“We’ve shown that by using high quality transcriptomic data we can answer a long-standing question to the best of our current techniques,” said Dr. Konstantin Khalturin, Staff Scientist in OIST’s Marine Genomics Unit and first author of the paper published in Science Advances.

A genome is the full set of genetic information found in every cell. It is subdivided into genes. These genes are made up of DNA base pairs and each gene contains the instructions needed to create a protein, and thus leads to the proper care and maintenance of a cell. For the instructions to be carried out, the DNA must first be transcribed into RNA. A transcriptome is the result of this, like the reflection of a genome but written in RNA base pairs rather than DNA.

This genetic information differs among species. Those who are closely related have very similar genetic information, while a greater evolutionary distance results in more genetic differences. By using this data, researchers have improved our knowledge of animal evolution, but some questions still prove difficult to answer.

As Kamptozoa and Bryozoa are closely related to mollusks, annelids, and nemertea, small mistakes in the dataset, or missing data, can result in an incorrect placement on the evolutionary tree. Furthermore, while collecting these tiny animals, it’s easy to pick up other organisms, such as algae, that contaminate the sample. Dr. Khalturin highlighted that they were careful to avoid contamination and later screened their dataset for RNA of algae and small animals to remove any that might have come from them.

In total, the researchers sequenced the transcriptome of four species of Kamptozoa and two species of Bryozoa, but to a far higher quality level than had previously been achieved. While past datasets had completeness of 20-60%, in this study, the transcriptome completeness was over 96%.

Using these transcriptomes, they predicted proteins and compared them to similar data of 31 other species, some of which were closely related to Kamptozoa and Bryozoa, such as clams and bristleworms, and others which were more distant, such as frogs, starfish, insects, and jellyfish. The high-quality datasets meant that they could compare many different genes and proteins simultaneously. Dr. Khalturin credited the powerful computational capabilities that the researchers could access at OIST.

“Our main finding is that the two phyla belong together,” said Dr. Khalturin. “This result was originally proposed in the 19th century by biologists who were grouping animals based on what they looked like.”

While Dr. Khalturin stated that this question had now been answered to the best ability available, he also highlighted that the dataset could answer other fundamental evolutionary questions — such as the more precise location of mollusks and annelids on the tree of life, and how life diversified.

The paper in the journal Science Advances brought together experts in salmon ecology, watershed science, mining impacts and mining policy to integrate knowledge across research fields that often work independently from one another. Led by UM researchers at the Flathead Lake Biological Station, the team found past and present mining pressures are extensive across the region and often overlap with important populations of salmon, trout and char.

“Our paper highlights the mosaic of more than 3,600 active and abandoned mines sitting amongst some of the most valuable fish habitat in western North America,” said Chris Sergeant, an FLBS research scientist and the paper’s lead author. “The largest of these mines processes around 160,000 metric tons of earth every day.”

Sergeant said not all mines pose the same level of risk, but their review revealed that harm from mining can be severe and long-lasting. The extent of mining pressures on these watersheds underscores the importance of accurately assessing risk to water, fish and communities.

The study reviewed the ecological complexity of rivers and how mines can impact culturally and economically important fish species such as salmon by contaminating waters with heavy metals, burying stream habitat and diverting water for processing ore. When not managed properly, these cumulative impacts can be impossible to reverse and degrade landscapes for decades to centuries.

“Unfortunately, in some cases, we are learning the hard way that mines can have profound impacts on aquatic ecosystems, leaching far down the watershed from the actual mine site, at scales that were not anticipated in the original impact assessment,” said Erin Sexton, a paper co-author and FLBS senior scientist. “For example, impacts from the Elk Valley coal mining complex in southeast British Columbia have been documented over 155 miles downstream of the mines, crossing the U.S.-Canada international boundary.”

The authors emphasize that up-to-date and transparent science has an important role to play in managing the potential impacts of mines. Emerging science on salmonid ecology, cumulative effects and how climate change is altering these landscapes can improve risk assessment of mines.

The authors highlighted four key issues that will be foundational to modern, science-based risk assessment and mitigation: understanding stressor complexity and uncertainty, accounting for cumulative effects of mining activities across a mine’s life cycle, developing realistic mitigation strategies and recognizing the potential for climate change to magnify risk.

“Emerging science is revealing the complex realities of how salmon watersheds work in this era of climate change and also the many different risk pathways posed by mines,” said co-author Jonathan Moore of Simon Fraser University in British Columbia. “Informed decision-making will need risk assessments that embrace these challenging topics, ranging from cumulative effects to climate change.”

While a low-carbon future will depend to some extent on mined minerals, it is important to consider whether current and future mining projects are operated in such a way that protects fish, water and well-functioning watersheds.

“Our paper is not for or against mining, but it does describe current environmental challenges and gaps in the application of science to mining governance,” Sergeant said. “We identify a need and opportunity for strong science-based and transparent risk assessment, as well as the integration of goals and values of impacted communities. In the end, it is possible that some specific places might just be too valuable to risk with major mines.”

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Materials provided by The University of Montana. Note: Content may be edited for style and length.

UC Santa Barbara Professor Ben Mazin is developing precision optical sensors for telescopes and observatories. In a paper published in Physical Review Letters, he and his team improved the spectra resolution of their superconducting sensor, a major step in their ultimate goal: analyzing the composition of exoplanets.

“We were able to roughly double the spectral resolving power of our detectors,” said first author Nicholas Zobrist, a doctoral student in the Mazin Lab.

“This is the largest energy resolution increase we’ve ever seen,” added Mazin. “It opens up a whole new pathway to science goals that we couldn’t achieve before.”

The Mazin lab works with a type of sensor called an MKID. Most light detectors — like the CMOS sensor in a phone camera — are semiconductors based on silicon. These operate via the photo-electric effect: a photon strikes the sensor, knocking off an electron that can then be detected as a signal suitable for processing by a microprocessor.

An MKID uses a superconductor, in which electricity can flow with no resistance. In addition to zero resistance, these materials have other useful properties. For instance, semiconductors have a gap energy that needs to be overcome to knock the electron out. The related gap energy in a superconductor is about 10,000 times less, so it can detect even faint signals.

What’s more, a single photon can knock many electrons off of a superconductor, as opposed to only one in a semiconductor. By measuring the number of mobile electrons, an MKID can actually determine the energy (or wavelength) of the incoming light. “And the energy of the photon, or its spectra, tells us a lot about the physics of what emitted that photon,” Mazin said.

Leaking energy

The researchers had hit a limit as to how sensitive they could make these MKIDs. After much scrutiny, they discovered that energy was leaking from the superconductor into the sapphire crystal wafer that the device is made on. As a result, the signal appeared weaker than it truly was.

In typical electronics, current is carried by mobile electrons. But these have a tendency to interact with their surroundings, scattering and losing energy in what’s known as resistance. In a superconductor, two electrons will pair up — one spin up and one spin down — and this Cooper pair, as it’s called, is able to move about without resistance.

“It’s like a couple at a club,” Mazin explained. “You’ve got two people who pair up, and then they can move together through the crowd without any resistance. Whereas a single person stops to talk to everybody along the way, slowing them down.”

In a superconductor, all the electrons are paired up. “They’re all dancing together, moving around without interacting with other couples very much because they’re all gazing deeply into each other’s eyes.

“A photon hitting the sensor is like someone coming in and spilling a drink on one of the partners,” he continued. “This breaks the couple up, causing one partner to stumble into other couples and create a disturbance.” This is the cascade of mobile electrons that the MKID measures.

But sometimes this happens at the edge of the dancefloor. The offended party stumbles out of the club without knocking into anyone else. Great for the rest of the dancers, but not for the scientists. If this happens in the MKID, then the light signal will seem weaker than it actually was.

Fencing them in

Mazin, Zobrist and their co-authors discovered that a thin layer of the metal indium — placed between the superconducting sensor and the substrate — drastically reduced the energy leaking out of the sensor. The indium essentially acted like a fence around the dancefloor, keeping the jostled dancers in the room and interacting with the rest of the crowd.

They chose indium because it is also a superconductor at the temperatures at which the MKID will operate, and adjacent superconductors tend to cooperate if they are thin. The metal did present a challenge to the team, though. Indium is softer than lead, so it has a tendency to clump up. That’s not great for making the thin, uniform layer the researchers needed.

But their time and effort paid off. The technique cut down the wavelength measurement uncertainty from 10% to 5%, the study reports. For example, photons with a wavelength of 1,000 nanometers can now be measured to a precision of 50 nm with this system. “This has real implications for the science we can do,” Mazin said, “because we can better resolve the spectra of the objects that we’re looking at.”

Different phenomena emit photons with specific spectra (or wavelengths), and different molecules absorb photons of different wavelengths. Using this light, scientists can use spectroscopy to identify the composition of objects both nearby and across the entire visible universe.

Mazin is particularly interested in applying these detectors to exoplanet science. Right now, scientists can only do spectroscopy for a tiny subset of exoplanets. The planet needs to pass between its star and Earth, and it must have a thick atmosphere so that enough light passes through it for researchers to work with. Still, the signal to noise ratio is abysmal, especially for rocky planets, Mazin said.

With better MKIDs, scientists can use light reflected off the surface of a planet, rather than transmitted through its narrow atmosphere alone. This will soon be possible with the capabilities of the next generation of 30-meter telescopes.

The Mazin group is also experimenting with a completely different approach to the energy-loss issue. Although the results from this paper are impressive, Mazin said he believes the indium technique could be obsolete if his team is successful with this new endeavor. Either way, he added, the scientists are rapidly closing in on their goals.

In a new study, scientists use gene expression patterns, called transcriptomics, to investigate the ancient origins of one organ: the placenta, which is vital to pregnancy.

“In some mammals, like humans, the placenta is really invasive, so it invades all the way through the wall of the uterus, into the maternal tissue. In other mammals, the placenta just touches the wall of the uterus. And then there’s everything in between,” says senior author Vincent J. Lynch, PhD, associate professor of biological sciences in the University at Buffalo College of Arts and Sciences.

“So what kind of placentas were early placentas?” he says. “We use gene expression patterns to reconstruct the evolution of the placenta and predict what the placenta of the last common ancestor of eutherian mammals looked like. Our data tells us that this placenta was invasive, and that non-invasive placentas evolved multiple times among mammals. This addresses a 150-year-old mystery: People have been debating what kind of placenta the first one was since then.”

As Lynch explains, all living mammals other than marsupials and egg-laying monotremes are eutherians, which have long pregnancies in which the developing fetus evokes a strong physiological response in the mother.

The research was published on June 30 in eLife. Lynch led the study with first author Katelyn Mika, PhD, University of Chicago postdoctoral scholar in human genetics and in organismal biology and anatomy. Camilla M. Whittington, PhD, and Bronwyn M. McAllan, PhD, both at the University of Sydney, are also co-authors.

“Our ability to ask how the placenta might have functioned at different points during its evolution by using the gene expression profiles of currently existing animals to reconstruct the ancestors is a really cool approach and provides us more information on how changing gene expression can contribute to the evolution of a new trait,” Mika says.

To conduct the analysis, the team compared the genes active in the uterus of various mammals during pregnancy. After finding that these gene expression profiles correlated with the degree of placental invasiveness, the scientists used their data to predict what ancestral mammalian placentas looked like.

The study included about 20 species, such as the egg-laying platypus, pouch-bearing marsupials, and a range of eutherian mammals that give birth to live young.

The small subset is one limitation of the analysis: The authors write in eLife that research on a larger number of species is needed to help determine the strength of the findings.

Nevertheless, the study makes important contributions in understanding how pregnancy evolved, Lynch says. The results could also benefit modern medicine.

“Knowing which genes are active among different species during pregnancy tells us about how evolution works,” he says. “But it also tells us about what makes a healthy pregnancy, and how things might go wrong. We’re finding the genes that establish the right kind of environment for healthy human pregnancies. If those genes are not expressed in the right way, that might give rise to problems.”

This study was supported by grants from the March of Dimes and the Burroughs Wellcome Fund Preterm Birth Initiative.

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Materials provided by University at Buffalo. Original written by Charlotte Hsu. Note: Content may be edited for style and length.

“The study of DNA methylation is part of the field of epigenetics. It is important because it helps us understand why one particular type of bacteria causes a more severe disease than another or how a normal cell can change and give rise to diseases, such as cancer,” said corresponding author Dr. Tao Wu, assistant professor of molecular and human genetics at Baylor College of Medicine. The Wu Lab is a cancer epigenetics lab. Its long-term goal is to overcome cancer therapeutic resistance by better understanding the role of epigenetics in this disease.

In bacteria, there are three different forms of DNA methylation. The most common is one that tags the DNA base or building block adenine (N6-methyladenine or 6mA). The other two tag the DNA base cytosine (N4-methylcytosine or 4mC and 5-methylcytosine or 5mC). Although there are many methods to study DNA methylation, a few can efficiently map the three types simultaneously, Wu explained.

“It was thought that organisms other than bacteria, including mammals, mostly only used methyl-cytosine tags — the 5mC — to regulate gene activity. But in 2016, when I was at Yale University, we reported in Nature the discovery that DNA 6mA also is present in mammals,” Wu said. “This finding opened a whole new set of possibilities in the study of cancer epigenetics.”

The traditional methods to study the 5mC do not capture the adenine methylation in mammalian tissues. “This motivated us to develop a novel method to profile not only 6mA, but also 4mC and 5mC,” Wu said.

In the current study, published in the journal Genome Biology, Wu and his colleagues report the development of a chemical-based sequencing method to quantify different epigenetic markers simultaneously. Their method, called NT-seq, short for nitrite treatment followed by next-generation sequencing, is a sequencing method for detecting multiple types of DNA methylation genome-wide. The method also can amplify limited clinical samples, something other methods cannot do.

“We show that NT-seq can detect 6mA, 4mC and 5mC both in bacterial and non-bacterial cells, including mammalian cells,” Wu said. “Compared to other methods, NT-seq is efficient, cost-effective, quicker and has high resolution. Some of its limitations are specific to the particular composition of some genomes. We have suggestions in the paper on how to compensate for this limitation.”

“We are excited about NT-seq,” Wu said. “It can uncover new DNA methylation patterns or motifs, validate results obtained with other methods, generate datasets for developing machine-learning tools for methylation analysis and paves the way to further the epigenetic study of genomic DNA 6mA in non-bacterial organisms, including studies on the epigenetics of cancer.”

Other contributors to this work include leading first author Xuwen Li, Shiyuan Guo, Yan Cui, Zijian Zhang, Xinlong Luo, Margarita T. Angelova, Laura F. Landweber and Yinsheng Wang. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, University of California Riverside, Columbia University, Baylor’s Huffington Center on Aging and Dan L Duncan Comprehensive Cancer Center.

This work is supported by grants from CPRIT (RR180072), NIH (R35 ES031707) and a Rivkin Center Scientific Scholar Award.

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Materials provided by Baylor College of Medicine. Original written by Ana María Rodríguez, Ph.D.. Note: Content may be edited for style and length.

Publishing July 1 in the journal Science Advances, a team of biologists at the University of California San Diego that includes postdoctoral scholar Sitara Roy, specialist Annabel Guichard and Professor Ethan Bier describes a new, safer approach that may correct genetic defects in the future. Their strategy, which makes use of natural DNA repair machinery, provides a foundation for novel gene therapy strategies with the potential to cure a large spectrum of genetic diseases.

In many cases, those suffering from genetic disorders carry distinct mutations in the two copies of genes inherited from their parents. This means that often, a mutation on one chromosome will have a functional sequence counterpart on the other chromosome. The researchers employed CRISPR genetic editing tools to exploit this fact.

“The healthy variant can be used by the cell’s repair machinery to correct the defective mutation after cutting the mutant DNA,” said Guichard, the senior author of the study, “Remarkably, this can be achieved even more efficiently by a simple harmless nick.”

Working in fruit flies, the researchers designed mutants permitting visualization of such “homologous chromosome-templated repair,” or HTR, by the production of pigments in their eyes. Such mutants initially featured entirely white eyes. But when the same flies expressed CRISPR components (a guide RNA plus Cas9), they displayed large red patches across their eyes, a sign that the cell’s DNA repair machinery had succeeded in reversing the mutation using the functional DNA from the other chromosome.

They then tested their new system with Cas9 variants known as “nickases” that targeted just one strand of DNA instead of both. Surprisingly, the authors found that such nicks also gave rise to high-level restoration of red eye color nearly on par with normal (non-mutated) healthy flies. They found a 50-70% repair success rate with the nickase compared with just 20-30% in dual-strand cutting Cas9, which also generates frequent mutations and targets other sites throughout the genome (so-called off-target mutations). “I could not believe how well the nickase worked — it was completely unanticipated,” said Roy, the lead author of the study. The versatility of the new system could serve as a model for fixing genetic mutations in mammals, the researchers noted.

“We don’t know yet how this process will translate to human cells and if we can apply it to any gene,” said Guichard. “Some adjustment may be needed to obtain efficient HTR for disease-causing mutations carried by human chromosomes.”

The new research extends the group’s previous achievements in precision-editing with “allelic-drives,” which expand on principles of gene-drives with a guide RNA that directs the CRISPR system to cut undesired variants of a gene and replace them with a preferred version of the gene.

A key feature of the team’s research is that their nickase-based system causes far fewer on- and off-target mutations, as is known to happen with more traditional Cas9-based CRISPR edits. They also say a slow, continuous delivery of nickase components across several days may prove more beneficial than one-time deliveries.

“Another notable advantage of this approach is its simplicity,” said Bier. “It relies on very few components and DNA nicks are ‘soft,’ unlike Cas9, which produces full DNA breaks often accompanied by mutations.”

“If the frequency of such events could be increased either by promoting interhomolog pairing or by optimizing nick-specific repair processes, such strategies could be harnessed to correct numerous dominant or trans-heterozygous disease-causing mutations,” said Roy.

The Science Advances paper’s complete author list: Sitara Roy, Sara Sanz Juste, Marketta Sneider, Ankush Auradkar, Carissa Klanseck, Zhiqian Li, Alison Henrique Ferreira Julio, Victor Lopez del Amo, Ethan Bier and Annabel Guichard.

Support for the research was provided by the National Institutes of Health (grant R01 GM117321), a Paul G. Allen Frontiers Group Distinguished Investigators Award and a gift from the Tata Trusts in India to the Tata Institute for Genetics and Society (TIGS)-UC San Diego and TIGS India.

Competing interest note: Bier has equity interest in two companies he co-founded: Synbal Inc. and Agragene, Inc., which may potentially benefit from the research results. He also serves on Synbal’s board of directors and the scientific advisory board for both companies.

We know that the world was generally hot and steamy during the Triassic Period, which preceded the extinction, and during the following Jurassic, which kicked off the age of dinosaurs. However, a new study turns the idea of heat-loving dinosaurs on its head: It presents the first physical evidence that Triassic dinosaur species — then a minor group largely relegated to the polar regions — regularly endured freezing conditions there. The telltale indicators: dinosaur footprints along with odd rock fragments that only could have been deposited by ice. The study’s authors say that during the extinction, cold snaps already happening at the poles spread to lower latitudes, killing off the coldblooded reptiles. Dinosaurs, already adapted, survived the evolutionary bottleneck and spread out. The rest is ancient history.

“Dinosaurs were there during the Triassic under the radar all the time,” said Paul Olsen, a geologist at Columbia University’s Lamont-Doherty Earth Observatory, and lead author of the study. “The key to their eventual dominance was very simple. They were fundamentally cold-adapted animals. When it got cold everywhere, they were ready, and other animals weren’t.”

The study, based on recent excavations in the remote desert of northwest China’s Junggar Basin, was just published in the journal Science Advances.

Dinosaurs are thought to have first appeared during the Triassic Period in temperate southerly latitudes about 231 million years ago, when most of the planet’s land was joined together in one giant continent geologists call Pangaea. They made it to the far north by about 214 million years ago. Until the mass extinction at 202 million years, the more expansive tropical and subtropical regions in between were dominated by reptiles including relatives of crocodiles and other fearsome creatures.

During the Triassic, and for most of the Jurassic, atmospheric concentrations of carbon dioxide ranged at or above 2000 parts per million — five times today’s levels — so temperatures must have been intense. There is no evidence of polar ice caps then, and excavations have shown that deciduous forests grew in polar regions. However, some climate models suggest that the high latitudes were chilly some of the time; even with all that CO2, they would have received little sunlight much of the year, and temperatures would decline at least seasonally. But until now, no one has produced any physical evidence that they froze.

At the end of the Triassic, a geologically brief period of perhaps a million years saw the extinction of more than three quarters of all terrestrial and marine species on the planet, including shelled creatures, corals and all sizable reptiles. Some animals living in burrows, such as turtles, made it through, as did a few early mammals. It is unclear exactly what happened, but many scientists connect it to a series of massive volcanic eruptions that could have lasted hundreds of years at a stretch. At this time, Pangaea started to split apart, opening what is now the Atlantic Ocean, and separating what are now the Americas from Europe, Africa and Asia. Among other things, the eruptions would have caused atmospheric carbon dioxide to skyrocket beyond its already high levels, causing deadly temperatures spikes on land, and turning ocean waters too acid for many creatures to survive.

The authors of the new study cite a third factor: During the eruptions’ fiercest phases, they would have belched sulfur aerosols that deflected so much sunlight, they caused repeated global volcanic winters that overpowered high greenhouse-gas levels. These winters might have lasted a decade or more; even the tropics may have seen sustained freezing conditions. This killed uninsulated reptiles, but cold-adapted, insulated dinosaurs were able to hang on, say the scientists.

The researchers’ evidence: fine-grained sandstone and siltstone formations left by sediments in shallow ancient lake bottoms in the Junggar Basin. The sediments formed 206 million years ago during the late Triassic, through the mass extinction and beyond. At that time, before landmasses rearranged themselves, the basin lay at about 71 degrees north, well above the Arctic Circle. Footprints found by the authors and others show that dinosaurs were present along shorelines. Meanwhile, in the lakes themselves, the researchers found abundant pebbles up to about 1.5 centimeters across within the normally fine sediments. Far from any apparent shoreline, the pebbles had no business being there. The only plausible explanation for their presence: they were ice-rafted debris (IRD).

Briefly, IRD is created when ice forms against a coastal landmass and incorporates bits of underlying rock. At some point the ice becomes unmoored and drifts away into the adjoining water body. When it melts, the rocks drop to the bottom, mixing with normal fine sediments. Geologists have extensively studied ancient IRD in the oceans, where it is delivered by glacial icebergs, but rarely in lake beds; the Junggar Basin discovery adds to the scant record. The authors say the pebbles were likely picked up during winter, when lake waters froze along pebbly shorelines. When warm weather returned, chunks of that ice floated off with samples of the pebbles in tow, and later dropped them.

“This shows that these areas froze regularly, and the dinosaurs did just fine,” said study co-author Dennis Kent, a geologist at Lamont-Doherty.

How did they do it? Evidence has been building since the 1990s that many if not all non-avian dinosaurs including tyrannosaurs had primitive feathers. If not for flight, some coverings could have used for mating display purposes, but the researchers say their main purpose was insulation. There is also good evidence that, unlike the cold-blooded reptiles, many dinosaurs possessed warm-blooded, high-metabolism systems. Both qualities would have helped dinosaurs in chilly conditions.

“Severe wintery episodes during volcanic eruptions may have brought freezing temperatures to the tropics, which is where many of the extinctions of big, naked, unfeathered vertebrates seem to have occurred,” said Kent. “Whereas our fine feathered friends acclimated to colder temperatures in higher latitudes did OK.”

The findings defy the conventional imagery of dinosaurs, but some prominent specialists say they are convinced. “There is a stereotype that dinosaurs always lived in lush tropical jungles, but this new research shows that the higher latitudes would have been freezing and even covered in ice during parts of the year,” said Stephen Brusatte, a professor of paleontology and evolution at the University of Edinburgh. “Dinosaurs living at high latitudes just so happened to already have winter coats [while] many of their Triassic competitors died out.”

Randall Irmis, curator of paleontology at the Natural History Museum of Utah, and specialist in early dinosaurs, agrees. “This is the first detailed evidence from the high paleolatitudes, the first evidence for the last 10 million years of the Triassic Period, and the first evidence of truly icy conditions,” he said. “People are used to thinking of this as being a time when the entire globe was hot and humid, but that just wasn’t the case.”

Olsen says the next step to better understand this period is for more researchers to look for fossils in former polar areas like the Junggar Basin. “The fossil record is very bad, and no one is prospecting,” he said. “These rocks are gray and black, and it is much harder to prospect [for fossils] in these strata. Most paleontologists are attracted to the late Jurassic, where it’s known there are many big skeletons to be had. The paleo-Arctic is basically ignored.”

The study was co-authored Jingeng Sha and Yanan Fang of Nanjing Institute of Geology and Paleontology; Clara Chang and Sean Kinney of Lamont-Doherty Earth Observatory; Jessica Whiteside of the University of Southampton; Hans-Dieter Sues of the Smithsonian Institution; Morgan Schaller of Rensselaer Polytechnic Institute; and Vivi Vajda of the Swedish Museum of Natural History.

It is the first comprehensive effort by an interdisciplinary group of experts that explicitly links mining policy to our current understanding of watershed ecology and salmonid biology.

“Our paper is not for or against mining, but it does describe current environmental challenges and gaps in the application of science to mining governance. We believe it will provide critically needed scientific clarity for this controversial topic,” said lead author Chris Sergeant, a graduate student at the University of Alaska Fairbanks College of Fisheries and Ocean Sciences and a research scientist at the University of Montana.

For the study, experts integrated and reviewed information on hydrology, river ecology, aquatic toxicology, biology and mining policy. Their robust assessment maps more than 3,600 mines throughout Montana, Washington, British Columbia, the Yukon and Alaska. The size of the mines ranges from family-run placer sites to massive open-pit projects.

The study shows that, despite impact assessments intended to evaluate risk and inform mitigation, mines continue to harm salmonid-bearing watersheds through contaminants, stream channel burial and streamflow alteration. Silt suffocates eggs, and embryos may not survive contaminated groundwater. Heavy metals compromise a salmon’s sense of smell, which affects their ability to react to predators and find their way back from the ocean to spawn.

“Not all mines pose the same level of risk, but our review revealed that harm from mining can be severe and long-lasting. The extent of mining pressures on these watersheds underscores the importance of accurately assessing risk to water, fish and communities,” said Sergeant.

The paper also describes how some mining policies do not account for the breadth and length of mining impacts on the environment, or the increasing effects of climate change.

“The crux of the issue is that salmon use so much of the watershed during their life cycle. They move throughout watersheds, whereas the impact assessments of mining projects tend to be very locally focused, and they don’t sufficiently consider all of the compounding and downstream effects of mining,” said salmon biologist and CFOS faculty member Megan McPhee.

She explained that some impact assessments don’t fully assess the infrastructure required to operate a mine, such as roads, electricity generation and water removal.

“Another thing is that most mines, after closure, have to be mitigated in perpetuity. That’s a problem because most corporations aren’t structured that way. Also, most mitigation strategies don’t take into account environmental change, including permafrost melting, and climate change-induced flooding,” said McPhee.

Moving forward, the authors highlighted four key issues that will be foundational to modern, science-based risk assessment and mitigation, beginning with understanding stressor complexity and uncertainty. Stressors include impacts such as altered hydrology and temperature, habitat modification and loss, and pollutants.

Other key issues are accounting for cumulative effects of mining activities across a mine’s life cycle, developing realistic mitigation strategies and recognizing the potential for climate change to magnify risk.

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Materials provided by University of Alaska Fairbanks. Original written by Alice Bailey. Note: Content may be edited for style and length.

While ASD is distinct from ID, a significant proportion — approximately 31% — of people with ASD also exhibit ID. Neither condition is well-understood at the molecular level.

“Given the vast number of genes known to be involved in ASD/ID and the many potential mechanisms contributing to the disorders, it is exciting to find a shared process between two different genes at the molecular level that could be underlying the behavioral changes,” said Megan Conrow-Graham, PhD, first author and an MD/PhD candidate in the Jacobs School of Medicine and Biomedical Sciences at UB.

Published today in the journal Brain, the paper focuses on ADNP and POGZ, the two top-ranked risk factor genes for ASD/ID. The research demonstrates that mutations in these genes result in abnormal activation and overexpression of immune response genes and genes for a type of immune cell in the brain called microglia.

“Our finding opens the possibility of targeting microglia and immune genes for treating ASD/ID, but much remains to be studied, given the heterogeneity and complexity of these brain disorders,” said Zhen Yan, PhD, senior author and SUNY Distinguished Professor in the Department of Physiology and Biophysics in the Jacobs School.

The UB scientists found that mutations in the two genes studied activate microglia and cause immune genes in the brain to be overexpressed. The hypothesized result is the abnormal function of synapses in the brain, a characteristic of ASD/ID.

The research involved studies on postmortem brain tissue from humans with ASD/ID, as well as studies on mice in which ADNP and POGZ were silenced through viral delivery of small interference RNA. These mice exhibited impaired cognitive task performance, such as spatial memory, object recognition memory and long-term memory.

Weakening a repressive function

“Under normal conditions, cells in the central nervous system should not express large quantities of genes that activate the immune system,” said Conrow-Graham. “ADNP and POGZ both work to repress these genes so that inflammatory pathways are not continuously activated, which could damage surrounding cells. When that repression is weakened, these immune and inflammatory genes are then able to be expressed in large quantities.”

The upregulated genes in the mouse prefrontal cortex caused by the deficiencies in ADNP or POGZ activated the pro-inflammatory response.

“This is consistent with what we see in upregulated genes in the prefrontal cortex of humans with ASD/ID,” said Conrow-Graham. The prefrontal cortex is the part of the brain responsible for executive function, such as cognition and emotional control.

The mutated genes also activate the glial cells in the brain called microglia, which serve as support cells for neurons and have an immune function in the brain; they comprise 10-15% of all brain cells.

Sensitive microglia

“Microglia are very sensitive to pathological changes in the central nervous system and are the main form of active immune defense to maintain brain health,” explained Yan. “Aberrant activation of microglia, which we demonstrate occurs as a result of deficiency in ADNP or POGZ, could lead to the damage and loss of synapses and neurons.”

The researchers are hopeful that future research will determine whether chronic neuroinflammation could be directly contributing to at least some cases of ASD/ID, in which targeting microglia or inflammatory signaling pathways could prove to be a useful treatment.

The researchers pointed out that the clinical presentation of both ASD and ID is incredibly varied. Significant variation also likely is present in the kinds of mechanisms responsible for the symptoms of ASD and/or ID.

“We found that changes in two risk genes lead to a convergent mechanism, likely involving immune activation,” said Conrow-Graham. “However, this probably isn’t the case for all individuals with ASD/ID. When designing clinical trials to evaluate treatment effectiveness, I think our research underscores the importance of considering the genetic factors involved in an individual’s ASD/ID.”

The research is the culmination of Conrow-Graham’s PhD work; she has now returned to complete the last two years of the MD degree in the Jacobs School. She described her experience pursuing both an MD and a PhD as extremely complementary.

The immune system has a role

“My training at each level was super helpful to supplement the other,” she said. “When I began my PhD, I had completed two years of MD training, so I was familiar with the basics of physiology, anatomy and pathology. Because of this, I was able to bring a broader perspective to my neuroscience research, identifying how the immune system might be playing a role. Prior to this, our lab had not really investigated immunology-related pathways, so having that background insight was really beneficial.”

She added that she learned so much from all of her colleagues in Yan’s lab, including faculty members, lab technicians and other students. “I learned so many technical skills that I had never used before joining the lab, thanks to the dedication of lab co-workers for my training,” she said.

Her experience at the lab bench working on the basic science underlying neuropsychiatric disorders will definitely influence her work as a clinician.

“I plan to pursue a career as a child and adolescent psychiatrist, so I may be able to work directly with this patient population,” she said. “We’re learning now that better care may be able to be provided by taking a personalized medicine approach, taking into account genetics, psychosocial factors and others. Being able to take a very deep dive into the field of psychiatric genetics was a privilege that I hope will help me to provide the best care for patients.”

The research was funded by the Nancy Lurie Marks Family Foundation and by a National Institutes of Health Ruth L. Kirschstein Individual Predoctoral NRSA for MD/PhD F30 fellowship for Conrow-Graham.

In addition to Conrow-Graham and Yan, co-authors are Jamal B. Williams, PhD, former graduate student; Jennifer Martin, PhD, former postdoctoral fellow; Ping Zhong, PhD, senior research scientist; Qing Cao, PhD, postdoctoral fellow; and Benjamin Rein, PhD, former graduate student.

All are current or former members of Yan’s lab.