What makes the human brain different? Study reveals clues

 

Baby chimpanzee

What makes the human brain distinct from that of all other animals -- including even our closest primate relatives? In an analysis of cell types in the prefrontal cortex of four primate species, Yale researchers identified species-specific -- particularly human-specific -- features, they report Aug. 25 in the journal Science.

And they found that what makes us human may also makes us susceptible to neuropsychiatric diseases.

For the study, the researchers looked specifically at the dorsolateral prefrontal cortex (dlPFC), a brain region that is unique to primates and essential for higher-order cognition. Using a single cell RNA-sequencing technique, they profiled expression levels of genes in hundreds of thousands of cells collected from the dlPFC of adult humans, chimpanzees, macaque, and marmoset monkeys.

"Today, we view the dorsolateral prefrontal cortex as the core component of human identity, but still we don't know what makes this unique in humans and distinguishes us from other primate species." said Nenad Sestan, the Harvey and Kate Cushing Professor of Neuroscience at Yale, professor of comparative medicine, of genetics. and of psychiatry, and the lead senior author of the paper. "Now we have more clues."

To answer this, the researchers first asked whether there are there any cell types uniquely present in humans or other analyzed non-human primate species. After grouping cells with similar expression profiles they revealed 109 shared primate cell types but also five that were not common to all species. These included a type of microglia, or brain-specific immune cell, that was present only in humans and a second type shared by only humans and chimpanzees.

The human-specific microglia type exists throughout development and adulthood, the researchers found, suggesting the cells play a role in maintenance of the brain upkeep rather than combatting disease.

"We humans live in a very different environment with a unique lifestyle compared to other primate species; and glia cells, including microglia, are very sensitive to these differences," Sestan said. "The type of microglia found in the human brain might represent an immune response to the environment."

An analysis of gene expression in the microglia revealed another human-specific surprise -- the presence of the gene FOXP2. This discovery raised great interest because variants of FOXP2 have been linked to verbal dyspraxia, a condition in which patients have difficulty producing language or speech. Other studies have also shown that FOXP2 is associated with other neuropsychiatric diseases, such as autism, schizophrenia, and epilepsy.

Sestan and colleagues found that this gene exhibits primate-specific expression in a subset of excitatory neurons and human-specific expression in microglia.

"FOXP2 has intrigued many scientists for decades, but still we had no idea of what makes it unique in humans versus other primate species," said Shaojie Ma, a postdoctoral associate in Sestan's lab and co-lead author. We are extremely excited about the FOXP2 findings because they open new directions in the study of language and diseases."

The research was funded by the National Institutes of Health and National Institute of Mental Health.

Other authors include co-lead author Mario Skarica, associate research scientist in neuroscience at Yale School of Medicine; co-senior author Andre Sousa, assistant professor of neuroscience at the University of Wisconsin-Madison; and co-senior author Stephen M. Strittmatter, the Vincent Coates Professor of Neurology and professor of neuroscience at Yale, chair of the Department of Neuroscience, and director of the Kavli Institute for Neuroscience.

Mosquitoes have neuronal fail-safes to make sure they can always smell humans

Mosquito on skin

When female mosquitoes are looking for a human to bite, they smell a unique cocktail of body odors that we emit into the air. These odors then stimulate receptors in the mosquitoes' antenna. Scientists have tried deleting these receptors in attempts to make humans undetectable to mosquitoes.

However, even after knocking out an entire family of odor-sensing receptors from the mosquito genome, mosquitoes still find a way to bite us. Now, a group of researchers, publishing in the journal Cell on August 18, found that mosquitoes have evolved redundant fail-safes in their olfactory system that make sure they can always smell our scents.

"Mosquitoes are breaking all of our favorite rules of how animals smell things," says Margo Herre, a scientist at Rockefeller University and one of the lead authors of the paper.

In most animals, an olfactory neuron is only responsible for detecting one type of odor. "If you're a human and you lose a single odorant receptor, all of the neurons that express that receptor will lose the ability to smell that smell," says Leslie Vosshall of the Howard Hughes Medical Institute and a professor at Rockefeller University and the senior author of the paper. But she and her colleagues found that this is not the case in mosquitoes.

"You need to work harder to break mosquitoes because getting rid of a single receptor has no effect," says Vosshall. "Any future attempts to control mosquitoes by repellents or anything else has to take into account how unbreakable their attraction is to us."

"This project really started unexpectedly when we were looking at how human odor was encoded in the mosquito brain," says Meg Younger, a professor at Boston University and one of the lead authors of the paper.

They found that neurons stimulated by the human odor 1-octen-3-ol are also stimulated by amines, another type of chemical mosquitoes use to look for humans. This is unusual since according to all existing rules of how animals smell, neurons encode odor with narrow specificity, suggesting that 1-octen-3-ol neurons should not detect amines.

"Surprisingly, the neurons for detecting humans through 1-octen-3-ol and amine receptors were not separate populations," says Younger. This may allow all human-related odors to activate "the human-detecting part" of the mosquito brain even if some of the receptors are lost, acting as a fail-safe.

The team also utilized single-nucleus RNA sequencing to see what other receptors individual mosquito olfactory neurons are expressing. "The result gave us a broad view of just how common co-expression of receptors is in mosquitoes," says Olivia Goldman, another lead author of the paper.

Vosshall thinks that other insects may have a similar mechanism. Christopher Potter's research group at Johns Hopkins University recently reported that fruit flies have similar co-expression of receptors in their neurons. "This may be a general strategy for insects that depend heavily on their sense of smell," says Vosshall.

 

How scary are spacewalks?

 TO ALEXEI LEONOV, the colours in space were much more beautiful than those on Earth. No photograph could match what the late Russian cosmonaut experienced while floating hundreds of miles above his home planet in 1965: the distant curve of blue suspended in the deep black of space; the sunset as lines of reds, greens, and yellows skimming the horizon. Other explorers have shared this otherworldly perspective, but back then no one saw it as Leonov did—from beyond the safety of a spacecraft during history’s earliest spacewalk.

With only a 16-foot tether as his lifeline, the pilot of the Voskhod 2 mission drifted alone through low Earth orbit. But after 12 minutes, awe turned to panic when his suit ballooned to the point where he couldn’t fit back through the shuttle’s airlock door. He feared that as the first to explore the vastness of space in a suit, he might also be the first to get lost in it. These days, spacewalks, also known as extravehicular activities or EVAs, are commonplace. Astronauts aboard the International Space Station (ISS) have conducted 250 of them since 1998, spending hours in the extra-terrestrial elements to install or fix scientific equipment. But even as astronauts have become more adept at roaming outside controlled environment and the technology behind their suits has improved, the risks of accidents or death remain. In Leonov’s case, the drop in atmospheric pressure caused the air in his suit to swell to dangerous proportions. If he tried to release the gas and reduce pressure, he risked bleeding off too much oxygen and asphyxiating himself. He decided to take the chance and quickly opened a valve in his suit to slim it down some, then slipped back indoors. Meanwhile, the Soviet space agency cut off a national broadcast of the mission to avoid public alarm. Leonov returned to a hero’s welcome on Earth, and it wasn’t until he shared his story that everyone realized the danger he’d faced. Since Leonov’s pioneering foray, countries have stepped up safety and training standards for spacewalks. NASA astronauts practice EVA procedures in water tanks and zero-gravity airplanes, spending nearly seven hours submerged for each hour in orbit. More recently, they’ve practiced in virtual reality. As a result, astronauts today are well prepared for EVAs, retired NASA payload commander Jeff Hoffman says. He performed four spacewalks throughout his career. His debut, in 1985, happened to be the first unplanned one in the agency’s history, when he ventured outside his shuttle to try to fix a broken satellite. “It showed how good the training [for spacewalking] was,” Hoffman said of the three-hour EVA. “I felt very comfortable, even though it was unplanned.” Equipment has improved since Leonov’s era too, enabling astronauts to trek around for longer. Almost like individual spaceships, spacesuits supply oxygen, regulate temperature, and vent exhaled carbon dioxide. Other small additions make EVAs more secure and comfortable, including devices crewmembers use to propel themselves around in short bursts, guardrails on the facades of structures that improve manoeuvrability, anti-fog coating inside helmets, and warm gloves made of many layers of insulation and tough, flexible fabric.

Still, the dangers are real. In 2013, Italian astronaut Luca Parmitano almost drowned during a spacewalk when his helmet flooded with water that had leaked earlier from the suit’s cooling system. Astronauts might also face exhaustion or blood-bubbling “bends,” caused by the same rapid pressure changes that also endanger scuba divers. Space junk, traveling at 18,000 miles per hour, poses another risk—one that Hoffman says is getting worse as stuff accumulates in Earth’s orbit. In late 2021, NASA cancelled an ISS EVA because of floating debris. Though no astronaut has been hit yet, a punctured suit could turn fatal fast. Even as spacewalks become more regular, the potential for disaster will never be fully eliminated. After all, Hoffman says, it’s part of a job that involves sitting on a loaded rocket. “I was fully confident that if anything happened that we could do something about, we’d do the right thing. And if something happened that we couldn’t do anything about—why worry?” he explains. “I took the risk because we had useful work to do.”

Risk of volcano catastrophe 'a roll of the dice'

Mount Rinjani, Indonesia

 The world is "woefully underprepared" for a massive volcanic eruption and the likely repercussions on global supply chains, climate and food, according to experts from the University of Cambridge's Centre for the Study of Existential Risk (CSER), and the University of Birmingham.

In an article published in the journal Nature, they say there is a "broad misconception" that risks of major eruptions are low, and describe current lack of governmental investment in monitoring and responding to potential volcano disasters as "reckless."

However, the researchers argue that steps can be taken to protect against volcanic devastation -- from improved surveillance to increased public education and magma manipulation -- and the resources needed to do so are long overdue.

"Data gathered from ice cores on the frequency of eruptions over deep time suggests there is a one-in-six chance of a magnitude seven explosion in the next one hundred years. That's a roll of the dice," said article co-author and CSER researcher Dr Lara Mani, an expert in global risk.

"Such gigantic eruptions have caused abrupt climate change and collapse of civilisations in the distant past."

Mani compares the risk of a giant eruption to that of a 1km-wide asteroid crashing into Earth. Such events would have similar climatic consequences, but the likelihood of a volcanic catastrophe is hundreds of times higher than the combined chances of an asteroid or comet collision.

"Hundreds of millions of dollars are pumped into asteroid threats every year, yet there is a severe lack of global financing and coordination for volcano preparedness," Mani said. "This urgently needs to change. We are completely underestimating the risk to our societies that volcanoes pose."

An eruption in Tonga in January was the largest ever instrumentally recorded. The researchers argue that if it had gone on longer, released more ash and gas, or occurred in an area full of critical infrastructure -- such as the Mediterranean -- then global shock waves could have been devastating.

"The Tonga eruption was the volcanic equivalent of an asteroid just missing the Earth, and needs to be treated as a wake-up call," said Mani.

The CSER experts cite recent research detecting the regularity of major eruptions by analysing traces of sulphur spikes in ancient ice samples. An eruption ten to a hundred times larger than the Tonga blast occurs once every 625 years -- twice as often as had been previously thought.

"The last magnitude seven eruption was in 1815 in Indonesia," said co-author Dr Mike Cassidy, a volcano expert and visiting CSER researcher, now based at the University of Birmingham.

"An estimated 100,000 people died locally, and global temperatures dropped by a degree on average, causing mass crop failures that led to famine, violent uprisings and epidemics in what was known as the year without summer," he said.

"We now live in a world with eight times the population and over forty times the level of trade. Our complex global networks could make us even more vulnerable to the shocks of a major eruption."

Financial losses from a large magnitude eruption would be in the multi-trillions, and on a comparable scale to the pandemic, say the experts.

Mani and Cassidy outline steps they say need to be taken to help forecast and manage the possibility of a planet-altering eruption, and help mitigate damage from smaller, more frequent eruptions.

These include a more accurate pinpointing of risks. We only know locations of a handful of the 97 eruptions classed as large magnitude on the "Volcano Explosivity Index" over the last 60,000 years. This means there could be dozens of dangerous volcanoes dotted the world over with the potential for extreme destruction, about which humanity has no clue.

"We may not know about even relatively recent eruptions due to a lack of research into marine and lake cores, particularly in neglected regions such as Southeast Asia," said Cassidy. "Volcanoes can lie dormant for a long time, but still be capable of sudden and extraordinary destruction."

Monitoring must be improved, say the CSER experts. Only 27% of eruptions since 1950 have had a seismometer anywhere near them, and only a third of that data again has been fed into the global database for "volcanic unrest."

"Volcanologists have been calling for a dedicated volcano-monitoring satellite for over twenty years," said Mani. "Sometimes we have to rely on the generosity of private satellite companies for rapid imagery."

The experts also call for increased research into volcano "geoengineering." This includes the need to study means of countering aerosols released by a massive eruption, which could lead to a "volcanic winter." They also say that work to investigate manipulating pockets of magma beneath active volcanoes should be undertaken.

Bioengineering: Better photosynthesis increases yields in food crops

Soybean field 

.For the first time, RIPE researchers have proven that multigene bioengineering of photosynthesis increases the yield of a major food crop in field trials. After more than a decade of working toward this goal, a collaborative team led by the University of Illinois has transgenically altered soybean plants to increase the efficiency of photosynthesis, resulting in greater yields without loss of quality.

Results of this magnitude couldn't come at a more crucial time. The most recent UN report, The State of Food Security and Nutrition in the World 2022, found that in 2021 nearly 10% of the world population was hungry, a situation that has been steadily worsening over the last few years and eclipsing all other threats to global health in scale. According to UNICEF, by 2030, more than 660 million people are expected to face food scarcity and malnutrition. Two of the major causes of this are inefficient food supply chains (access to food) and harsher growing conditions for crops due to climate change. Improving access to food and improving the sustainability of food crops in impoverished areas are the key goals of this study and the RIPE project.

Realizing Increased Photosynthetic Efficiency, or RIPE, is an international research project that aims to increase global food production by improving photosynthetic efficiency in food crops for smallholder farmers in Sub-Saharan Africa with support from the Bill & Melinda Gates Foundation, Foundation for Food & Agriculture Research, and U.K. Foreign, Commonwealth & Development Office.

"The number of people affected by food insufficiency continues to grow, and projections clearly show that there needs to be a change at the food supply level to change the trajectory," said Amanda De Souza, RIPE project research scientist, and lead author. "Our research shows an effective way to contribute to food security for the people who need it most while avoiding more land being put into production. Improving photosynthesis is a major opportunity to gain the needed jump in yield potential."

Photosynthesis, the natural process all plants use to convert sunlight into energy and yield, is a surprisingly inefficient 100+ step process that RIPE researchers have been working to improve for more than a decade. In this first-of-its-kind work, recently published in Science, the group improved the VPZ construct within the soybean plant to improve photosynthesis and then conducted field trials to see if yield would be improved as a result.

The VPZ construct contains three genes that code for proteins of the xanthophyll cycle, which is a pigment cycle that helps in the photoprotection of the plants. Once in full sunlight, this cycle is activated in the leaves to protect them from damage, allowing leaves to dissipate the excess energy. However, when the leaves are shaded (by other leaves, clouds, or the sun moving in the sky) this photoprotection needs to switch off so the leaves can continue the photosynthesis process with a reserve of sunlight. It takes several minutes for the plant to switch off the protective mechanism, costing plants valuable time that could have been used for photosynthesis.

The overexpression of the three genes from the VPZ construct accelerates the process, so every time a leaf transitions from light to shade the photoprotection switches off faster. Leaves gain extra minutes of photosynthesis which, when added up throughout the entire growing season, increases the total photosynthetic rate. This research has shown that despite achieving a more than 20% increase in yield, seed quality was not impacted.

"Despite higher yield, seed protein content was unchanged. This suggests some of the extra energy gained from improved photosynthesis was likely diverted to the nitrogen-fixing bacteria in the plant's nodules," said RIPE Director Stephen Long, Ikenberry Endowed University Chair of Crop Sciences and Plant Biology at Illinois' Carl R. Woese Institute for Genomic Biology.

The researchers first tested their idea in tobacco plants because of the ease of transforming the crop's genetics and the amount of seeds that can be produced from a single plant. These factors allow researchers to go from genetic transformation to a field trial within months. Once the concept was proven in tobacco, they moved into the more complicated task of putting the genetics into a food crop, soybeans.

"Having now shown very substantial yield increases in both tobacco and soybean, two very different crops, suggests this has universal applicability," said Long. "Our study shows that realizing yield improvements is strongly affected by the environment. It is critical to determine the repeatability of this result across environments and further improvements to ensure the environmental stability of the gain."

Additional field tests of these transgenic soybean plants are being conducted this year, with results expected in early 2023.

"The major impact of this work is to open the roads for showing that we can bioengineer photosynthesis and improve yields to increase food production in major crops," said De Souza. "It is the beginning of the confirmation that the ideas ingrained by the RIPE project are a successful means to improve yield in major food crops."

The RIPE project and its sponsors are committed to ensuring Global Access and making the project's technologies available to the farmers who need them the most.

"This has been a road of more than a quarter century for me personally," said Long. "Starting first with a theoretical analysis of theoretical efficiency of crop photosynthesis, simulation of the complete process by high-performance computation, followed by application of optimization routines that indicated several bottlenecks in the process in our crops. Funding support over the past ten years has now allowed us to engineer alleviation of some of these indicated bottlenecks and test the products at field scale. After years of trial and tribulation, it is wonderfully rewarding to see such a spectacular result for the team."