Tuesday, September 14, 2021

Killing Covid, a spray away.

Credit: University of Queensland
 An antiviral surface coating technology sprayed on face masks could provide an extra layer of protection against COVID-19 and the flu.    

The coating developed at The University of Queensland has already proven effective in killing the virus that causes COVID-19, and shows promise as a barrier against transmission on surfaces and face masks.

UQ’s Australian Institute for Bioengineering and Nanotechnology researcher Professor Michael Monteiro said the water-based coating deployed worm-like structures that attack the virus.

“When surgical masks were sprayed with these ‘nanoworms’, it resulted in complete inactivation of the Alpha variant of Sars-CoV-2 and influenza A,” Professor Monteiro said.

The coating was developed with Boeing as a joint research project, and was tested at the Peter Doherty Institute for Infection and Immunity at The University of Melbourne.

 “These polymer ‘nanoworms’ rupture the membrane of virus droplets transmitted through coughing, sneezing or saliva and damage their RNA,” Professor Monteiro said.

“The chemistry involved is versatile, so the coating can be readily redesigned to target emerging viruses and aid in controlling future pandemics.”

Professor Monteiro said face masks would continue to be an important part of helping prevent or reduce community transmission of COVID-19.

“Antiviral coatings applied on mask surfaces could reduce infection and provide long-lasting control measures to eliminate both surface and aerosolized transmission,” he said.

“We know that COVID-19 remains infectious for many hours or days on some surfaces, and provides a direct route to infection.

“Therefore, there is greater emphasis on eliminating both surface and airborne transmission to complement vaccination of the population to stop the current pandemic.”

The coating is environmentally friendly, water-based and its synthesis aligns with manufacturing techniques used in the paint and coatings industry. 

The research is published in ACS Nano (doi.org/10.1021/acsnano.1c05075)

Source/Credit: University of Queensland

Weather Extremes by 2060

In this visualization, based on weather and climate observations from NASA's MERRA dataset, the northern hemisphere's polar jet stream is seen as a meandering, fast-moving belt of westerly winds traversing the lower layers of the atmosphere. Credit: NASA

 New research provides insights into how the position and intensity of the North Atlantic jet stream has changed during the past 1,250 years. The findings suggest that the position of the jet stream could migrate outside of the range of natural variability by as early as the year 2060 under unabated greenhouse gas emissions, with potentially drastic weather-related consequences for societies on both sides of the Atlantic.

Matthew Osman steadies an ice core
drilling barrel into the Greenland Ice Sheet
Credit: Sarah Das/Woods Hole Oceanographic Institution
Led by Matthew Osman, a postdoctoral research associate at the University of Arizona Climate Systems Center, the study is published in Proceedings of the National Academy of Sciences.

Familiar to air travelers flying between North America and Europe, the North Atlantic jet stream is the ribbon of prevailing westerly winds circling the Arctic. Often called the "polar jet," these high-altitude winds impact weather and climate across eastern North America and western Europe, accounting for between 10% and 50% of variance in annual precipitation and temperature in both regions. However, little is known about how the jet stream varied during the past, or how it might change in the future.  

Osman's research team collected glacial ice core samples from nearly 50 sites spanning the Greenland ice sheet to reconstruct changes in windiness across the North Atlantic dating back to the eighth century.  The reconstructions suggest that natural variability has thus far masked the effect of human-caused warming on mid-latitude atmospheric dynamics across annual and longer timescales.

"For most places on Earth, direct climate observations typically do not span more than a few decades," Osman said. "So, we haven't had a great sense of how or why the jet stream changes over longer periods of time. What we do know is that extraordinary variations in the jet stream can have severe societal implications, such as floods and droughts, due to its impacts on weather patterns and so, in terms of thinking about the future, we can now begin to use the past as a sort of a prologue."

The work reveals that although natural variability has largely controlled the position of the North Atlantic jet stream, continued warming could cause significant deviations from the norm. In particular, model projections forecast a northward migration of the North Atlantic jet stream under 21st-century warming scenarios. Such migration could render the jet stream significantly different within a matter of decades.

Although the polar jet stream blows most swiftly near the typical cruising altitudes of planes, the band of winds actually extends all the way to the ground. While of lesser intensity, Osman explained, near the ground the winds are often referred to as storm tracks. Storm tracks impact weather and climate across Greenland, affecting the island's precipitation and temperature changes. By analyzing year-to-year variations in the amount of

snowfall archived in Greenland ice cores, as well as the chemical makeup of the water molecules comprising those annual snow layers, the researchers were able to extract centuries-old clues into how the jet stream changed.

"These layers tell us about how much precipitation fell in a given year and also about the temperatures that air masses were exposed to," Osman said.

Weather events like this summer's heat wave in the Pacific Northwest and the floods in Europe are some recent examples of how the jet stream affects weather patterns based on its intensity or location in the short term, Osman said. But societally significant changes also occur across longer time scales; reconstructing the jet stream's past revealed that in some years, it could be far north, only to venture more than 10 degrees farther south a few years later.

"Such variations have huge implications on the types of weather that people might experience at a given place," Osman said. "For example, when the jet stream is situated farther south, the normally dry Iberian Peninsula tends to experience milder, moister conditions. But, as the jet stream migrates northward, much of that moisture also moves away from Iberia towards already-wet regions of Scandinavia. A poleward-shifted jet stream in the future thus might have similar, but more permanent, consequences."

The team was able to match certain changes in wind speed and geographical shifts to historical weather-related calamities. For example, during a famine that gripped the Iberian Peninsula in 1374, the jet stream was situated unusually far north. Similarly, two famine events in the British Isles and Ireland in 1728 and 1740 coincided with years that winds blew at nearly half their usual intensity, dramatically cooling temperatures and reducing precipitation. The latter of these events, in 1740, is estimated to have cost the lives of nearly half a million people.

Osman and his co-authors expect that any future shifts in the North Atlantic jet stream would also have dramatic implications on day-to-day weather and ecosystems, with trickle-down effects impacting national economies and societies.

"Our results serve as a warning: Although pushing the jet stream beyond its natural range would be problematic, its ultimate trajectory is still largely in our control," he said.

Source/Credit: University of Arizona/Daniel Stolte


Pandemic proofing our future

Dr Kirsty Short Credit: University of Queensland
A project developing a test and treatments that would be effective against multiple viral threats could become a cornerstone of the world’s response to future pandemics.

University of Queensland virologist Dr Kirsty Short has been awarded $1.37 million from the National Health and Medical Research Council (NHRMC) to use her understanding of the immune response in COVID-19 and influenza to investigate a future pandemic response.

“The reality is the world was not prepared for COVID-19, so our aim is start developing broad spectrum diagnostics and drugs that work against multiple viruses,” Dr Short said.

“If we develop these things now, we can stockpile them so that any time there’s a viral outbreak, we have them on hand, ready to deploy.”

Dr Short said the project would look for a genetic marker or ‘signature’ in people with COVID-19 that could be used in a rapid test that can be picked up before the viral genetic material can be detected by standard diagnostic PCR.

“We’re working with health authorities to access samples from people going through hotel quarantine and we’re combining that with machine learning to try and identify a signature that will then allow for the development of early diagnostics.”

While existing anti-viral therapies are developed for a specific virus, Dr Short’s project will investigate a treatment that targets the immune response to multiple viruses.

“An out-of-control inflammatory response is the reason some people become seriously ill in a coronavirus infection, in a flu infection and in many other pandemic viruses,” she said.

“By targeting that response, we can develop an effective therapy that is useful against any pandemic virus that you could anticipate.”

Dr Short said identifying a ‘host signature of infection’ would also allow for earlier detection of any virus, benefiting both the public health response and individual patients.

“If we take SARS-COV-2 as an example, you can be infected with the virus but initially get a negative PCR test and maybe five days later you test positive.

“With an early diagnostic test, we could determine whether an individual carries the ‘host signature’, which would allow us to identify those likely to come down with an infection.

“If you didn’t have the signature, you might be released earlier from quarantine or maybe allowed to home quarantine, making the process less arduous for everyone.”

The test and therapies would initially be rolled out in Australia, but Dr Short hoped they would also make a difference elsewhere.

“Ideally, we could have this as part of a global pandemic preparedness plan, because ultimately there will be another,” Dr Short said.

 “What I really fundamentally hope is that this project will ensure that the next outbreak will be of much reduced severity and consequences compared to the COVID-19 pandemic.”

UQ received NHMRC grants for five Centers for Research Excellence (CRE), two Partnership Projects and 29 Investigator Grants in the latest round of funding.

Source/Credit: University of Queensland


Molecular Achilles heel of cancer cells discovered

Tissue samples from 144 patients with colorectal cancer were analyzed
by mass spectrometry as part of the study. Image: W. Filser / TUM
 Changes in fat metabolism of colorectal cancer cells demonstrated for the first time Molecular Achilles heel of cancer cells discovered

Where does a malignant tumor obtain the energy to keep growing? That is a key question in cancer research. If the energy source were known, the tumor could be “starved”. Researchers have now laid the foundation for this approach: For the first time, they have demonstrated a fundamental difference in the fat metabolism of healthy cells in the inner lining of the intestinal tract and colorectal cancer cells. This could point the way to new treatment options targeting the changed metabolism of the tumor.

Some past measurements have also indicated significant differences in how fat is metabolized by healthy and cancerous cells. However, the results of this work have been highly inconsistent. Some investigations appeared to support such differences while others reported contrary results. “This question has been hotly debated”, says Prof. Klaus-Peter Janssen, a biologist at TUM’s university hospital Klinikum rechts der Isar.

To obtain clarity, surgeons at Klinikum rechts der Isar took tissue samples from the surgically removed tumors of 144 colorectal cancer (CRC) patients. The samples were immediately prepared onsite and then analyzed using mass spectrometry at the Institute for Food & Health (ZIEL) in Freising and at the University Hospital Regensburg. This is a biochemical procedure for the quantitative measurement of the type and mass of certain molecules in specially prepared tissue samples – in this case around 200 different fat molecules.

To prove that the results were reproducible, and not merely accidental, the patients were divided into two cohorts. The tissue samples were then analyzed separately and the results compared. In addition, the researchers incorporated the analysis of samples from another cohort of 20 CRC patients investigated independently at the University of Dresden.

In all three cohorts, the researchers were able to show that “CRC cells indeed have a specific lipid signature,” says Janssen. This means that they show a certain pattern of different lipid molecules – “A fingerprint, in a sense, with which we can distinguish between cancer cells and normal cells with a high degree of certainty. This signature also has prognostic relevance. In other words, it can be used to predict the course of the illness.”

The changes in the lipidome – i.e. the totality of lipids in a cell – related mainly to sphingo- and glycerolipids. These differences were also reflected at the genomic level: The team showed that the activity of certain genes that provide the blueprint for various enzymes was also significantly altered. Enzymes are functional proteins that play an important role in the production of metabolic products such as lipids, for example. This might be a starting point for cutting off the energy supply to cancer cells and thus slowing their growth – by finding drugs to activate or inhibit individual enzymes in order to starve the cancer.

“Lipids in tissue samples are highly sensitive molecules that are sometimes subject to rapid change or decay,” says Janssen. Unless tissue samples are shock-frozen immediately after dissection and properly handled and stored, some of the highly sensitive lipids will already be destroyed. This will invalidate the results of the analysis. That could be a reason for the inconsistent results of past studies: This kind of close cooperation is not guaranteed everywhere.

Janssen and his team were also able to clearly demonstrate that the lipid profile of the tissue samples undergoes changes when stored under sub-optimal conditions and over extended periods. They showed that some lipids remain stable in tissue samples and are therefore suitable as biomarkers, while others rapidly deteriorate and in some cases are entirely degraded within just an hour of the operation.

The metabolisms of healthy and diseased cells are different – and thus the types and quantity of the molecules produced in them such as sugars, proteins and lipids - i.e. fatty molecules. Lipids are important for obtaining and storing energy in cells, but also as important building blocks for cell membranes and as signaling molecules.

As the totality of all lipids in a cell is referred to as the lipidome, this term gives rise to “lipidomics” – an entirely new field of research. It compares the lipidome of different cells and seeks to draw conclusions based on the differences and changes: For example, how does the lipid profile of a CRC cell differ from that of a healthy cell in the lining of the intestinal tract? Are there changes typically seen in cancerous cells – and how can this knowledge be used to develop new drugs?

Lipidomics a subfield of the better-known area of metabolomics, which includes all metabolic products of a cell – the “metabolome”. Many research groups working in this area have generally focused on sugars, nucleic acids (DNA, RNA) and proteins, which are easier to analyze. Lipids are not only more sensitive. “For a long time, it was also difficult and time-consuming to measure them with conventional methods,” says Janssen. “They have become a focal point of research only since that changed.”


Josef Ecker, Elisa Benedetti, Alida S.D. Kindt, Marcus Höring, Markus Perl, Andrea Christel Machmüller, Anna Sichler, Johannes Plagge, Yuting Wang, Sebastian Zeissig, Andrej Shevchenko, Ralph Burkhardt, Jan Krumsiek, Gerhard Liebisch, Klaus-Peter Janssen: The Colorectal Cancer Lipidome: Identification of a Robust Tumor-Specific Lipid Species Signature, Gastroenterology, Volume 161, Issue 3 (2021).

Source/Credit: Technical University of Munich


Flipping the “genetic paradox of invasions”

A close-up look at a green crab. Image credit: Ted Grosholz

The green crab, Carcinus maenas, is considered a globally distributed invasive species, an organism introduced by humans that eventually becomes overpopulated, with increased potential to negatively alter its new environment. Traditionally, it’s been assumed that successful populations contain high genetic diversity, or a variety of characteristics allowing them to adapt and thrive. On the contrary, the green crab - like many successful invasive populations - has low genetic diversity, while still spreading rapidly in a new part of the world.

A new study led by Carolyn Tepolt, an associate scientist of biology at Woods Hole Oceanographic Institution, is investigating the adaptive mechanisms of the green crab along the west coast of North America, where it has shown extensive dispersal in the last decade despite minimal genetic diversity. The study was published recently in Molecular Ecology and is a collaboration between WHOI, the University of California at Davis, Portland State University, and the Smithsonian Environmental Research Center.

“Invasive species like these are generally unwelcome. Green crabs can compete with native species, rip up eelgrass ‘nurseries’, and eat small shellfish before they have a chance to be harvested. Green crabs can be an ecological menace and an economic burden,” Tepolt said. “In this study, we found that one of the world's most serious marine invasive species has evolved specific genetic variation that likely helps it adapt to new environments really quickly, even when it's lost a lot of genetic diversity overall.”

Genetic diversity refers to small individual-to-individual differences in DNA, and often translates into a range of different inherited traits within a species. A population with high genetic diversity is more likely to include individuals with a wide range of different traits. In order for a population to adjust to changing environments, this variation can be crucial - or so scientists have often thought. Invasive species often challenge this assumption, successfully spreading in new regions despite low genetic diversity caused by descending from a small number of initial colonists.

This study focuses on a northwest Pacific population of green crab that has spread within the last 35 years from a single source. High-profile marine invasive species, such as green crabs, often live across thousands of kilometers of ocean, spanning countless environmental differences, both small and large. Using six U.S. west coast locations spanning over 900 miles from central California to British Columbia, Tepolt and her team examined the species’ genetic structure at thousands of places across its genome. While this population has lost a large amount of overall genetic diversity relative to its European source, a piece of DNA associated with cold tolerance in a prior study appears to be under strong selection from north to south across its invasive West Coast range.

This may represent a type of genetic feature - a balanced polymorphism - that evolved to promote rapid adaptation in variable environments despite high gene flow, and which now contributes to successful invasion and spread in a novel environment. Researchers do occasionally find incredibly successful populations that have passed through severe bottlenecks, dramatically decreasing their genetic diversity relative to their source. This study is amplifying the need to consider that diversity at specific parts of the genome (rather than genome-wide diversity) may play a critical role in resilience in new or changing environments.

“This is exciting for two main reasons. First, the study tests a partial resolution to ‘the genetic paradox of invasions’, demonstrating that variation at key parts of the genome permits rapid adaptation even in a population with low overall genetic diversity. Second, it suggests that high gene flow in a widespread species’ native range may generate evolutionary mechanisms, like this one, which provide that species with the substrate for rapid adaptive change as it spreads across new environments,” Tepolt explained.

Identifying invasive species spread can also be a job for non-scientists. As the climate changes and as humans get better and better at moving stuff around the globe, there’s more potential for species to come along for the ride and expand into new environments. Tepolt says it’s important to keep an eye out for cues, changes in the environment and possible new species in places they haven’t been before. She recommends seizing the opportunity to tell officials and researchers if there is something unusual at the coastline. There may be signs at beaches and boat ramps asking people to keep a lookout for particular species and giving contact information. If there are suddenly green crabs in an area for the first time, for example, on the West Coast in the Salish Sea and in Alaska, they likely should not be there and should be reported.

Source/Credit: Woods Hole Oceanographic Institution


Monday, September 13, 2021

New global dashboard sheds light on reasons behind COVID vaccine hesitancy, refusal


A woman works in a face mask manufacturing in factory in Harare, Zimbabwe. 
In an ongoing global survey, more than half of those who are unvaccinated in more than 50 countries indicated in August that they definitely or probably won't get a COVID-19 vaccine. A new dashboard, launched today by the Johns Hopkins Center for Communication Programs, unpacks that survey data to help explain why—and how experts can work to increase acceptance rates.

The researchers found that the primary reasons around the world for resisting vaccination include fears about side effects, a desire to wait until more people have had the shots so they know they are safe, and a lack of confidence in whether the vaccine really works.

"Our analysis of this large trove of data finds that while vaccine hesitancy is real, there are many people around the globe who can be encouraged to get their doses—if public health officials can build and share their messages to address their concerns."

Dominick Shattuck
Johns Hopkins Center for Communication Programs

These latest survey results, based on responses gathered between Aug. 16 and 31, can be found in the new COVID Behaviors dashboard, an interactive tool created with data collected from more than 12 million people from 115 countries. The survey—believed to be the world's largest daily survey of global COVID knowledge, attitudes, and practices—has been fielded every day since May 20, 2021. It is expected to continue until the end of this year, and new data will become available every two weeks.

The dashboard is intended to be used by policymakers, government officials, and public health practitioners at national and sub-national levels to better understand the behavioral drivers behind vaccine uptake, masking, and physical distancing that can prevent the spread of COVID-19.

"Our analysis of this large trove of data finds that while vaccine hesitancy is real, there are many people around the globe who can be encouraged to get their doses—if public health officials can build and share their messages to address their concerns," says Dominick Shattuck, CCP's director of monitoring evaluation and learning and one of the leaders of the COVID behaviors project.

Adds Marla Shaivitz, CCP's director of digital strategy: "The dashboard can be used as a roadmap for policymakers to identify and engage with citizens to encourage them to be vaccinated to protect themselves and their families from COVID-19. In many countries, this dashboard fills an important data gap. It offers the most comprehensive data some governments have access to on how COVID behaviors are changing and what they can do to intervene."

The dashboard is the product of a collaboration among CCP, the World Health Organization's Global Outbreak Alert and Response Network, and Facebook. The data are generated from the COVID-19 Trends and Impact Survey, which is administered in the United States by the Delphi Group at Carnegie Mellon University and in other countries by the University of Maryland Social Data Science Center. The two universities collect the survey data from a random sample of Facebook users and CCP analyzes the responses.

A previous COVID behaviors dashboard, also led by CCP, was based on smaller, less frequent surveys from June 2020 through March 2021.

In this latest survey, reasons for vaccine hesitancy vary by country. In Senegal, the two most common reasons for hesitancy are concerns about side effects and whether the vaccine will work. Education around vaccine science and side effects could work to encourage vaccine uptake in Senegal. In the Netherlands, however, unvaccinated respondents were most likely to say that they don't believe they need a vaccine. When asked why not, their main reasons were because they are not a member of a high-risk group, or they don't believe COVID-19 is a serious illness. Each underlying perception requires a different messaging response.

The dashboard sheds light on how other behaviors have evolved over the last four months as well. In the United States, for example, 65% of those who responded to the survey between Aug. 16 and 31 said they had been shopping indoors in the previous 24 hours, and two-thirds those who had been shopping said they wore masks. Mask wearing steadily decreased in the U.S. until the middle of July but has been rising since the highly transmissible Delta variant became the dominant strain, and case counts and hospitalizations began rising again to record levels in many states.

In India, where an outbreak has fallen from its May peak, only 29% of respondents had been shopping indoors in the previous 24 hours and the vast majority of them (87%) were wearing masks, suggesting there is a long way to go before things get back to normal.

Since March 2020, a staggering 223 million COVID cases—and 4.6 million deaths—have been reported around the world, according to Johns Hopkins University's COVID-19 dashboard. More than 5.3 billion vaccine doses have been administered globally, though just over 2% of those doses have been administered in Africa.

USAID has sent more than 110 million doses to low- and middle-income countries and COVAX, a worldwide initiative aimed at equitable access to COVID-19 vaccines, has distributed more than 236 million doses. As vaccine access increases, governments will need to develop strategies to sensitize citizens to accurate information and the benefits of vaccines.

In addition to findings about vaccine hesitancy, the dashboard also features data on why many people who want vaccines can't seem to access them. In Brazil, for example, where 65% of the unvaccinated respondents in the Aug. 16-31 survey period said they probably or definitely want a vaccine, 23% of those who want one said they couldn't get a shot because they are not eligible for one, and 34% said there were no appointments available.

Armed with knowledge from the dashboard, officials in those countries can aim to work with local communities to make vaccine appointments more accessible—once vaccines are widely available—and to better spread the word about appointments that are available and when, where, and how to secure them.

"We are at a critical time for global COVID-19 vaccine rollouts, yet populations are oversaturated with information, disinformation, and rumors," says Jeni Stolow of WHO's Global Outbreak Alert and Response Network. "Continuously producing timely evidence-based and effective health communication is a major challenge in this second year of the pandemic. This dashboard can support public health practitioners around the globe in their endeavors to tailor, target, and reinvigorate their local COVID-19 vaccine outreach efforts."

While many unvaccinated people around the world say they are unlikely to get vaccinated, in many countries, large percentages of the population say they would choose to get their children vaccinated once a vaccine becomes available. In India and Guatemala, well over 90% of survey respondents said they would definitely or probably vaccinate their children. Data from Aug. 16 through 31 show the figure was 86% in Mozambique, 72% in the United States, and 47% in Serbia.

"The volume of data that has and will continue to be collected on COVID-19 will be of great value to policymakers and health practitioners, if the data are strategically used," says Douglas Storey, CCP's director for communication science and research. "This dashboard offers deep insights into behaviors around the world and will be a guide for those aiming to stop the spread of this devastating disease."

Source/Credit: Johns Hopkins University


New tool for analyzing large superconducting circuits

The next generation of computing and information processing lies in the intriguing world of quantum mechanics. Quantum computers are expected to be capable of solving large, extremely complex problems that are beyond the capacity of today’s most powerful supercomputers.

New research tools are needed to advance the field and fully develop quantum computers. Now Northwestern University researchers have developed and tested a theoretical tool for analyzing large superconducting circuits. These circuits use superconducting quantum bits, or qubits, the smallest units of a quantum computer, to store information.

Circuit size is important since protection from detrimental noise tends to come at the cost of increased circuit complexity. Currently there are few tools that tackle the modeling of large circuits, making the Northwestern method an important contribution to the research community.

“Our framework is inspired by methods originally developed for the study of electrons in crystals and allows us to obtain quantitative predictions for circuits that were previously hard or impossible to access,” said Daniel Weiss, corresponding and first author of the paper. He is a fourth-year graduate student in the research group of Jens Koch, an expert in superconducting qubits.

Koch, an associate professor of physics and astronomy in Weinberg College of Arts and Sciences, is a member of the Superconducting Quantum Materials and Systems Center (SQMS) and the Co-design Center for Quantum Advantage (C2QA). Both national centers were established last year by the U.S. Department of Energy (DOE). SQMS is focused on building and deploying a beyond-state-of-the-art quantum computer based on superconducting technologies. C2QA is building the fundamental tools necessary to create scalable, distributed and fault-tolerant quantum computer systems.

“We are excited to contribute to the missions pursued by these two DOE centers and to add to Northwestern’s visibility in the field of quantum information science,” Koch said. 

In their study, the Northwestern researchers illustrate the use of their theoretical tool by extracting from a protected circuit quantitative information that was unobtainable using standard techniques. 

Details were published in the open access journal Physical Review Research.

The researchers specifically studied protected qubits. These qubits are protected from detrimental noise by design and could yield coherence times (how long quantum information is retained) that are much longer than current state-of-the-art qubits.  

These superconducting circuits are necessarily large, and the Northwestern tool is a means for quantifying the behavior of these circuits. There are some existing tools that can analyze large superconducting circuits, but each works well only when certain conditions are met. The Northwestern method is complementary and works well when these other tools may give suboptimal results.

The research was supported by the Army Research Office (Contract No. W911NF-17-C-0024).

Source/Credit: Northwestern University/Megan Fellman


Fountain of youth for ageing stem cells in bone marrow

Stained calcium (dark brown) in stem cells from the bone marrow: 
Young stem cells (left) produce more material for bone than old stem cells (center). 
They can be rejuvenated by adding sodium acetate (right).
Credit/Source: Pouikli/Max Planck Institute for Biology of Ageing
As we age, our bones become thinner, we suffer fractures more often, and bone-diseases such as osteoporosis are more likely to occur. One responsible mechanism involves the impaired function of the bone-marrow stem cells, which are required for the maintenance of bone integrity. Researchers from the Max Planck Institute for Biology of Ageing and CECAD Cluster of Excellence for Ageing Research at the University of Cologne have now shown that the reduced stem cell function upon ageing is due to changes in their epigenome. They were able to reverse these changes in isolated stem cells by adding acetate. This fountain of youth for the epigenome could become important for the treatment of diseases such as osteoporosis.

Ageing Researchers have been looking at epigenetics as a cause of ageing processes for some time. Epigenetics looks at changes in genetic information and chromosomes that do not alter the sequence of the genes themselves, but do affect their activity. One possibility is changes in proteins called histones, which package the DNA in our cells and thus control access to DNA. The Cologne research group of Peter Tessarz has now studied the epigenome of mesenchymal stem cells. These stem cells are found in bone marrow and can give rise to different types of cells such as cartilage, bone and fat cells.

The epigenetic changes of ageing stem cells

"We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow. To do this, we compared the epigenome of stem cells from young and old mice," explains Andromachi Pouikli, first author of the study. "We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected."

Rejuvenation of the epigenome

The researchers then investigated whether the epigenome of stem cells could be rejuvenated. To do this, they treated isolated stem cells from mouse bone marrow with a nutrient solution which contained sodium acetate. The cell converts the acetate into a building block that enzymes can attach to histones to increase access to genes, thereby boosting their activity. "This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells," Pouikli said.

To clarify whether this change in the epigenome could also be the cause of the increased risk in old age for bone fractures or osteoporosis in humans, the researchers studied human mesenchymal stem cells from patients after hip surgery. The cells from elderly patients who also suffered from osteoporosis showed the same epigenetic changes as previously observed in the mice.

A new therapeutic approach against osteoporosis?

"Sodium acetate is also available as a food additive, however, it is not advisable to use it in this form against osteoporosis, as our observed effect is very specific to certain cells. However, there are already first experiences with stem cell therapies for osteoporosis. Such a treatment with acetate could also work in such a case. However, we still need to investigate in more detail the effects on the whole organism in order to exclude possible risks and side effects," explains Peter Tessarz, who led the study.

Source/Credit: Max-Planck-Gesellschaft


Engineers grow pancreatic organoids


MIT and Cancer Research UK Manchester Institute researchers have
developed a synthetic gel that can be used to grow tiny
pancreatic organoids, seen here, from human pancreatic cells.
Credits: Courtesy of the researchers.
MIT engineers, in collaboration with scientists at Cancer Research UK Manchester Institute, have developed a new way to grow tiny replicas of the pancreas, using either healthy or cancerous pancreatic cells. Their new models could help researchers develop and test potential drugs for pancreatic cancer, which is currently one of the most difficult types of cancer to treat.

Using a specialized gel that mimics the extracellular environment surrounding the pancreas, the researchers were able to grow pancreatic “organoids,” allowing them to study the important interactions between pancreatic tumors and their environment. Unlike some of the gels now used to grow tissue, the new MIT gel is completely synthetic, easy to assemble and can be produced with a consistent composition every time.

“The issue of reproducibility is a major one,” says Linda Griffith, the School of Engineering Professor of Teaching Innovation and a professor of biological engineering and mechanical engineering. “The research community has been looking for ways to do more methodical cultures of these kinds of organoids, and especially to control the microenvironment.”

The researchers have also shown that their new gel can be used to grow other types of tissue, including intestinal and endometrial tissue.

Griffith and Claus Jorgensen, a group leader at the Cancer Research UK Manchester Institute, are the senior authors of the paper, which appears today in Nature Materials. The lead author is Christopher Below, a former graduate student at the Cancer Research UK Manchester Institute.

Mimicking the microenvironment

The researchers were also able to use their system to grow
supportive cells such as fibroblasts (green) and macrophages (orange)
surrounding the pancreatic organoids.
Credits: Joanna Kelly and Christopher Below
Traditionally, labs have used commercially available tissue-derived gel to grow organoids in a lab dish. However, as the most widely used commercial gel is a complex mixture of proteins, proteoglycans, and growth factors derived from a tumor grown in mice, it is variable from lot to lot and has undesirable components present, Griffith says. It also doesn’t always allow for growth of multiple types of cells. About 10 years ago, Griffith’s lab started to work on designing a synthetic gel that could be used to grow epithelial cells, which form the sheets that line most organs, along with other supportive cells.

The gel they developed is based on polyethylene glycol (PEG), a polymer that is often used for medical applications because it doesn’t interact with living cells. By studying the biochemical and biophysical properties of the extracellular matrix, which surrounds organs in the body, the researchers were able to identify features they could incorporate into the PEG gel to help cells grow in it.

One key feature is the presence of molecules called peptide ligands, which interact with cell surface proteins called integrins. The sticky binding between ligands and integrins allows cells to adhere to the gel and form organoids. The researchers found that incorporating small synthetic peptides derived from fibronectin and collagen in their gels allowed them to grow a variety of epithelial tissues, including intestinal tissue. They showed that supportive cells called stromal cells, along with immune cells, can also thrive in this environment.

In the new study, Griffith and Jorgensen wanted to see if the gel could also be used to support the growth of normal pancreatic organoids and pancreatic tumors. Traditionally, it has been difficult to grow pancreatic tissue in a manner that replicates both the cancerous cells and the supporting environment, because once pancreatic tumor cells are removed from the body, they lose their distinctive cancerous traits.

Griffith’s lab developed a protocol to produce the new gel, and then teamed up with Jorgensen’s lab, which studies the biology of pancreatic cancer, to test it. Jorgensen and his students were able to produce the gel and use it to grow pancreatic organoids, using healthy or cancerous pancreatic cells derived from mice.

“We got the protocol from Linda and we got the reagents in, and then it just worked,” Jorgensen says. “I think that speaks volumes of how robust the system is and how easy it is to implement in the lab.”

Other approaches they had tried were too complicated or did not recapitulate the microenvironment seen in living tissues, he says. Using this gel, Jorgensen’s lab was able to compare the pancreatic organoids to tissues they have studied in living mice, and they found that the tumor organoids express many of the same integrins seen in pancreatic tumors. Furthermore, other types of cells that normally surround tumors, including macrophages (a type of immune cells) and fibroblasts (a type of supportive cells), were also able to grow in the microenvironment.

Patient-derived cells

The researchers also showed that they can use their gel to grow organoids from pancreatic cancer cells from patients. They believe it could also be useful for studying lung, colorectal, and other cancers. Such systems could be used to analyze how potential cancer drugs affect tumors and their microenvironment.

“The discoveries described in this paper will facilitate further important questions concerning responses to novel drug treatment approaches,” says Hilary Critchley, a professor of reproductive medicine and co-deputy director of the MRC Centre for Reproductive Health at the University of Edinburgh, who was not involved in the study. “The cancer field has long relied upon other approaches (mouse models or isolated cell studies), and the contribution of the organoid approach, and notably the gel structure in which these mini groups of cells grow, will be pivotal to research advancement.”

Griffith also plans to use the gel to grow and study tissue from patients with endometriosis, a condition that causes the tissue that lines the uterus to grow outside the uterus. This can lead to pain and sometimes infertility.

One of the advantages of the new gel is that it is completely synthetic, and can be made easily in a lab by mixing together specific precursors, including PEG and some polypeptides. The researchers have filed a patent on the technology and are in the process of licensing it to a company that could produce the gel commercially.

The research was funded by Cancer Research UK, the Rosetrees Trust, a European Research Council Consolidator Award, the National Science Foundation, the National Institutes of Health, and the Defense Advanced Research Projects Agency.

Source/Credit: Massachusetts Institute of Technology


Researchers Create Materials for Shape-Shifting Architecture


Source/Credit: North Carolina State University

Researchers at North Carolina State University have developed materials that can be used to create structures capable of transforming into multiple different architectures. The researchers envision applications ranging from construction to robotics.

“The system we’ve developed was inspired by metamorphosis,” says Jie Yin, corresponding author of a paper on the work and an associate professor of mechanical and aerospace engineering at NC State. “With metamorphosis in nature, animals change their fundamental shape. We’ve created a class of materials that can be used to create structures that change their fundamental architecture.”

Kirigami is a fundamental concept for Yin’s work. Kirigami is a variation of origami that involves cutting and folding paper. But while kirigami traditionally uses two-dimensional materials, Yin applies the same principles to three-dimensional materials.

The metamorphosis system starts with a single unit of 3D kirigami. Each unit can form multiple shapes in itself. But these units are also modular – they can be connected to form increasingly complex structures. Because the individual units themselves can form multiple shapes, and can connect to other units in multiple ways, the overall system is capable of forming a wide variety of architectures.

“Think of what you can build with conventional materials,” Yin says. “Now imagine what you can build when each basic building block is capable of transforming in multiple ways.”

Yin’s lab previously demonstrated a similar concept, in which 3D kirigami units were stacked on each other. In that system, the units could be used to assemble a structure – but the structure could also then be disassembled.

The metamorphosis system involves actually connecting the kirigami units. In other words, once the units are connected to each other they cannot be disconnected. However, the larger structures they create are capable of transforming into multiple, different architectures.

“There are two big differences between our first kirigami system and the metamorphosis system,” Yin explains.

“The first kirigami system involved units that could be assembled into architectures and then disassembled, which is an advantage. However, when the units were assembled, the architecture wouldn’t be capable of transforming. Because the sides of the unit were not rigid and fixed at 90-degree angles, the assembled structure could bend and move – but it could not fundamentally change its geometry.

“The metamorphosis kirigami system does not allow you to disassemble a structure,” Yin says. “And because the sides of each cubic unit are rigid and fixed at 90-degree angles, the assembled structure does not bend or flex very much. However, the finished structure is capable of transforming into different architectures.”

In proof-of-concept testing, the researchers demonstrated that the metamorphosis system was capable of creating many different structures that are capable of bearing significant weight while maintaining their structural integrity.

That structural integrity is important, because Yin thinks construction is one potential application for the metamorphosis system.

“If you scale this approach up, it could be the basis for a new generation of construction materials that can be used to create rapidly deployable structures,” Yin says. “Think of the medical units that have had to be expanded on short notice during the pandemic, or the need for emergency housing shelters in the wake of a disaster.”

The researchers also think the metamorphosis system could be used to create a variety of robotic devices that can transform in order to respond to external stimuli or to perform different functions.

“We also think this system could be used to create a new line of toys – particularly toys that can help people explore some fundamental STEM concepts related to physics and engineering,” Yin says. “We’re open to working with industry collaborators to pursue these and other potential applications for the system.”

The paper, “Metamorphosis of three-dimensional kirigami-inspired reconfigurable and reprogrammable architected matter,” is published in the journal Materials Today Physics. First author of the paper is Yanbin Li, a Ph.D. student at NC State. The work was done with support from the National Science Foundation, under grant 2005374.

Source/Credit: North Carolina State University


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