University of California, Berkeley, scientists have now found brain cells that help clean up these tangles and prolong life — at least in worms (Caenorhabditis elegans) and possibly mice. This could lead to drugs that improve muscle health or extend a healthy human lifespan.

The research team’s most recent discovery, published Jan. 24 in the journal Science, is that a mere four glial cells in the worm’s brain control the stress response in cells throughout its body and increase the worm’s lifespan by 75%. That was a surprise, since glial cells are often dismissed as mere support cells for the neurons that do the brain’s real work, like learning and memory.

This finding follows a 2013 study in which the UC Berkeley group reported that neurons help regulate the stress response in peripheral cells, though in a different way than glial cells, and lengthen a worm’s life by about 25%. In mice, boosting neuronal regulation increases lifespan by about 10%.

Together, these results paint a picture of the brain’s two-pronged approach to keeping the body’s cells healthy. When the brain senses a stressful environment — invading bacteria or viruses, for example — a subset of neurons sends electrical signals to peripheral cells to get them mobilized to respond to the stress, such as through breaking up tangles, boosting protein production and mobilizing stored fat. But because electrical signals produce only a short-lived response, the glial cells kick in to send out a long-lasting hormone, so far unidentified, that maintains a long-term, anti-stress response.

“We have been discovering that if we turn on these responses in the brain, they communicate to the periphery to protect the whole organism from the age onset decline that naturally happens. It rewires their metabolism, it also protects against protein aggregation,” said Andrew Dillin, UC Berkeley professor of molecular and cell biology and Howard Hughes Medical Institute (HHMI) investigator. As a result of the new study, “We think that glia are going to be more important than neurons.”

While the roundworm C. elegans is a long way evolutionarily from humans, the fact that glial cells seem to have a similar effect in mice suggests that the same may be true of humans. If so, it may lead to drugs that combat muscle wasting and obesity and perhaps increase a healthy lifespan.

“If you look at humans with sarcopenia or at older mice and humans, they have protein aggregates in their muscle,” Dillin said. “If we can find this hormone, perhaps it can keep muscle mass higher in older people. There is a huge opportunity here.”

In a commentary in the same Jan. 24 issue of Science, two Stanford University scientists, Jason Wayne Miklas and Anne Brunet, echoed that potential. “Understanding how glial cells respond to stress and what neuropeptides they secrete may help identify specific therapeutic interventions to maintain or rebalance these pathways during aging and age-related diseases,” they wrote.

How to extend lifespan

Dillin studies the seemingly simultaneous deterioration of cells throughout the body as it ages into death. He has shown in worms and mice that hormones and neurotransmitters released by the brain keep this breakdown in check by activating a stress response in the body’s cells and tuning up their metabolism. The response likely originated to fight infection, with the side effect of keeping tissues healthy and extending lifespan. Why our cells stop responding to these signals as we age is the big question.

Over the past decade, he and his colleagues have identified three techniques used by worms to keep their cells healthy and, consequently, longer-lived. Activating the body’s heat shock response, for example, protects the cytoplasm of the cell. Stimulating the unfolded protein response protects the cells’ energy producing structures, the mitochondria. The unfolded protein response is the cell’s way of making sure proteins assume their proper 3D structure, which is crucial for proper functioning inside the cell.

His latest discovery is that glia, as well as neurons, stimulate the unfolded protein response in the endoplasmic reticulum (ER). The ER is the cellular structure that hosts the ribosomes that make proteins — the ER is estimated to be responsible for the folding and maturation of as many as 13 million proteins per minute.

“A lot of the work we have done has uncovered that certain parts of the brain control the aging of the rest of the animal, in organisms from worms to mice and probably humans,” Dillin said.

Two other interventions also increase lifespan in worms: diet restriction, which may call into play other anti-aging mechanisms, and reducing the production of a hormone called insulin-like growth factor (IGF-1).

Dillin’s discoveries have already led to new treatments for diseases. He cofounded a company, Mitobridge Inc. (recently acquired by Astellas Pharma Inc.), based on the finding that certain proteins help tune up mitochondria. A drug the company developed is now in phase II clinical trials for treating the damage that occurs when kidneys restart after sudden failure, such as during an operation.

He cofounded another company, Proteostatis Therapeutics, to develop a treatment for cystic fibrosis that is based on activating the unfolded protein response to repair ion channels in people with the disease.

The new discovery about how neurotransmitter and hormones impact the ER could have implications for diseases that involve muscle wasting, such as Huntington’s disease and forms of myocytis.

Glial cells

In 2013, Dillin and his colleagues discovered that boosting expression of a protein called xbp-1s in sensory nerve cells in the worm brain boosts the misfolded protein response throughout the worm’s body. Shortly afterward, postdoctoral fellow Ashley Frakes decided to see if the glial cells enshrouding these neurons were also involved. When she overexpressed the same protein, xbp-1s, in a subset of these glia (cephalic astrocyte-like sheath glia, or CEPsh), she discovered an even larger effect on peripheral cells, as measured by how they deal with a high-fat diet.

Frakes was able to pinpoint the four CEPsh glia responsible for triggering the ER response, because the C. elegans body is so well studied. There are only 959 cells in the entire worm, 302 of which are nerve cells, and 56 are glial cells.

The CEP neurons and CEPsh glia work differently, but additively, to improve metabolism and clean up protein aggregates as the worms slim down and live twice as long as worms without this protection from a high-fat diet.

“The fact that just a few cells control the entire organism’s future is mind-boggling,” Dillin said. “Glia work 10 times better than neurons in promoting this response and about twice as good in extending lifespan.”

Frakes is currently trying to identify the signaling hormone produced by these glial cells, a first step toward finding a way to activate the response in cells that are declining in function and perhaps to create a drug to tune up human cells and stave off the effects of aging, obesity or other types of stress.

Frakes also found that the worms slimmed down because their fat stores, in the form of lipid droplets, were turned into ER. Another research group in Texas has shown that activating xbp-1s in the neurons of mice also has the effect of reducing fat stores and slimming the mice, protecting them from the effects of a high-fat diet and extending their lifespan.

“When they activate it in the neurons, they see the liver getting rid of fat, redistributing metabolic demands,” Dillin said. “I think we would see the same thing in humans, as well.”

But, in recent years, that growth has slowed and the hopes for China’s wind-powered future have dampened.

Why? Location, location, location.

Populous coastal provinces, including Guangdong and Jiangsu, consume about 80 percent of the nation’s total electricity but the vast majority of China’s wind capacity comes from land-based wind farms in places like Inner Mongolia, more than a thousand miles away from most major cities.

To make matters worse, recent climate studies have suggested that the weakening land-sea temperature gradient due to global climate change is making historically windy regions, like Inner Mongolia, less windy.

In addition, much of the wind power from those regions isn’t being used because of when it’s produced. Research has suggested that some 16 percent of total potential wind generation was wasted between 2010 and 2016, costing more $1.2 billion.

If China is to meet and exceed its Paris goal by 2030, it’s going to need to find a way to increase its wind capacity.

In a recent study, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and Huazhong University of Science and Technology in China, found that offshore wind could be a big part of the solution.

The research is published in Science Advances.

“This is an important new contribution, recognition that China has abundant off-shore wind potential that can be developed and brought on shore to the power hungry coastal provinces at costs competitive with existing coal-fired polluting power plants,” said Michael McElroy, the Gilbert Butler Professor of Environmental Studies at SEAS and senior author of the paper.

To calculate the capacity and cost of offshore wind in China, the researchers first identified the regions where offshore wind farms could be built, excluding shipping zones, environmentally protected areas and water depths higher than 60 meters. They calculated the wind speeds in those areas and estimated the hourly capacity for each of the turbines.

They found that the total potential wind power from wind farms built along the Chinese coast is 5.4 times larger than the current coastal demand for power.

The researchers also found that this power would be cost-efficient.

“We estimate offshore wind costs according to a range of values derived from recent offshore wind farm developments,” said Peter Sherman, a graduate student at the department of Earth and Planetary Science and first author of the paper. “Offshore wind turbines have historically been prohibitively expensive, but it is clear now that, because of significant technological advances, the economics have changed such that offshore wind could be cost-competitive now with coal and nuclear power in China.”

The researchers estimated that if electricity prices are high, offshore wind could provide more than 1,000 terawatt-hours, or about 36 percent of all coastal energy demand. If electricity prices are low, it could provide more than 6,000 terawatt-hours, or 200 percent of total energy demand.

“Our research demonstrates the potential for cost-effective, offshore wind to power coastal regions, reduce greenhouse gas emissions and improve air quality in China,” said McElroy.

But, under the effects of climate change, this signature crop may not fare so well. As the world tries to feed a population skyrocketing to nine billion by 2050, that has major implications. So, what can we do about it? The answer might be exotic.

A multi-institutional team led by University of Delaware plant geneticist Randy Wisser decoded the genetic map for how maize from tropical environments can be adapted to the temperate U.S. summer growing season. Wisser sees these exotic varieties, which are rarely used in breeding, as key to creating next-era varieties of corn.

The research team included scientists from UD, North Carolina State University, University of Wisconsin, University of Missouri, Iowa State University, Texas A&M University and the U.S. Department of Agriculture-Agricultural Research Service. The resulting study, highlighted by the editorial board of Genetics, provides a new lens into the future viability of one of the world’s most important grains.

“If we can expand the genetic base by using exotic varieties, perhaps we can counter stresses such as emerging diseases and drought associated with growing corn in a changing climate,” said Wisser, associate professor in UD’s Department of Plant and Soil Sciences. “That is critical to ensuring ample production for the billions of people who depend on it for food and other products.”

Modern maize strains were created from only a small fraction of the global maize population. This limited infusion of diversity raises concerns about the vulnerability of American corn in a shifting climate. The U.S. Department of Agriculture (USDA) seed bank includes tens of thousands of varieties, but many are just not being used.

“We know that the tropical maize varieties represent our greatest reservoir of genetic diversity,” said study co-author Jim Holland, a plant geneticist with the USDA Agricultural Research Service at North Carolina State. “This study improved our understanding of those genetics, so we can use this information to guide future breeding efforts to safeguard the corn crop.”

Certain exotic strains of maize better handle drought or waterlogging or low-nitrogen soil, for example. But because these strains have evolved outside the U.S., they are not immediately suited to states like Delaware. So, exotics first need to be pre-adapted.

In prior work, Wisser and his colleagues showed how 10 years of repeated genetic selection was required to adapt a tropical strain of maize to the temperate U.S. Co-author Arnel Hallauer spent a decade adapting the population through selective breeding, so it could flourish in an environment like Delaware.

“What’s so cool now is that we could go back to the original generations from Dr. Hallauer and grow them side by side in the same field,” Wisser said of the first-of-its-kind experimental design. “This allows us to rule out the influence of the environment on each trait, directly exposing the genetic component of evolution. This has opened a ‘back to the future’ channel where we can redesign our approach to developing modern varieties.”

While extremely impressive, a decade to adapt exotic maize to new environments is a lot of time when the climate change clock is ticking.

“Unfortunately, this process takes 10 years, which is not counting ongoing evaluations and integrating the exotic variations into more commonly used types of maize,” Wisser said. “With the climate threats we face, that’s a long time. So, gaining insights into this evolutionary process will help us devise ways to shorten the time span.”

Accelerating adaptation

Wisser isn’t wasting any time as he explores ways to bolster corn’s ability to survive and thrive. He and Holland are working on a new project to cut that time span in half.

In cutting-edge research funded by the U.S. Department of Agriculture’s National Institute of Food and Agriculture, the team is analyzing how corn genomes behave in a target environment as they aim to formulate a predictive model for fitness.

“What we’re doing is sequencing the genomes and measuring traits like flowering time or disease for individuals in one generation. From this, we can generate a lookup table that allows us to foresee which individuals in the next generation have the best traits based on their genetic profiles alone,” Wisser said. “And our lookup table can be tailored to predict how the individuals will behave in a particular environment or location like Delaware.”

That means plant breeders could grow a second generation of corn anywhere outside of Delaware, but still predict which individuals would be the most fit for Delaware’s environment.

“For instance, even if the plants are grown at a location where a disease is not present, our prediction model can still select the resistant plants and cross them to enrich the genes that underlie resistance,” Wisser said.

With this approach, researchers don’t have to wait out a Delaware winter, so they can continue to pre-adapt the population for at least one extra generation per year. That’s how 10 years of selective breeding for pre-adaptation could become five, providing a quicker route to access exotic genes.

This new effort connects to the Genomes To Fields (G2F) Initiative, developed in 2013 for understanding and capitalizing on the link between genomes and crop performance for the benefit of growers, consumers and society.

If Wisser and Holland can develop a method to rapidly pre-adapt exotics, this opens a lane for G2F to test the impact of these unique genomes on crop performance.

“Our goal is to advance the science so breeders can draw on a wider array of the diversity that has accumulated across thousands of years of evolution,” explained Wisser, who has been involved in the public-private initiative since its beginning. “In turn, they can produce improved varieties for producers and consumers facing the challenges of climate change.”

Robotic technology is used in surgery and cardiology, but not for brain vascular procedures. In this study, Canadian researchers report the results of the first robotic brain vascular procedures. They used a robotic system specifically adapted for neurovascular procedures. Software and hardware adaptations enable it to accommodate microcatheters, guidewires and the other devices used for endovascular procedures in the brain. These modifications also provide the operator additional precise fine-motor control compared to previous system models.

“This experience is the first step towards achieving our vision of remote neurovascular procedures,” said lead researcher Vitor Mendes Pereira, M.D., M.Sc., a neurosurgeon and neuroradiologist at the Toronto Western Hospital, and professor of medical imaging and surgery at the University of Toronto in Canada. “The ability to robotically perform intracranial aneurysm treatment is a major step forward in neuro-endovascular intervention.”

In the first case, a 64-year-old female patient presented with an unruptured aneurysm at the base of her skull. The surgical team successfully used the robot to place a stent and then, using the same microcatheter, entered the aneurysm sac and secured the aneurysm by placing various coils. All intracranial steps were performed with the robotic arm. Since this first case, the team has successfully performed five additional aneurysm treatments using the robot, which included deploying various devices such as flow-diverting stents.

“The expectation is that future robotic systems will be able to be controlled remotely. For example, I could be at my hospital and deliver therapy to a patient hundreds or even thousands of kilometers away,” Mendes Pereira said. “The ability to deliver rapid care through remote robotics for time-critical procedures such as stroke could have a huge impact on improving patient outcomes and allow us to deliver cutting-edge care to patients everywhere, regardless of geography.”

“Our experience, and that of future operators of this technology, will help develop the workflows and processes necessary to implement successful robotic programs, which will ultimately help establish remote care networks in the future,” Mendes Pereira said.

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Current pharmaceutical treatments for heart failure — including ACE inhibitors and beta blockers — center on trying to stop a vicious cycle of heart muscle loss as strain further damages remaining heart muscle, causing more cells to die, explains UT Southwestern physician-researcher Hesham A. Sadek, M.D., Ph.D., the J. Fred Schoellkopf, Jr. Chair in Cardiology. There are no existing treatments for rebuilding heart muscle.

Nine years ago, Sadek and his colleagues discovered that mammalian hearts can regenerate if they’re damaged in the first few days of life, spurred by the division of cardiomyocytes, the cells responsible for a heart’s contractile force. However, this capacity is completely lost by 7 days old, an abrupt turning point in which division of these cells dramatically slows.

Subsequent research has shown that this change in regenerative capacity appears to stem, at least in part, from damaging free radicals generated by organelles known as mitochondria, which power cells. These free radicals damage cells’ DNA, a phenomenon called DNA damage, which prompts them to stop dividing.

The shift in free radical production appears to be spurred by a change in what mitochondria in the cardiomyocytes consume for energy, Sadek explains. Although mitochondria rely on glucose in utero and at birth, they switch to fatty acids in the days after birth to utilize these energy-dense molecules in breast milk.

Sadek and his colleagues wondered whether forcing mitochondria to continue to consume glucose might stymie DNA damage and, in turn, extend the window for heart cell regeneration. To test this idea, the researchers tried two different experiments.

In the first, they followed mouse pups whose mothers were genetically altered to produce low-fat breastmilk and that fed on low-fat chow after they weaned. The researchers found that these rodents’ hearts maintained regenerative capacity weeks later than normal, with their cardiomyocytes continuing to express genes associated with cell division for a significantly longer window than those fed a diet of regular breastmilk and chow. However, this effect didn’t last into adulthood — their livers eventually made up the deficit by synthesizing the fats that their diets were missing, which significantly reduced their hearts’ regenerative capacity.

In the second experiment, the researchers created genetically altered animals in which the researchers could delete an enzyme, known as pyruvate dehydrogenase kinase 4 (PDK4), necessary for the heart cells’ mitochondria to digest fatty acids. When the researchers delivered a drug to turn off PDK4 production, the animals’ cardiomyocytes switched to consuming glucose instead of fatty acids, even in adulthood. After researchers simulated a heart attack, these animals experienced improvement in heart function, which was accompanied by markers in gene expression that suggested their cardiomyocytes were still actively dividing.

Sadek notes that these findings provide proof of principle that it’s possible to reopen the window for heart cell regeneration by manipulating what cardiomyocyte mitochondria consume for energy.

“Eventually,” he says, “it may be possible to develop drugs that change what cardiomyocytes eat to make them divide again, reversing heart failure and representing a true cure.”

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Maculaferrum blaisi, described in a study published in Acta Palaeontologica Polonica, is the first hemipteran insect (true bug) to be discovered at the Redmond Formation, a fossil site from the Cretaceous period near Schefferville, Labrador.

Alexandre Demers-Potvin, a Master’s student under the supervision of Professor Hans Larsson, Director of the Redpath Museum at McGill, said that a single wing was sufficient to identify the family to which the insect belonged.

“We were easily able to demonstrate that the insect belonged to the Tettigarctidae family thanks to the pattern of the veins we observed on its wing,” said Demers-Potvin, who is also a 2018 National Geographic Explorer.

The genus name (Maculaferrum) is derived from the Latin words macula — spot — because of the spotted pattern found on parts of the wing and ferrum — iron — due to the high iron content of the red rocks found at the Redmond site. The species name — blaisi — is in honour of Roger A. Blais, who conducted the first survey of the Redmond Formation and of its fossils in 1957 while working for the Iron Ore Company of Canada.

“This gives us a better understanding of the site’s insect biodiversity during the Cretaceous, a time before the dinosaurs were wiped out,” Demers-Potvin added. “The finding also illustrates that rare species can be found at the Redmond mine and that it deserves the attention from the palaeontological community.”

“The find is exciting because it represents the oldest, diverse insect locality in Canada. It’s also from an exciting time during an evolutionary explosion of flowering plants and pollinating insects, that evolved into the terrestrial ecosystems of today,” said Larsson.

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