Brain

In 2019, Anaïs Llorens and Athina Tzovara -- one a current, the other a former University of California, Berkeley, postdoctoral scholar at the Helen Wills Neuroscience Institute (HWNI) -- were attending a scientific meeting and pleased that one session, on gender bias in academia, attracted nearly a full house. The problem: The audience of some 300 was almost all women.

Where were the men, they wondered? More than 75% of all tenured faculty in Ph.D. programs around the world are men, making their participation key to solving the problem of gender bias, which negatively impacts the careers, work-life balance and mental health of all women in science, and even more so for minority women and members of the LGBTQ+ community.

"If they are not on board, and they don't feel that this is also their fight, then nothing will change," Llorens said.

That was only one of the incidents that led the two women to round up 45 men and women from 40 institutions across 10 countries and 18 nationalities, divide them into small groups and task them with scouring the literature for practical tips -- proven and unproven -- on how best to counteract all aspects of gender bias in academia. The study, with Llorens and Tzovara as first authors, appears today in the journal Neuron, and provides a comprehensive summary of the many forms that gender bias takes, along with a checklist that individuals, lab leaders, university administrators, journal editors and grant reviewers at funding agencies can use to remedy them.

Both women thank their mentor, Bob Knight, a UC Berkeley professor of psychology and neuroscience in the HWNI, for his enthusiastic support of women researchers and of their project, which they admit was substantially different from their main fields of research: how the brain deals with language and conscious perception of the environment. But as the two women transition to the next stages of their careers -- Tzovara, originally from Greece, left two years ago to become an assistant professor at the University of Bern in Switzerland, while Llorens, who is French, is finishing up her postdoctoral research at UC Berkeley -- they wanted to leave a legacy for women who follow them in neuroscience.

In a Q&A, Llorens and Tzovara talk about their motivations and the problem of gender bias in the ivied halls.

What drove you to undertake this year-long project?

Llorens: The starting point was at the end of 2019, when we went to a neuroscience conference, a big one, and we talked with many of our women colleagues and realized how many of us were struggling to find a correct balance between having a family, a life, and also finding a permanent position. In science, you often have to move abroad, for most of us in Europe, especially, and it is a long process before you can settle down and find a permanent position.

Then, at this very same conference, we attended a workshop on how to strive as a woman in neuroscience, and we really felt the discrepancy between what we were actually living as scientists and what the panelists were telling us. There were five successful women who managed to have a perfectly balanced life, with 300 women listening. When we came out of the room, we felt like we were the issue, because, obviously, they made it. Maybe we are the problem?

Tzovara: There is this notion of survivorship bias -- often we look at people who have made it, and we forget all the people who did not have a straightforward career path and are not there yet. That helped us to identify this gap between what others described, and what we experienced ourselves, and realize that the more we talk about bias, the more interest we find from men and women. That is why we wanted to give voice to all these discussions that we had among ourselves and write them down, hoping that these will be the beginning of a bigger conversation.

Llorens: After that workshop, I felt that had I wasted my time, because nothing will change by simply listening to successful women, if I may say so; we need more than that to actually see some improvements. That is why, for us, it was important to have as many men on board in this project who felt concerned and also wanted to fight for equity. It is something we need to discuss together.

Hasn't the situation improved for women in STEM fields over the past generation?

Llorens: Absolutely. We can really see improvement in many aspects of science. In many countries, between 20% and 25% of women are professors. We can also see progress in preventing sexual harassment. It is better, but we are far from equity. It is still not safe enough and still not equal enough.

Tzovara: I've observed improvements even in the last five or 10 years. These days, if there are conferences that have men-only panels, they will be called out. If there are journals where the editorial board is composed exclusively of men, they will be called out. So, there is concrete change compared to some years ago. I think it might be like a cascade effect -- the more we talk about bias, the more people are aware of it, the more we can realize that we need to take action. All this together has the power to bring positive change.

Llorens: But now some people think, "Ok, there is some improvement, so maybe we don't need to work as hard to make things better." And that is a problem, because equity won't just come magically; we need to keep working on it. And that is also an issue when we talk to people and they say, "It's better, it is just a matter of time." No, it isn't, actually. It is a matter of people making that change. We still need actions to make things right. There is progress, for sure. We are moving in the right direction. But we need to keep making the effort.

You provide many suggestions, but one is having a gender target in grants to improve equity, which some people -- women, as well as men -- might object to in the same way that people have objected to affirmative action for people of color.

Llorens: We advocate for a more equitable distribution of funding. Funding agencies should make an extra effort to insure a fairer distribution of the resources between genders. That said, during my career, I was hired through a grant promoting diversity by potentially hiring a woman, and I must admit when I read that I wondered, "Did I get the job because I was the best applicant or because I was a woman?" That is the tricky thing with positive actions: We still need them, as academia is still imbalanced for now, but we must somewhat force it. But I also had to work on my own self-esteem to understand that this is the way that things have to be done. It is not because I am not good, but it is just because we have to make things right.

Tzovara: Sometimes it is just about giving the right opportunities to people who are not traditionally represented in academia and then giving them some space. And that can often be enough by itself to let individuals that are traditionally underrepresented shine.

Do men suffer from the same pressures when trying to succeed in academia?

Tzovara: That reminds me of a discussion we had with one of our men co-authors who was trying to understand the way that women experience science. He, too, felt that he had experienced similar issues: difficulties moving abroad or difficulties with his family. But as women, we experience it much, much worse. Sometimes bias and discrimination or micro- and macro aggressions pile on top of the usual challenges associated with working in science.

Llorens: Biology is different. Men don't feel the same pressure as we do because, for us, literally, everything happens at the same time. In this window between 28 and 36 years of age, we need to find a position, but this is also when we have to be the most mobile, and it is the right age to build a family. For men, they can wait. It is challenging for everyone to keep relationships, but it is not the same pressure.

If you had to prioritize the most important interventions for reducing gender bias, where would you start?

Llorens: There are existing tools that people can use to mitigate bias pretty easily. For instance, regarding equitable citations in journal articles or in syllabi for teaching. These are easy actions that can be taken right now to make things better, and they are already known to be valuable.

For me, the biggest challenge, and I think the most impactful, would be to change mindsets. Everyone needs to be on board with this topic to make real change. If men are on board, then we will have allies at the top, because most of the leaders are men. We also need more action around sexual harassment. Stopping sexual harassment is everyone's job, of course, but the leaders need to be strict and clear with sexual harassment policies; they have to lead by example. Change has to come from the top. It is really important to make the working environment safe.

Tzovara: There are so many different things that we can do, and I think everybody should do both the smaller and the larger things. If they see injustice or bias, they should speak up. If someone is representing an institute, like a university or funding agency, they should make sure that the work of the institute represents equity. They should make sure that funding is equally distributed, that the institute doesn't only hire men, that promotions take gender bias into account, and so on. If someone has the power to change society and change mindsets, they should start working on that. And that is the message we tried to convey with this manuscript, where we split the suggested solutions into three levels of individual, institutional and societal to show that everybody has a responsibility, depending on their position and abilities.

Llorens: And also removing the burden that we have as women. On top of having to represent ourselves as women, we have to be part of committees and to add some extra work to represent women in science. If we can have everyone on board, meaning everyone advocates for underrepresented groups, even though they are not part of a one of those groups themselves, then the burden will be shared, and it will become easier for everyone. For me, that will be the most impactful action, for everyone to be more aware of these issues and take a stand and help us with that.

I also think that transparency is key. For instance, institutions must be transparent regarding negotiations, such as about the scale you can ask for salaries. The institution has to make things easier for everyone to navigate academia, to be honest. And because most of the biases are implicit, we need to call them out and make them explicit because many people think that they are not biased. I feel like I, too, am part of the problem. I have my own biases, everyone has their own bias. But I think acknowledging them, making them explicit, is also a step forward that people need to take.

How would you characterize UC Berkeley's response to gender bias?

Llorens: I think the way that they advertise now for positions -- making it mandatory to have women applicants -- is a good step forward. It means that the department has to actually do research when they are hiring for a position. When we talk now with students about gender bias, some of them are worried that if we do that, it means that we might need to go for someone who is not the best candidate. When I mentioned this to Bob Knight, who has been part of recruiting committees for many, many years, he said that the fact that you actually have to look for a broader pool of people you might not have thought of before was actually a good thing, that they never, ever chose someone that wasn't the top choice. For him, it didn't change the way he was recruiting people, it only diversified and increased the pool of subjects. The best candidate was offered the job. It just might not have been the best person they thought about before.

Also, in the past few years UC Berkeley has done a good job of increasing awareness of sexual assault and sexual harassment. The kinds of services and help offered by the university, including the Path to Care Center, for example, I found really interesting. Not all institutions have that. I also would add that UC Berkeley has really tried to raise awareness about women in science this year with the emphasis on 150 Years of Women at Berkeley. It is always important to try to raise awareness of this topic.

But UC Berkeley is a bubble.

Tzovara: And the lab we were in is a bubble within a bubble. I think I speak for a lot of people in the lab that we felt secure that, if something happened, Bob would have our backs. It is very important for members of any institution or individual lab to know that their mentors have their backs and speak up when they see injustice.

Llorens: You know the imposter syndrome -- it impacts women and men, but mostly women. When you have a PI who makes sure you are in a safe environment and makes you feel like you can do it, it helps a lot. It is not like that in many places, to be honest with you. Bob and Nina Dronkers (an adjunct professor of psychology who also is a co-senior author of the paper) were wonderful mentors.

How did you put together these checklists?

Tzovara: We wanted to base the paper on data. We read a lot -- we have almost 300 references in the paper -- and tried to back up everything with science and describe what worked and what didn't in remedying gender bias. We wanted to give examples of which of the proposed solutions can work and have been actually tested, and which are implemented in some parts of the world, but may still have uncertain results. The goal is to start from there and see what can be done to improve things on the individual, institutional and societal level.

What are your hopes for this paper?

Llorens: We want this paper to be disseminated widely and across different borders in academia. We are also now giving workshops at various scientific meetings and talking to undergraduate students.

Tzovara: Other activities that we plan to pursue include organizing mentoring seminars for women in science. One of the next steps is to also reach out to even younger ages. We would like to start talking about bias to young students in schools when their mindsets are still being shaped, in order to have an impact on the next generation.

Llorens: Gender bias is a sensitive topic, but we just want to get the discussion rolling. Hopefully, we can do a follow-up study in five years and say which suggestions worked to mitigate gender bias, and keep making progress on that topic so that we will end up with a checklist that each lab can refer to.

Using an exceptionally preserved fossil from South Africa, a particle accelerator, and high-powered x-rays, an international team including a University of Minnesota researcher has discovered that not all dinosaurs breathed in the same way. The findings give scientists more insight into how a major group of dinosaurs, including well-known creatures like the triceratops and stegosaurus, evolved.

The study is published in eLife, a peer-reviewed open access scientific journal for the biomedical and life sciences.

Not all animals use the same techniques and organs to breathe. Humans expand and contract their lungs. Birds have air sacs outside their lungs that pump oxygen in, and their lungs don't actually move. For a long time, paleontologists assumed that all dinosaurs breathed like birds, since they had similar breathing anatomy. This study, however, found that Heterodontosaurus did not--it instead had paddle-shaped ribs and small, toothpick-like bones, and expanded both its chest and belly in order to breathe.

Heterodontosaurus is the oldest dinosaur in the Ornithischian line, one of three major dinosaur groups that includes Triceratops, Stegosaurus, and other duck-billed dinosaurs. The other groups are sauropods, or longnecks, and theropods like the T-Rex.

"We actually have never known how these [Ornithischians] breathed," said Viktor Radermacher, lead author of the study and a Ph.D. student in the University of Minnesota's Department of Earth and Environmental Sciences. "The interesting thing is that Heterodontosaurus is the ancestor of this group and it has these [newly discovered] pieces of anatomy, but its descendants don't. What that means is that Heterodontosaurus is a missing link between the ancestors of dinosaurs and the bigger, charismatic species we know. This gives us a whole bunch of information and fills in some pretty glaring gaps in our knowledge of the biology of these dinosaurs."

The researchers analyzed the new Heterodontosaurus specimen with high-powered x-rays generated from a synchrotron--a giant, donut-shaped particle accelerator that spins electrons at the speed of light--at the European Synchrotron Radiation Facility (ESRF) in France. Using those x-rays, they were able to digitally reconstruct the skeleton and identify the dinosaur's unique features.

"The takeaway message is that there are many ways to breathe," Radermacher said. "And the really interesting thing about life on Earth is that we all have different strategies to do the same thing, and we've just identified a new strategy of breathing. This shows that utilizing dinosaurs and paleontology, we can learn more about the diversity of animals on Earth and how they breathe."

Climate change is causing increased flooding and prolonged waterlogging in northern Europe, but also in many other parts of the world. This can damage meadow grasses, field crops or other plants - their leaves die, the roots rot.

The damage is caused by a lack of oxygen and the accumulation of acids. How do plants perceive this over-acidification, how do they react to it? This is what researchers from Würzburg, Jena (Germany) and Talca (Chile) describe in the journal Current Biology.

Biophysicists Dr. Tobias Maierhofer and Professor Rainer Hedrich from the Chair of Molecular Plant Physiology and Biophysics at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, were in charge of the study.

Anion channel recognises acidification

Everyone is probably familiar with the effect of over-acidification from their own experience: When exercising too hard, muscles are undersupplied with oxygen and acidosis occurs. Muscle pain and poor performance are the consequences.

"In plants, a lack of oxygen also causes acidification of the cells," says Tobias Maierhofer. The team led by the JMU researcher has now discovered the sensor in the model plant Arabidopsis thaliana (thale cress) that perceives the acidification and translates it into an electrical signal. It is a protein in the cell membrane, the anion channel SLAH3.

Super-resolution microscopy clarifies structure

Professor Markus Sauer of the JMU Chair of Biotechnology and Biophysics has developed a microscopy method that can be used to look at proteins in high resolution. With the help of his methodology, the team was able to clarify how the anion channel SLAH3 reacts during acidification.

In the non-active state, the channel is present as a complex of two subunits in the cell membrane. With a lack of oxygen, the acidity and thus the proton content in the cell increases, and protons bind to two specific amino acids of the channel.

"This protonation changes the structure of SLAH3 and the channel breaks down into its two subunits," explains Maierhofer, who is an expert on anion channels. As single copies, the two units now become conductive for anions, which leads to electrical excitation of the cell membrane.

Mutants react weaker to flooding

The electrical signal in turn triggers further reactions in the plant. Among other things, photosynthesis is reduced. "We assume that this is an adaptation to the flooding stress: the plants switch to a kind of resting state," says Maierhofer.

The JMU researchers also investigated how Arabidopsis mutants lacking SLAH3 react to flooding. These plants did not try to reduce their photosynthetic output - even though photosynthesis is not possible at all in the muddy, murky flood water where too little light reaches the leaves.

Investigating genetic control during flooding

The anion channel SLAH3 can thus convert an acidification of the cell interior directly into an electrical signal. In this way, it functions like a pH sensor.

Next, the researchers want to investigate how the electrical signal is transported in the plant and translated into a stress-avoiding response. The necessary tools for this, such as pH-insensitive mutants, are available. This makes it possible to study in detail the genetic rerouting of the physiology of plants during flooding.

The results of this basic research could prove significant for agricultural practice: "With the knowledge we are gaining, we can take a targeted approach to breed crops that are more tolerant to waterlogging," says JMU researcher Maierhofer.

Abu Dhabi, UAE, July 5, 2021: NYU Abu Dhabi (NYUAD) researchers uncovered a code that sets the genome of the liver to account for the remarkable ability for this organ to regenerate. This finding offers new insight into how the specific genes that promote regeneration can be activated when part of the liver is removed. These findings have the potential to inform the development of a new form of regenerative medicine that could help non-regenerative organs regrow in mice and humans.

While other animals can regenerate most organs, humans, mice, and other mammals can only regenerate their liver in response to an injury or when a piece is removed. NYUAD researchers hypothesized that the genes that drive regeneration in the liver would be controlled by a specific code that allows them to be activated in response to injury or resection. They hone in on the epigenome, which is the modifications on the DNA that alter the gene expression, as opposed to changing the genetic code itself.

Using a mouse liver model, the team of NYUAD researchers, led by Professor of Biology Kirsten Sadler Edepli, identified the elements of the epigenetic code present in quiescent liver cells - cells that are currently not replicating but have the ability to proliferate under the right conditions - that activate specific genes to regenerate. Genes involved in liver cell proliferation are silenced in livers that are not regenerating, but the surprising finding was that they reside in parts of the genome where most genes are active. The researchers found that these pro-regenerative genes were marked with a specific modification - H3K27me3. During regeneration, H3K27me3 is depleted from these genes, enabling their dynamic expression and driving proliferation.

In the paper Chromatin states shaped by an epigenetic code confer regenerative potential to the mouse liver published in the journal Nature Communications, Sadler and the lead research scientist on her team, Chi Zhang, present the discovery that the mouse liver contains elements of the epigenetic code that allow pro-regenerative genes to activate when signaled. Epigenetic patterns are a well-established mechanism that coordinate gene expression. However, the way epigenetic patterns contribute to gene expression in the liver or how they impact liver regeneration was previously unknown. Their research uncovered six distinct chromatin states in the mouse liver corresponding to specific epigenetic marks, providing the first chromatin map of this important organ and showing that the elements of this map are essential for liver regeneration. This finding provides a mechanism that keeps cells in the liver in a "ready-set-go" state, in preparation for the signal to regenerate.

"The secret to regeneration is locked in a code in the liver epigenome. We are now studying the 'writers' of the epigenetic code -- the enzymes that create the epigenetic marks -- to see how this epigenetic code responds to aging, as the liver's ability to regenerate declines in older animals - including humans," said Sadler. "The continued study of the liver's remarkable ability to regenerate provides promise for the development of regenerative medicine; perhaps we can even try to write the code that allows regeneration in the young liver to cells in older animals, or even to tweak this code in other organs that don't regenerate and currently can only be replaced using complex, high-risk transplants."

BUFFALO, N.Y. - How the media frame stories about science affects the public's perception about scientific accuracy and reliability, and one particular type of narrative can help ameliorate the harm to science's reputation sometimes caused by different journalistic approaches to scientific storytelling, according to a new study led by a University at Buffalo researcher.

"What our experiment shows is that the way the news media talk about science focuses too much attention on individuals in a way that doesn't accurately describe the way science actually works," says Yotam Ophir, an assistant professor of communication in UB's College of Arts and Sciences and the paper's lead author.

Ophir stresses that the public benefits from reports of scientific errors, but that benefit can be even greater if media coverage of failure includes mention that ongoing scrutiny is one of the hallmarks of the scientific enterprise.

Science is a process. It's not a set of eureka moments and brilliant discoveries. It's about a community of scholars who continuously, skeptically and constructively check each other's work, Ophir points out. And since much of the public's knowledge about science comes from the media, the absence of reporting on the community-based, self-correcting nature of science is worrisome.

"This becomes a problem when science makes mistakes - and science will inevitably make mistakes," says Ophir, an expert on the effect of media content on audiences. "When this happens, the narrative frequently shifts to a description of crisis, a moment that could lead people to lose faith in the reliability of science itself."

He says the media can better communicate the values of science by explaining how identifying and correcting scientific mistakes is evidence of a healthy scientific process. And the key is a new type of story, according to the study's findings published in the journal Public Understanding of Science.

Ophir and co-author Kathleen Hall Jamieson, a professor of communication at the University of Pennsylvania, call this story "problem explored." Its efficacy for explaining how science works emerged from their online study involving nearly 4,500 participants between the ages of 18 and 81.

To begin, the researchers performed a comprehensive content analysis. They identified that science stories generally fall into three broad categories:

There is the "honorable quest," a story that chronicles a scientific achievement with a hero scientist who has produced reliable and consequential knowledge.

The "counterfeit quest" is a story that initially reports a scientific success later found to be fraudulent, unethical or methodologically flawed.

"Science is broken" relates to issues of replicability, an inherent part of the scientific process through which scientists repeat an experiment to see if their results match those of a previous published experiment. Replicability failures are often framed as evidence that science is broken.

Ophir and Jamieson also introduced, along with a control story unrelated to science, another narrative.

"In this new condition, which we call 'problem explored,' stories of replication failures and those about prominent research that's later found to be wrong remain part of the narrative, but failures are explained to be part of the scientific process," he says.

"We found the scientific failure narratives to be most detrimental to trust in science," says Ophir. "But if you better contextualize a failure story, we found it possible to ameliorate those detrimental effects.

"Contextualizing explains the nature of science. It's this processes of reassessment and re-evaluation that makes science strong."

As an example, Ophir points to the U.S. Centers for Disease Control and Prevention's temporary halting of delivery of Johnson & Johnson's COVID-19 vaccine after reports surfaced of rare clotting events in some patients.

"The vaccine received federal approval, but was then pulled. How do you talk about this without creating distrust in science?" he asks. "The cynical way would be to use the case as evidence that science doesn't work, but that's misleading. What happened is that science worked exactly as it should. Concerns arose after approval; the data was re-examined; and scientists concluded that the risks were minimal and redeployed the vaccine."

The "problem explored" narrative, in addition to putting scientific failures in context, also generates a slipstream that restores some of the lost faith resulting from "science is broken" stories.

That the "problem explored" narrative didn't surface as part of the researchers' content analysis could be due to a number of factors. News directors might question whether such stories are newsworthy. Researchers themselves might be reluctant to share stories of successful replication as opposed to more novel advances.

But it's not just the media, and Ophir says this research is not about finger pointing.

"There is an interaction between sources and journalists," he says. "The 'science is broken' story, which is relatively recent, is something that came from scientists themselves. However well intentioned, the narrative they promoted and the way journalists accepted and framed the stories created indications of scientific unreliability."

Just as Ophir says this study suggests how a contextually framed story can provide insights into a healthy scientific process, the research also speaks to a healthy relationship between scientists and journalists.

"This is not about blame," he says. "I strongly believe that journalists do their best to serve the public. It's our job as scientists to provide them with stories that better contextualize our work."

Veterinarians at the University of California, Davis, have found that a cat's DNA alters how it responds to a life-saving medication used to treat hypertrophic cardiomyopathy, or HCM, a heart disease that affects 1 in 7 cats. The study was published in the Nature Portfolio journal, Scientific Reports.

HCM causes a cat's heart muscle to thicken. As the condition worsens, cats can form blood clots in their hearts that may later dislodge and cause extreme pain, distress and even sudden death. Clopidogrel, or Plavix®, is one of the most commonly prescribed medications used to prevent blood clots in cats with HCM.

"We were consistently seeing cats that despite being on clopidogrel, were still forming blood clots," said corresponding author Josh Stern, professor of veterinary cardiology and geneticist with the UC Davis School of Veterinary Medicine. This led Stern and the research team to begin research in this area and identify mutations in the drug pathway that looked important. Data showed that nearly 20% of cats had resistance to the clopidogrel therapy, which is widely used by practitioners all over the world.

"This study was about figuring out why some cats weren't responding as expected to clopidogrel therapy and leading us towards a more effective prescription," Stern said.

SIMPLE GENETIC TEST

Researchers began a clinical trial on cats with HCM. They first tested the cats' ability to form blood clots. The cats' owners administered clopidogrel for 14 days, and the cats were tested again. Researchers were then able to test whether genetic mutations that they had identified within the drug pathway were responsible for reducing the drug's effectiveness.

"The end result is the ability to use a simple genetic test to make an educated decision about which drug therapy may be best for preventing blood clots in cats with HCM," Stern said.

While testing like this is not yet commercially available, researchers hope that eventually veterinarians will be able to rapidly test cats with HCM for these mutations as they are making prescribing decisions.

"We are very excited to be approaching this era where personalized or precision medicine in animals can catch up to precision medicine in humans," said co-author Ronald Li, an assistant professor of veterinary emergency and critical care and coagulation researcher, whose lab conducted much of the functional testing of the anticoagulant therapies. "Just as we can't expect every human to respond to medication in the same way, we can't expect all cats to respond the same way either."

Researchers are hoping that in the future, personalized medicine for cats would allow veterinarians to test kittens for a whole host of genetic variants that would help inform medical decisions and treatments as they grow and require veterinary care.

A new national study published in Psychiatric Services finds that over a quarter of US adults with depression or anxiety symptoms reported needing mental health counseling but were not able to access it during the COVID-19 pandemic. Researchers analyzed data from nearly 70,000 adults surveyed in the US Census Household Pulse Survey in December 2020.

"Social isolation, COVID-related anxiety, disruptions in normal routines, job loss, and food insecurity have led to a surge in mental illness during the pandemic," said lead author, Jason Nagata, MD, assistant professor of pediatrics at the University of California, San Francisco.

Nearly 40% of adults in the study reported depression or anxiety symptoms during the pandemic. Overall, 12.8% of adults reported an unmet need for mental health counseling, including 25.2% of those who reported depression or anxiety symptoms. Women were nearly twice as likely to report an unmet need for mental health counseling than men. Young adults also were more likely to report an unmet need for mental health counseling than older adults.

"Women have disproportionately borne the burden of childcare and caregiving for older adults during the pandemic," said Nagata. "Young adults have felt socially isolated and experienced high rates of job loss."

"Medical professionals, social workers, and clinicians need to proactively take steps to screen for symptoms of anxiety and depression and help clients to access mental health care," said co-author, Kyle T. Ganson, PhD, assistant professor at the University of Toronto's Factor-Inwentash Faculty of Social Work. "Telepsychiatry and telemental health services can improve access for people with unmet mental health needs."

"Patients have experienced several month waitlists for counseling or therapy during the pandemic," said Nagata. "Policymakers should include more funding for mental health services as part of pandemic relief legislation and extend the use of telehealth to address the widespread unmet mental health needs of Americans."

LAWRENCE -- A new paper from a lead author based at the University of Kansas finds wetlands constructed along waterways are the most cost-effective way to reduce nitrate and sediment loads in large streams and rivers. Rather than focusing on individual farms, the research suggests conservation efforts using wetlands should be implemented at the watershed scale.

The paper, just published in the Proceedings of the National Academy of Sciences, relied on computer modeling to examine the Le Sueur River Basin in southern Minnesota, a watershed subject to runoff from intense agricultural production of corn and soybeans -- crops characteristic of the entire Upper Midwest region.

"Excessive nitrate or sediment affect local fish populations, the amount of money we have to spend to treat drinking water, and there's a downstream effect also," said lead author Amy Hansen, assistant professor of civil, environmental & architectural engineering at KU. "Our rivers integrate what's happening across the landscape, so that location that you love to go and fish or swim -- whether that continues to be a great place to fish or swim has a lot to do with the choices that people are making further upstream. Excess pollution goes to a water body downstream like a reservoir or the ocean and causes algal blooms or hypoxic or 'dead zones.' The dead zone in the northern Gulf of Mexico is directly correlated with nitrate that comes from the Mississippi River Basin."

The research team compared potential watershed approaches to improving water quality, such as cutting runoff from farms and adding wetlands, then gauged the economic costs of each. Because most methods rely on voluntary participation by individual farms and are implemented by a patchwork of different agencies, the researchers found they're less effective.

"Currently, there's individual management or conservation practices, and those include cover crop, high-precision fertilizer application, reduced tillage, constructed wetlands and ravine tip management. Those are some of the different practices we considered," Hansen said. "But management of non-point sources is voluntary in the U.S. through incentive programs, and the scale these conservation practices are often considered at is the individual farmer when a coordinated approach is much more effective. In a way, it's like a recycling program where you're saying, 'Anyone recycling one thing is better than no one recycling.' This is true, some recycling is better than no recycling, but a coordinated approach will save money and be more effective."

Hansen and her co-authors found constructed wetlands are the most effective of these practices, especially if the size and location are evaluated at the scale of a watershed -- an entire region that drains into a common waterway. The KU researcher said wetlands do two things well: They slow down water as it heads toward streams and rivers and contain vegetation and microbes that can process nutrients used as fertilizer on crops.

"Microbes and plants within wetlands are actually removing the nitrate from the water," Hansen said. "With sediment, on the other hand, what the fluvial wetlands are doing is holding water back during these high flows -- and by holding that water back you're getting lower peak stream flows, which is reducing the amount of near channel sediment that's being transported downstream."

While Hansen's research expertise is in water quality, her co-authors from the University of Minnesota, the University of California-Irvine and other institutions across the United States brought multidisciplinary perspectives to the challenge of improving agricultural water quality. The collaboration was supported by an award from the National Science Foundation.

"This work would not have been possible without the diverse expertise and perspective of the team composed of hydrologists, ecologists, geomorphologists, biogeochemists, social scientists and environmental economists," said Efi Foufoula, the lead principal investigator on the project from the University of California-Irvine. "The sustained NSF support allowed us to take a fresh view of the problem and take the time needed to collect extensive field data, build new models and engage with stakeholders. We hope that our results will affect policy and management as the clock ticks to meet the water quality targets of the state."

Indeed, a key aspect of the new study focuses on the economics of implementing small, shallow fluvial wetlands and stabilizing ravines. According to the investigators, such measures "were clearly more cost-effective than field management." But the researchers found the performance of wetlands required optimal placement, and often cost-effective wetlands can be too expensive for a single farm or one agency to put in place.

The PNAS paper concludes a comprehensive strategy must address an entire watershed as a system, combining funds from different programs and agencies and pinpointing locations for fluvial wetlands that will lead to the greatest reduction in nitrates and sediments reaching waterways.

"This work shows that we can't make real progress toward our goals for improving water quality in agricultural areas with more of a business-as-usual approach," said study co-author Jacques Finlay, a professor in the College of Biological Sciences at the University of Minnesota. "Instead, conservation actions, and the investments that support them, can be more effective if they consider the interactions that underlie the source of water pollution and how different management options influence them."

The researchers used the Le Sueur River Basin as a proof-of-concept watershed but say their findings could be applied to agricultural regions throughout the Midwest.

A unique study of ancient diamonds has shown that the basic chemical composition of the Earth's atmosphere which makes it suitable for life's explosion of diversity was laid down at least 2.7 billion years ago. Volatile gases conserved in diamonds found in ancient rocks were present in similar proportions to those found in today's mantle, which in turn indicates that there has been no fundamental change in the proportions of volatiles in the atmosphere over the last few billion years. This shows that one of the basic conditions necessary to support life, the presence of life-giving elements in sufficient quantity, appeared soon after Earth formed, and has remained fairly constant ever since.

Presenting the work at the Goldschmidt Geochemistry conference, lead researcher Dr Michael Broadly said, "The proportion and make-up of volatiles in the atmosphere reflects that found in the mantle, and we have no evidence of a significant change since these diamonds were formed 2.7 billion years ago".

Volatiles, such as hydrogen, nitrogen, neon, and carbon-bearing species are light chemical elements and compounds, which can be readily vaporised due to heat, or pressure changes. They are necessary for life, especially carbon and nitrogen. Not all planets are rich in volatiles; Earth is volatile rich, as is Venus, but Mars and the Moon lost most of their volatiles into space. Generally, a planet rich in volatiles has a better chance of sustaining life, which is why much of the search for life on planets surrounding distant stars (exoplanets) has focused on looking for volatiles.

On Earth, volatile substances mostly bubble up from the inside of the planet, and are brought to the surface through such things as volcanic eruptions. Knowing when the volatiles arrived in the Earth's atmosphere is key to understanding when the conditions on Earth were suitable for the origin and development of life, but until now there has been no way of understanding these conditions in the deep past.

Now French and Canadian researchers have used ancient diamonds as a time capsule, to examine the conditions deep inside the Earth's mantle in the distant past. Studies of the gases trapped in these diamonds show that the volatile composition of the mantle has changed little over the last 2.7 billion years.

Lead researcher, Michael Broadley (University of Lorraine, France) said "Studying the composition of the Earth's modern mantle is relatively simple. On average the mantle layer begins around 30km below the Earth's surface, and so we can collect samples thrown up by volcanoes and study the fluids and gases trapped inside. However, the constant churning of the Earth's crust via plate tectonics means that older samples have mostly been destroyed. Diamonds however, are comparatively indestructible, they're ideal time capsules".

We managed to study diamonds trapped in 2.7 billion year old highly preserved rock from Wawa, on Lake Superior in Canada. This means that the diamonds are at least as old as the rocks they are found in - probably older. It's difficult to date diamonds, so this gave us a lucky opportunity to be sure of the minimum age. These diamonds are incredibly rare, and are not like the beautiful gems we think of when we think of diamonds. We heated them to over 2000 C to transform them into graphite, which then released tiny quantities of gas for measurement".

The team measured the isotopes of Helium, Neon, and Argon, and found that they were present in similar proportions to those found in the upper mantle today. This means that there has probably been little change in the proportion of volatiles generally, and that the distribution of essential volatile elements between the mantle and the atmosphere are likely to have remained fairly stable throughout the majority of Earth's life. The mantle is the part between the Earth's crust and the core, it comprises around 84% of the Earth's volume.

Dr Broadley continued "This was a surprising result. It means the volatile-rich environment we see around us today is not a recent development, so providing the right conditions for life to develop. Our work shows that these conditions were present at least 2.7 billion years ago, but the diamonds we use may be much older, so it's likely that these conditions were set well before our 2.7 billion year threshold".

Commenting, Dr Suzette Timmerman (University of Alberta, Canada) said:

"Diamonds are unique samples, as they lock in compositions during their formation. The Wawa fibrous diamonds specifically were a great selection to study - being more than 2.7 billion years old - and they provide important clues into the volatile composition in this period, the Neoarchean period. It is interesting that the upper mantle already appears degassed more than 2.7 billion years ago. This work is an important step towards understanding the mantle (and atmosphere) in the first half of Earth's history and leads the way to further questions and research".

Dr Timmerman was not involved in this work, this is an independent comment.

Research published today has demonstrated the viability of 3D-printed tissue scaffolds that harmlessly degrade while promoting tissue regeneration following implantation.

The scaffolds showed highly promising tissue-healing performance, including the ability to support cell migration, the 'ingrowth' of tissues, and revascularisation (blood vessel growth).

Professor Andrew Dove, from the University of Birmingham's School of Chemistry, led the research group and is the lead author on the paper published in Nature Communications, which characterises the physical properties of the scaffolds, and explains how their 'shape memory' is key to promoting tissue regeneration.

Professor Dove commented: "The scaffolds have evenly distributed and interconnected pores that allow diffusion of nutrients from surrounding tissues. The shape memory means this structure is retained when the scaffold is implanted into tissues, and this supports the infiltration of cells into the scaffold while encouraging tissue regeneration and revascularisation."

The scaffolds were created using 3D printing resin 'inks' developed during a major programme of biomaterials research led by Professor Andrew Dove at the University of Birmingham and Warwick University. The resins are being commercialised under the tradename 4Degra™ by 4D Biomaterials, a spinout from University of Birmingham Enterprise and Warwick Innovations that was launched in May 2020.

The scaffolds showed several major advantages over current approaches used to fill soft tissue voids that remain after trauma or surgery, including sufficient elasticity to conform to irregular spaces, the ability to undergo compression of up to 85% before returning to their original geometry, compatibility with tissues, and non-toxic biodegradation.

The paper describes several compositions for the 4Degra™ resins that enable materials of a wide range of strengths to be manufactured. All of the compositions include a photoinitiator and a photoinhibitor to ensure the resins rapidly turn into gel on exposure to light in the visible spectrum to enable their 3D printing into a range of scaffold geometries.

The researchers showed that the materials were non toxic to cells and they also performed mechanical testing to ensure the scaffolds could regain their shape, geometry and pore size after compression, and performed tests that showed the scaffolds can fill an irregular shaped void in alginate gel which was used as a mimic of soft tissue.

Laboratory studies demonstrated that the scaffold degrades by surface erosion into non-acidic products, which means the scaffold structure allows for slow, continuous tissue infiltration.

The findings were confirmed in a mouse model that simulates implantation into adipose (fat) tissue. These studies showed infiltration of adipocytes and fibroblasts and vascularisation at two months, and a tissue arrangement and macrophage presence that was indicative of normal tissue restoration rather than damaged, scarred tissue or an inflammatory response.

At four months, the researchers found small, mature blood vessels in the surrounding tissue. The scaffolds also demonstrated excellent biocompatibility. The collagen capsule formed around implants was less than 200 μm thick, which is well below the 500 μm threshold used for biocompatibility in other studies, and there was no calcification or necrosis.

Also at four months, 80% of the scaffold was still present, demonstrating the slow degradation predicted by the laboratory studies, and indicating the scaffolds would provide support for more than a year, allowing sufficient time for mature tissue ingrowth. The controls, which used poly(L-lactic acid) (PLLA) as a comparator, did not show a significant reduction over the four month period.

Professor Dove comments: "3D printed materials have received a lot of attention in the tissue engineering world. However void-filling materials to provide mechanical support, biocompatibility, and surface erosion characteristics that ensure consistent tissue support during the healing process, and this means a fourth dimension (time) needs to be considered in material design.

"We have demonstrated that it's possible to produce highly porous scaffolds with shape memory, and our processes and materials will enable production of self-fitting scaffolds that take on soft tissue void geometry in a minimally invasive surgery without deforming or applying pressure to the surrounding tissues. Over time, the scaffold erodes with minimal swelling, allowing slow continuous tissue infiltration without mechanical degradation."

4D Biomaterials has made fast progress in scaling up production of the 4Degra™ resin-inks at its laboratory in MediCity, Nottingham (UK) and is now offering technical grade material for commercial supply to 3D printing companies and medical device manufacturers.

CEO Phil Smith said "We are looking to collaborate with innovative companies in Europe and North America to develop a new generation of 3D-printed medical devices that translate the unique advantages of the 4Degra™ resin-ink platform into improved treatment outcomes for patients". With the first customer shipments dispatched and a funding round about to close, Phil added "We will be making further announcements shortly."

Researchers at Uppsala University have discovered lymph node-like structures close to the tumour in brain cancer patients, where immune cells can be activated to attack the tumour. They also found that immunotherapy enhanced the formation of these structures in a mouse model. This discovery suggests new opportunities to regulate the anti-tumour response of the immune system.

Glioma is a deadly brain tumour with a dismal prognosis. One reason why brain tumours are very hard to treat is that our immune system, which is designed to detect and destroy foreign cells including cancer cells, cannot easily reach the tumour site due to the barriers that surround the brain.

To fight a developing tumour, killer immune cells such as T lymphocytes must be activated and primed in our lymph nodes, before travelling to the tumour site to effectively kill the cancer cells. Because of the barriers around the brain, it is a challenging process for T lymphocytes to reach the tumour.

In the study now published in the journal Nature Communications, the researchers describe their discovery of structures similar to lymph nodes in the brain where T lymphocytes could be activated.

"It was extremely exciting to discover for the first time the presence of lymph node-like structures in glioma patients. These structures are known as tertiary lymphoid structures (TLS) and they are not found in healthy individuals. They have all the components needed to support lymphocyte activation on-site which means that they could have a positive effect on the anti-tumour immune response," says Alessandra Vaccaro, PhD student at the Department of Immunology, Genetics and Pathology and shared first author of the study.

The researchers also showed that the formation of TLS in the brain can be induced by a type of immunotherapy in glioma-bearing mice. Indeed, when they treated the mice with immunostimulatory antibodies called αCD40, the formation of TLS was enhanced and always occurred in proximity to tumours.

"Learning that immunotherapies can modulate the formation of tertiary lymphoid structures in the brain offers exciting opportunities to find new ways of regulating the anti-tumour immune response in glioma," says Anna Dimberg who has led the study.

αCD40 is currently being tested to treat brain tumours in a number of clinical trials. In the study now published, the researchers found that while αCD40 boosted TLS formation, it also counterproductively inhibited the tumour-killing ability of the T lymphocytes. The study has therefore provided important insights into the multifaceted effects of αCD40 therapy.

Land plants - plants that live primarily in terrestrial habitats and form vegetation on earth - are anchored to the ground through their roots, and their performance depends on both the belowground soil conditions and the aboveground climate. Plants utilize sunlight to grow through the process of photosynthesis where light energy is converted to chemical energy in chloroplasts, the powerhouses of plant cells. Therefore, the amount and quality of light perceived by chloroplasts through light absorbing pigments, such as chlorophyll, is a defining factor in plant growth and health. A substantial amount of the chemical compounds produced during the conversion of light energy to chemical energy, termed photoassimilates (mainly sugars), is translocated to the plant root compartment and invested in the surrounding soil to sustain microbial growth. Consequently, roots harbour complex microbial communities of bacteria and filamentous eukaryotes (i.e., fungi and oomycetes), and the composition of these communities profoundly influences plant performance. However, the extent to which plants can take advantage of belowground microbes to orchestrate aboveground stress responses remains largely unexplored. Now, in a new study published in Nature Plants, Stéphane Hacquard and his colleagues from the Department of Plant-Microbe Interactions at the MPIPZ in Cologne, Germany, shed light on these aboveground-belowground connections.

To tackle this question, the first author of the study Shiji Hou performed experiments where the aboveground light conditions and the belowground microbial conditions could be controlled. By comparing the growth of Arabidopsis thaliana (Thale Cress) grown in the absence of root microbes (i.e., germ-free) to those colonized by a complex community of 183 bacteria, 24 fungi and 7 oomycetes, the researchers observed that the presence of microbes rescued the plant growth-deficiency observed under low light conditions. Inoculation experiments with leaf pathogens further indicated that plants colonized by microbes were also more resistant to aboveground leaf pathogens than germ-free control plants, indicating that the presence of root microbes can promote both plant growth and defense under low light.

By comparing growth and defense responses of colonized plants between the two light conditions, the scientists observed that investment in growth under low light conditions came at the cost of defense, since microbiota-induced defense responses were reduced and plants were more susceptible to leaf pathogens under low light. Based on this observation, the authors of the study then hypothesized that when light conditions are suboptimal, plants favor microbe-induced growth over microbe-induced defense responses. To test this hypothesis, the researchers screened different A. thaliana mutants to identify those that failed to invest in growth under low light. Consistent with their hypothesis, the identified mutants were better at resisting leaf pathogens instead. Furthermore, the scientists found that the presence of the host transcription factor MYC2 was crucial to tip the balance in favor of microbiota-induced growth instead of microbiota-induced defense under low light conditions.

The researchers then went on to investigate whether the make-up of the microbial community belowground could explain aboveground investment in growth at the expense of defense under low light. To do this, they analyzed the composition of the root microbiota across the different A. thaliana mutants and observed that the bacterial community composition was markedly different depending on whether the different plants invested in growth under low light. This experiment led to the identification of 67 bacterial strains that were predicted to be associated with plant growth rescue under low light. To test a potential causal link, the researchers prepared three different bacterial communities composed of either: 1) all 183 strains, 2) the 183 strains lacking the 67 strains predicted to be important for growth rescue or 3) the 67 strains alone. Remarkably, A. thaliana wild-type plants colonized with the 67-member community invested in growth under low light, whereas those colonized by the community lacking these bacterial strains did not, instead favoring better resistance to leaf infection by pathogens.

In the words of study lead Stéphane Hacquard: "Our results suggest that plant growth and defense responses are engaged in different feedback loops with the root microbiota depending on aboveground light conditions. It is likely that light-induced change in root exudation profiles is an important mechanism that stimulates the growth of particular beneficial bacterial root commensals that boost plant growth, in the expense of defense responses under low light". The observation that microbiota-root-shoot-circuits exist in plants is reminiscent of recent results obtained in the context of the microbiota-gut-brain axis in animals, where a direct link between gut commensals and brain functions was uncovered. The results suggest that bacterial root and gut commensals have important functions in modulating stress responses not only locally, but also in distant host organs.

These findings have important applications for utilizing belowground microbes to promote aboveground stress responses in plants. By applying the knowledge gained in this study it would now be conceivable to design synthetic microbial communities with modular functions that could be used to promote plant resistance to particular biotic or abiotic stresses, and ultimately promote plant health in nature.

An international study has elucidated the structure of a protein that is required for the assembly and stability of photosynthetic membranes.

Plants, algae and cyanobacteria convert carbon dioxide and water into biomass and oxygen with the aid of photosynthesis. This process forms the basis of most forms of life on Earth. Global warming is exposing photosynthetic organisms to increasing levels of stress. This reduces growth rates, and in the longer term presents a threat to food supplies for human populations. An international project, in which Ludwig-Maximilians-Universitaet (LMU) in Munich biologist Kärin Nickelsen and his research group played a significant role, has now determined the three-dimensional structure of a protein involved in the formation and maintenance of the membranes in which photosynthesis takes place. The insights provided by the study will facilitate biotechnological efforts to boost the ability of plants to cope with environmental stresses.

The initial steps in photosynthesis take place within the 'thylakoid' membranes, which harbor pigment-protein complexes that absorb energy from sunlight. It has been known for decades that, in virtually all photosynthetic organisms, a protein called VIPP1 (which stands for 'vesicle-inducing protein in plastids') is indispensable for the assembly of thylakoids. "However, how VIPP1 actually performs this essential function has remained enigmatic up to now," says Steffen Heinz, a postdoc in Nickelsen's group and joint first author of the new publication. Thanks to the new study, which was led by the Helmholtz Zentrum München, researchers now know a great deal more.

Assembly of photosynthetic membranes

The team used cryo-electron microscopy to determine the three-dimensional structure of VIPP1 at high resolution. Analysis of this structure, in combination with functional investigation of the protein's mode of action, demonstrated how small numbers of VIPP1 molecules form short strands, which are interwoven to form a basket-like structure. This then serves as a scaffold for the assembly of the thylakoid membrane, and determines its curvature.  Using a related technique known as cryo-electron tomography, the scientists were also able to image VIPP1 membranes in their natural state in algal cells. By introducing site-specific mutations into VIPP1, they showed that the interaction of VIPP1 with thylakoid membranes is vital for the maintenance of their structural integrity under high levels of light stress. This finding demonstrates that the protein not only mediates the assembly of thylakoids, but also plays a role in enabling them to adapt to environmental fluctuations.

The results provide the basis for a better understanding of the mechanisms that underlie the formation and stabilization of thylakoids. They will also open up new opportunities to enhance the ability of green plants to withstand extreme environmental stresses. 

East Hanover, NJ. July 2, 2021. Among wheelchair users with spinal cord injury 42 percent reported adverse consequences related to needing wheelchair repair, according to a team of experts in spinal cord injury rehabilitation. The research team, comprised of investigators from the Spinal Cord Injury Model System, determined that this ongoing problem requires action such as higher standards of wheelchair performance, access to faster repair service, and enhanced user training on wheelchair maintenance and repair.

The article, "Factors Influencing Incidence of Wheelchair Repairs and Consequences Among Individuals with Spinal Cord Injury" (doi: 10.1016/j.apmr.2021.01.094) was published online in Archives of Physical Medicine and Rehabilitation on April 9, 2021.

Denise C. Fyffe, PhD, and Trevor A. Dyson-Hudson, MD, of Kessler Foundation co-authored this manuscript with Lynn A. Worobey, PhD, DPT, ATP (lead author), and Michael L. Boninger, MD, of University of Pittsburgh and Veterans Affairs Pittsburgh Healthcare System; Allen W. Heinemann, PhD, of Shirley Ryan Ability Lab; Kim D. Anderson, PhD, of MetroHealth Rehabilitation Institute; and Theresa Berner, OTR/L, ATP, of The Ohio State University Wexner Medical Center.

For many people with spinal cord injury, wheelchairs are a lifeline. They enable mobility, which in turn facilitates independence and community engagement. In addition, wheelchairs help people manage pain and discomfort by enabling them to change position and manage pressure. It cannot be overstated how critical it is for this population--which, at last count in 2015, numbers 2.7 million in the United States--to have a working wheelchair.

Yet research shows that up to 88 percent of wheelchair users experience a failure, leaving them without a means to get to work, attend medical appointments or educational classes, or maintain a social life outside the home. In some cases, wheelchair failure can result in injury, with breakdowns making people with spinal cord injury almost twice as likely to be re-hospitalized than those with a working wheelchair.

Currently, there are no clinical or industry standards for expected wheelchair maintenance, and fewer than 50 percent of wheelchair users are trained in wheelchair maintenance. This lack of official guidance prevents the implementation of best practices that could significantly reduce adverse consequences related to wheelchair breakdown and time for repair.

In this study, researchers surveyed 533 wheelchair users at nine Spinal Cord Injury Model Systems Centers located across the United States about their experience over the prior six months. The research team aimed to determine how often people require wheelchair repairs, and what the consequences were of needing a repair; how long these consequences were experienced; and whether any trends emerged regarding which users, or which types of wheelchairs, are more likely to need repair.

"We identified a range of adverse consequences of being without a wheelchair that aligned with the lived experience of wheelchair users," said co-author Dr. Dyson-Hudson, co-director of the Northern New Jersey Spinal Cord Injury System. "The list includes being stranded outside the home or in the home, getting an injury, missing work, school, or a medical appointment, or missing other social events. Our hope is that by finding out more about the most common reasons people need repairs, we can take targeted action to reduce the incidence of repair and the associated cost and other consequences."

The results demonstrated that more than 50 percent of wheelchair users needed wheelchair repairs within the last six months, with significant associated financial cost and personal consequences. Power wheelchair users and those who were Black were more likely to experience repairs and consequences. For many, consequences lasted for more than two weeks.

Furthermore, adverse consequences appear to hit those most vulnerable with the least financial resources, including users who rely on public insurance. Many participants reported that the cost of repair limited participation inside and outside the home, so as to reduce the risk of damaging the wheelchair. Others reported that the cost of repair prevented them from repairing the wheelchair altogether.

"Based on what we learned in the survey, there are some simple measures, such as providing a borrowed wheelchair to people so they have mobility while their chair is being repaired, that could reduce the adverse consequences," said Dr. Dyson-Hudson. "Other facilitators include increasing the speed of repairs, training people in wheelchair maintenance, and routinely scheduling follow-up appointments after a repair is made, so any subsequent problems can be caught early."

This insight is the result of the close collaboration of several research groups at the Max Planck Institute for Marine Microbiology. A team around Cedric Hahn and Gunter Wegener recently discovered ethane-degrading microbes at hydrothermal vents of the Guaymas Basin at a water depth of 2,000 meters in the Gulf of California. They named it Ethanoperedens thermophilum, which means "heat-loving ethane-eater". Cedric Hahn a PhD student from the research group Molecular Ecology cultured the ethane-degrading microbes in the laboratory. Hahn, Wegener and colleagues of the research group Microbial Metabolism, Tristan Wagner and Olivier Lemaire took a closer look at these microorganisms. This collaborative work unraveled the secrets behind the ethane fixation. "We were astonished by what we found. Besides a global similarity, some features of the enzyme differ fundamentally from its counterpart - the enzyme responsible for the degradation of methane," says Gunter Wegener, scientist in the Research Group for Deep-Sea Ecology and Technology.

Ethane-eaters depend on the same enzyme as Methane-eaters

In deep-sea sediments, geothermal heat leads to the degradation of organic matter to oil and natural gases such as ethane. The ethane is consumed by different microorganisms that form a so-called consortium: archaea, which break down the natural gas, and bacteria, which couple the electrons released in the process to the reduction of sulfate, an abundant compound in the ocean. The discovery of the ethane-eating microbes has brought a breath of fresh air to the research. Compared to microbes eating methane that take a lot of time to grow, the ethane specialists grow much faster and double every week. Thus, the time of biomass production is reduced, which allow attempts of purification and characterization of key enzymes catalyzing the oxidation of natural gas.

To test similarities between the enzymes catalyzing the activation of ethane and methane, Cedric Hahn added a well-known molecular inhibitor of methane oxidation to his culture. This treatment abolished also ethane oxidation. "This suggested that the ethane-oxidizing archaea activate ethane in similar enzymatic reactions as those acting in methane degradation/generation" says Cedric Hahn. Such enzymes are a key expertise of Tristan Wagner who studied them for several years.

A structure visualized at an astonishing level of precision

Cedric Hahn and Olivier Lemaire, the two first authors of the paper now published in Science, then tried to purify the enzyme responsible for ethane fixation. "The project was highly challenging," says Olivier Lemaire. "Usually we purify the enzymes from much larger amounts of biomass from a culture containing one microorganism. However, we finally yielded sufficient amounts of pure enzymes for structural analyses."

The next critical step was to obtain crystals of the enzyme to determine its tri-dimensional structure. "X-ray crystallography gave previous excellent results on this group of enzymes" says Tristan Wagner, head of the Microbial Metabolism research group and expert on this technique. "We analyzed these crystals by X-ray diffraction and solved the enzyme structure at an unprecedented atomic resolution. We can thus determine the position of individual atoms and obtain therefore an extremely precise picture of the structure".

The structure exhibits several unprecedented features. "We noticed that the catalytic chamber in which the chemical reaction takes place is twice as large as in enzymes capturing methane, which makes sense considering that ethane is bigger than methane," says Olivier Lemaire. The cofactor, catalyst of the reaction, contains two additional methyl groups. These methyl groups were confirmed by Jörg Kahnt from the Max Planck Institute for Terrestrial Microbiology, a worldwide expert on this cofactor. "We found a protein that could be responsible for these methylations, and it is only found in ethane-consumers," says Cedric Hahn. Since the chamber is more voluminous, a normal cofactor would simply not fit properly and would impair the reaction. The methylations on the cofactor anchor it in the correct position.

Furthermore, the enzyme contains a tunnel connecting the exterior to the catalytic chamber. This tunnel does not exist in any characterized similar enzymes. The researchers experimentally proved the existence of this tunnel through a collaboration with Sylvain Engilberge at the Paul Scherrer Institute in Switzerland, where the protein crystals were gassed with xenon. Xenon was detected in the catalytic chamber and the predicted gas tunnel, proving its existence. The tunnel is maintained and stabilized by modified amino acids and additional extensions.

Now the spotlight turns to propane and butane

The enzyme structure illustrates how these microbes from geothermally active seeps became specialized in ethane capture. This work allows a deeper understanding of the first step in ethane degradation, the only source of energy of these archaea. "Our finding that the enzyme responsible for the process has specific traits to recognize ethane rather than other alkanes is a big step forward, however the understanding of the whole degradation process is still a long way off", concludes Tristan Wagner.

So, how to proceed the research? "Our previous works show that the activation of longer alkanes requires similar enzymes" says Gunter Wegener. "As a next step, we want to investigate what could be the specific features of the enzymes that catalyze the activation of propane and butane".