Using computers to design proteins allows researchers to make tunable hydrogels that can form both inside and outside of cells

When researchers want to study how COVID makes us sick, or what diseases such as Alzheimer’s do to the body, one approach is to look at what’s happening inside individual cells.

Researchers sometimes grow the cells in a 3D scaffold called a “hydrogel.” This network of proteins or molecules mimics the environment the cells would live in inside the body.

New research led by the University of Washington demonstrates a new class of hydrogels that can form not just outside cells, but also inside of them. The team created these hydrogels from protein building blocks designed using a computer to form a specific structure. These hydrogels exhibited similar mechanical properties both inside and outside of cells, providing researchers with a new tool to group proteins together inside of cells.

The team published these results Jan. 30 in the Proceedings of the National Academy of Sciences.

“In the past 10 years, there’s been a shift in the world of cell biology,” said co-senior author Cole DeForest, a UW associate professor of chemical engineering and of bioengineering. “Classically, folks have attributed much of the cell’s interior organization to membrane-bound organelles, such as mitochondria or the nucleus. But now scientists are realizing that the cell actually has other ways to locally concentrate certain molecules or proteins without using membranes, for example, by protein-protein interactions. This concentrating allows the cell to turn on or off specific functions that can be helpful or ultimately lead to disease.”

DeForest continued: “What I think is pretty exciting here is that we have good mechanical control of our hydrogels — even when they are made inside human cells. This means we can tune them to essentially function as a synthetic version of whatever sequestering phenomenon we want to study, such as how protein aggregation can lead to Alzheimer’s.”

One key element of this research was that the protein building blocks were designed from scratch — they don’t exist anywhere in nature — using computers.

“You can imagine a protein as a string of subunits called amino acids. That string folds up to form a three-dimensional structure. There are 20 different amino acids, and a typical protein is made up of 100 to 200 of them. That makes the system very complex, because how do you know how it’s going to fold?” said co-lead author Rubul Mout, who completed this research as a UW postdoctoral researcher at the Institute for Protein Design and is now a research fellow at Harvard Medical School and Boston Children’s Hospital. “That’s where the computer comes into play — it does calculations to estimate the most likely three-dimensional shape. And similarly, you can tell it what shape you want and it tells you what sequence you need to build the protein.”

To make a variety of hydrogels with different properties, the team used computational design to control how floppy or rigid the protein building blocks were and how the building blocks organized and connected to create the hydrogel. The researchers also used two different methods to link the building blocks together: One linked them irreversibly and the other allowed the proteins to disconnect and reconnect.

“Irreversibly crosslinked systems are going to be intrinsically more stable, making them better for long-term cell culture and functional tissue engineering,” said DeForest, who is also a faculty member with the UW Molecular Engineering and Sciences Institute and the UW Institute for Stem Cell and Regenerative Medicine. “But the reversibly crosslinked systems are more fluid, which may be better for driving specific protein-protein interactions within living cells.”

To determine if the hydrogels in cells had similar characteristics compared to their extracellular counterparts, the researchers examined whether building blocks within the hydrogels could move around. A stiffer hydrogel would be more likely to trap the proteins in one position compared to a more fluid gel. The mechanical properties of each type of hydrogel remained even when inside a cell.

The team plans to further explore this system, including being able to better control how hydrogels form and localize within cells.

The most crucial part of this project, the researchers said, was the collaboration between protein designers and chemical and biological engineers.

“Our cross-disciplinary collaboration with Cole’s group has been very exciting, and has opened up routes to new classes of biomaterials with a wide range of applications,” said co-senior author David Baker, the director of the Institute for Protein Design.

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West Midlands has 75% of England’s measles cases

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How dangerous is vaping and what is the disposable vape ban?

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Elon Musk says Neuralink implanted wireless brain chip

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NHS adds digital prescriptions to app after successful trial

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Staggering structure in 19 nearby spiral galaxies

It’s oh-so-easy to be absolutely mesmerized by these spiral galaxies. Follow their clearly defined arms, which are brimming with stars, to their centers, where there may be old star clusters and — sometimes — active supermassive black holes. Only NASA’s James Webb Space Telescope can deliver highly detailed scenes of nearby galaxies in a combination of near- and mid-infrared light — and a set of these images was publicly released today.

These Webb images are part of a large, long-standing project, the Physics at High Angular resolution in Nearby GalaxieS (PHANGS) program, which is supported by more than 150 astronomers worldwide. Before Webb took these images, PHANGS was already brimming with data from NASA’s Hubble Space Telescope, the Very Large Telescope’s Multi-Unit Spectroscopic Explorer, and the Atacama Large Millimeter/submillimeter Array, including observations in ultraviolet, visible, and radio light. Webb’s near- and mid-infrared contributions have provided several new puzzle pieces.

“Webb’s new images are extraordinary,” said Janice Lee, a project scientist for strategic initiatives at the Space Telescope Science Institute in Baltimore. “They’re mind-blowing even for researchers who have studied these same galaxies for decades. Bubbles and filaments are resolved down to the smallest scales ever observed, and tell a story about the star formation cycle.”

Excitement rapidly spread throughout the team as the Webb images flooded in. “I feel like our team lives in a constant state of being overwhelmed — in a positive way — by the amount of detail in these images,” added Thomas Williams, a postdoctoral researcher at the University of Oxford in the United Kingdom.

Follow the Spiral Arms

It’s oh-so-easy to be absolutely mesmerized by these spiral galaxies. Follow their clearly defined arms, which are brimming with stars, to their centers, where there may be old star clusters and — sometimes — active supermassive black holes. Only NASA’s James Webb Space Telescope can deliver highly detailed scenes of nearby galaxies in a combination of near- and mid-infrared light.

Webb’s NIRCam (Near-Infrared Camera) captured millions of stars in these images, which sparkle in blue tones. Some stars are spread throughout the spiral arms, but others are clumped tightly together in star clusters.

The telescope’s MIRI (Mid-Infrared Instrument) data highlights glowing dust, showing us where it exists around and between stars. It also spotlights stars that haven’t yet fully formed — they are still encased in the gas and dust that feed their growth, like bright red seeds at the tips of dusty peaks. “These are where we can find the newest, most massive stars in the galaxies,” said Erik Rosolowsky, a professor of physics at the University of Alberta in Edmonton, Canada.

Something else that amazed astronomers? Webb’s images show large, spherical shells in the gas and dust. “These holes may have been created by one or more stars that exploded, carving out giant holes in the interstellar material,” explained Adam Leroy, a professor of astronomy at the Ohio State University in Columbus.

Now, trace the spiral arms to find extended regions of gas that appear red and orange. “These structures tend to follow the same pattern in certain parts of the galaxies,” Rosolowsky added. “We think of these like waves, and their spacing tells us a lot about how a galaxy distributes its gas and dust.” Study of these structures will provide key insights about how galaxies build, maintain, and shut off star formation.

Dive Into the Interior

Evidence shows that galaxies grow from inside out — star formation begins at galaxies’ cores and spreads along their arms, spiraling away from the center. The farther a star is from the galaxy’s core, the more likely it is to be younger. In contrast, the areas near the cores that look lit by a blue spotlight are populations of older stars.

What about galaxy cores that are awash in pink-and-red diffraction spikes? “That’s a clear sign that there may be an active supermassive black hole,” said Eva Schinnerer, a staff scientist at the Max Planck Institute for Astronomy in Heidelberg, Germany. “Or, the star clusters toward the center are so bright that they have saturated that area of the image.”

Research Galore

There are many avenues of research that scientists can begin to pursue with the combined PHANGS data, but the unprecedented number of stars Webb resolved are a great place to begin. “Stars can live for billions or trillions of years,” Leroy said. “By precisely cataloging all types of stars, we can build a more reliable, holistic view of their life cycles.”

In addition to immediately releasing these images, the PHANGS team has also released the largest catalog to date of roughly 100,000 star clusters. “The amount of analysis that can be done with these images is vastly larger than anything our team could possibly handle,” Rosolowsky emphasized. “We’re excited to support the community so all researchers can contribute.”

The James Webb Space Telescope is the world’s premier space science observatory. Webb is solving mysteries in our solar system, looking beyond to distant worlds around other stars, and probing the mysterious structures and origins of our universe and our place in it. Webb is an international program led by NASA with its partners, ESA (European Space Agency) and the Canadian Space Agency.

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Do tree-planting campaigns follow best practices for successful forest restoration?

Global tree-planting campaigns have reached fad-like proportions over the past decade, and it’s easy to understand their appeal. Healthy forests help in the fight against climate change by absorbing some of our excess carbon dioxide emissions, and they can provide wildlife habitat and quality-of-life benefits for local human communities too. So why not plant more trees? It seems like an easy win.

But the problem is, there’s a huge difference between simply planting a tree and making sure that trees survive and grow over the long-term. And without the necessary ecological understanding or long-term planning and follow-up that goes into successful reforestation projects, tree-planting efforts can end up being useless, wasteful, or even actively harmful to people and the planet.

That’s why restoration ecologists, like UC Santa Cruz Environmental Studies Professor Karen Holl, have been working to educate tree-planting organizations and the public about best practices for successful reforestation. The latest paper by Holl’s research team set out to examine the possible impact of those education efforts.

“One of the common problems is that organizations will just say, ‘We’re going to put this many trees in the ground,’ but the important question is, ‘What comes afterward?’,” Holl said. “There are many documented failures from tree-planting campaigns, so we would hope to see organizations improving their practices and taking on more accountability, including through publicly reporting data.”

To examine these issues, UCSC postdoctoral researcher Spencer Schubert led an analysis of publicly available web content for 99 organizations that coordinate large-scale tree-planting programs around the globe. The research team, which included three undergraduates and one graduate student from UCSC, rated each organization based on how well their public information demonstrated a commitment to best practices.

“We reviewed websites as well as annual reports and other linked documents to really get a broad view of the information that organizations reveal to the public,” Schubert said. “We wanted to focus on how transparent organizations are about their practices, because that’s what allows potential donors or investors to evaluate what these organizations are promising.”

Specifically, researchers rated the organizations against a set of 10 guidelines established by Holl’s prior work. Those guidelines focus on community engagement, addressing underlying causes of deforestation, preventing unintended harms, and committing to long-term management and monitoring of projects. The more specific an organization was about their goals and demonstrating their impacts in these areas, the higher they were rated.

Study shows some progress, but many challenges remain

Researchers compared the findings of their analysis with those of prior research to see how trends in application of best practices have changed over time. One improvement area was community involvement, which critics have often called out as a missing element. The team’s analysis showed that 91% of organizations now recognize community involvement as a key component of successful reforestation, and almost all organizations discussed benefits that their projects would provide to local communities. However only 38% of organizations actually reported data demonstrating how communities benefited from projects.

Meanwhile, 78% of organizations successfully provided information about specific drivers of deforestation in their working regions, and 75% of those discussed how they would address these issues. The study showed some positive progress around monitoring of projects. A 2021 study had previously found that only 18% of organizations mentioned monitoring on their websites, but in the current study, that measure had risen to 70%.

However, only 41% of organizations actually reported data on tree survival rates, and 61% of all organizations failed to specify how long projects would be maintained, monitored, or financed. Only 10% of organizations mentioned required commitments to their projects beyond 10 years. And only 19% discussed any potential negative consequences of tree planting, although those that did also presented strategies to avoid those issues.

“Overall, there are still many gaps in the details and data that we’re seeing,” Schubert said. “That and the general lack of clarity about long-term management, financing, and protection for these projects raises some serious concerns. This doesn’t necessarily mean that reforestation is not being successful, but there is a lot of uncertainty about whether these emerging global tree growing efforts will achieve their desired long-term benefits.”

Holl said she did find it heartening that some organizations are clearly beginning to pay more attention to recommendations from the scientific community, and she hopes that trend will continue.

“Things are moving in the right direction with some of these organizations,” Holl said. “The next step they’ll need to take is to go beyond generalities and be more specific about how they’re going to implement best practices, including making longer term commitments and focusing on data collection to back up what they’re saying they’re going to do.”

By deepening their focus on improving practices, tree-planting organizations and their supporters will have the best possible chance of achieving positive impact and avoiding unintended consequences.

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People are inclined to hide a contagious illness while around others, research shows

A startling number of people conceal an infectious illness to avoid missing work, travel, or social events, new research at the University of Michigan suggests.

The findings are reported in Psychological Science, a journal of the Association for Psychological Science. Across a series of studies involving healthy and sick adults, 75% of the 4,110 participants said they had either hidden an infectious illness from others at least once or might do so in the future. Many participants reported boarding planes, going on dates, and engaging in other social interactions while secretly sick. More than 61% of healthcare workers participating in the study also said they had concealed an infectious illness.

Interestingly, the researchers found a difference between how people believe they would act when ill and how they actually behave, said Wilson N. Merrell, a doctoral candidate and lead author on the study.

“Healthy people forecasted that they would be unlikely to hide harmful illnesses — those that spread easily and have severe symptoms — but actively sick people reported high levels of concealment regardless of how harmful their illness was to others,” Merrell said.

In the first study, Merrell and his colleagues — psychology professor Joshua M. Ackerman and PhD student Soyeon Choi — recruited 399 university healthcare employees and 505 students. The participants reported the number of days they felt symptoms of an infectious illness, starting in March 2020, when the COVID-19 pandemic began. They then rated how often they actively covered up symptoms from others, came to campus or work without telling others they were feeling ill, or falsified mandatory symptom screeners that the university had required for anyone using campus facilities.

More than 70% of the participants reported covering up their symptoms. Many said they hid their illness because it would conflict with social plans, while a small percentage of participants cited pressure from institutional policies (e.g., lack of paid time off). Only five participants reported hiding a COVID-19 infection.

In a second study, the researchers recruited 946 participants online and randomly assigned them to one of nine conditions in which they imagined being either moderately or severely sick while in a social situation. In each condition, the risk of spreading the illness was designated as low, medium, or high. (To control for the special stigma associated with COVID-19 at the time, the researchers asked participants not to imagine being sick with that disease.) Participants were most likely to envision themselves hiding their sickness when symptom severity was low, and least likely to conceal when symptoms were severe and highly communicable.

In another study, Merrell and colleagues used an online research tool to recruit 900 people —

including some who were actively sick — and asked them to rate the transmissibility of their real or imagined illness. The participants were also asked to rate their likelihood of covering up an illness in a hypothetical meeting with another person.

Results showed that compared to healthy participants who only imagined being sick, those who were actively ill were more likely to conceal their illness regardless of its transmissibility.

“This suggests that sick people and healthy people evaluate the consequences of concealment in different ways,” Merrell said, “with sick people being relatively insensitive to how spreadable and severe their illness may be for others.”

The COVID-19 crisis may have shaped the way the participants thought about concealing an illness, Merrell said, adding that future research could explore how ecological factors (e.g., pandemics) and medical advances such as vaccines influence people’s disease-related behavior. The research team is also expanding this line of investigation to other countries to uncover potential cultural differences in concealment behaviors, he said.

Overall, the findings carry significant public health implications, illuminating the motivations and tradeoffs we make in social interactions when we’re sick, Merrell added.

“After all, people tend to react negatively to, find less attractive, and steer clear of people who are sick with infectious illness,” he said. “It therefore makes sense that we may take steps to cover up our sickness in social situations. This suggests that solutions to the problem of disease concealment may need to rely on more than just individual good will.”

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Medicine stopped in 1980s linked to rare Alzheimer’s cases

Contaminated injections of growth hormone may have caused five rare cases of dementia, scientists think.

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How did humans learn to walk? New evolutionary study offers an earful

Humans and our closest relatives, living apes, display a remarkable diversity of types of locomotion — from walking upright on two legs to climbing in trees and walking using all four limbs.

While scientists have long been intrigued by the question of how humans’ bipedal stance and movement evolved from a quadrupedal ancestor, neither past studies nor fossil records have permitted the reconstruction of a clear and definitive history of the early evolutionary stages that led to human bipedalism.

However, a new study, which centers on recently discovered evidence from skulls of a 6-million-year-old fossil ape, Lufengpithecus, offers important clues about the origins of bipedal locomotion courtesy of a novel method: analyzing its bony inner ear region using three-dimensional CT-scanning.

“The semicircular canals, located in the skull between our brains and the external ear, are critical to providing our sense of balance and position when we move, and they provide a fundamental component of our locomotion that most people are probably unaware of,” explains Yinan Zhang, a doctoral student at the Institute of Vertebrate Paleontology and Paleoanthropology of the Chinese Academy of Sciences (IVPP) and the lead author of the paper, which appears in the journal the Innovation. “The size and shape of the semicircular canals correlate with how mammals, including apes and humans, move around their environment. Using modern imaging technologies, we were able to visualize the internal structure of fossil skulls and study the anatomical details of the semicircular canals to reveal how extinct mammals moved.”

“Our study points to a three-step evolution of human bipedalism,” adds Terry Harrison, a New York University anthropologist and one of the paper’s co-authors. “First, the earliest apes moved in the trees in a style that was most similar to aspects of the way that gibbons in Asia do today. Second, the last common ancestor of apes and humans was similar in its locomotor repertoire to Lufengpithecus, using a combination of climbing and clambering, forelimb suspension, arboreal bipedalism, and terrestrial quadrupedalism. It is from this broad ancestral locomotor repertoire that human bipedalism evolved.”

Most studies of the evolution of ape locomotion had focused on comparisons of the bones of the limbs, shoulders, pelvis, and spine and the way they are associated with the different types of locomotor behaviors seen in living apes and humans. However, the diversity of locomotor behaviors in living apes and the incompleteness of the fossil record have hampered the development of a clear picture of human bipedalism’s origins.

The skulls of Lufengpithecus — originally discovered in China’s Yunnan Province in the early 1980s — have given scientists the opportunity to address, in new ways, unanswered questions about the evolution of locomotion. However, the heavy compression and distortion of the skulls obscured the bony ear region and led previous researchers to believe that the delicate semicircular canals were not preserved.

To better explore this region, Zhang, Ni and Harrison, along with other researchers at IVPP and the Yunnan Institute of Cultural Relics and Archaeology (YICRA), used three dimensional scanning technologies to illuminate these portions of the skulls to create a virtual reconstruction of the inner ear’s bony canals. They then compared these scans to those collected from other living and fossil apes and humans from Asia, Europe, and Africa.

“Our analyses show that early apes shared a locomotor repertoire that was ancestral to human bipedalism,” explains IVPP Professor Xijun Ni, who led the project. “It appears that the inner ear provides a unique record of the evolutionary history of ape locomotion that offers an invaluable alternative to the study of the postcranial skeleton.”

“Most fossil apes and their inferred ancestors are intermediate in locomotor mode between gibbons and African apes,” adds Ni. “Later, the human lineage diverged from the great apes with the acquisition of bipedalism, as seen in Australopithecus, an early human relative from Africa.”

By studying the rate of evolutionary change in the bony labyrinth, the international team proposed that climate change may have been an important environmental catalyst in promoting the locomotor diversification of apes and humans.

“Cooler global temperatures, associated with the build up of glacial ice sheets in the northern hemisphere approximately 3.2 million years ago, correspond with an uptick in the rate of change of the bony labyrinth and this may signal a rapid increase in the pace of ape and human locomotor evolution,” explains Harrison.

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