“Previous publications from our lab have mainly focused on neuronal protection,” said Li-Huei Tsai, Picower Professor in The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences at MIT and senior author of the new study in Nature Communications. Tsai also lead’s MIT’s Aging Brain Initiative. “But this study shows that it’s not just the gray matter, but also the white matter that’s protected by this method.”

This year Cognito Therapeutics, the spin-off company that licensed MIT’s sensory stimulation technology, published phase II human trial results in the Journal of Alzheimer’s Disease indicating that 40Hz light and sound stimulation significantly slowed the loss of myelin in volunteers with Alzheimer’s. Also this year Tsai’s lab published a study showing that gamma sensory stimulation helped mice withstand neurological effects of chemotherapy medicines, including by preserving myelin. In the new study, members of Tsai’s lab led by former postdoc Daniela Rodrigues Amorim used a common mouse model of myelin loss — a diet with the chemical cuprizone — to explore how sensory stimulation preserves myelination.

Amorim and Tsai’s team found that 40Hz light and sound not only preserved myelination in the brains of cuprizone-exposed mice, it also appeared to protect oligodendrocytes (the cells that myelinate neural axons), sustain the electrical performance of neurons, and preserve a key marker of axon structural integrity. When the team looked into the molecular underpinnings of these benefits, they found clear signs of specific mechanisms including preservation of neural circuit connections called synapses; a reduction in a cause of oligodendrocyte death called “ferroptosis;” reduced inflammation; and an increase in the ability of microglia brain cells to clean up myelin damage so that new myelin could be restored.

“Gamma stimulation promotes a healthy environment,” said Amorim who is now a Marie Curie Fellow at the University of Galway in Ireland. “There are several ways we are seeing different effects.”

The findings suggest that gamma sensory stimulation may help not only Alzheimer’s disease patients but also people battling other diseases involving myelin loss, such as multiple sclerosis, the authors wrote in the study.

Maintaining myelin

To conduct the study, Tsai and Amorim’s team fed some male mice a diet with cuprizone and gave other male mice a normal diet for six weeks. Halfway into that period, when cuprizone is known to begin causing its most acute effects on myelination, they exposed some mice from each group to gamma sensory stimulation for the remaining three weeks. In this way they had four groups: completely unaffected mice, mice that received no cuprizone but did get gamma stimulation, mice that received cuprizone and constant (but not 40Hz) light and sound as a control, and mice that received cuprizone and also gamma stimulation.

After the six weeks elapsed, the scientists measured signs of myelination throughout the brains of the mice in each group. Mice that weren’t fed cuprizone maintained healthy levels, as expected. Mice that were fed cuprizone and didn’t receive 40Hz gamma sensory stimulation showed drastic levels of myelin loss. Cuprizone-fed mice that received 40Hz stimulation retained significantly more myelin, rivaling the health of mice never fed cuprizone by some, but not all, measures.

The researchers also looked at numbers of oligodendrocytes to see if they survived better with sensory stimulation. Several measures revealed that in mice fed cuprizone, oligodendrocytes in the corpus callosum region of the brain (a key point for the transit of neural signals because it connects the brain’s hemispheres) were markedly reduced. But in mice fed cuprizone and also treated with gamma stimulation, the number of cells were much closer to healthy levels.

Electrophysiological tests among neural axons in the corpus callosum showed that gamma sensory stimulation was associated with improved electrical performance in cuprizone-fed mice who received gamma stimulation compared to cuprizone-fed mice left untreated by 40Hz stimulation. And when researchers looked in the anterior cingulate cortex region of the brain, they saw that MAP2, a protein that signals the structural integrity of axons, was much better preserved in mice that received cuprizone and gamma stimulation compared to cuprizone-fed mice who did not.

Molecular mechanisms

A key goal of the study was to identify possible ways in which 40Hz sensory stimulation may protect myelin.

To find out, the researchers conducted a sweeping assessment of protein expression in each mouse group and identified which proteins were differentially expressed based on cuprizone diet and exposure to gamma frequency stimulation. The analysis revealed distinct sets of effects between the cuprizone mice exposed to control stimulation and cuprizone-plus-gamma mice.

A highlight of one set of effects was the increase in MAP2 in gamma-treated cuprizone-fed mice. A highlight of another set was that cuprizone mice who received control stimulation showed a substantial deficit in expression of proteins associated with synapses. The gamma-treated cuprizone-fed mice did not show any significant loss, mirroring results in a 2019 Alzheimer’s 40Hz study that showed synaptic preservation. This result is important, the researchers wrote, because neural circuit activity, which depends on maintaining synapses, is associated with preserving myelin. They confirmed the protein expression results by looking directly at brain tissues.

Another set of protein expression results hinted at another important mechanism: ferroptosis. This phenomenon, in which errant metabolism of iron leads to a lethal buildup of reactive oxygen species in cells, is a known problem for oligodendrocytes in the cuprizone mouse model. Among the signs was an increase in cuprizone-fed, control stimulation mice in expression of the protein HMGB1, which is a marker of ferroptosis-associated damage that triggers an inflammatory response. Gamma stimulation, however, reduced levels of HMGB1.

Looking more deeply at the cellular and molecular response to cuprizone demyelination and the effects of gamma stimulation, the team assessed gene expression using single-cell RNA sequencing technology. They found that astrocytes and microglia became very inflammatory in cuprizone-control mice but gamma stimulation calmed that response. Fewer cells became inflammatory and direct observations of tissue showed that microglia became more proficient at clearing away myelin debris, a key step in effecting repairs.

The team also learned more about how oligodendrocytes in cuprizone-fed mice exposed to 40Hz sensory stimulation managed to survive better. Expression of protective proteins such as HSP70 increased and as did expression of GPX4, a master regulator of processes that constrain ferroptosis.

In addition to Amorim and Tsai, the paper’s other authors are Lorenzo Bozzelli, TaeHyun Kim, Liwang Liu, Oliver Gibson, Cheng-Yi Yang, Mitch Murdock, Fabiola Galiana-Meléndez, Brooke Schatz, Alexis Davison, Md Rezaul Islam, Dong Shin Park, Ravikiran M. Raju, Fatema Abdurrob, Alissa J. Nelson, Jian Min Ren, Vicky Yang and Matthew P. Stokes.

Fundacion Bancaria la Caixa, The JPB Foundation, The Picower Institute for Learning and Memory, the Carol and Gene Ludwig Family Foundation, Lester A. Gimpelson, Eduardo Eurnekian, The Dolby Family, Kathy and Miguel Octavio, the Marc Haas Foundation, Ben Lenail and Laurie Yoler, and the National Institutes of Health provided funding for the study.

“I ignored it for years because I thought ‘I am a limnologist, methane is in lakes,'” she said.

But when a local reporter contacted Walter Anthony, who is a research professor at the Institute of Northern Engineering at University of Alaska Fairbanks, to inspect the waterbed-like ground at a nearby golf course, she started to pay attention. Like others in Fairbanks, they lit “turf bubbles” on fire and confirmed the presence of methane gas.

Then, when Walter Anthony looked at nearby sites, she was shocked that methane wasn’t just coming out of a grassland. “I went through the forest, the birch trees and the spruce trees, and there was methane gas coming out of the ground in large, strong streams,” she said.

“We just had to study that more,” Walter Anthony said.

With funding from the National Science Foundation, she and her colleagues launched a comprehensive survey of dryland ecosystems in Interior and Arctic Alaska to determine whether it was a one-off oddity or unforeseen concern.

Their study, published in the journal Nature Communications this July, reported that upland landscapes were releasing some of the highest methane emissions yet documented among northern terrestrial ecosystems. Even more, the methane consisted of carbon thousands of years older than what researchers had previously seen from upland environments.

“It’s a totally different paradigm from the way anyone thinks about methane,” Walter Anthony said.

Because methane is 25 to 34 times more potent than carbon dioxide, the discovery brings new concerns to the potential for permafrost thaw to accelerate global climate change.

The findings challenge current climate models, which predict that these environments will be an insignificant source of methane or even a sink as the Arctic warms.

Typically, methane emissions are associated with wetlands, where low oxygen levels in water-saturated soils favor microbes that produce the gas. Yet methane emissions at the study’s well-drained, drier sites were in some cases higher than those measured in wetlands.

This was especially true for winter emissions, which were five times higher at some sites than emissions from northern wetlands.

Digging into the source

“I needed to prove to myself and everyone else that this is not a golf course thing,” Walter Anthony said.

She and colleagues identified 25 additional sites across Alaska’s dry upland forests, grasslands and tundra and measured methane flux at over 1,200 locations year-round across three years. The sites encompassed areas with high silt and ice content in their soils and signs of permafrost thaw known as thermokarst mounds, where thawing ground ice causes some parts of the land to sink. This leaves behind an “egg carton” like pattern of conical hills and sunken trenches.

The researchers found all but three sites were emitting methane.

The research team, which included scientists at UAF’s Institute of Arctic Biology and the Geophysical Institute, combined flux measurements with an array of research techniques, including radiocarbon dating, geophysical measurements, microbial genetics and directly drilling into soils.

They found that unique formations known as taliks, where deep, expansive pockets of buried soil remain unfrozen year-round, were likely responsible for the elevated methane releases.

These warm winter havens allow soil microbes to stay active, decomposing and respiring carbon during a season that they normally wouldn’t be contributing to carbon emissions.

Walter Anthony said that upland taliks have been an emerging concern for scientists because of their potential to increase permafrost carbon emissions. “But everyone’s been thinking about the associated carbon dioxide release, not methane,” she said.

The research team emphasized that methane emissions are especially high for sites with Pleistocene-era Yedoma deposits. These soils contain large stocks of carbon that extend tens of meters below the ground surface. Walter Anthony suspects that their high silt content prevents oxygen from reaching deeply thawed soils in taliks, which in turn favors microbes that produce methane.

Walter Anthony said it’s these carbon-rich deposits that make their new discovery a global concern. Even though Yedoma soils only cover 3% of the permafrost region, they contain over 25% of the total carbon stored in northern permafrost soils.

The study also found through remote sensing and numerical modeling that thermokarst mounds are developing across the pan-Arctic Yedoma domain. Their taliks are projected to be formed extensively by the 22nd century with continued Arctic warming.

“Everywhere you have upland Yedoma that forms a talik, we can expect a strong source of methane, especially in the winter,” Walter Anthony said.

“It means the permafrost carbon feedback is going to be a lot bigger this century than anybody thought,” she said.

The study, published in the journal Physiology & Behavior, shows that cutting calories by 20% did not significantly reduce the distance that mice voluntarily chose to run each day.

The researchers set out to understand what happens to mice when the amount of food available to them is reduced. The findings, they hoped, would be relevant to wild animals that do not always get as much food as they want on a given day, and also to humans, whose doctors often prescribe dieting.

It is somewhat difficult to obtain accurate data on the amount of voluntary exercise that humans engage in. Though it is easy to categorize what people recognize as voluntary exercise, like a trip to the gym, there is much gray area that’s hard to quantify, such as walking to a cafeteria to purchase lunch instead of eating a meal from a nearby lunch box.

Tracking what lab mice choose to do is much easier, and lab mice generally like to run on wheels for many hours per day. In this study, researchers saw the mice chose to run at similar levels, regardless of how much they ate.

“Voluntary exercise was remarkably resistant to reducing the amount of food by 20% and even by 40%,” said UCR biologist and corresponding study author Theodore Garland, Jr. “They just kept running.”

The researchers spent three weeks getting a baseline level of running activity for the mice, then a week with calories reduced by 20%, and another week at minus 40%. This experiment was done both with regular mice as well as “high runner” mice bred to enjoy running.

Though the high runners reduced their total distance slightly with 40% calorie restriction, the distance was only an 11% reduction. As they started out running three times farther per day than normal mice, the reduction is considered slight. “They’re still running at extremely high levels,” Garland said. The regular mice did not reduce their daily distance, even at 40% calorie reduction.

Because running gives a “runners high,” in part by increasing dopamine and cannabinoid levels in the brain, the researchers believe the mice were motivated to keep going even with less food. “Wheel running is a self-rewarding behavior,” Garland said.

In addition, the researchers were surprised to find that body mass was not significantly affected by the 20% reduction in calories in either the regular or high-runner mice. Although there was some drop in body mass with a 40% reduction, it was not as high as predicted.

“People often lose about 4% of their body mass when they’re dieting. That’s in the same range as these mice,” Garland said.

This study contributes to our understanding of why some people like to exercise and others don’t. In the future, the researchers are planning additional studies to understand why both the amount of voluntary exercise and body mass are so resistant to calorie restriction.

“There has to be some type of compensation going on if your food goes down by 40% and your weight doesn’t go down very much,” Garland said. “Maybe that’s reducing other types of activities, or becoming metabolically more efficient, which we didn’t yet measure.”

As habitat destruction causes food shortages for wild animals, this type of information could be instrumental for people trying to preserve species. And for the many people interested in improving their health, the implications could be similarly significant.

“We don’t want people on diets to say, ‘I don’t have enough energy, so I’ll make up for it by not exercising.’ That would be counterproductive, and now we know, it doesn’t have to be this way,” Garland said.

Climate change is one of the most significant environmental challenges of present times, leading to extreme weather events, including droughts, forest fires, and floods. The primary driver for climate change is the release of greenhouse gases into the atmosphere due to human activities, which trap heat and raise Earth’s temperature. Aerosols (such as particulate matter, PM_2.5) not only affect public health but also influence the Earth’s climate by absorbing and scattering sunlight and altering cloud properties. Although future climate change predictions are being reported, it is possible that the impacts of climate change could be more severe than predicted. Therefore, it is necessary to detect climate change accurately and as early as possible.

Building on these insights, a research team from Japan, led by Professor Hitoshi Irie from the Center for Environmental Remote Sensing at Chiba University, utilized long-term observational data to study the effect of climate change on transboundary air pollution in the downwind area of China by using aerosols. They utilized a completely unique perspective on how aerosols impact climate and developed a new metric to detect climate change by considering aerosols as tracers.

“The significance of this study lies in the fact that most of its results are derived from observational data. In natural sciences focused on Earth studies, the ultimate goal is to piece together highly accurate data obtained from observations to quantitatively understand the processes occurring on Earth and to pursue immutable truths. Therefore, the more observational data we have, the better. With the continued Earth observations by Japan’s major Earth observation satellites (such as the GCOM series, GOSAT series, Himawari series, and ALOS series), we aim to complement these efforts with numerical simulations and data science methodologies to achieve a safe and secure global environment that mitigates the impacts of the climate crisis.” explains Prof. Irie.

The research team included Ms. Ying Cai from the Graduate School of Science and Engineering, Chiba University, Dr. Alessandro Damiani from the Center for Climate Change Adaptation, National Institute for Environmental Studies, Dr. Syuichi Itahashi and Professor Toshihiko Takemura from the Research Institute for Applied Mechanics, Kyushu University, and Dr. Pradeep Khatri from Faculty of Science and Engineering, Soka University. Their study was made available online on May 23, 2024, and published in Science of The Total Environment on August 20, 2024.

China is a major contributor to air pollution in East Asia. The downwind area of China analyzed in this study is a unique open ocean area with minimal human interference yet an important zone of transboundary air pollution pathways, making it an ideal location for studying meteorological variations due to climate change.

In their study, the researchers analyzed aerosol optical depth (AOD) datasets derived from satellites, reanalysis datasets, and numerical simulations focused on the Pacific Ocean in the downwind area of China, over 19 years from 2003 to 2021. AOD, a measure of the amount of sunlight blocked by aerosols, is a key factor is analyzing aerosols and their impact on climate change.

The researchers developed a new metric called R_AOD which utilized the potential of aerosols as tracers to evaluate the impact of climate change on transboundary air pollution pathways. Using R_AOD the researchers were able to quantify significant temporal variations in aerosol transport. They discovered that long-term changes in R_AOD due to climate change were outweighed by larger year-to-year variations in the meteorological field. Moreover, seasonal trends showed that aerosols moved west to east during spring and winter, and northward in summer. They concluded that the probability of aerosols from China to be transported far eastward was low, highlighting a shift in transboundary pollution pathways due to global warming. In this study the authors successfully detected climate change using long-term satellite observational data, in contrast to most existing studies that tracked transboundary air pollution using model simulations.

“These results suggest that R_AOD is a valuable metric for quantifying the long-term changes in transboundary air pollution pathways due to climate change. These results are particularly significant because most of them are derived from observational data,” says Prof. Irie, highlighting the importance of the study. Sharing the future implications of their study he concludes, “The effects of climate change could be more severe than currently predicted. This study will help verify climate change predictions from an unconventional perspective of ‘aerosol observation,’ enabling a more accurate understanding of climate change progression and implementation of rational countermeasures.”

In summary, this study demonstrates an innovative use of aerosols as climate change tracers, marking a significant step forward in the global effort to tackle the pressing issue of climate change.

A team of scientists created a new method to 3D print vascular networks that consist of interconnected blood vessels possessing a distinct “shell” of smooth muscle cells and endothelial cells surrounding a hollow “core” through which fluid can flow, embedded inside a human cardiac tissue. This vascular architecture closely mimics that of naturally occurring blood vessels and represents significant progress toward being able to manufacture implantable human organs. The achievement is published in Advanced Materials.

“In prior work, we developed a new 3D bioprinting method, known as “sacrificial writing in functional tissue” (SWIFT), for patterning hollow channels within a living cellular matrix. Here, building on this method, we introduce coaxial SWIFT (co-SWIFT) that recapitulates the multilayer architecture found in native blood vessels, making it easier to form an interconnected endothelium and more robust to withstand the internal pressure of blood flow,” said first author Paul Stankey, a graduate student at SEAS in the lab of co-senior author and Wyss Core Faculty member Jennifer Lewis, Sc.D.

The key innovation developed by the team was a unique core-shell nozzle with two independently controllable fluid channels for the “inks” that make up the printed vessels: a collagen-based shell ink and a gelatin-based core ink. The interior core chamber of the nozzle extends slightly beyond the shell chamber so that the nozzle can fully puncture a previously printed vessel to create interconnected branching networks for sufficient oxygenation of human tissues and organs via perfusion. The size of the vessels can be varied during printing by changing either the printing speed or the ink flow rates.

To confirm the new co-SWIFT method worked, the team first printed their multilayer vessels into a transparent granular hydrogel matrix. Next, they printed vessels into a recently created matrix called uPOROS composed of a porous collagen-based material that replicates the dense, fibrous structure of living muscle tissue. They were able to successfully print branching vascular networks in both of these cell-free matrices. After these biomimetic vessels were printed, the matrix was heated, which caused collagen in the matrix and shell ink to crosslink, and the sacrificial gelatin core ink to melt, enabling its easy removal and resulting in an open, perfusable vasculature.

Moving into even more biologically relevant materials, the team repeated the printing process using a shell ink that was infused with smooth muscle cells (SMCs), which comprise the outer layer of human blood vessels. After melting out the gelatin core ink, they then perfused endothelial cells (ECs), which form the inner layer of human blood vessels, into their vasculature. After seven days of perfusion, both the SMCs and the ECs were alive and functioning as vessel walls — there was a three-fold decrease in the permeability of the vessels compared to those without ECs.

Finally, they were ready to test their method inside living human tissue. They constructed hundreds of thousands of cardiac organ building blocks (OBBs) — tiny spheres of beating human heart cells, which are compressed into a dense cellular matrix. Next, using co-SWIFT, they printed a biomimetic vessel network into the cardiac tissue. Finally, they removed the sacrificial core ink and seeded the inner surface of their SMC-laden vessels with ECs via perfusion and evaluated their performance.

Not only did these printed biomimetic vessels display the characteristic double-layer structure of human blood vessels, but after five days of perfusion with a blood-mimicking fluid, the cardiac OBBs started to beat synchronously — indicative of healthy and functional heart tissue. The tissues also responded to common cardiac drugs — isoproterenol caused them to beat faster, and blebbistatin stopped them from beating. The team even 3D-printed a model of the branching vasculature of a real patient’s left coronary artery into OBBs, demonstrating its potential for personalized medicine.

“We were able to successfully 3D-print a model of the vasculature of the left coronary artery based on data from a real patient, which demonstrates the potential utility of co-SWIFT for creating patient-specific, vascularized human organs,” said Lewis, who is also the Hansjörg Wyss Professor of Biologically Inspired Engineering at SEAS.

In future work, Lewis’ team plans to generate self-assembled networks of capillaries and integrate them with their 3D-printed blood vessel networks to more fully replicate the structure of human blood vessels on the microscale and enhance the function of lab-grown tissues.

“To say that engineering functional living human tissues in the lab is difficult is an understatement. I’m proud of the determination and creativity this team showed in proving that they could indeed build better blood vessels within living, beating human cardiac tissues. I look forward to their continued success on their quest to one day implant lab-grown tissue into patients,” said Wyss Founding Director Donald Ingber, M.D., Ph.D. Ingber is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Children’s Hospital and Hansjörg Wyss Professor of Biologically Inspired Engineering at SEAS.

Additional authors of the paper include Katharina Kroll, Alexander Ainscough, Daniel Reynolds, Alexander Elamine, Ben Fichtenkort, and Sebastien Uzel. This work was supported by the Vannevar Bush Faculty Fellowship Program sponsored by the Basic Research Office of the Assistant Secretary of Defense for Research and Engineering through the Office of Naval Research Grant N00014-21-1-2958 and the National Science Foundation through CELL-MET ERC (#EEC-1647837).

Chronic wounds are open wounds that heal slowly, if they heal at all. For example, sores that occur in some patients with diabetes are chronic wounds. These wounds are particularly problematic because they often recur after treatment and significantly increase the risk of amputation and death.

One of the challenges associated with chronic wounds is that existing treatment options are extremely expensive, which can create additional problems for patients.

“Our goal here was to develop a far less expensive technology that accelerates healing in patients with chronic wounds,” says Amay Bandodkar, co-corresponding author of the work and an assistant professor of electrical and computer engineering at North Carolina State University. “We also wanted to make sure that the technology is easy enough for people to use at home, rather than something that patients can only receive in clinical settings.”

“This project is part of a bigger DARPA project to accelerate wound healing with personalized wound dressings,” says Sam Sia, co-corresponding author of the work and professor of biomedical engineering at Columbia University. “This collaborative project shows that these lightweight bandages, which can provide electrical stimulation simply by adding water, healed wounds faster than the control, at a similar rate as bulkier and more expensive wound treatment.”

Specifically, the research team developed water-powered, electronics-free dressings (WPEDs), which are disposable wound dressings that have electrodes on one side and a small, biocompatible battery on the other. The dressing is applied to a patient so that the electrodes come into contact with the wound. A drop of water is then applied to the battery, activating it. Once activated, the bandage produces an electric field for several hours.

“That electric field is critical, because it’s well established that electric fields accelerate healing in chronic wounds,” says Rajaram Kaveti, co-first author of the study and a post-doctoral researcher at NC State.

The electrodes are designed in a way that allows them to bend with the bandage and conform to the surface of the chronic wounds, which are often deep and irregularly shaped.

“This ability to conform is critical, because we want the electric field to be directed from the periphery of the wound toward the wound’s center,” says Kaveti. “In order to focus the electric field effectively, you want electrodes to be in contact with the patient at both the periphery and center of the wound itself. And since these wounds can be asymmetrical and deep, you need to have electrodes that can conform to a wide variety of surface features.”

“We tested the wound dressings in diabetic mice, which are a commonly used model for human wound healing,” says Maggie Jakus, co-first author of the study and a graduate student at Columbia. “We found that the electrical stimulation from the device sped up the rate of wound closure, promoted new blood vessel formation, and reduced inflammation, all of which point to overall improved wound healing.”

Specifically, the researchers found that mice who received treatment with WPEDs healed about 30% faster than mice who received conventional bandages.

“But it is equally important that these bandages can be produced at relatively low cost — we’re talking about a couple of dollars per dressing in overhead costs.” says Bandodkar.

“Diabetic foot ulceration is a serious problem that can lead to lower extremity amputations,” says Aristidis Veves, a co-author of the study and professor of surgery at Beth Israel Deaconess Center. “There is urgent need for new therapeutic approaches, as the last one that was approved by the Food and Drug Administration was developed more than 25 years ago. My team is very lucky to participate in this project that investigates innovative and efficient new techniques that have the potential to revolutionize the management of diabetic foot ulcers.”

In addition, the WPEDs can be applied quickly and easily. And once applied, patients can move around and take part in daily activities. This functionality means that patients can receive treatment at home and are more likely to comply with treatment. In other words, patients are less likely to skip treatment sessions or take shortcuts, since they aren’t required to come to a clinic or remain immobile for hours.

“Next steps for us include additional work to fine-tune our ability to reduce fluctuations in the electric field and extend the duration of the field. We are also moving forward with additional testing that will get us closer to clinical trials and — ultimately — practical use that can help people,” says Bandodkar.

The paper, “Water-powered, electronics-free dressings that electrically stimulate wounds for rapid wound closure,” will be published Aug. 7 in the open-access journal Science Advances. The paper’s co-authors include Henry Chen, an undergraduate in the joint biomedical engineering department at NC State and UNC; Bhavya Jain, Navya Mishra, Nivesh Sharma and Baha Erim Uzuno?lu, Ph.D. students at NC State; Darragh Kennedy and Elizabeth Caso of Columbia; Georgios Theocharidis and Brandon Sumpio of Beth Israel Deaconess Medical Center; Won Bae Han of Korea University and the Georgia Institute of Technology; Tae-Min Jang of Korea University; and Suk-Won Hwang of Korea University and the Korea Institute of Science and Technology.

This work was done with support from the Defense Advanced Research Projects Agency under grant D20AC00004 and from the Center for Advanced Self-Powered Systems of Integrated Sensors and Technologies at NC State, which is funded by National Science Foundation grant 1160483. Bandodkar and Kaveti are inventors on a patent application related to this work.

As with humans, nematodes’ guts are a common target of disease-causing bacteria. The nematode reacts by destroying iron-containing organelles called mitochondria, which produce a cell’s energy, to protect this critical element from iron-stealing bacteria. Iron is a key catalyst in many enzymatic reactions in cells — in particular, the generation of the body’s energy currency, ATP (adenosine triphophate).

The presence in C. elegans of this protective response to odors produced by microbes suggests that the intestinal cells of other organisms, including mammals, may also retain the ability to respond protectively to the smell of pathogens, said the study’s senior author, Andrew Dillin, UC Berkeley professor of molecular and cell biology and a Howard Hughes Medical Institute (HHMI) investigator.

“Is there actually a smell coming off of pathogens that we can pick up on and help us fight off an infection?” he said. “We’ve been trying to show this in mice. If we can actually figure out that humans smell a pathogen and subsequently protect themselves, you can envision down the road something like a pathogen-protecting perfume.”

So far, however, there’s only evidence of this response in C. elegans. Nevertheless, the new finding is a surprise, considering that the nematode is one of the most thoroughly studied organisms in the laboratory. Biologists have counted and tracked every cell in the organism from embryo to death.

“The novelty is that C. elegans is getting ready for a pathogen before it even meets the pathogen,” said Julian Dishart, who recently received his UC Berkeley Ph.D. and is the first author of the study. “There’s also evidence that there’s probably a lot more going on in addition to this mitochondrial response, that there might be more of a generalized immune response just by smelling bacterial odors. Because olfaction is conserved in animals, in terms of regulating physiology and metabolism, I think it’s totally possible that smell is doing something similar in mammals as it’s doing in C. elegans.”

The work was published June 21 in the journal Science Advances.

Mitochondria communicate with one another

Dillin is a pioneer in studying how stress in the nervous system triggers protective responses in cells — in particular, the activation of a suite of genes that stabilize proteins made in the endoplasmic reticulum. This activation, the so-called unfolded protein response (UPR), is “like a first aid kit for the mitochondria,” he said.

Mitochondria are not only the powerhouses of the cell, burning nutrients for energy, but also play a key role in signaling, cell death and growth.

Dillin has shown that errors in the UPR network can lead to disease and aging, and that mitochondrial stress in one cell is communicated to the mitochondria of cells throughout the body.

One key piece of the puzzle was missing, however. If the nervous system can communicate stress through a network of neurons to the cells doing the day-to-day work of protein building and metabolism, what in the environment triggers the nervous system?

“Our nervous system evolved to pick up on cues from the environment and create homeostasis for the entire organism,” Dillin said. “Julian actually figured out that smell neurons are picking up environmental cues and which types of odorants from the pathogens turn on this response.”

Previous work in Dillin’s lab showed the importance of smell in mammalian metabolism. When mice are deprived of smell, he found, they gained less weight while eating the same amount of food as normal mice. Dillin and Dishart suspect that the smell of food may trigger a protective response, like the response to pathogens, in order to prepare the gut for the damaging effects of ingesting foreign substances and converting that food to fuel.

“Surviving infections was the most important thing we did evolutionarily,” Dillin said. “And the most risky and taxing thing we do every single day is eat, because pathogens are going to be in our food.”

“When you eat food, it’s also incredibly stressful, because the body is metabolizing the food but also generating ATP in the mitochondria from the nutrients that they’re incorporating. And that generation of ATP causes a by-product called reactive oxygen species, which is very damaging to cells,” Dishart said. “Cells have to deal with this increased existence of reactive oxygen species. So perhaps smelling food can prepare us to deal with that enhanced reactive oxygen species load.”

Dillin speculates further that mitochondria’s sensitivity to the smell of pathogenic bacteria may be a holdover from an era when mitochondria were free-living bacteria, before they were incorporated into other cells as power plants to become eukaryotes some 2 billion years ago. Eukaryotes eventually evolved into multicellular organisms with differentiated organs — so-called metazoans, like animals and humans.

“There’s a lot of evidence that bacteria sense their environment in some way, though it’s not always clear how they do it. These mitochondria have retained one aspect of that after being subsumed into metazoans,” he said.

In his experiments with C. elegans, Dishart found that the smell of pathogens triggers an inhibitory response, which unleashes a signal to the rest of the body. This became clear when he ablated olfactory neurons in the worm and found that all peripheral cells, but primarily intestinal cells, showed the stress response typical of mitochondria that are being threatened. This study and others also showed that serotonin is a key neurotransmitter communicating this information throughout the body.

Dillin and his lab colleagues are tracking the neural circuits that lead from smell neurons to peripheral cells and the neurotransmitters involved along the way. And he’s looking for a similar response in mice.

“I always hate it when I get sick. I’m like, ‘Body, why didn’t you prepare for this better?’ It seems really stupid that you turn on response mechanisms only once you’re infected,” Dillin said. “If there are earlier detection mechanisms to increase our chances of survival, I think that’s a huge evolutionary win. And if we could harness that biomedically, that would be pretty wild.”

Other UC Berkeley authors of the paper are Corinne Pender, Koning Shen, Hanlin Zhang, Megan Ly and Madison Webb. The work is supported by HHMI and the National Institutes of Health (R01ES021667, F32AG065381, K99AG071935).

Now, a new study from Simon Fraser University has given scientists the clearest picture yet when the giant mammals roamed Vancouver Island.

As part of SFU researcher Laura Termes’ PhD and published earlier this month in the Canadian Journal of Earth Sciences, the study examined 32 suspected mammoth samples collected on Vancouver Island. Of those samples, just 16 were deemed suitable for radiocarbon dating.

The youngest sample was found to be around 23,000 years old and the oldest turned out to be beyond the range radiocarbon dating could measure, meaning it was older than 45,000 years.

Prior to the study, only two mammoth remains found on Vancouver Island had ever been dated before. Both lived around 21,000 years ago, so the Termes’ study provides a greater understanding of when the massive mammals lived in the area.

“This is really exciting because it shows that mammoths have lived on Vancouver Island for a long time,” says Termes, a PhD candidate in the Department of Archaeology. “We were expecting similar results [to the two samples previously dated] but what we found were mammoths that were much older. It is fantastic that they could be preserved for that long.”

Termes says having the curatorial support at the Royal BC Museum and the Courtenay and District Museum and Palaeontology Centre allowing access to their collections was invaluable to the study.

“This research highlights the important role of museum collections for understanding how life has evolved and changed in British Columbia’s deep history,” says Victoria Arbour, curator of palentology at the Royal BC Museum. “It’s great to see Woolly’s relatives in the Royal BC Museum’s collections in the spotlight through this research study.”

The UBC ADaPT Facility (which was instrumental in helping determine if samples were indeed mammoths and not whales or other animals) also played an important role in the research, Termes says.

And archaeologists need all the help they can get because while mammoths were enormous, finding intact samples in British Columbia is actually quite rare.

“When we imagine great big giant animals of the last ice age being found, we might have imagined fully articulated and complete skeletons being systematically excavated. But in southern B.C., that simply does not happen,” says Termes. “Instead, we may get an isolated molar that’s been tumbled around in the water for a long time, or maybe a piece of a tusk. And these are what everyday people are encountering.”

For example, one sample she examined was a piece of mammoth tooth found by a child in the gravel at a local playground.

“So maybe it’s a dog owner, taking their puppy for a walk on a rainy day, or a gravel pit operator at work,” says Termes, who grew up in Qualicum Beach. “I really like how these magnificent animals are finding their way into people’s lives in routine and everyday ways.”

Termes says the study is part of a larger look at megafauna in B.C. and she plans on radiocarbon dating mammoth samples from other parts of the province.

In a groundbreaking study published Aug. 7 in Science Advances, researchers from the University of Chicago, Northwestern University, and the University of Central Florida have proposed a revolutionary approach towards terraforming Mars. This new method, using engineered dust particles released to the atmosphere, could potentially warm the Red Planet by more than 50 degrees Fahrenheit, to temperatures suitable for microbial life — a crucial first step towards making Mars habitable.

The proposed method is over 5,000 times more efficient than previous schemes to globally warm Mars, representing a significant leap forward in our ability to modify the Martian environment.

What sets this approach apart is its use of resources readily available on Mars, making it far more feasible than earlier proposals that relied on importing materials from Earth or mining rare Martian resources.

This strategy would take decades. But it appears logistically easier than other plans proposed so far.

“This suggests that the barrier to warming Mars to allow liquid water is not as high as previously thought,” said Edwin Kite, an associate professor of geophysical sciences at the University of Chicago and corresponding author on the study. The lead author was Samaneh Ansari, a graduate student in Prof. Hooman Mohseni’s group at Northwestern University.

Astronauts still won’t be able to breathe Mars’ thin air; making the planet suitable for humans to walk on the surface unaided requires much more work. But perhaps groundwork could be laid, by making the planet habitable for microbes and food crops that could gradually add oxygen to the atmosphere — much as they have done for Earth during its geologic history.

A new approach to an age-old dream

There is a rich history of proposals to make Mars habitable; Carl Sagan himself came up with one back in 1971. These have ranged from outright daydreams, such as science fiction writers depicting turning one of Mars’ moons into a sun, to more recent and scientifically plausible ideas, such as engineering transparent gel tiles to trap heat.

Any plan to make Mars habitable must address several hurdles, including deadly UV rays and salty soil. But the biggest is the planet’s temperature; the surface of Mars averages about -80 degrees Fahrenheit.

One strategy to warm the planet could be the same method that humans are unintentionally using here on Earth: releasing material into the atmosphere, which would enhance Mars’ natural greenhouse effect, trapping solar heat at the surface.

The trouble is that you would need tons of these materials — literally. Previous schemes depended on bringing gases from Earth to Mars, or attempting to mine Mars for a large mass of ingredients that aren’t very common there — both are costly and difficult propositions. But the team wondered whether it could be done by processing materials that already exist abundantly on Mars.

We know from rovers like Curiosity that dust on Mars is rich in iron and aluminum. By themselves, those dust particles aren’t suitable to warm the planet; their size and composition mean they tend to cool the surface slightly rather than warm it. But if we engineered dust particles that had different shapes or compositions, the researchers hypothesized, perhaps they could trap heat more efficiently.

The researchers designed particles shaped like short rods — similar in size to commercially available glitter. These particles are designed to trap escaping heat and scatter sunlight towards the surface, enhancing Mars’ natural greenhouse effect.

“How light interacts with sub-wavelength objects is fascinating. Importantly, engineering

nanoparticles can lead to optical effects that far exceed what is conventionally expected from

such small particles,” said Ansari. Mohseni, who is a co-author, believes that they have just scratched the surface: “We believe it is possible to design nanoparticles with higher efficiency, and even those that can dynamically change their optical properties.”

“You’d still need millions of tons to warm the planet, but that’s five thousand times less than you would need with previous proposals to globally warm Mars,” said Kite. “This significantly increases the feasibility of the project.”

Calculations indicate that if the particles were released into Mars’ atmosphere continuously at 30 liters per second, the planet would warm by more than 50 degrees Fahrenheit — and the effect could be noticeable within as soon as months. Similarly, the warming would be reversible, stopping within a few years if release was switched off.

Potential impact and future research

Much work remains to be done, the scientists said. We don’t know exactly how fast the engineered dust would cycle out of Mars’ atmosphere, for example. Mars does have water and clouds, and, as the planet warms, it’s possible that water would increasingly start to condense around the particles and fall back to the surface as rain.

“Climate feedbacks are really difficult to model accurately,” Kite cautioned. “To implement something like this, we would need more data from both Mars and Earth, and we’d need to proceed slowly and reversibly to ensure the effects work as intended.”

While this method represents a significant leap forward in terraforming research, the researchers emphasize that the study focuses on warming Mars to temperatures suitable for microbial life and possibly growing food crops — not on creating a breathable atmosphere for humans.

“This research opens new avenues for exploration and potentially brings us one step closer to the long-held dream of establishing a sustainable human presence on Mars,” said Kite.

Ansari is the lead author of the study. Other coauthors of the study were Ramses Ramirez of the University of Central Florida and Liam Steele, formerly a postdoctoral researcher at UChicago, now with the European Center for Medium-Range Weather Forecasts.

The authors used the Quest high-performance computing facility at Northwestern and the University of Chicago Research Computing Center.