model system. They discovered that the symbiotic algae lose their capacity to infect the host once they are exposed to heat stress. These results suggest that recovery from bleaching can be limited by the loss of symbiont infectivity following bleaching-inducing heat stress.

Coral reefs are the cornerstone of biologically enriched coral reef ecosystems, but their existence is in danger due to global change and warming. Coral-algae symbiosis is sensitive to increased seawater temperature, resulting in coral bleaching through loss of the algal symbionts, zooxanthellae. Corals can recover from bleaching by recruiting algae into their cells from the residual symbiont population or from the external environment. However, in the field, recovery from bleaching is often limited, resulting in mortality of corals due to starvation.

In a study published in The ISME Journal, graduate student of the National Institute for Basic Biology, Mariko Kishimoto, focused on the ability of symbiotic algae to infect the host following to heat stress and identified a factor limiting recovery from bleaching.

"In this study, we used Aiptasia (sea-anemone), instead of corals, as Aiptasia are very easy to maintain and use for experiments in the laboratory. And importantly, Aiptasia form the symbiotic relationship with the symbiotic algae, zooxanthellae, and also show bleaching under heat stress like corals do." Ms. Kishimoto said.

Symbiotic algae (CS-164) were cultured at 25 ºC or 32 ºC for 3 days and then their infectivity was tested at 25 ºC by counting the number of symbiotic algae in Aiptasia tentacles.

"The infectivity of algae was apparently lost after culturing at 32 ºC."

"Importantly, culturing Aiptasia, instead of algae, at 32 ºC did not influence infectivity."

"So our results showed that recovery from bleaching can be limited by the loss of symbiont infectivity following bleaching-inducing heat stress.", Ms. Kishimoto said.

Further study showed incubation at 32 ºC was non-lethal for the symbiotic algae which showed recovery of the loss of infectivity after culturing at optimal growth conditions.

The team also found that a different algal strain (CCMP2459) did not lose their infectivity after exposure to heat stress.

Associate Professor Shunichi Takahashi of the National Institute for Basic Biology, who led the research team, said, "Our findings suggest that heat tolerant algal symbionts might give a chance for bleached corals to recover".

Credit: 
National Institutes of Natural Sciences

Awakening after a sleeping pill

Patient with serious brain injury can temporarily talk, walk, and recognize family members

Awakening after a sleeping pill

A patient who could not move and talk spontaneously for eight years started to do so again after being administered a sleeping pill. The spectacular but temporary effect was visualized with brain scans, giving researchers from Radboud university medical center and Amsterdam UMC a better understanding of this disorder's underlying neurophysiological processes. The article has been published in Cortex.

Eight years ago, Richard, at the time a man in his late 20s, was hospitalized after a serious lack of oxygen. He survived but suffered a severe brain injury. Richard was no longer able to talk, eat independently, or move spontaneously. He was admitted to a specialized nursing home. Willemijn van Erp, an elderly care physician and researcher at Radboud university medical center, was still in training when she met Richard. "It was clear that Richard saw and heard us," she says, "but because of his brain injury, he was barely able to respond to us." This rare condition is known as akinetic mutism. Akinetic means that the patient is no longer able to move consciously. Mutism refers to the absence of speech.

Remarkable effect
There is a small chance that patients with this condition will temporarily recover after administering the Zolpidem sleeping medication. Van Erp: "Because Richard's situation seemed hopeless, the family and I decided to administer this medication to Richard. Against all expectations, Zolpidem had remarkable effects. After taking the sleep pill, Richard started talking, wanted to call his father, and started recognizing his brothers again. With some help, he could even get up from his wheelchair and walk short distances."

Overactive brain
Researchers at Amsterdam UMC, including neurosurgeon resident Hisse Arnts, have used brain scans to demonstrate the differences between the two situations. This provided them with information that could be important for Richard and other patients with severe non-congenital brain injuries. Arnts: "Richard's brain scans show overactivity in certain parts of the brain. This overactivity causes noise and somehow shuts down the 'good brain activity'. We have discovered that administering this sleeping medication can suppress this unwanted brain overactivity, creating space for speech and movement."

Research continues
The researchers presented their findings and a video of Richard in the magazine Cortex. The research has since continued. Zolpidem's positive effects have a limited duration, which is why the researchers are now looking for a more permanent solution for Richard and other patients with this specific form of severe brain injury.

Credit: 
Radboud University Medical Center

Pattern in whale songs predicts migration

image: Photo of William Oestreich aboard the research vessel John Martin (Moss Landing Marine Laboratories) with the blow from a blue whale in the background.

Image: 
Jeremy Goldbogen

The blue whale is the largest animal on Earth. It's also among the loudest.

"Sound is a vital mode of communication in the ocean environment, especially over long distances," said William Oestreich, a graduate student in biology at Stanford University's Hopkins Marine Station. "Light, or any sort of visual cue, is often not as effective in the ocean as it is on land. So many marine organisms use sound for a variety of purposes, including communicating and targeting food through echolocation."

Although whale songs have been studied for decades, researchers have had limited success in deciphering their meaning. Now, by recording both individual whales and their greater populations in the Northeast Pacific, researchers from Stanford and the Monterey Bay Aquarium Research Institute (MBARI) have identified patterns in the trills and bellows of blue whales that indicate when the animals are migrating from their feeding grounds off the North American coast to their breeding grounds off Central America. Their research was published Oct. 1 in Current Biology.

"We decided to compare daytime and nighttime song patterns from month to month, and there, in the divergence and convergence of two lines, was this beautiful signal that neither of us really expected," said John Ryan, a biological oceanographer at MBARI and senior author of the paper. "As soon as that image popped up on the screen, Will and I were both like, 'Hello, behavior.'"

Further analysis across the five years of hydrophone recordings could reveal new information about blue whale migration, a 4,000-mile journey that ranks among the longest in the world - and which the creatures repeat every year. Despite the immensity of blue whales and their travels, scientists know very little about their behaviors, such as how they are responding to changes in the ecosystem and food supply from year to year. Being able to predict the travel of whales along this important route could also help prevent ship strikes.

Supping and singing

To capture whales singing solo and in chorus, the researchers used two advanced recording technologies: an underwater microphone - or hydrophone - and tags that the researchers placed on individual whales.

In 2015, MBARI deposited a hydrophone 18 miles off the Monterey coast, 3,000 feet (900 meters) under sea level. The hydrophone is wired to their MARS undersea cabled observatory, which provides it with power and communications. This seafloor eavesdropper has recorded the deep ocean soundscape almost continuously for more than five years.

"The hydrophone fits in your hand," said Ryan, who recommends listening to the hydrophone livestream in fall for optimal whale music (although only the humpback whale song can be heard through ordinary speakers). "It's a little instrument that produces big data - about two terabytes per month."

By focusing on the whale song wavelengths in the hydrophone data, the researchers noticed a distinct change over several months. Through the summers, the whale arias grew louder and were sung mostly at nighttime. Over the five years of data, the whale chorus was loudest around October and November, and singing happened more at nighttime. Following each annual peak in song activity, as the whales began to depart for warmer waters, singing became more of a daytime activity.

While daytime versus nighttime differences in singing behavior had been noted in previous research, the whale-borne tags, developed by the lab of Stanford biologist Jeremy Goldbogen, helped explain what these 24-hour patterns and their inversion in late autumn could mean. Fifteen tags tracked the sounds of their carriers through accelerometer measurements - which monitor vibrations - and, in some cases, integrated hydrophones. In the summer, the whales spent much of the daytime feasting, bulking up for the long journey ahead and reserved their musical interludes for nighttime. When the time came, migration was again accompanied by daytime songs.

"In the hydrophone data, we saw really strong patterns over this enormous spatial domain. When we saw the exact same pattern on individual animals, we realized that what we'd been measuring over hundreds of kilometers is actually a real behavioral signal - and one that represents the behavior of many different whales," said Oestreich. "As an ecologist, it's very exciting to observe so many whales, simultaneously, using one instrument."

Listening and learning

This research lays the groundwork for possibly predicting blue whale migration based on the transitions between the different song schedules - such forecasts could be used to warn shipping lanes further down the coast, like air traffic control but for the ocean. The researchers also hope that further analysis of the acoustic data will reveal more about whale behavior in response to environmental changes, such as warming waters and fickle food supplies.

"If, for example, we can detect differences in migration and foraging in response to changes in the environment, that is a really powerful and important way to keep an eye on this critically endangered species," said Goldbogen, who is an assistant professor of biology in the School of Humanities and Sciences and also senior author of the paper. "That's economically important, ecologically important and also culturally important."

Already, Oestreich is pursuing a related question: If we can use this signal to determine whether whales are foraging or migrating, are whales using it that way too? It's possible, said Oestreich, that a lone whale might listen around before giving up on feeding and heading south.

"Blue whales exist at incredibly low densities with enormous distances between them but, clearly, are sharing information in some way," said Oestreich. "Trying to understand that information sharing is one motivation, but also potentially using that signaling as a means to study them is another exciting possibility."

Credit: 
Stanford University

Sticking together

image: Determination of neural progenitor cell-cell de-adhesion forces using micropipette aspiration

Image: 
IST Austria

Going from the ventral to the dorsal side, the neural tube, the precursor to the central nervous system, is strikingly organized into domains of cells with different identities and fates. One hypothesis for how this pattern is created is the so-called French Flag model. According to this hypothesis, a signaling molecule sets up a gradient across a field of cells, and a cell "knows" its location within the field, and consequently its identity, by the amount of signaling molecule it receives. However, cells move around as an organism develops, disrupting the strict division into domains. An additional mechanism is needed to maintain the domains. Combining a range of genetic, developmental and biophysical experiments, the groups of Carl-Philipp Heisenberg and Sean Megason, with first author Tony Tsai carrying out experiments in both labs, have been able to solve the puzzle: Adhesion, or the "stickiness" of cells, is the factor that keeps cells of the same domain together, and cells of different domains apart.

Differences in binding induce cell sorting

The Heisenberg lab at IST Austria has developed several biophysical tools with which they can test how strongly cells stick together - for example, by measuring how much force is needed to pull cells apart. Applying this to cells from the zebrafish neural tube, the researchers found that cells belonging to the same domain stick together tightly, while cells from different domains are more easily separated. "This difference in the binding force can induce sorting processes", explains Heisenberg.

The difference in "stickiness" corresponds with a differential expression of adhesion proteins in the domains, the researchers further found. The different cell types express different classes of cadherins: N-cadherin, Cadherin 11, and Protocadherin 19. When the researchers interfere with this expression, making cells express more or less of a certain cadherin, preferential adhesion and correct cell sorting are lost. "Our experiments show that a sorting process based on adhesion, together with a gradient of the signaling molecule Sonic Hedgehog, leads to a precise sorting of cells into domains based on their cell type", concludes Heisenberg. "By combining experiments from biophysics, genetics, and developmental biology, we were able to successfully solve this long-standing question."

Credit: 
Institute of Science and Technology Austria

Amazon study shows big conservation gains possible for imperilled freshwater ecosystems

image: Zenithoptera lanei

Image: 
Victor Rennan

A new study by an international team of environmental scientists in the Brazilian Amazon shows that redesigned conservation projects could deliver big gains for critical freshwater ecosystems - raising hopes for the futures of thousands of species.

Although occupying less than one per cent of the Earth's surface, fresh water hosts around a tenth of all known species - including a third of all vertebrates.

They are also vital for regulating climates, and as a source of food and fuel for local people.

Despite their critical nature, freshwater ecosystems are far more imperilled than their land and marine counter-parts.

Over the last 50 years, populations of freshwater vertebrates have plummeted by 83 per cent - more than twice the fall of terrestrial and marine vertebrates, which have declined by around 40 per cent over the same period.

This dramatic fall in freshwater biodiversity has been caused through a mixture of human-driven factors including: habitat loss and degradation; over-exploitation and over-fishing; algal blooms; dam building; and the introduction of non-native species. These pressures are now being amplified by additional stresses such as climate change, microplastics and biochemical pollution.

New conservation measures are urgently needed globally to help address the plight of freshwater ecosystems, and the species that live in them. Yet, despite all this, ecosystems on land have gained much more attention from conservation scientists than freshwater ecosystems.

Published in the journal Science, the new study assessed more than 1,500 freshwater and land species in the Brazilian Amazon. The major groups of freshwater species they scientists looked at included fish, dragonflies, mayfly, stoneflies and caddisflies. They also looked at land species including plants, birds and dung beetles.

The research, undertaken by the Sustainable Amazon Network - a research collaboration involving scientists from Brazil, Europe, USA and Australia - looked at how well freshwater species are protected through conservation efforts directed at land species.

Co-lead author Dr Cecilia Gontijo Leal from the University of São Paulo explained: "Conservation projects generally focus on protecting species that live on land. If freshwater species are considered at all, it is simply assumed that they will be protected incidentally - that is, by chance, as a result of efforts to conserve land species. However, we show that land-based conservation initiatives are likely to protect just 20% of the freshwater species that would have been protected through freshwater-focused conservation. To address the freshwater biodiversity crisis, freshwater species need to be explicitly incorporated into conservation planning."

The researchers then considered how much freshwater protection could be increased through conservation actions that simultaneously considered both freshwater and land species.

They found that conservation efforts with increased focus on freshwater environments could deliver big positive gains for these ecosystems, without adversely affecting ecosystems on land.

Co-lead author Dr Gareth Lennox from Lancaster University said: "Through integrated planning that incorporates information on both freshwater and land species, we found that protection of freshwater species can be increased by up to 600% with no reduction in land species protection. This presents a great opportunity for conservation, where protection for one species group does not require either losses of protection for others or significant funding increases."

The study also addressed the challenge of how to put this into practice. Land species have generally been the focus of conservation efforts, therefore information on the distribution of freshwater species is lacking in many places, especially in tropical regions where most species are found. This poses a problem for conservation planning: how do you protect species if you don't know where they are?

The researchers developed a new method for protecting freshwater species in these circumstances. Professor Silvio Ferraz from the University of São Paulo explained: "Freshwater species crucially depend on the connectivity of river systems. By designing conservation reserve networks that take such connectivity into consideration, we found that freshwater protection could still be doubled in the absence of species distribution data. This shows that there are few impediments to vastly improving freshwater conservation in data-poor regions of the world."

Professor Jos Barlow from Lancaster University summed up the implications of the study: "The urgency of the biodiversity crisis now facing humanity means that we can no longer overlook the many important and endangered species that inhabit freshwaters. Our findings show that conservation that thinks across ecosystems and habitats can provide substantially improved outcomes compared to more narrowly focused efforts."

Although the study did not address specific conservation methods for freshwater or terrestrial species, it can be used as a guide to identify priority areas elsewhere, which will inform the development and deployment of the most suitable conservation methods.

The research is outlined in the paper 'Integrated terrestrial-freshwater planning doubles conservation of tropical aquatic species'.

Credit: 
Lancaster University

University of Ottawa study finds self-harm may be socially contagious among adolescents

image: Dr. Ian Colman, Associate Professor, Faculty of Medicine, and holder of the Canada Research Chair in Mental Health Epidemiology.

Image: 
University of Ottawa

A new study led by University of Ottawa epidemiologist Dr. Ian Colman suggests non-suicidal self-injury--behaviours like cutting oneself without the intent to die--may be contagious among teenagers, who are more likely to harm themselves when they know someone who has.

The study, titled 'Adolescents' knowledge of a peer's non-suicidal self-injury and own non?suicidal self?injury and suicidality' and published in the peer-reviewed journal Acta Psychiatrica Scandinavica, uses 2014 data collected from over 1,400 Ontario teenagers between the ages of 14-17. Dr. Colman and his team focused on the answers to the question, "Has a friend of yours ever hurt themselves without the intention to die?" A positive response saw the respondent two to three times as likely to answer 'Yes' to the question of whether they have thought about, or done, the same.

These results are of concern, especially during the COVID-19 pandemic, because, apart from being a sign of acute distress, non-suicidal self-injury is a predictor of later suicidal behaviour and more widespread.

"Non-suicidal self-injury is much more common than suicide attempts--twice as common in this study--and many, many times more common than death by suicide," says Dr. Colman, an Associate Professor in the Faculty of Medicine and holder of the Canada Research Chair in Mental Health Epidemiology.

Dr. Colman's study builds on previous research showing teens who are exposed to suicide among their peers are more than twice as likely to demonstrate suicidal behaviour or harbour suicidal thoughts than those who are not exposed. This sort of communication of ideation and behaviour is a form of contagion, and its spread can be tracked by epidemiologists just as physically communicable diseases are studied.

Knowing that suicide is made more likely by knowledge about someone else's suicide, societal measures have been put in place to protect vulnerable populations from exposure. Less obvious are the measures that can slow or protect against socially contagious behaviours among teens, who can be expected to communicate freely among themselves, without referring to guidelines.

Communication is key, according to experts. Conversations with a trusted adult who lends a listening ear, with no threat of judgment, can be helpful throughout adolescence, including for someone who is having thoughts of self-harm.

"There's a belief that a parent talking to their child about suicide may increase the risk of suicide or self-harm," says Dr. Colman, whose previous studies on teen suicide found an association between exposure to suicide and suicidality outcomes in Canadian youth. "(But) there is very little evidence to support that."

Credit: 
University of Ottawa

Repurposed anti-malarial compounds kill diarrheal parasite, study finds

image: Cryptosporidium is a protozoan parasite that is a leading cause of diarrheal disease and death in children.

Image: 
Image courtesy of Sumiti Vinayak

CHAMPAIGN, Ill. -- A class of compounds used for malaria treatment also kill the intestinal parasite Cryptosporidium, a leading cause of diarrheal disease and death in children that has no cure, a multi-institution collaboration of researchers found in a new study.

The compounds, called bicyclic azetidines, specifically target an enzyme responsible for protein production within the parasite, the authors report in the journal Science Translational Medicine.

"There's an urgent need because young children are dying of this diarrheal pathogen, and there's no effective medicine to treat the infection nor vaccine to prevent the disease," said the study's lead author, Sumiti Vinayak, a pathobiology professor at the University of Illinois Urbana-Champaign. "Immunocompromised patients and agricultural animals, especially young calves, are also very susceptible to Cryptosporidium. This is the first time we have had validation of a compound working on a specific target in this parasite."

The researchers began by performing a broad analytical study of existing drugs, looking for any with the potential for repurposing as a Cryptosporidium treatment. After looking at many classes of anti-microbial compounds, they determined that the anti-malarial bicyclic azetidines was a candidate and tested them against Cryptosporidium.

After the compounds proved very effective at killing the parasite in cell cultures, the researchers tested them in immunocompromised mice with Cryptosporidium infections. They found that one oral dose a day for four days rid the mice of infection.

"This study provides a new way of targeting Cryptosporidium. Significantly, because we are repurposing compounds from an anti-malarial program in development, it allows us to apply insights from that program to the treatment of cryptosporidiosis," said Eamon Comer, who led the study at the Broad Institute in Cambridge, Massachusetts. Professors Boris Striepen of the University of Pennsylvania and Christopher D. Huston of the University of Vermont also co-led the study.

The researchers then performed comprehensive biochemical and genetic studies to determine how the compounds attacked the parasite. They found that the bicyclic azetidines targeted an enzyme that makes transfer RNA, the molecule that carries amino acids when the cell makes proteins. The Cryptosporidium enzyme is very similar to that of the parasite that causes malaria, but different from the analogous enzyme in humans, Vinayak said, making it an effective drug target.

Using CRISPR-Cas9 gene-editing technology, the researchers changed one letter in the DNA of the Cryptosporidium gene for the target enzyme, making it just different enough that the drug would not attack it. That one change made the parasite resistant to the drugs, further confirming that blocking this enzyme is the mechanism by which the drug kills Cryptosporidium, Vinayak said.

"This is the first time that the mechanism of action of an anti-Cryptosporidium drug candidate has been confirmed," Vinayak said. "It's a good steppingstone to find these compounds that we can feed into the drug-development pipeline. Future research will further evaluate safety and clinical effectiveness, but the discovery of a new and potent series of compounds with a known target puts us on a promising path forward in this important effort to develop urgently needed treatments."

Credit: 
University of Illinois at Urbana-Champaign, News Bureau

Using machine learning to predict pediatric brain injury

image: ECMO machines such as this one save countless lives, but in some cases can lead to brain injury. A UT Southwestern study used machine learning to accurately predict which babies and children might be most at risk of injury from ECMO treatment.

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UT Southwestern Medical Center

DALLAS - Oct. 1, 2020 - When newborn babies or children with heart or lung distress are struggling to survive, doctors often turn to a form of life support that uses artificial lungs. This treatment, called Extracorporeal Membrane Oxygenation (ECMO), has been credited with saving countless lives. But in some cases, it can also lead to long-term brain injury.

Now, a research team led by UT Southwestern scientists has shown that a machine learning program can predict, more accurately than doctors, which babies and children are most likely to suffer brain injury after ECMO. The study was published last month in the Journal of Clinical Medicine.

"Doctors have always had some intuition about who might be at risk, but until now we really haven't had good data to pinpoint what factors are precipitating brain injury from ECMO," says study leader Lakshmi Raman, M.D., associate professor of pediatrics at UT Southwestern and a critical care specialist at Children's Health. "I don't think we'll be able to fully eliminate these injuries, but I hope that with better predictions we can mitigate the risk."

ECMO works by routing blood out of a patient's body, pumping it through a device that adds oxygen, removes carbon dioxide, and keeps the blood warm before returning it to the body. ECMO is used in both children and adults, but the most frequent patients are newborns. The therapy takes pressure off the heart and lungs while they mature or recover from injury.

Many patients treated with ECMO end up with brain complications, however, and doctors don't fully understand why. The brain injuries have often been attributed to blood-thinning drugs given during ECMO, but studies have failed to back up that link.

"I became really interested to see whether we could come up with an algorithm that takes all these different factors and tries to identify what predisposes some patients to brain injury," says Raman.

Raman and her collaborators used data on 174 patients under the age of 18, including 70 babies under 30 days old, who were treated with ECMO at Children's Medical Center Dallas between 2010 and 2019. In each case, CT or MRI images of the patient's brain after ECMO was available. Brain injury was detected by a scan in 81, or 51 percent, of the patients.

The researchers entered data on each patient - including age, weight, gender, medications, type of ECMO, primary reason for ECMO, and how long they received ECMO - into a machine learning program called a neural network that is designed to identify patterns in datasets. The program analyzed over 35,000 clinical hours of ECMO treatment and 1.4 million data points across 35 variables.

The resulting model had a 73 percent sensitivity rate of predicting brain injury after ECMO and 80 percent specificity rate. This beat out the prediction power of clinicians, who had suspected brain injury in 61 patients, with a sensitivity of 39 percent and a specificity of 69 percent.

Surprisingly, whether a patient was on anti-coagulant drugs, or the dosage of those drugs, had little effect on brain injury. A patient's heart rate and blood pressure, however, were found to help the model predict brain damage.

"I think this probably means we need to focus more attention on those blood flow variables," says Raman. "We're already starting to do work in that direction."

The prediction model isn't going to be used clinically anytime soon; Raman and her colleagues are planning larger studies that include ECMO patients at other medical centers. The researchers hope to identify characteristics that can help doctors predict which patients will most benefit from ECMO with the least risk.

Credit: 
UT Southwestern Medical Center

Ice Age manatees may have called Texas home

image: Manatees lived in Texas during the last ice age, according to fossil evidencefound along Texas beaches.

Image: 
Robert Bonde / U.S. Geological Survey.

Manatees don't live year-round in Texas, but these gentle, slow-moving sea cows are known to occasionally visit, swimming in for a "summer vacation" from Florida and Mexico and returning to warmer waters for the winter.

Research led by The University of Texas at Austin has found fossil evidence for manatees along the Texas coast dating back to the most recent ice age. The discovery raises questions about whether manatees have been making the visit for thousands of years, or if an ancient population of ice age manatees once called Texas home somewhere between 11,000 and 240,000 years ago.

The findings were published in Palaeontologia Electronica.

"This was an unexpected thing for me because I don't think about manatees being on the Texas coast today," said lead author Christopher Bell, a professor at the UT Jackson School of Geosciences. "But they're here. They're just not well known."

The paper co-authors are Sam Houston State University Natural History Collections curator William Godwin, SHSU alumna Kelsey Jenkins (now a graduate student at Yale University), and SHSU Professor Patrick Lewis.

The eight fossils described in the paper include manatee jawbones and rib fragments from the Pleistocene, the geological epoch of the last ice age. Most of the bones were collected from McFaddin Beach near Port Arthur and Caplen Beach near Galveston during the past 50 years by amateur fossil collectors who donated their finds to the SHSU collections.

"We have them from one decade to another, so we know it's not from some old manatee that washed up, and we have them from different places," Godwin said. "All these lines of evidence support that manatee bones were coming up in a constant way."

The Jackson Museum of Earth History at UT holds two of the specimens.

A lower jawbone fossil, which was donated to the SHSU collections by amateur collector Joe Liggio, jumpstarted the research.

"I decided my collection would be better served in a museum," Liggio said. "The manatee jaw was one of many unidentified bones in my collection."

Manatee jawbones have a distinct S-shaped curve that immediately caught Godwin's eye. But Godwin said he was met with skepticism when he sought other manatee fossils for comparison. He recalls reaching out to a fossil seller who told him point-blank "there are no Pleistocene manatees in Texas."

But examination of the fossils by Bell and Lewis proved otherwise. The bones belonged to the same species of manatee that visits the Texas coast today, Trichechus manatus. An upper jawbone donated by U.S. Rep. Brian Babin was found to belong to an extinct form of the manatee, Trichechus manatus bakerorum.

The age of the manatee fossils is based on their association with better-known ice age fossils and paleo-indian artifacts that have been found on the same beaches.

It's assumed that the cooler ice age climate would have made Texas waters even less hospitable to manatees than they are today. But the fact that manatees were in Texas -- whether as visitors or residents -- raises questions about the ancient environment and ancient manatees, Bell said. Either the coastal climate was warmer than is generally thought, or ice age manatees were more resilient to cooler temperatures than manatees of today.

The Texas coast stretched much farther into the Gulf of Mexico and hosted wider river outlets during the ice age than it does now, said Jackson School Professor David Mohrig, who was not part of the research team.

"Subsurface imaging of the now flooded modern continental shelf reveals both a greater number of coastal embayments and the presence of significantly wider channels during ice age times," said Mohrig, an expert on how sedimentary landscapes evolve.

If there was a population of ice age manatees in Texas, it's plausible that they would have rode out winters in these warmer river outlets, like how they do today in Florida and Mexico.

Credit: 
University of Texas at Austin

Ice discharge in the North Pacific set off series of climate events during last ice age

image: The JOIDES Resolution, a research vessel that drills into the ocean floor to collect and study core samples is seen at the Port of Valdez. The JR is a part of the International Ocean Discovery Program and is funded by the National Science Foundation.

Image: 
Bill Mills, IODP/TAMU [Photo ID: exp346_003]

CORVALLIS, Ore. - Repeated catastrophic ice discharges from western North America into the North Pacific contributed to, and perhaps triggered, hemispheric-scale changes in the Earth's climate during the last ice age, new research published online today in Science reveals.

The discovery provides new insight into the impact rapidly melting ice flowing into the North Pacific may have on the climate across the planet, said Maureen Walczak, a paleoclimatologist in Oregon State University's College of Earth, Ocean, and Atmospheric Sciences and the study's lead author.

"Understanding how the ocean has interacted with glacial ice in the past helps us predict what could happen next," Walczak said.

The Cordilleran ice sheet once covered large portions of western North America from Alaska to Washington state and western Montana. Radiocarbon dating and analyses of the marine sediment record revealed that recurrent episodes of discharge from this ice sheet over the past 42,000 years were early events in a chain reaction of disturbances to the global climate. These disturbances triggered changes in deep ocean circulation and retreat of ice sheets in the North Atlantic.

The findings challenge theories that those massive, globally-reaching disturbances originated in the North Atlantic as rapid ice loss from the Laurentide ice sheet, another massive ice sheet that covered much of Canada and the northern United States, including the upper Midwest and Northeast. The Laurentide ice loss events are known as Heinrich Events.

"The outcome of this research was unexpected. The data irrevocably says that the Pacific ice goes first, with Heinrich Events and other changes following in a rhythm. The Pacific Ocean sets the drum beat," Walczak said. "This is a paradigm shift in our thinking about how these events are connected."

To gain insight into the climate history of the North Pacific, an international team of researchers collected and analyzed sediment cores from the northern Gulf of Alaska that were recovered by drilling as part of the International Ocean Discovery Program.

"Getting these new insights took years of work. We first mapped the seafloor and recovered short sediment cores in 2004, drilled longer cores in 2013 and had 16 years of painstaking laboratory work involving several Ph.D. students," said Alan Mix, the project's principal investigator and co-author of the paper.

"This was a virtually unknown area when we started, and now it offers among the most detailed and best-dated long records of ocean change on the planet during the ice age," said Mix, a distinguished professor in OSU's College of Earth, Ocean, and Atmospheric Sciences.

Researchers measured radioactive isotopes of carbon using two particle accelerators to establish the chronology of events and also added meticulous counts of small rocks dropped by icebergs known as ice-rafted debris.

The research team traced the source of the ice-rafted debris back to purges of massive ice streams emanating from the Cordilleran ice sheet, which covered northern Washington, most of British Columbia and southern Alaska from about 70,000 to 17,000 years ago.

Dirty icebergs broke off from surging ice streams and drifted northward in ocean currents, carrying and eventually dropping their load of sand, pebbles and gravel, leaving a record of rapid ice retreat buried in the deep sea like sunken treasure.

The authors of the study named these Alaskan iceberg dumps "Siku Events" after the Inuit word for ice. The big surprise, discovered by combining the record of glacial debris with the radiocarbon chronology, was that Siku Events immediately preceded Heinrich events, which are a similar type of ice purge in the North Atlantic.

Scientists have been aware of Heinrich Events, from similar evidence of ice-rafted debris in the North Atlantic, for more than 30 years but the trigger for those events has never been convincingly explained, the researchers said.

It makes sense for the Pacific Ocean to be involved in major planetary changes, Mix said. The Pacific Ocean is connected to the rest of the world by large-scale atmospheric circulation and physically around Antarctica, and during times of high sea level, through the Bering Strait and the Arctic Ocean to the North Atlantic.

"The Pacific Ocean is the largest exchangeable reservoir of heat and water and carbon dioxide on Earth, simply because of its massive size," he said. "It really is the 800-pound gorilla in the zoo of climate beasts."

Today the ice that remains along the coast of Alaska is mostly retreating and may be gone within this century as the climate warms. The melting ice will drain to the Pacific and the Arctic, contributing to sea level rise and impacting the balance of buoyant fresh and dense salty water in the ocean, much as it did in the past.

If the current ice melt follows patterns of the past, and happens quickly, it could contribute to the retreat of distant glacial systems in the North Atlantic and the Arctic.

"This is yet another reason that it is prudent to slow down warming by reducing our fossil-fuel use," Mix said.

"The new findings are likely to fuel increased interest in the North Pacific, an area that has not been as well-studied as other parts of the planet," Walczak said.

One thing that remains unclear is why the discharges from the Cordilleran ice sheet occurred. Researchers also would like to better understand the relationship between the discharges of the Cordilleran and the other climate events.

"Why did the other ice sheets respond to the retreat of the Cordilleran? How fast do the dominoes fall in this sequence of events?" Walczak asked. Those are among the questions the research team is continuing to investigate.

Credit: 
Oregon State University