While many parrot owners clip their birds’ wings to reduce their flight abilities, free-flight involves training an intact parrot to come when called, follow basic commands, recognize natural dangers, and otherwise safely fly in open areas.

In a recently published paper in Diversity 2021, Constance Woodman, a doctoral graduate student of the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVMBS), and Donald Brightsmith, a CVMBS associate professor, shared their findings from a project with Chris Biro, a globally recognized free-flight trainer, that included documenting Biro’s training process step by step so that conservationists can apply his methods when releasing birds into the wild.

Biro, one of the most experienced free-flight trainers, has trained more than 400 students from more than 30 countries on how to free-fly their birds, but his process had previously only been captured via video.

“We have colleagues up and down the Americas raising and releasing birds, but their main objective is conservation and they don’t have the chance to write up a lot of the science,” Brightsmith said. “A&M’s role in this project is to make sure that this information gets put into a place and a format so the rest of the world can read it, criticize it, use it, and improve it. If information hasn’t made it into scientific literature, it’s not improving the future of the science of macaw and parrot conservation, it’s just helping one or two populations.”

Woodman, supported by a National Science Foundation fellowship, and Biro spent several years training three different flocks of multiple parrot species using Biro’s techniques, thoroughly documenting every step of the process.

These 37 birds, which collectively spent 500 months in free-flight, were hand-raised from chicks to build a strong bond with the trainer before being gradually taught new commands and introduced to increasingly complex environments to learn the skills necessary to safely fly in open, uncontrolled areas.

“As scientists, one of the most important things we can do for conservation is offer ready-to-use solutions for practitioners on the ground who are trying to save animals and ecosystems,” said Woodman, who now serves as program manager for the CVMBS’ Conservation Innovation Grant program. “By learning from communities that already work with the target species, in this case parrot owners and trainers, we can take their knowledge and transform it into a conservation tool.”

The birds learned to recognize, evade, and even intimidate predators; forage for food and recognize safe vs. unsafe options; fly in flocks; navigate and mentally map the environment; and avoid unsafe situations, like dogs and cars.

During the entire training process, Biro’s methods were proven successful by the fact that neither trainer lost a single bird to predators or had a bird leave the training area.

Taking Flight

As the next step in this process, the team will work to adapt the training in support of parrot conservation.

Texas A&M and Biro’s nonprofit, Bird Recovery International, will be among the first to test free-flight as a conservation tool through collaborative projects in Brazil and Honduras.

Traditionally, attempting to release hand-reared parrots has resulted in birds that show little fear of humans, which increases their chances of being trapped by poachers or killed by people.

By using a “kernel flock” — human-socialized birds trained in free-flight — to teach survival behaviors to other parrots, conservationists should be able to release wild birds without having to train them themselves.

“The idea of using a kernel flock is a way to cut the difference when human socialization is not desirable in your wild birds,” Woodman said.

After the kernel flock trains the non-socialized birds, the kernel flock could be recalled and moved to another location, leaving behind a well-established colony of wild parrots.

“This is a really, really important project,” Biro said. “For example, the Spix’s macaw is extinct in the wild and there are only about 150 or so left in captivity. One of the problems of putting the Spix’s macaw back into Brazil is that there are limited options for introducing birds into environments where no flock exists. This project produces a flock where there isn’t one.”

Woodman said there are many groups of animal keepers, fanciers and breeders with specialty knowledge, “but they may not be plugged into conservation communities.”

“The work we’ve done — spending years working with a group to learn how they do what they do and then translating that into something useful for scientists and practitioners — is critically important to moving conservation forward,” Woodman said.

For parrot owners who are interested in learning free-flight, Woodman recommends finding a local free-flight community to learn more.

“Free-flight is highly technical and it almost requires an apprenticeship-type learning system to do well, just like with falconry,” Woodman said. “To free-fly a parrot safely, you’ve got to be involved in the free-flight community, because there’s always a risk of losing an animal and that risk goes up without proper training.”

However, studying how brain networks interact with each other is complicated. Brain networks can be explored by delivering brief pulses of electrical current in one area of a patient’s brain while measuring voltage responses in other areas. In principle, one should be able to infer the structure of brain networks from these data. However, with real-world data, the problem is difficult because the recorded signals are complex, and a limited amount of measurements can be made.

To make the problem manageable, Mayo Clinic researchers developed a set of paradigms, or viewpoints, that simplify comparisons between effects of electrical stimulation on the brain. Because a mathematical technique to characterize how assemblies of inputs converge in human brain regions did not exist in the scientific literature, the Mayo team collaborated with an international expert in artificial intelligence (AI) algorithms to develop a new type of algorithm called “basis profile curve identification.”

In a study published in PLOS Computational Biology, a patient with a brain tumor underwent placement of an electrocorticographic electrode array to locate seizures and map brain function before a tumor was removed. Every electrode interaction resulted in hundreds to thousands of time points to be studied using the new algorithm.

“Our findings show that this new type of algorithm may help us understand which brain regions directly interact with one another, which in turn may help guide placement of electrodes for stimulating devices to treat network brain diseases,” says Kai Miller, M.D., Ph.D., a Mayo Clinic neurosurgeon and first author of the study. “As new technology emerges, this type of algorithm may help us to better treat patients with epilepsy, movement disorders like Parkinson’s disease, and psychiatric illnesses like obsessive compulsive disorder and depression.”

“Neurologic data to date is perhaps the most challenging and exciting data to model for AI researchers,” says Klaus-Robert Mueller, Ph.D., study co-author and member of the Google Research Brain Team. Dr. Mueller is co-director of the Berlin Institute for the Foundations of Learning and Data and director of the Machine Learning Group — both at Technical University of Berlin.

In the study, the authors provide a downloadable code package so others may explore the technique. “Sharing the developed code is a core part of our efforts to help reproducibility of research,” says Dora Hermes, Ph.D., a Mayo Clinic biomedical engineer and senior author.

This research was supported by National Institutes of Health’s National Center for Advancing Translational Science Clinical and Translational Science Award, National Institute of Mental Health Collaborative Research in Computational Neuroscience, and the Federal Ministry of Education and Research.

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Materials provided by Mayo Clinic. Original written by Susan Barber Lindquist. Note: Content may be edited for style and length.

As it turns out, neuroscientists are very similar to travelers in this regard, constantly developing and practicing new ways to take perfect, crystal-clear images. But instead of picturesque natural backdrops or striking city scenes, neuroscientists are interested in detailed snapshots of brain cells and their small-scale structures.

The Yasuda Lab at MPFI is incredibly well versed in small-scale structures of the brain, focused on studying the dynamic changes to tiny synaptic compartments called dendritic spines. Robust changes in spine structure known as structural plasticity, allow synapses to robustly modulate their connection strength. By doing so, cells in the brain can actively strengthen important connections and weaken those that are less needed. This process is thought to underlie how we learn and remember. But revealing the fine structures of spines in detail during such a dynamic process is a difficult undertaking. Until recently, imaging methodologies lacked the capabilities to do so.

In a recent publication in The Journal of Neuroscience, researchers in the Yasuda Lab have developed a powerful new imaging strategy capable of visualizing the fine, ultrastructural changes to dendritic spines during structural plasticity. By modifying and building off an established imaging technique known as correlative light and electron microscopy (CLEM), MPFI scientists have harnessed the best that both imaging modalities can provide.

“Dendritic spines are such small-scale neuronal compartments, that it’s difficult to get an accurate picture of what’s actually occurring in terms of structural changes using traditional imaging methods,” explains Dr. Ryohei Yasuda, Scientific Director at MPFI. “Using more standard optical techniques like 2-photon microscopy, dendritic spines look like smooth spheres. In actuality, we know from using more powerful imaging methods, like electron microscopy, that the actual size and shape of spines are far more complex. So, we were interested in learning what changes occur during the various stages of structural plasticity, at a resolution where we could take a deeper look at the spine’s complexity.”

The MPFI team first induced structural plasticity in single dendritic spines using 2-photon optical microscopy and glutamate uncaging. The induced spine was then fixed in time at one of three distinct timepoints, representing the major stages of structural plasticity. In close collaboration with MPFI’s Electron Microscopy (EM) Core, brain tissue samples containing the stimulated spines were cut into ultra-thin sections using a specialized device called ATUMtome. These sections were then re-imaged using the extreme resolving power of the Electron Microscope to reveal the ultrastructural details and reconstruct accurate pictures of the spine’s complex topography.

“When we started this project, our goal was to see if it was even possible to collect spines at various stages of structural plasticity, successfully relocate them, and resolve their ultrastructure using EM,” describes Ye Sun, Ph.D., former Graduate Student in the Yasuda Lab and first author of the publication. “Single, spine-specific forms of structural plasticity have never been imaged in this way before. Dr. Naomi kamasawa, Head of MPFI’s EM Core, was instrumental in helping to establish and optimize our EM workflow for the project.”

Examining the reconstructed spine images, the MPFI team noticed unique changes to a protein-rich region of dendritic spines, called the postsynaptic density (PSD). This region is critically important for the spine, implicated in regulating synaptic strength and plasticity. MPFI researchers found that compared to control spines, the area and size of the PSD region was significantly greater in spines that underwent structural plasticity. PSD growth in these spines occurred on a slower timescale, needing hours to reach its maximal change. Interestingly while growth was on a slower scale, PSD structure in stimulated spines reorganized at a rapid pace. After the induction of structural plasticity, PSD complexity immediately increased, dramatically transforming in shape and structural features.

“Our imaging strategy synergizes the best of both optical and EM microscopies, allowing us to study spine structural changes never before seen in nanoscale resolution,” notes Dr. Yasuda. “For the future, our lab is interested in using this new protocol in combination with advanced molecular techniques, such as SLENDR, to study individual protein dynamics in tandem with finely detailed structural changes during spine structural plasticity.

Complex interplay: the gut-immune-brain axis

The early development of the gut, the brain and the immune system are closely interrelated. Researchers refer to this as the gut-immune-brain axis. Bacteria in the gut cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses to them. In addition, the gut is in contact with the brain via the vagus nerve as well as via the immune system. “We investigated the role this axis plays in the brain development of extreme preterm infants,” says the first author of the study, David Seki. “The microorganisms of the gut microbiome — which is a vital collection of hundreds of species of bacteria, fungi, viruses and other microbes — are in equilibrium in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to develop fully, shifts are quite likely to occur. These shifts may result in negative effects on the brain,” explains the microbiologist and immunologist.

Patterns in the microbiome provide clues to brain damage

“In fact, we have been able to identify certain patterns in the microbiome and immune response that are clearly linked to the progression and severity of brain injury,” adds David Berry, microbiologist and head of the research group at the Centre for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna as well as Operational Director of the Joint Microbiome Facility of the Medical University of Vienna and University of Vienna. “Crucially, such patterns often show up prior to changes in the brain. This suggests a critical time window during which brain damage of extremely premature infants may be prevented from worsening or even avoided.”

Comprehensive study of the development of extremely premature infants

Starting points for the development of appropriate therapies are provided by the biomarkers that the interdisciplinary team was able to identify. “Our data show that excessive growth of the bacterium Klebsiella and the associated elevated ??-T-cell levels can apparently exacerbate brain damage,” explains Lukas Wisgrill, Neonatologist from the Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics at the Department of Pediatric and Adolescent Medicine at the Medical University of Vienna. “We were able to track down these patterns because, for a very specific group of newborns, for the first time we explored in detail how the gut microbiome, the immune system and the brain develop and how they interact in this process,” he adds. The study monitored a total of 60 premature infants, born before 28 weeks gestation and weighing less than 1 kilogram, for several weeks or even months. Using state-of-the-art methods — the team examined the microbiome using 16S rRNA gene sequencing, among other methods — the researchers analysed blood and stool samples, brain wave recordings (e.g. aEEG) and MRI images of the infants’ brains.

Research continues with two studies

The study, which is an inter-university clusterproject under the joint leadership by Angelika Berger (Medical University of Vienna) and David Berry (University of Vienna), is the starting point for a research project that will investigate the microbiome and its significance for the neurological development of prematurely born children even more thoroughly. In addition, the researchers will continue to follow the children of the initial study. “How the children’s motoric and cognitive skills develop only becomes apparent over several years,” explains Angelika Berger. “We aim to understand how this very early development of the gut-immune-brain axis plays out in the long term. ” The most important cooperation partners for the project are already on board: “The children’s parents have supported us in the study with great interest and openness,” says David Seki. “Ultimately, this is the only reason we were able to gain these important insights. We are very grateful for that.”

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“If pregnant women were admitted for severe infection, even after they’re discharged and they recover from that infection, there was an increased risk of complications related to pregnancy that are associated with core placental dysfunction,” said Stephanie Gaw, MD, PhD, assistant professor of Obstetrics, Gynecology & Reproductive Sciences at UCSF, and senior author of the paper, which appears September 3, 2021, in JAMA Network Open.

Sepsis is a life-threatening condition caused by an unusually severe response to an infection, which leads to widespread inflammation in the body and, potentially, organ failure and death. Maternal sepsis is the second leading cause of maternal mortality in the United States, according to the Centers for Disease Control and Prevention (CDC).

The timing of infection also impacts outcomes for mother and baby. The cohort study found that patients with sepsis before delivery were twice as likely to have placental dysfunction compared to pregnant patients without sepsis.

During the study, the mean gestational age at the time of infection was 24.6 weeks. Early infection, at less than 24 weeks of gestation, was associated with the greatest risk of placental dysfunction, maternal hypertensive disorder, and newborns who were small for gestational age.

Downstream Consequences of COVID or Other Infections

Although the study used pre-pandemic data, Gaw says the findings are an important reflection of the potential long-term consequences of any acute infection.

“Even after you’ve recovered from COVID, or any other infection, there may be downstream consequences that we should pay attention to,” Gaw said, noting that women with septic infections during pregnancy should receive increased surveillance for the remainder of their pregnancy.

“Having a baby that was small for gestational age was more common if you had sepsis during pregnancy than if you didn’t, even after controlling for other risk factors,” she said. “One thing that could be changed in current prenatal care practice would be to add another ultrasound to monitor the baby’s growth. In the third trimester, that was not routinely done for all of these patients and isn’t routinely done in clinical practice right now.”

First to Assess Later Consequences of Infection

The UCSF study was the first of its kind to examine pregnancy outcomes among individuals who recover from their infections prior to delivery.

“All the prior studies only looked at sepsis and delivery during the same admission, so delivery right after sepsis,” explained Gaw. “But with the majority of sepsis cases that happen during pregnancy, the moms are treated with antibiotics or other medications and they get better. Nobody had looked at what happens to moms that are really sick at some point during their pregnancy, recover from that acute episode, and go home. Do they go on to have normal pregnancies? Do the babies do okay?”

To find out, Gaw and a team of researchers looked at 14,565 patients who delivered at UCSF over a six-year period from 2012 to 2018. There were 59 individuals in the sepsis group that recovered from illness and were discharged, and 14,506 individuals in the non-sepsis group. In the sepsis group, the most common infections were urinary tract infections (24 patients, 41%) and pulmonary infections (22 patients, 37%).

In a subgroup analyses of 26 patients, earlier gestational age at the time of infection (less than 24 weeks) was associated with higher odds of placental dysfunction (46% of patients), hypertensive disease of pregnancy (31% of patients), and newborns small for gestational age (23%).

Patients with sepsis were younger, with a mean delivery age of 30.6 years, compared to 33.1 years for the study overall, more likely to have pregestational diabetes, and had higher pregestational body mass index scores. After adjusting for possible confounders, including maternal age, number of previous childbirths, body mass index (BMI), and medical comorbidities, the study found patients with sepsis during pregnancy had 2-fold higher odds of perinatal complications.

Gaw, who also studies malaria in pregnant women around the globe, hopes the study will lead to more research about the mother’s response to infection in pregnancy and treatments to improve outcomes for mother and baby. “We need more data to identify potential interventions — whether a woman gets malaria, COVID, or another type of infection — to slow the inflammatory process, so that these long term, permanent changes to the placenta don’t happen,” she said.

Co-authors on the paper were Christine Blauvelt, MD; Kiana C. Nguyen; Arianna G. Cassidy, MD, from UCSF. Gaw was supported by grant NIAID K08AI141728 from the National Institutes of Health.

“Therapies that use the immune system to destroy cancer have been a game changer for patients with lung and other cancers,” said Nikhil Joshi, PhD, Assistant Professor of Immunobiology, a member of the Center of Immuno-Oncology at Yale Cancer Center, and senior author of the study. “But not all people respond to immunotherapy drugs, so it was important for us to discover the role of these special T cells in tumor growth.”

In this study, researchers first developed a new animal model where they could look at the stem-like T cells in tumors over the course of several months of tumor growth, and determine how the stem-like T cells survive. They discovered the stem-like T cells do not persist in the tumor for very long, which meant they are resupplied from somewhere else in the body. Nearby lymph nodes, an immune organ containing many of these stem-like T cells, were replenishing the supply. Every so often, a few stem-like T cells leave the lymph node and travel to the tumor. This keeps the tumor supplied with fresh cancer fighting T cells. Researchers believe this is important for slowing the growth of cancer. An analysis of immune cells isolated from patients with lung cancer confirmed that stem-like T cells are in lymph nodes near the lung.

“T cells in tumors become exhausted, but our study results show the stem-like T cells within the nearby lymph nodes do not experience exhaustion during the course of disease,” said Kelli A. Connolly, a post-doctoral fellow at Yale Cancer Center and lead author of the study. “This could be an important treatment advance as the potential to respond to immunotherapy is preserved.”

“We are focused on developing therapies that will activate the stem-like T cells in the nearby lymph node and bring them into the fight against cancer,” adds Joshi. “We plan to continue this work and focus on how to improve these therapeutic responses to help patients.”

Funding for the study was supported by the American Lung Association, the National Cancer Institute, the Lung Cancer Research Foundation, and the Yale SPORE in Lung Cancer.

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By streamlining a longstanding process in which CO₂ is converted to methane, the researchers’ new method reduces the materials needed to run the reaction, the energy needed to fuel it and, ultimately, the selling price of the gas.

A key chemical player known as EEMPA makes the process possible. EEMPA is a PNNL-developed solvent that snatches CO₂ from power plant flue gas, binding the greenhouse gas so it can be converted into useful chemicals.

Earlier this year, PNNL researchers revealed that using EEMPA in power plants could slash the price of carbon capture to 19 percent lower than standard industry costs — the lowest documented price of carbon capture. Now, in a study published Friday, August 21 in the journal ChemSusChem, the team reveals a new incentive — in cheaper natural gas — to further drive down costs.

When compared to the conventional method of methane conversion, the new process requires an initial investment that costs 32 percent less. Operation and maintenance costs are 35 percent cheaper, bringing the selling price of synthetic natural gas down by 12 percent.

Methane’s role in carbon capture

Different methods for converting CO₂ into methane have long been known. However, most processes rely on high temperatures and are often too expensive for widespread commercial use.

In addition to geologic production, methane can be produced from renewable or recycled CO₂ sources, and can be used as fuel itself or as an H₂ energy carrier. Though it is a greenhouse gas and requires careful supply chain management, methane has many applications, ranging from household use to industrial processes, said lead author and PNNL chemist Jotheeswari Kothandaraman.

“Right now a large fraction of the natural gas used in the U.S. has to be pumped out of the ground,” said Kothandaraman, “and demand is expected to increase over time, even under climate change mitigation pathways. The methane produced by this process — made using waste CO₂ and renewably sourced hydrogen — could offer an alternative for utilities and consumers looking for natural gas with a renewable component and a lower carbon footprint.”

Calculating costs and capturing carbon

To explore the use of EEMPA in converting CO₂ to methane, Kothandaraman and her fellow authors studied the reaction’s molecular underpinnings, then assessed the cost of running the process at scale in a 550-megawatt power plant.

Conventionally, plant operators can capture CO₂ by using special solvents that douse flue gas before it’s emitted from plant chimneys. But these traditional solvents have relatively high water content, making methane conversion difficult.

Using EEMPA instead reduces the energy needed to fuel such a reaction. The savings stem partly from EEMPA’s ability to make CO₂ dissolve more easily, which means less pressure is needed to run the conversion.

The authors’ assessment identified further cost savings, in that CO₂ captured by EEMPA can be converted to methane on site. Traditionally, CO₂ is stripped from water-rich solvents and sent off site to be converted or stored underground. Under the new method, captured CO₂ can be mixed with renewable hydrogen and a catalyst in a simple chamber, then heated to half the pressure used in conventional methods to make methane.

The reaction is efficient, the authors said, converting over 90 percent of captured CO₂ to methane, though the ultimate greenhouse gas footprint depends on what the methane is used to do. And EEMPA captures over 95 percent of CO₂ emitted in flue gas. The new process gives off excess heat, too, providing steam for power generation.

Making more from CO₂

The chemical process highlighted in the paper represents one path among many, said Kothandaraman, where captured CO₂ can be used as a feedstock to produce other valuable chemicals.

“I’ll be glad when I can make this process work for methanol as efficiently as it does for methane now,” she said. “That’s my long-term goal.” Methanol has many more applications than methane, said Kothandaraman, who has sought to uncover the catalytic reactions that could produce methanol from CO₂ for roughly a decade. Creating plastics from captured CO₂ is another route the team plans to explore.

“It’s important that we not only capture CO₂, but find valuable ways to use it,” said Ron Kent, Advanced Technologies Development Manager at SoCalGas, “and this study offers a cost-effective pathway toward making something valuable out of waste CO₂.”

This study, “Integrated Capture and Conversion of CO₂ Using a Water-lean, Post-Combustion CO₂ Capture Solvent,” was supported by SoCalGas and the Department of Energy’s Technology Commercialization Fund and Office of Science.

In addition to Kothandaraman, authors include PNNL scientists Johnny Saavedra Lopez, Yuan Jiang, Eric D. Walter, Sarah D. Burton, Robert A. Dagle and David J. Heldebrant, who holds a joint appointment at Washington State University.