Carbon dioxide levels reflect COVID-19 risk

University of Colorado Boulder duo confirms value of measuring carbon dioxide to estimate infection risk

UNIVERSITY OF COLORADO AT BOULDER

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IMAGE: BECAUSE INFECTIOUS PEOPLE EXHALE CO2 AND VIRUSES TOGETHER, TRACKING CARBON DIOXIDE LEVELS INDOORS IS AN INEXPENSIVE AND POWERFUL WAY TO MONITOR THE RISK OF PEOPLE GETTING COVID-19, ACCORDING TO A... view more 

CREDIT: IMAGE COURTESY OF SPANISH NEWSPAPER EL PAIS: HTTPS://TINYURL.COM/C2JSB8R9

Tracking carbon dioxide levels indoors is an inexpensive and powerful way to monitor the risk of people getting COVID-19, according to new research from the Cooperative Institute for Research in Environmental Sciences (CIRES) and the University of Colorado Boulder. In any given indoor environment, when excess CO2 levels double, the risk of transmission also roughly doubles, two scientists reported this week in Environmental Science & Technology Letters.

The chemists relied on a simple fact already put to use by other researchers more than a decade ago: Infectious people exhale airborne viruses at the same time as they exhale carbon dioxide. That means CO2 can serve as a "proxy" for the number of viruses in the air.

"You're never safe indoors sharing air with others, but you can reduce the risk," said Jose-Luis Jimenez, co-author of the new assessment, a CIRES Fellow and professor of chemistry at the University of Colorado Boulder.

"And CO2 monitoring is really the only low-cost and practical option we have for monitoring," said Zhe Peng, a CIRES and chemistry researcher, and lead author of the new paper. "There is nothing else."

For many months, researchers around the world have been searching for a way to continually monitor COVID-19 infection risk indoors, whether in churches or bars, buses or hospitals. Some are developing instruments that can detect viruses in the air continually, to warn of a spike or to indicate relative safety. Others tested existing laboratory-grade equipment that costs tens of thousands of dollars.

Jimenez and colleagues turned to commercially available carbon dioxide monitors, which can cost just a few hundred dollars. First, they confirmed in the laboratory that the detectors were accurate. Then, they created a mathematical "box model" of how an infected person exhales viruses and CO2, how others in the room inhaled and exhaled, and how the viruses and gas accumulate in the air of a room or are removed by ventilation. The model takes into consideration infection numbers in the local community, but it does not detail air flow through rooms--that kind of modeling requires expensive, custom analysis for each room.

It's important to understand that there is no single CO2 level at which a person can assume a shared indoor space is "safe," Peng emphasized. That's partly because activity matters: Are people in the room singing and talking loudly or exercising, or are they sitting quietly and reading or resting? A CO2 level of 1,000 ppm, which is well above outside levels of about 400 ppm, could be relatively safe in a quiet library with masks but not in an active gym without masks.

But in each indoor space, the model can illuminate "relative" risk: If CO2 levels in a gym drop from 2,800 to 1,000 ppm (~2,400 above background levels to 600), the risk of COVID-19 transmission drops, too, to one-quarter of the original risk. In the library, if an influx of people makes CO2 jump from 800 to 1,600 (400 to 1,200 above background), COVID transmission risk triples.

In the new paper, Peng and Jimenez also shared a set of mathematical formulae and tools that experts in building systems and public health can use to pin down actual, not just relative, risk. But the most important conclusion is that to minimize risk, keep the CO2 levels in all the spaces where we share air as low as practically possible.

"Wherever you are sharing air, the lower the CO2, the lower risk of infection," Jimenez said.

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Surgical sutures inspired by human tendons

Next-generation sutures can deliver drugs, prevent infections, and monitor wounds

MCGILL UNIVERSITY

Research News

 

IMAGE: SCANNING ELECTRON MICROSCOPE IMAGE OF THE CROSS-SECTION OF TGS SUTURE. view more 

CREDIT: ZHENWEI MA, MCGILL UNIVERSITY

Sutures are used to close wounds and speed up the natural healing process, but they can also complicate matters by causing damage to soft tissues with their stiff fibers. To remedy the problem, researchers from Montreal have developed innovative tough gel sheathed (TGS) sutures inspired by the human tendon.

These next-generation sutures contain a slippery, yet tough gel envelop, imitating the structure of soft connective tissues. In putting the TGS sutures to the test, the researchers found that the nearly frictionless gel surface mitigated the damage typically caused by traditional sutures.

Conventional sutures have been around for centuries and are used to hold wounds together until the healing process is complete. But they are far from ideal for tissue repair. The rough fibers can slice and damage already fragile tissues, leading to discomfort and post-surgery complications.

Part of the problem lies in the mismatch between our soft tissues and the rigid sutures that rub against contacting tissue, say the researchers from McGill University and the INRS Énergie Matériaux Télécommunications Research Centre.

Inspired by the tendon

To tackle the problem, the team developed a new technology that mimics the mechanics of tendons. "Our design is inspired by the human body, the endotenon sheath, which is both tough and strong due to its double-network structure. It binds collagen fibers together while its elastin network strengthens it," says lead author Zhenwei Ma, a PhD student under the supervision of Assistant Professor Jianyu Li at McGill University.

The endotenon sheath not only forms a slippery surface to reduce friction with surrounding tissues in joints, but it also delivers necessary materials for tissue repair in a tendon injury. In the same way, TGS sutures can be engineered to provide personalized medicine based on a patient's needs, say the researchers.

Personalized wound treatment

"This technology provides a versatile tool for advanced wound management. We believe it could be used to deliver drugs, prevent infections, or even monitor wounds with near-infrared imaging," says Li of the Department of Mechanical Engineering.

"The ability to monitor wounds locally and adjust the treatment strategy for better healing is an exciting direction to explore," says Li, who is also a Canada Research Chair in Biomaterials and Musculoskeletal Health.

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About this study

"Bioinspired tough gel sheath for robust and versatile surface functionalization" by Zhenwei Ma, Zhen Yang, Qiman Gao, Guangyu Bao, Amin Valiei, Fan Yang, Ran Huo, Chen Wang, Guolong Song, Dongling Ma, Zu-Hua Gao, and Jianyu Li was published in Science Advances.

DOI: http://doi.org/10.1126/sciadv.abc3012
Link: https://advances.sciencemag.org/content/7/15/eabc3012

New biosensor makes control hormone auxin visible in cells

Scientists at the University of Bayreuth and the Max Planck Institute for Developmental Biology in Tübingen have developed a novel sensor that provides real-time insights into the inner life of plants

UNIVERSITÄT BAYREUTH

Research News

 

IMAGE: SEEDLING OF THALE CRESS (ARABIDOPSIS THALIANA). THE MAGNIFYING GLASS SHOWS THE ROOT TIP. THE CELL NUCLEI ARE COLOURED FROM BLUE TO GREEN AND YELLOW TO RED AS THE AMOUNT OF... view more 

CREDIT: GRAPHIC: S. SHANMUGARATNAM, A.C. STIEL, M. KOLB.

The hormone auxin is of central importance for the development of plants. Scientists at the University of Bayreuth and the Max Planck Institute for Developmental Biology in Tübingen have now developed a novel sensor that makes the spatial distribution of auxin in the cells of living plants visible in real time. The sensor opens up completely new insights into the inner workings of plants for researchers. Moreover, the influences of changing environmental conditions on growth can now also be quickly detected. The team presents its research results in the journal Nature.

The effects of the plant hormone auxin were first described scientifically almost 100 years ago. Today we know that auxin controls countless processes in plant cells - be it in the development of the embryo in the seed, the formation of the root system, or the orientation of growth to incident sunlight. In all cases, the hormone has the function of coordinating the plant's responses to external stimuli. To do this, it must always be present in the cell tissue where the response to an external stimulus needs to be triggered. Indeed, it is often the case that auxin is needed at very different places in the cell tissue within a very short space of time. This leads to rapid spatial redistribution. With the new biosensor, called AuxSen for short, the dynamics of these processes can be observed in real time for the first time. Light signals indicate where the auxin is located in the cell tissue. What is special about this sensor is that it is not a technical device that has to be introduced into the plants, but an artificial protein that the plants are engineered to produce themselves.

The application of the biosensor has already led to some surprising findings. One example is the rapid redistribution of auxin when a plant is turned upside down. When the root tip no longer points downwards but diagonally upwards, the auxin molecules responsible for root growth collect on the new underside of the root tip within just one minute. And upon being placed right-side up, the old distribution of auxin is restored after just one minute.

Protein biochemistry and plant biology in combination

The development of the biosensor is the result of many years of interdisciplinary collaboration. A team led by Prof. Dr. Birte Höcker, Professor of Protein Design at the University of Bayreuth, and a team led by Prof. Dr. Gerd Jürgens at the Max Planck Institute for Developmental Biology, have combined their knowledge and many years of experience. "It is to be expected that the new biosensor will uncover many more unforeseen insights into the inner workings of plants and their reaction to external stimuli over the coming years. The development of the sensor has been a long process in which we have gained fundamental insights into how proteins can be selectively altered to bind specific small molecules," says Prof. Dr. Birte Höcker.

"There is already a great deal of interest in the new sensor, and it is to be expected that optimised variants of AuxSen will be developed over the next few years to enable even better analysis of the diverse auxin-regulated processes in plants. With our new publication in Nature, we wish to encourage the scientific community to increase research in this direction. Our results so far are an example of how fruitful interdisciplinary cooperation can be in this field," explains Prof. Dr. Gerd Jürgens from the Max Planck Institute for Developmental Biology in Tübingen.

Advantages of the biosensor: High signal quality and optimal binding strength to auxin

At the beginning of the biosensor's development was a protein in the bacterium E. coli, which binds to the amino acid tryptophan, but much more poorly to the chemically-related auxin. This protein was coupled with two proteins that fluoresce when excited with light of a certain wavelength. If these partner proteins come very close to each other, their fluorescence increases considerably. A fluorescence resonance energy transfer (FRET) then occurs. The next step was crucial: the initial protein was to be genetically modified so that it binds better to auxin and less well to tryptophan. At the same time, the FRET effect of the partner molecules should always occur when the protein binds to auxin, and only then. With this goal in mind, about 2,000 variants of the protein were created and tested until finally a molecule was found that fulfilled all requirements. Thus, the biosensor AuxSen was born: strong fluorescent signals indicating where in the cell tissue the vital hormone is located.

Another challenge was to enable plants to produce AuxSen themselves. On the one hand, it had to be ensured that AuxSen would bind to the existing auxin molecules in as many cells as possible. This was the only way to map the spatial distribution of auxin in the cell completely and to produce high signal quality. On the other hand, however, the auxin molecules were not to be permanently prevented from fulfilling their original tasks in the plant organism because of binding to AuxSen. Nevertheless, the two research teams succeeded in finding a compromise solution. Plants were genetically modified in such a way as to produce a large amount of AuxSen throughout their cell tissue. But this would only happen when stimulated to do so by a special substance - and then only for a short time. In this way, the biosensor provides precise snapshots of auxin distribution in cells without permanently affecting the processes controlled by auxin.

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Better solutions for making hydrogen may lie just at the surface

DOE/ARGONNE NATIONAL LABORATORY

Research News

 

IMAGE: THE UNIQUE INTERACTIONS BETWEEN PEROVSKITE OXIDE, ITS CHANGING SURFACE LAYER, AND IRON SPECIES THAT ARE ACTIVE TOWARD THE OER PAVES A NEW PATH FOR THE DESIGN OF ACTIVE AND STABLE... view more 

CREDIT: ARGONNE NATIONAL LABORATORY

A clean energy future propelled by hydrogen fuel depends on figuring out how to reliably and efficiently split water. That's because, even though hydrogen is abundant, it must be derived from another substance that contains it -- and today, that substance is often methane gas. Scientists are seeking ways to isolate this energy-carrying element without using fossil fuels. That would pave the way for hydrogen-fueled cars, for example, that emit only water and warm air at the tailpipe.

Water, or H2O, unites hydrogen and oxygen. Hydrogen atoms in the form of molecular hydrogen must be separated out from this compound. That process depends on a key -- but often slow -- step: the oxygen evolution reaction (OER). The OER is what frees up molecular oxygen from water, and controlling this reaction is important not only to hydrogen production but a variety of chemical processes, including ones found in batteries.

"The oxygen evolution reaction is a part of so many processes, so the applicability here is quite broad." -- Pietro Papa Lopes, Argonne assistant scientist

A study led by scientists at the U.S. Department of Energy's (DOE) Argonne National Laboratory illuminates a shape-shifting quality in perovskite oxides, a promising type of material for speeding up the OER. Perovskite oxides encompass a range of compounds that all have a similar crystalline structure. They typically contain an alkaline earth metal or lanthanides such as La and Sr in the A-site, and a transition metal such as Co in the B-site, combined with oxygen in the formula ABO3. The research lends insight that could be used to design new materials not only for making renewable fuels but also storing energy.

Perovskite oxides can bring about the OER, and they are less expensive than precious metals such as iridium or ruthenium that also do the job. But perovskite oxides are not as active (in other words, efficient at accelerating the OER) as these metals, and they tend to slowly degrade.

"Understanding how these materials can be active and stable was a big driving force for us," said Pietro Papa Lopes, an assistant scientist in Argonne's Materials Science division who led the study. "We wanted to explore the relationship between these two properties and how that connects to the properties of the perovskite itself."

Previous research has focused on the bulk properties of perovskite materials and how those relate to the OER activity. The researchers wondered, however, whether there was more to the story. After all, the surface of a material, where it reacts with its surroundings, can be completely different from the rest. Examples like this are everywhere in nature: think of a halved avocado that quickly browns where it meets the air but remains green inside. For perovskite materials, a surface that becomes different from the bulk could have important implications for how we understand their properties.

In water electrolyzer systems, which split water into hydrogen and oxygen, perovskite oxides interact with an electrolyte made of water and special salt species, creating an interface that allows the device to operate. As electrical current is applied, that interface is critical in kicking off the water-splitting process. "The material's surface is the most important aspect of how the oxygen evolution reaction will proceed: How much voltage you need, and how much oxygen and hydrogen you're going to be producing," Lopes said.

Not only is the perovskite oxide's surface different from the rest of the material, it also changes over time. "Once it's in an electrochemical system, the perovskite surface evolves and turns into a thin, amorphous film," Lopes said. "It's never really the same as the material you start with."

The researchers combined theoretical calculations and experiments to determine how the surface of a perovskite material evolves during the OER. To do so with precision, they studied lanthanum cobalt oxide perovskite and tuned it by "doping" the lanthanum with strontium, a more reactive metal. The more strontium was added to the initial material, the faster its surface evolved and became active for the OER -- a process the researchers were able to observe at atomic resolution with transmission electron microscopy. The researchers found that strontium dissolution and oxygen loss from the perovskite were driving the formation of this amorphous surface layer, which was further explained by computational modelling performed using the Center for Nanoscale Materials, a DOE Office of Science User Facility.

"The last missing piece to understand why the perovskites were active towards the OER was to explore the role of small amounts of iron present in the electrolyte," Lopes said. The same group of researchers recently discovered that traces of iron can improve the OER on other amorphous oxide surfaces. Once they determined that a perovskite surface evolves into an amorphous oxide, then it became clear why iron was so important.

"Computational studies help scientists understand reaction mechanisms that involve both the perovskite surface and the electrolyte," said Peter Zapol, a physicist at Argonne and study co-author. "We focused on reaction mechanisms that drive both activity and stability trends in perovskite materials. This is not typically done in computational studies, which tend to focus solely on the reaction mechanisms responsible for the activity."

The study found that the perovskite oxide's surface evolved into a cobalt-rich amorphous film just a few nanometers thick. When iron was present in the electrolyte, the iron helped accelerate the OER, while the cobalt-rich film had a stabilizing effect on the iron, keeping it active at the surface.

The results suggest new potential strategies for designing perovskite materials -- one can imagine creating a two-layer system, Lopes said, that is even more stable and capable of promoting the OER.

"The OER is a part of so many processes, so the applicability here is quite broad," Lopes said. "Understanding the dynamics of materials and their effect on the surface processes is how we can make energy conversion and storage systems better, more efficient and affordable."

CAPTION

Surface evolution of a lanthanum cobalt oxide perovskite during electrochemical cycling occurs via A-site dissolution and oxygen lattice evolution, forming an amorphous film that is active for oxygen evolution.

CREDIT

Argonne National Laboratory

The study is described in a paper published and highlighted on the Feb. 24 cover of the Journal of the American Chemical Society, "Dynamically Stable Active Sites from Surface Evolution of Perovskite Materials during the Oxygen Evolution." In addition to Lopes and Zapol, coauthors include Dong Young Chung, Hong Zheng, Pedro Farinazzo Bergamo Dias Martins, Dusan Strmcnik, Vojislav Stamenkovic, Nenad Markovic and John Mitchell at Argonne; Xue Rui and Robert Klie at the University of Illinois at Chicago; and Haiying He at Valparaiso University. This research was funded by DOE's Office of Basic Energy Sciences.

About Argonne's Center for Nanoscale Materials

The Center for Nanoscale Materials is one of the five DOE Nanoscale Science Research Centers, premier national user facilities for interdisciplinary research at the nanoscale supported by the DOE Office of Science. Together the NSRCs comprise a suite of complementary facilities that provide researchers with state-of-the-art capabilities to fabricate, process, characterize and model nanoscale materials, and constitute the largest infrastructure investment of the National Nanotechnology Initiative. The NSRCs are located at DOE's Argonne, Brookhaven, Lawrence Berkeley, Oak Ridge, Sandia and Los Alamos National Laboratories. For more information about the DOE NSRCs, please visit https://science.osti.gov/User-Facilities/User-Facilities-at-a-Glance.

Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation's first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America's scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy's Office of Science.

The U.S. Department of Energy's Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science.

Why our brains miss opportunities to improve through subtraction

UNIVERSITY OF VIRGINIA SCHOOL OF ENGINEERING AND APPLIED SCIENCE

Research News

 

IMAGE: HOW WOULD YOU STABILIZE THIS LEGO STRUCTURE TO SUPPORT THE WEIGHT OF A MASONRY BRICK PLACED ON THE TOP PLATFORM? UNIVERSITY OF VIRGINIA RESEARCHERS FOUND MOST PEOPLE IN THEIR STUDY... view more 

CREDIT: UNIVERSITY OF VIRGINIA

CHARLOTTESVILLE, Va. -- If, as the saying goes, less is more, why do we humans overdo so much?

In a new paper featured on the cover of Nature, University of Virginia researchers explain why people rarely look at a situation, object or idea that needs improving -- in all kinds of contexts -- and think to remove something as a solution. Instead, we almost always add some element, whether it helps or not.

The team's findings suggest a fundamental reason that people struggle with overwhelming schedules, that institutions bog down in proliferating red tape, and, of particular interest to researchers, that humanity is exhausting the planet's resources.

"It happens in engineering design, which is my main interest," said Leidy Klotz, Copenhaver Associate Professor in the Department of Engineering Systems and Environment. "But it also happens in writing, cooking and everything else -- just think about your own work and you will see it. The first thing that comes to our minds is, what can we add to make it better. Our paper shows we do this to our detriment, even when the only right answer is to subtract. Even with financial incentive, we still don't think to take away."

Klotz, whose research explores the overlaps between engineering and behavioral science, teamed with three colleagues from the Batten School of Leadership and Public Policy on the interdisciplinary research that shows just how additive we are by nature. Batten public policy and psychology faculty, assistant professor Gabrielle Adams and associate professor Benjamin Converse, and former Batten postdoctoral fellow Andrew Hales, collaborated with Klotz on a series of observational studies and experiments to study the phenomenon.

When considering two broad possibilities for why people systematically default to addition -- either they generate ideas for both possibilities and disproportionately discard subtractive solutions or they overlook subtractive ideas altogether -- the researchers focused on the latter.

"Additive ideas come to mind quickly and easily, but subtractive ideas require more cognitive effort," Converse said. "Because people are often moving fast and working with the first ideas that come to mind, they end up accepting additive solutions without considering subtraction at all."

The researchers think there may be a self-reinforcing effect.

"The more often people rely on additive strategies, the more cognitively accessible they become," Adams said. "Over time, the habit of looking for additive ideas may get stronger and stronger, and in the long run, we end up missing out on many opportunities to improve the world by subtraction."

Klotz has a book that takes a wider view of the topic, Subtract: The Untapped Science of Less, coming out a week after the Nature paper. Although the timing is coincidence, both the paper and book are products of the interdisciplinary and collaborative research environment at UVA, he said.

"It's an incredibly interesting finding, and I think our research has tremendous implications across contexts, but especially in engineering to improve how we design technology to benefit humanity," Klotz said.

The researcher's findings are also described in this video produced by Nature.

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About UVA Engineering:

As part of the top-ranked, comprehensive University of Virginia, UVA Engineering is one of the nation's oldest and most respected engineering schools. Our mission is to make the world a better place by creating and disseminating knowledge and by preparing future engineering leaders. Outstanding students and faculty from around the world choose UVA Engineering because of our growing and internationally recognized education and research programs. UVA is the No. 1 public engineering school in the country for the percentage of women graduates, among schools with at least 75 degree earners; the No. 1 public engineering school in the United States for the four-year graduation rate of undergraduate students; and the top public engineering school in the country for the rate of Ph.D. enrollment growth since 2015. Learn more at engineering.virginia.edu.

About UVA's Department of Engineering Systems and Environment:

As the home of civil, systems and environmental engineering at UVA, the department combines research expertise in cyber-physical and systems approaches with deep domain knowledge in such areas as transportation, the environment, human health, defense and public safety. Our research focus areas are 1) health care systems engineering, 2) smart cities, 3) environmental engineering, 4) intelligent decision and control systems, 5) systems assurance and resilience and 6) cyber-human systems. Beyond developing or improving new technologies, Engineering Systems and Environment is committed to understanding how people might use engineering systems and the opportunities these systems present for societal impact. Learn more at engineering.virginia.edu/ese.

About UVA's Frank Batten School of Leadership and Public Policy:

At the Batten School, we are committed to solving the world's toughest policy challenges. We know the complex issues of our time demand innovative, collaborative, cross-sector relationships within our walls and beyond. Our multidisciplinary approach to problem-solving and emphasis on ethics reinforce our focus on how leadership works, why context matters in decision-making and which actions lead to tangible results. Learn more at batten.virginia.edu.

 

Parkinson's discovery points to possible future treatment approaches

More than 20 years after the discovery of the parkin gene linked to young-onset Parkinson's disease, researchers at The Ottawa Hospital and the University of Ottawa may have finally figured out how this mysterious gene protects the brain

UNIVERSITY OF OTTAWA

Research News

 

IMAGE: MEMBERS OF THE SCHLOSSMACHER TEAM INCLUDE (FROM LEFT TO RIGHT) JACQUELINE TOKAREW, BOJAN SHUTINOSKI, JULIANNA TOMLINSON, ANGELA NGUYEN, MICHAEL SCHLOSSMACHER, DANIEL EL-KODSI AND NATHALIE LENGACHER. OTHER KEY CONTRIBUTORS TO THE... view more 

CREDIT: THE OTTAWA HOSPITAL

More than 20 years after the discovery of the parkin gene linked to young-onset Parkinson's disease, researchers at The Ottawa Hospital and the University of Ottawa may have finally figured out how this mysterious gene protects the brain.

Using human and mouse brain samples and engineered cells, they found that the parkin protein works in two ways. First, it acts like a powerful antioxidant that disarms potentially harmful oxidants in the brain, including dopamine radicals. Second, as the brain ages and dopamine radicals continue to build up, parkin sequesters these harmful molecules in a special storage site within vulnerable nerve cells, so they can continue to function normally throughout our lifespan.

In people with mutations in both copies of the parkin gene, these protective effects are missing, and as a result Parkinson's develops before the age of 40 years. If confirmed, the results could point the way towards the development of new treatments.

"If we could deliver antioxidants or a healthy copy of the parkin gene into the brains of people with these mutations, this could help slow down or even halt early-onset Parkinson's," said co-corresponding author and scientific project manager Dr. Julianna Tomlinson.

"What we don't know yet is whether such an approach could also benefit individuals with late-onset Parkinson's that is not linked to the parkin gene," added co-corresponding author Dr. Michael Schlossmacher, neurologist and Director of Neuroscience at The Ottawa Hospital. "We are eager to investigate this."

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Dr. Schlossmacher is also a professor at the University of Ottawa Brain and Mind Research Institute and holds the Bhargava Family Research Chair in Neurodegeneration at The Ottawa Hospital.

This research was possible because of a large team effort, with important contributions from several graduate students, including Jacqueline Tokarew, Daniel El-Kodsi, Nathalie Lengacher and Travis Fehr.

Drs. Schlossmacher, Tomlinson and John Pezacki of the Department of Chemistry at uOttawa were recently awarded a new project grant from the Canadian Institutes of Health Research to continue this work. They are also making their unique research tools available around the world through a partnership between BioLegend and the Ottawa Hospital Research Institute.

Parkinson's, cancer, type 2 diabetes share a key element that drives disease

Enzyme with central role in cancer and type 2 diabetes also activates "clean-up" protein in Parkinson's

SALK INSTITUTE

Research News

 

IMAGE: PARKIN PROTEIN (GREEN SIGNAL) IS IN A DIFFERENT PART OF THE CELL THAN THE MITOCHONDRIA (RED SIGNAL) AT TIME 0 (LEFT IMAGE) BUT THEN CO-LOCALIZES WITH THE MITOCHONDRIA AFTER 60... view more 

CREDIT: SALK INSTITUTE

LA JOLLA--(April 7, 2021) When cells are stressed, chemical alarms go off, setting in motion a flurry of activity that protects the cell's most important players. During the rush, a protein called Parkin hurries to protect the mitochondria, the power stations that generate energy for the cell. Now Salk researchers have discovered a direct link between a master sensor of cell stress and Parkin itself. The same pathway is also tied to type 2 diabetes and cancer, which could open a new avenue for treating all three diseases.

"Our findings represent the earliest step in Parkin's alarm response that anyone's ever found by a long shot. All the other known biochemical events happen at one hour; we've now found something that happens within five minutes," says Professor Reuben Shaw, director of the NCI-designated Salk Cancer Center and senior author of the new work, detailed in Science Advances on April 7, 2021. "Decoding this major step in the way cells dispose of defective mitochondria has implications for a number of diseases."

Parkin's job is to clear away mitochondria that have been damaged by cellular stress so that new ones can take their place, a process called mitophagy. However, Parkin is mutated in familial Parkinson's disease, making the protein unable to clear away damaged mitochondria. While scientists have known for some time that Parkin somehow senses mitochondrial stress and initiates the process of mitophagy, no one understood exactly how Parkin was first sensing problems with the mitochondria--Parkin somehow knew to migrate to the mitochondria after mitochondrial damage, but there was no known signal to Parkin until after it arrived there.

Shaw's lab, which is well known for their work in the fields of metabolism and cancer, spent years intensely researching how the cell regulates a more general process of cellular cleaning and recycling called autophagy. About ten years ago, they discovered that an enzyme called AMPK, which is highly sensitive to cellular stress of many kinds, including mitochondrial damage, controls autophagy by activating an enzyme called ULK1.

Following that discovery, Shaw and graduate student Portia Lombardo began searching for autophagy-related proteins directly activated by ULK1. They screened about 50 different proteins, expecting about 10 percent to fit. They were shocked when Parkin topped the list. Biochemical pathways are usually very convoluted, involving up to 50 participants, each activating the next. Finding that a process as important as mitophagy is initiated by only three participants--first AMPK, then ULK1, then Parkin--was so surprising that Shaw could scarcely believe it.

To confirm the findings were correct, the team used mass spectrometry to reveal precisely where ULK1 was attaching a phosphate group to Parkin. They found that it landed in a new region other researchers had recently found to be critical for Parkin activation but hadn't known why. A postdoctoral fellow in Shaw's lab, Chien-Min Hung, then did precise biochemical studies to prove each aspect of the timeline and delineated which proteins were doing what, and where. Shaw's research now begins to explain this key first step in Parkin activation, which Shaw hypothesizes may serve as a "heads-up" signal from AMPK down the chain of command through ULK1 to Parkin to go check out the mitochondria after a first wave of incoming damage, and, if necessary, trigger destruction of those mitochondria that are too gravely damaged to regain function.

The findings have wide-ranging implications. AMPK, the central sensor of the cell's metabolism, is itself activated by a tumor suppressor protein called LKB1 that is involved in a number of cancers, as established by Shaw in prior work, and it is activated by a type 2 diabetes drug called metformin. Meanwhile, numerous studies show that diabetes patients taking metformin exhibit lower risks of both cancer and aging comorbidities. Indeed, metformin is currently being pursued as one of the first ever "anti-aging" therapeutics in clinical trials.

"The big takeaway for me is that metabolism and changes in the health of your mitochondria are critical in cancer, they're critical in diabetes, and they're critical in neurodegenerative diseases," says Shaw, who holds the William R. Brody Chair. "Our finding says that a diabetes drug that activates AMPK, which we previously showed can suppress cancer, may also help restore function in patients with neurodegenerative disease. That's because the general mechanisms that underpin the health of the cells in our bodies are way more integrated than anyone could have ever imagined."

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About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology, plant biology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.

Perinatal patients, nurses explain how hospital pandemic policies failed them

UNIVERSITY OF WASHINGTON

Research News

 

With a lethal, airborne virus spreading fast, hospitals had to change how they treated patients and policies for how caregivers provided that treatment. But for maternity patients and nurses some of those changes had negative outcomes, according to a new University of Washington study.

"We found that visitor restrictions and separation policies were harming families and nurses. The effects for patients included loneliness, isolation and mistrust, while nurses described mistrust and low morale," said Molly Altman, lead author of the study and assistant professor in the UW School of Nursing.

Importantly, Altman added, both nurses and patients described how COVID "amplified existing racially biased and disrespectful care experiences for Black women and birthing people, in part due to loss of protection and advocacy that support people provide."

The study, published March 31 in Global Qualitative Nursing Research, involved in-depth interviews with 15 patients from Washington state and 14 nurses from Washington, New York, Georgia and Michigan. Nearly half of participants in both groups self-identified as BIPOC and for slightly more than half this was their first birth.

Under COVID-19 restrictions, patients experienced a shift from in-person visits, a source of social and emotional support, to virtual conversations or telehealth and more perfunctory exchanges in offices with physical distancing. Pregnancy education and group classes all moved online, while family and friends were excluded from patient care when in the hospital or clinic. Meanwhile, nurses experienced shifting policies and procedures that led to a collective mistrust of management and administration.

In the interviews, researchers wrote, patient responses focused on how hospital adaptations "were inadequate to meet their needs" and, in addition to mistrust, nurse responses focused on how inconsistencies in policies and policy implementation affected their ability to "safely care for patients."

Here are a few verbatim transcriptions of statements patients gave researchers (with minor edits):

About telehealth ...

I want to be able to actually have a check-in and actually have a doctor be able to check everything's fine and make sure the baby's heartbeat is still okay or see how my uterus is measuring and things like that that are more concrete. ... I see the phone conversation just more being like, "Is everything okay," and me saying "Yes" and then that kind of being it.

Communication with providers ...

We don't talk about how this is affecting us or what it means for the future. It's just they leave you hanging like, "Okay, well I'm guessing everything's okay so I'm just going to walk on out of here." But if you could just say something nice, concise and brief but meaty it would be perfect.

Education and nursing support ...

I lost ... the classes that we were supposed to need. I was so excited to join those classes because I could get a chance to meet with other mothers that we may build connections, right? But because of COVID we just don't have the chance of doing that.

People were there [in labor] to support me and to make sure I was okay and then I felt like postpartum everyone disappeared.

Racial bias ...

Being [a person] of color, you already kind of deal with the standoffish approach from certain people and so like ... the virus kind of gives [them] that reason to, it's just like that. It's like even though I already feel this way, now I have a reason to act this way.

I'm an educated Black woman. I'm a nurse. I know what's going on with my body and I know how this stuff works and I still feel like so inferior, like to my [birth] team. That's crazy to me.

Following are a few verbatim transcriptions of statements nurses gave researchers (with minor edits):

Lack of planning ...

I was disappointed to see that in the, at least a month, more like six weeks since we'd had just the one COVID patient, that not a lot had been done to prepare in the meantime, both on a national scale and just at our hospital.

Policy changes ...

I felt like at times on my shift, policies would change literally every 15 to 30 minutes. You do something one way and you get an email within the hour that this now has changed and we're doing this procedure this way and it was just constant like nobody knows what they're doing so it was very stressful.

Morale problems ...

I'm just doing everything for this patient and then I'm not thinking about my own family. Even if I [say] let whatever happen to me ... I have responsibilities for my family too. I'm not just a nurse, right? I'm a mother. When I took the oath to be a nurse, before that maybe I took an oath to be a good mother.

[a patient complained and] that stung because I remember going to my manager's room that day and asking for more supplies so that I could go into the room more frequently without having to break the gowns and reuse the gowns and she said, "You use what you have and I'm not giving you anything else."

Racial bias ...

[obstetrical resident physician] went in to go talk to [a patient] about the need for induction and instead of including the father in the conversation or even introducing herself, she went in, completely turned her back on the dad ... I've been there 10 years and I have never seen that with any Caucasian couple.

"We need to really center the voices and experiences of marginalized people, especially BIPOC, in policy. We need to ensure that communication is transparent and that we are trustworthy to the groups we develop policies for -- patients, nurses, the public, everyone," said Meghan Eagen-Torkko, study co-author and assistant professor in UW Bothell School of Nursing and Health Studies. "We have to stop thinking of policy as a top-down process, because Covid has shown us quite clearly that this doesn't work."

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Co-authors include Amelia Gavin, UW School of Social Work; Selina Mohammed, UW Bothell School of Nursing and Health Studies; Ira Kantrowitz-Gordon, UW School of Nursing, Seattle; and Rue Khosa, The Perfect Push, LLC in Redmond. This research was funded by UW School of Nursing, Seattle.

For more information, contact Altman at mraltman@uw.edu.

[Inset BOX]

Altman, who spoke to UW News in December about this issue, suggests health care administrators take the following actions to counter the failures of current policies:

• Administrators need to collaborate on policy changes, particularly with communities that are directly affected by these changes
• Consider extending visitor policies to include multiple support people for patients in labor, as a way to mitigate risk of disrespectful care for marginalized communities
• Create educational resources to help patients understand policies that affect them and provide avenues for getting support and reassurance
• Develop clear, organized and transparent communication pathways about policy changes at all levels: patient, nurse and management
• Increase mental health assessment, support and services for both patients and nurses to help build well-being amid crisis
• Include bedside nurses in decisions about care planning, risk management and patient careS

 

The case for embedding equity into incident command

BRIGHAM AND WOMEN'S HOSPITAL

Research News

 

WHO Eric Goralnick, MD, MS, Medical Director of Emergency Preparedness, Department of Emergency Medicine and the Center for Surgery and Public Health, Brigham and Women's Hospital; co-author of a new editorial published in American Journal of Public Health

Cheryl R. Clark, MD, ScD, Director, Health Equity Research & Intervention, Center for Community Health and Health Equity, Hospitalist, Division of General Medicine & Primary Care, Brigham and Women's Hospital; co-author of a new editorial published in American Journal of Public Health

WHAT During recent large-scale disasters, including the COVID-19 pandemic and major hurricanes, many hospitals and health care systems have activated their Hospital Incident Command System (HICS) to clarify roles and responsibilities and offer a clear organizational structure during a crisis. While forms of these systems have existed since the 1980s, one key element has been missing from HICS national guidelines: a focus on equity.

In a new editorial published in AJPH, Clark and Goralnick, both from the Brigham, and their co-author Richard Serino, NREMT-P, from the Harvard T.H. Chan School of Public Health, make the case for why a structural change is needed in the national HICS guidelines to ensure inclusion of an Equity Officer and subject matter experts in health care equity.

"The absence of equity as an emergency management principle in responses to COVID-19 has resulted in a slow and incomplete hospital response to the disproportionate mortality and morbidity in several historically marginalized populations," the authors write. "Defining an Equity Officer as a mandatory, core member of the command and general staff is a first step in mitigating inequities."

The authors describe the experience at the Brigham, where a diversity, equity and community health response team was established during the COVID-19 pandemic. Results from an after-action review helped identify strengths and weaknesses of the Brigham's HICS response.

"Many of those involved in the process acknowledged that we are at the beginning and have much work to do to ensure that equity is a core function of our response during the COVID pandemic and in future disasters," the authors write. "On the basis of our observations, we recommend a structural change to the national HICS guidelines: including an Equity Officer and embedded health equity specialists within each section."

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