Earth

Carbon-loving materials designed to reduce industrial emissions

image: Researchers at Oak Ridge National Laboratory and the University of Tennessee, Knoxville, demonstrated a novel fabrication method for affordable gas membranes that can remove carbon dioxide from industrial emissions.

Image: 
Zhenzhen Yang/University of Tennessee

Researchers at the Department of Energy's Oak Ridge National Laboratory and the University of Tennessee, Knoxville, are advancing gas membrane materials to expand practical technology options for reducing industrial carbon emissions.

Results published in Chem demonstrate a fabrication method for membrane materials that can overcome current bottlenecks in selectivity and permeability, key variables that drive carbon-capturing performance in real environments.

"Often there is a trade-off in how selective or how permeable you can make membranes that filter out carbon dioxide without allowing other gases to pass through. The ideal scenario is to create materials with high permeability and selectivity," said Zhenzhen Yang of UT's Department of Chemistry.

Gas membranes are a promising but still developing technology for reducing post-combustion or flue gas emissions produced by fossil-fueled industries.

The concept is simple: a thin, porous membrane acts as a filter for exhaust gas mixtures, selectively allowing carbon dioxide, or CO2, to flow through freely into a collector that is kept under reduced pressure, but preventing oxygen, nitrogen and other gases from tagging along.

Unlike existing chemical methods to capture CO2 from industrial processes, membranes are easy to install and can operate unattended for long periods with no additional steps or added energy costs. The catch is that new, cost-effective materials are needed to scale up the technology for commercial adoption.

"Gas membranes need pressure on one side and typically a vacuum on the other to maintain a free-flow environment, which is why materials' selectivity and permeability are so important to developing the technology," said Ilja Popovs of ORNL's Chemical Sciences Division. "Underperforming materials require more energy to push gases through the system, so advanced materials are key to keeping energy costs low."

No natural and only a few synthetic materials have exceeded what is called the Robeson upper limit, a known boundary that constrains how selective and permeable most materials can be before these rates start to drop.

Materials with sufficiently high selectivity and permeability for efficient gas separations are rare and often made from expensive starting materials whose production requires either long and tedious synthesis or costly transition metal catalysts.

"We set out to test a hypothesis that introducing fluorine atoms into membrane materials could improve carbon-capture and separation performance," Yang said.

The element fluorine, used to make consumer products such as Teflon and toothpaste, offers carbon dioxide-philic properties that make it attractive for carbon-capture applications. It is also widely available, making it a relatively affordable option for low-cost fabrication methods. Research on fluorinated gas membranes has been limited because of fundamental challenges of incorporating fluorine into materials to realize its carbon-loving functionality.

"Our first step was to create a unique fluorine-based polymer using simple chemical methods and commercially available starting materials," Yang said.

Next, researchers transformed, or carbonized, the material using heat to give it the porous structure and functionality needed for capturing CO2. The two-step process preserved the fluorinated groups and boosted CO2 selectivity in the final material, overcoming a fundamental hurdle encountered in other synthetic methods.

"The approach resulted in a carbon dioxide-philic material with high surface area and ultra-micropores that is stable in high-temperature operating conditions," Yang said. "All of these factors make it a promising candidate for carbon-capture and separation membranes."

The material's novel design contributes to its exceptional performance, observed in high selectivity and permeability rates that exceed the Robeson upper limit, something only a handful of materials have accomplished.

"Our success was a material achievement that demonstrates feasible routes for leveraging fluorine in future membrane materials. Moreover, we achieved this goal using commercially available, inexpensive starting materials," Popovs said.

The basic discovery expands the limited library of practical options for carbon-capture membranes and opens new directions for developing fluorinated membranes with other task-specific functionalities.

Researchers aim to next investigate the mechanism by which fluorinated membranes absorb and transport CO2, a fundamental step that will inform the design of better carbon-capture systems with materials purposely tailored to grab CO2 emissions.

Credit: 
DOE/Oak Ridge National Laboratory

Why are the offspring of older mothers less fit to live long and prosper?

image: Mother rotifer (Brachionus manjavacas) carrying four eggs (right) and newly-hatched daughter (left). Image of live rotifers acquired using polychromatic polarization and phase contrast.

Image: 
Michael Shribak, Evgeny Ivashkin, Kristin Gribble

WOODS HOLE, Mass. - The offspring of older mothers don't fare as well as those of younger mothers, in humans and many other species. They aren't as healthy, or they don't live as long, or they have fewer offspring themselves. A longstanding puzzle is why evolution would maintain this maternal effect in so many species, since these late-born offspring are less fit to survive and reproduce.

In a new study in rotifers (microscopic invertebrates), scientists tested the evolutionary fitness of older-mother offspring in several real and simulated environments, including the relative luxury of laboratory culture, under threat of predation in the wild, or with reduced food supply. They confirmed that this effect of older maternal age, called maternal effect senescence, does reduce evolutionary fitness of the offspring in all environments, primarily through reduced fertility during their peak reproductive period. They also suggest an evolutionary mechanism for why this may occur.

The study, a collaboration between Kristin Gribble of the Marine Biological Laboratory, and Christina Hernández of Woods Hole Oceanographic Institution, and Silke van Daalen and Hal Caswell of the University of Amsterdam, is published this week in Proceedings of the National Academy of Sciences.

"This study is unique in that combines laboratory data from our prior work with mathematical modeling to address a longstanding question in the evolution of aging," Gribble says. "Natural selection should weed out these less-fit offspring of older mothers. So why do we see this phenomenon across so many species?"

To address this, Hernández and collaborators built mathematical models to calculate, for the first time, the strength of natural selection pressure on the survival and fertility of offspring populations as functions of the age of their mothers. They found this pressure, called the selection gradient, declines with maternal age.

"Because the selection pressure decreases as the mothers age, it may not be strong enough to remove these less-fit [offspring] from the population," Hernandez says.

"Because of this, maternal effect senescence will persist and continue to evolve in the population, even though it results in decreased fitness," Gribble adds. They don't yet fully understand the genetic mechanisms that cause offspring quality to decrease with maternal age.

The models that the team developed can be applied to a wide range of species to evaluate the fitness consequences of maternal effect senescence. "As long as you have experimental data, as we did, on lifespan and fecundity of offspring from mothers of different ages, you can address this question in many organisms," Gribble says.

Credit: 
Marine Biological Laboratory

Marijuana use while pregnant boosts risk of children's sleep problems

Use marijuana while pregnant, and your child is more likely to suffer sleep problems as much as a decade later, according to a new University of Colorado Boulder study of nearly 12,000 youth.

Published in Sleep Health: The Journal of The National Sleep Foundation, the paper is the latest to link prenatal cannabis use to developmental problems in children and the first to suggest it may impact sleep cycles long-term.

It comes at a time when - while the number of pregnant women drinking alcohol and smoking cigarettes has declined in the United States - It has risen to 7% of all pregnant women as legalization spreads and more dispensaries recommend it for morning sickness.

"As a society, it took us a while to understand that smoking and drinking alcohol are not advisable during pregnancy, but it is now seen as common sense," said senior author John Hewitt, director of the Institute for Behavioral Genetics at CU Boulder. "Studies like this suggest that it is prudent to extend that common sense advice to cannabis, even if use is now legal."

A landmark study

For the study, Hewitt and lead author Evan Winiger analyzed baseline data from the landmark Adolescent Brain and Cognitive Development (ABCD) study, which is following 11,875 youth from age 9 or 10 into early adulthood.

As part of an exhaustive questionnaire upon intake, participants' mothers were asked if they had ever used marijuana while pregnant and how frequently. (The study did not assess whether they used edibles or smoked pot). The mothers were also asked to fill out a survey regarding their child's sleep patterns, assessing 26 different items ranging from how easily they fell asleep and how long they slept to whether they snored or woke up frequently in the night and how sleepy they were during the day.

About 700 moms reported using marijuana while pregnant. Of those, 184 used it daily and 262 used twice or more daily.

After controlling for a host of other factors, including the mother's education, parent marital status and family income and race, a clear pattern emerged.

"Mothers who said they had used cannabis while pregnant were significantly more likely to report their children having clinical sleep problems," said Winiger, a graduate student in the Department of Psychology and Neuroscience.

Those who used marijuana frequently were more likely to report somnolence symptoms (symptoms of excess sleepiness) in their children, such as trouble waking in the morning and being excessively tired during the day.

The authors note that, while their sample size is large, the study has some limitations.

"We are asking mothers to remember if they smoked marijuana 10 years ago and to admit to a behavior that is frowned upon," said Winiger, suggesting actual rates of prenatal use may have been higher.

While the study doesn't prove that using cannabis while pregnant causes sleep problems, it builds on a small but growing body of evidence pointing to a link.

For instance, one small study found that children who had been exposed to marijuana in-utero woke up more in the night and had lower sleep quality at age 3. Another found that prenatal cannabis use impacted sleep in infancy.

And, in other previous work, Hewitt, Winiger and colleagues found that teenagers who frequently smoked marijuana were more likely to develop insomnia in adulthood.

The fetal brain on THC

Researchers aren't sure exactly how cannabis exposure during vulnerable developmental times might shape future sleep. But studies in animals suggest that THC and other so-called cannabinoids, the active ingredients in pot, attach to CB1 receptors in the developing brain, influencing regions that regulate sleep. The ABCD study, which is taking frequent brain scans of participants as they age, should provide more answers, they said.

Meantime, mothers-to-be should be wary of dispensaries billing weed as an antidote for morning sickness. According to CU research, about 70% of Colorado dispensaries recommend it for that use. But mounting evidence points to potential harms, including low birth weight and later cognitive problems. With marijuana on the market today including far higher THC levels than it did a decade ago, it's impacts on the fetal brain are likely more profound than they once were.

"This study is one more example of why pregnant women are advised to avoid substance use, including cannabis," said Hewitt. "For their children, it could have long-term consequences."

Credit: 
University of Colorado at Boulder

Popular chemotherapy drug may be less effective in overweight and obese women

Breast cancer patients who are overweight or obese might benefit less from treatment with docetaxel, a common chemotherapy drug, than lean patients. An international team of researchers based this conclusion on a retrospective analysis of data from a large clinical trial. Their study was published in the Journal of Clinical Oncology.

In most European countries, more than 50% of women are overweight or obese (with a body mass index (BMI) above 25 kg/m2, as defined by the WHO). In the United States this is the case for over 63% of women and this proportion is expected to further increase in the coming years. It is not widely known, but obese women have a higher risk of getting breast cancer and obese breast cancer patients have a higher risk of relapsing. Moreover, while many cancer patients are overweight or obese, the efficacy of anticancer drugs according to their BMI is generally not known.

Analysis of 2,800 patients

For the study, a team led by researchers from KU Leuven and the Institut Jules Bordet (Belgium), the University of Milan and National Cancer Institute (Italy) analysed data from a clinical trial with over 2800 breast cancer patients that started around the turn of the millennium. Patient data were collected over the course of more than ten years. The patients in the trial were treated with a combination of chemotherapy drugs with or without docetaxel, one of the most widely used chemotherapy drugs in the world.

The researchers then looked at how many patients relapsed and how many had passed away. Their statistical analysis of the data shows that overweight and obese patients who received docetaxel as part of their treatment had poorer outcomes than lean patients (BMI between 18.5 and 25 kg/m2). This difference was not observed in patients who received the chemotherapy regimen that did not include docetaxel. "Docetaxel is a lipophilic drug, suggesting that fat present in the body could absorb part of the drug before it can reach the tumour," explains Professor Christine Desmedt from the KU Leuven Laboratory for Translational Breast Cancer Research.

Raising public awareness

The results raise concerns about treating overweight and obese cancer patients with docetaxel. "If follow-up research confirms that this finding is solely related to the pharmacological characteristics of docetaxel, this might also apply to patients with other cancer types that are treated with docetaxel, such as prostate or lung cancer. These results also make us wonder whether other chemotherapy drugs from the same family, like paclitaxel, will show the same effect."

"More research is needed before changes in treatment can be implemented. Patients who have concerns about docetaxel can discuss these with their doctor," explains Professor Desmedt. "In general, the public needs to be better informed about the link between BMI and breast cancer."

"In the medical and research world, we need to pay more attention to how obesity affects the biology, progression and treatment efficacy of breast cancer," says Professor Biganzoli of the Unit of Medical Statistics and the Data Science Research Center, University of Milan and the Italian National Cancer Institute. "Much work remains to be done in this field."

Credit: 
KU Leuven

Apgar score effective in assessing health of preterm infants

image: From left: Sven Cnattingius, Neda Razaz and Stefan Johansson at the Department of Medicine, Solna, Karolinska Institutet.

Image: 
Michael Fored

The vitality of preterm infants should be assessed with an Apgar score, a tool used to measure the health of newborns immediately after birth. That is the conclusion by researchers at Karolinska Institutet in Sweden who in a large observational study examined the value of Apgar scores for preterm infants. The findings are published in the New England Journal of Medicine.

The so-called Apgar score has been used since the 1950s to quickly assess the vitality of the infant soon after birth. Doctors and midwifes measure five parameters in the infant--heart activity, respiration, muscle tone, irritability and color--and give each parameter a score from 0-2. The total score can thus range from 0 to 10, where a higher number indicates better health and a greater chance of survival.

However, some have questioned the value of the Apgar score in preterm infants, since the immaturity of these infants may lead to lower scores compared with infants born at term. Therefore, the researchers in this study wanted to find out if the Apgar score could be used to predict the mortality risk of preterm infants during the first four weeks of life (the neonatal period).

Using Swedish nationwide register data, the researchers studied 113,000 non-malformed infants born after 22 to 36 weeks of pregnancy in the years 1992-2016. The risk of neonatal mortality was calculated for Apgar scores at five and ten minutes after birth, and separate analyses were performed for infants born at 22-24, 25-27, 28-31, 32-34 and 35-36 gestational weeks.

A total of 1,986 (1.8 percent) preterm infants died in the neonatal period. As expected, the neonatal death rate sharply increased with shorter pregnancy length, from 0.2 percent for infants born at 36 weeks to 76.5 percent for those born at 22 weeks. Regardless of pregnancy length, the risk of neonatal death increased with a lower Apgar score. For children born very prematurely, a lower Apgar score significantly increased the absolute risk of neonatal mortality. Even a slight increase in Apgar score from five to ten minutes after birth was associated with a lower risk of neonatal death.

"Our results show the importance of registering Apgar score also in preterm infants," says Sven Cnattingius, senior professor at the Department of Medicine, Solna, Karolinska Institutet, and the study's corresponding author. "It is important that infants with reduced scores receive full clinical attention regardless of gestational age."

"Heart activity and breathing are the cornerstones of the Apgar assessment," says co-author Stefan Johansson, associate professor at the Department of Medicine, Solna, Karolinska Institutet and neonatologist at the Sachsska children and youth hospital in Stockholm. "Our research indicates that the chance of survival increases the better you are at stabilizing the premature baby's circulation and breathing immediately after birth."

The researchers considered several confounding factors that could impact the outcome, including the mother's age, smoking, weight, blood-pressure, infant's mode of delivery and year of birth. The researchers note that the study is based on Swedish conditions and that the results may be different in other countries.

"Although it is frustrating that we usually cannot pinpoint the causes of a reduced Apgar score, we need to embrace that the score is, independent of gestational age, the best available tool we have to evaluate the newborn's health in the delivery room," says Neda Razaz, assistant professor in the same department.

Around 115,000 non-malformed children are born in Sweden annually, and slightly more than 5 percent are born preterm. Of these, around 150 children die during the neonatal period, of which around 100 are born preterm.

Credit: 
Karolinska Institutet

Moss protein corrects genetic defects of other plants

image: (here called RNA editor) with its target site. RNA editors correct specific errors in the mitochondria and chloroplasts.

Image: 
© Bastian Oldenkott/Uni Bonn

Almost all land plants employ an army of molecular editors who correct errors in their genetic information. Together with colleagues from Hanover, Ulm and Kyoto (Japan), researchers from the University of Bonn have now transferred one of these proofreaders from the moss Physcomitrium patens (previously known as Physcomitrella patens) into a flowering plant. Surprisingly, it performs its work there as reliably as in the moss itself. The strategy could be suitable for investigating certain functions of the plant energy metabolism in more detail. It may also be valuable for developing more efficient crops. The study will be published in the journal The Plant Cell.

Plants differ from animals in that they are capable of photosynthesis. They do this in specialized "mini-organs" (biologists speak of organelles), the chloroplasts. Chloroplasts produce sugar with the help of sunlight, which in turn is used in other organelles, the mitochondria, to produce energy.

Both chloroplasts and mitochondria have their own genetic material. And in both of them this genome contains a lot of errors. "At least that is the case with almost all land plants," explains Dr. Mareike Schallenberg-Rüdinger. The researcher heads a junior research group at the University of Bonn in the Department of Molecular Evolution under Prof. Volker Knoop. "They have to correct these errors so their power supply does not collapse."

In fact, land plants do the same, and in a very complicated way: They do not correct the errors in the genome itself. Instead, they correct the RNA copies that the cell makes of these DNA blueprints, which it then uses to produce certain enzymes, for example. So instead of correcting the original, it only irons out the inaccuracies afterwards in the copies.

Functional despite 400 million years of evolutionary history

Molecular proofreaders, the so-called PPR proteins, are responsible for this. Most of them are specialists for only one particular error in the many gene copies that the cell produces around the clock. These errors occur when, in the course of evolution, a certain chemical building block of DNA (a letter, if you like, in the genetic blueprint) is swapped for another. When the PPR proteins find such a swap, they convert the wrong letter in the RNA copy (the building block cytidine, abbreviated C) into the correct version (uridine, abbreviated U).

"We have now taken a gene for a PPR protein from the moss Physcomitrium patens and transferred it into a flowering plant, the thale cress Arabidopsis thaliana," explains Schallenberg-Rüdinger. "The protein then recognized and corrected the same error there for which it was also responsible in the moss." This is astonishing, since there are more than 400 million years of evolutionary history between Physcomitrium and Arabidopsis. The PPR proteins can therefore also differ significantly in their structure.

For instance, the thale cress contains PPR proteins that can identify errors but still require a separate "white-out" enzyme to correct them. In contrast, the PPR proteins of the moss Physcomitrium perform both tasks simultaneously. "In these cases, the transfer from moss to thale cress works, but the thale cress gene remains inactive in the moss," explains Bastian Oldenkott, doctoral student and lead author of the study. The macadamia nut appeared in evolution a little earlier than Arabidopsis. Its PPR protein being investigated is more similar to that of Physcomitrium. Once introduced into the moss, it therefore performs its service there without any problems.

The study may open up a new way to modify the genetic material of chloroplasts and mitochondria. "Especially for plant mitochondria, this is not yet possible at all," emphasizes Schallenberg-Rüdinger. Using special "designer" PPR genes, for example, one might specifically render certain genome transcripts unusable and test how this affects the plant. In the medium term, this may also result in new findings for breeding particularly high-yielding, high-performance varieties. First, however, the researchers hope to gain insights into the complex interaction of genes in the functioning of chloroplasts and mitochondria.

The research carried out by co-authors Prof. Hans-Peter Braun and Dr. Jennifer Senkler from the University of Hanover proves that this approach can actually work. They were able to clarify what the PPR protein from the moss is needed for: If it is missing, the plant is no longer able to correctly assemble the machinery for the so-called respiratory chain in the mitochondria, which is used to generate energy. The work in the thale cress was carried out in cooperation with Matthias Burger (University of Ulm) and Prof. Mizuki Takenaka (University of Kyoto), a fine example of successful international cooperation.

Credit: 
University of Bonn

New method measures temperature within 3D objects

MADISON, Wis. -- University of Wisconsin-Madison engineers have made it possible to remotely determine the temperature beneath the surface of certain materials using a new technique they call depth thermography. The method may be useful in applications where traditional temperature probes won't work, like monitoring semiconductor performance or next-generation nuclear reactors.

Many temperature sensors measure thermal radiation, most of which is in the infrared spectrum, coming off the surface of an object. The hotter the object, the more radiation it emits, which is the basis for gadgets like thermal imaging cameras.

Depth thermography, however, goes beyond the surface and works with a certain class of materials that are partially transparent to infrared radiation.

"We can measure the spectrum of thermal radiation emitted from the object and use a sophisticated algorithm to infer the temperature not just on the surface, but also underneath the surface, tens to hundreds of microns in," says Mikhail Kats, a UW-Madison professor of electrical and computer engineering. "We're able to do that precisely and accurately, at least in some instances."

Kats, his research associate Yuzhe Xiao and colleagues described the technique this spring in the journal ACS Photonics.

For the project, the team heated a piece of fused silica, a type of glass, and analyzed it using a spectrometer. They then measured temperature readings from various depths of the sample using computational tools previously developed by Xiao in which he calculated the thermal radiation given off from objects composed of multiple materials. Working backwards, they used the algorithm to determine the temperature gradient that best fit the experimental results.

Kats says this particular effort was a proof of concept. In future work, he hopes to apply the technique to more complicated multilayer materials and hopes to apply machine learning techniques to improve the process. Eventually, Kats wants to use depth thermography to measure semiconductor devices to gain insights into their temperature distributions as they operate.

That's not the only potential application of the technique. This type of 3D temperature profiling could also be used to measure and map clouds of high temperature gases and liquids.

"For example, we anticipate relevance to molten-salt nuclear reactors, where you want to know what's going on in terms of temperature of the salt throughout the volume," says Kats. "You want to do it without sticking in temperature probes that may not survive at 700 degrees Celsius for very long."

He also says the technique could aid in measuring the thermal conductivity and optical properties of materials without the need to attach temperature probes.

"This is a completely remote, non-contact way of measuring the thermal properties of materials in a way that you couldn't do before," Kats says.

Credit: 
University of Wisconsin-Madison

Tiny mineral particles are better vehicles for promising gene therapy

MADISON, Wis. -- University of Wisconsin-Madison researchers have developed a safer and more efficient way to deliver a promising new method for treating cancer and liver disorders and for vaccination -- including a COVID-19 vaccine from Moderna Therapeutics that has advanced to clinical trials with humans.

The technology relies on inserting into cells pieces of carefully designed messenger RNA (mRNA), a strip of genetic material that human cells typically transcribe from a person's DNA in order to make useful proteins and go about their business. Problems delivering mRNA safely and intact without running afoul of the immune system have held back mRNA-based therapy, but UW-Madison researchers are making tiny balls of minerals that appear to do the trick in mice.

"These microparticles have pores on their surface that are on the nanometer scale that allow them to pick up and carry molecules like proteins or messenger RNA," says William Murphy, a UW-Madison professor of biomedical engineering and orthopedics. "They mimic something commonly seen in archaeology, when we find intact protein or DNA on a bone sample or an eggshell from thousands of years ago. The mineral components helped to stabilize those molecules for all that time."

Murphy and UW-Madison collaborators used the mineral-coated microparticles (MCMs) -- which are 5 to 10 micrometers in diameter, about the size of a human cell -- in a series of experiments to deliver mRNA to cells surrounding wounds in diabetic mice. Wounds healed faster in MCM-treated mice, and cells in related experiments showed much more efficient pickup of the mRNA molecules than other delivery methods.

The researchers described their findings today in the journal Science Advances.

In a healthy cell, DNA is transcribed into mRNA, and mRNA serves as the instructions the cell's machinery uses to make proteins. A strip of mRNA created in a lab can be substituted into the process to tell a cell to make something new. If that something is a certain kind of antigen, a molecule that alerts the immune system to the presence of a potentially harmful virus, the mRNA has done the job of a vaccine.

The UW-Madison researchers coded mRNA with instructions directing cell ribosomes to pump out a growth factor, a protein that prompts healing processes that are otherwise slow to unfold or nonexistent in the diabetic mice (and many severely diabetic people).

mRNA is short-lived in the body, though, so to deliver enough to cells typically means administering large and frequent doses in which the mRNA strands are carried by containers made of molecules called cationic polymers.

"Oftentimes the cationic component is toxic. The more mRNA you deliver, the more therapeutic effect you get, but the more likely it is that you're going to see toxic effect, too. So, it's a trade-off," Murphy says. What we found is when we deliver from the MCMs, we don't see that toxicity. And because MCM delivery protects the mRNA from degrading, you can get more mRNA where you want it while mitigating the toxic effects."

The new study also paired mRNA with an immune-system-inhibiting protein, to make sure the target cells didn't pick the mRNA out as a foreign object and destroy or eject it.

Successful mRNA delivery usually keeps a cell working on new instructions for about 24 hours, and the molecules they produce disperse throughout the body. That's enough for vaccines and the antigens they produce. To keep lengthy processes like growing replacement tissue to heal skin or organs, the proteins or growth factors produced by the cells need to hang around for much longer.

"What we've seen with the MCMs is, once the cells take up the mRNA and start making protein, that protein will bind right back within the MCM particle," Murphy says. "Then it gets released over the course of weeks. We're basically taking something that would normally last maybe hours or even a day, and we're making it last for a long time."

And because the MCMs are large enough that they don't enter the bloodstream and float away, they stay right where they are needed to keep releasing helpful therapy. In the mice, that therapeutic activity kept going for more than 20 days.

"They are made of minerals similar to tooth enamel and bone, but designed to be reabsorbed by the body when they're not useful anymore," says Murphy, whose work is supported by the Environmental Protection Agency, the National Institutes of Health and the National Science Foundation and a donation from UW-Madison alums Michael and Mary Sue Shannon.

"We can control their lifespan by adjusting the way they're made, so they dissolve harmlessly when we want."

Credit: 
University of Wisconsin-Madison

Elderly people's response to COVID-19 not as expected

image: Compliance with preventive measures and age.

Local regression with a kernel (epanechnikov) function and a bandwidth of 0.8, with 84% confidence intervals included.

Image: 
Daoust, 2020 (PLOS ONE, CC BY)

Survey results from 27 countries suggest that, despite their increased risk of severe illness due to COVID-19, elderly people are not more willing to isolate when asked to, and are not more compliant with several COVID-19 preventive measures. Jean-François Daoust of the University of Edinburgh, U.K., presents these findings in the open-access journal PLOS ONE on July 2, 2020.

Among those who become ill with COVID-19, older adults appear to be more likely to be hospitalized or die from the disease. Because of their increased vulnerability, one might expect that elderly people would be more disciplined in complying with preventive measures. However, few studies have yet examined their response.

In the first in-depth study of elderly people's attitudes and compliance with COVID-19 preventative measures, Daoust examined survey results from 72,417 people of all ages across 27 different countries. The surveys asked about people's willingness to self-isolate if necessary, as well as their compliance with specific preventive measures, such as hand washing or wearing a mask.

The analysis suggests that elderly people are no more willing than those in their 50s and 60s to voluntarily self-isolate if they begin to feel ill or if they are advised to do so by a clinician or health official. People aged 60 to 80 are also less likely than younger age groups to wear a mask outside their home. However, older people are more likely to avoid public transportation and to avoid small gatherings or having guests over.

These findings suggest that efforts are needed to improve public health strategies to encourage older adults to comply with preventive measures. A deeper understanding of elderly people's attitudes and compliance could help inform such improvements and, ultimately, reduce the number of deaths to due to the pandemic.

Daoust adds: "Given the vulnerability of elderly people, we should expect nothing else but a greater level of compliance with preventive measures compared to their younger fellow citizens. However, Daoust finds that this expectation is not grounded in reality. The surprising (and quite shocking) findings entails major implications on how we managed and will manage the COVID-19 crises."

Credit: 
PLOS

Unlocking the key to an effective vaccine

image: A plasma cell, situated in its survival niche, putting out Y shaped antibodies. Long-lived plasma cells are needed for successful vaccines as they can produce anti-virus antibodies for decades.

Image: 
Image: Tarlinton lab

A recent study by Monash University has looked at the role plasma cells and their longevity play in the effectiveness of vaccines in the body and suggests that components within vaccine design are the key.

In the wake of the COVID-19 outbreak, a lot of research is focussed on developing a vaccine. For a vaccine to be successful, it has to do two things. First, it must signal the body to generate a lot of plasma cells making anti-virus antibodies. Second, these plasma cells have to live and produce antibodies for years or even decades for the vaccination to succeed. However, the reality is that most of them only survive a few days.

A recent study published in the journal Immunological Reviews, led by Professor David Tarlinton from Monash Central Clinical School's Immune Memory Laboratory, suggests that components within vaccines can play a major role in aiding the lifespan of individual plasma cells. Understanding the processes involved in long-lived plasma cell formation will open up ways of making vaccines more effective.

"One of the difficulties in designing an effective vaccine is that it is unclear exactly what determines how long a single plasma cell will survive. We only have a limited understanding of what might be special about those plasma cells that survive for the longer periods, and what it is in their development that tells them that they, specifically, should survive," said Professor Tarlinton.

The paper takes a further conceptual step, and outlines there is also likely competition between plasma cells for survival cues, such that there could be a 'survival of the fittest' bent to long-term antibody-based immunity.

Monash University research fellow, Dr Marcus Robinson in Professor Tarlinton's lab, says the paper outlines a framework that can be used to determine the individual signals that lead to long-lived antibody responses by the plasma cells.

"It is exciting to know we are on the cusp of understanding what is a complicated sequence of events, and that this understanding might feed into vaccine design in the near future", he said.

Credit: 
Monash University

Mothering in domestic violence: Protecting children behind closed doors

As emerging data shows an alarming rise of domestic violence during the pandemic, researchers at the University of South Australia are urging practitioners to look beyond clinical observations and focus on the strengths that mothers exercise to protect their children from domestic abuse.

The call follows UniSA research that upends the perception that abused women are unable to adequately protect their children, instead revealing the ways that women think and act to shield their children from abuse, often at the expense of their own personal safety.

In the past 12 months, more than 243 million women and girls (aged 15-49) across the globe, were subjected to sexual or physical violence by an intimate partner. In Australia, one in six (or 1.6 million women) have experienced physical or sexual violence with 80 per cent experiencing coercive control by a current or previous partner since the age of 15. More than a quarter of the women said that children in their care had witnessed this violence and abuse.

Lead researcher and experienced social worker, UniSA's Dr Fiona Buchanan, says practitioners need to recognise mothers' protective behaviour if they are to work towards increasing safety for women and children living in abusive environments.

"Far too often, women are perceived as passive victims of domestic abuse, who while enduring unconscionable abuse, are unable to protect their own children," Dr Buchanan says.

"But what many practitioners don't realise is that these women are protecting their children in many unseen ways, that hope to reduce the likelihood of an abusive partner lashing out.

"The mothers in our research talked about the things they did to avoid conflict with their partners, things like controlling the home environment - making sure dinner was ready and on the table; ensuring the children were clean and quiet; and by making sure the house was neat and tidy.

"By trying to pre-empt abuse, they sought to limit their partner's aggressive outbursts, effectively managing his mood and behaviour to safeguard their children's wellbeing."

The study also showed that mothers intentionally tried to 'keep the peace' by purposely avoiding conflict with aggressive partners.

"Protective behaviours could span anything from keeping the children out of harm's way when they thought an assault was likely to occur, to putting themselves physically close to their abuser to try and placate him," Dr Buchanan says.

"In this instance, despite wanting to put distance between them and their violent partner, they placed themselves closer to the danger, arguably increasing risk to themselves in order to reduce the risk to the children."

Using interviews and focus groups UniSA's Dr Buchanan and Professor Nicole Moulding explored the lived experiences of 16 women who had mothered children in domestic abuse, hoping to better understand their thoughts, feelings and actions during that time. Each of the women had left their abusive partner at least one year prior to participating in the study.

Dr Buchanan warns that practitioners who rely on attachment theory (the observed emotional bonds between children and caregivers) in child protection practice are at risk of overlooking invisible acts of protective agency.

"Despite the popularity of attachment theory in child protection, it does not offer much guidance about supporting women and children living in abusive home environments, especially as it categorises the child-mother relationship without context," Dr Buchanan says.

"Clinical observation downplays the protective role of mothers in abusive relationships and promotes a notion of 'bad mothering'.

"There is no evidence to assume that abused women are worse mothers.

"Instead of identifying deficits and assigning blame, practitioners should seek to understand the invisible behaviours that women engage in behind closed doors to protect their children from abuse.

"A strengths-based approach is essential if we are to move towards more positive and empowered practices of safety and protection.

"Sadly, we cannot remove women and children from these terrible scenarios without taking a good look at the society which tolerates domestic abuse and blames women for being victimized."

Credit: 
University of South Australia

Climate change threat to tropical plants

Tropical plants closer to the equator are most at risk from climate change because it is expected to become too hot for many species to germinate in the next 50 years, UNSW researchers have found.

Their study analysed almost 10,000 records for more than 1300 species from the Kew Gardens' global seed germination database.

The research, published in the journal Global Ecology and Biogeography recently, was the first to look at the big picture impact of climate change on such a large number of plant species worldwide.

Lead author Alex Sentinella, UNSW PhD researcher, said past research had found that animal species closer to the equator would be more at risk from climate change.

"The thought was that because tropical species come from a stable climate where it's always warm, they can only cope with a narrow range of temperatures - whereas species from higher latitudes can cope with a larger range of temperatures because they come from places where the weather varies widely," Mr Sentinella said.

"However, this idea had never been tested for plants.

"Because climate change is a huge issue globally, we wanted to understand these patterns on a global scale and build upon the many studies on plants at an individual level in their environment."

Seeds a key indicator of survival

The researchers examined seed germination data from the Millennium Seed Bank Partnership Data Warehouse, hosted by Kew Royal Botanic Gardens in London, to quantify global patterns in germination temperature.

They analysed 9737 records for 1312 plant species from every continent except Antarctica and excluded agricultural crops.

Mr Sentinella said they chose seed data because it was widely available and relevant to the ability of a species to cope with different temperatures.

"With seeds, you can experiment on them quickly, there are a lot of studies about them and importantly, germination directly relates to how a species will survive, because if the seed doesn't germinate the plant won't live," he said.

"So, we collated the data from the Kew Gardens database, examined all experiments on the same species from the same locations, and then determined the range of temperatures each species could tolerate in order to survive."

The researchers also examined climate data for the same locations as the plant species used in the study.

They looked at current temperature - the average temperature of the warmest three months from 1970 to 2000 - and predicted temperature for 2070.

The researchers then compared the temperatures the plants were experiencing now with the forecasted 2070 temperatures.

Tropical plants to hit or exceed temperature limits

The study discovered tropical plants do not have narrower temperature tolerances but were more at risk from global warming, because it would bring them close to their maximum seed germination temperatures.

Mr Sentinella said, on average, the closer a plant was to the equator, the more at risk it would be of exceeding its temperature ceiling by 2070.

"These plants could be more at risk because they are near their upper limits. So, even a small increase in temperature from climate change could push them over the edge," he said.

"The figures are quite shocking because by 2070, more than 20 per cent of tropical plant species, we predict, will face temperatures above their upper limit, which means they won't germinate, and so can't survive."

Mr Sentinella said the researchers also found that more than half of tropical species are expected to experience temperatures exceeding their optimum germination temperatures.

"That's even worse because if those plants can survive it would be at a reduced rate of germination and therefore, they might not be as successful," he said.

"If a seed's germination rate is 100 per cent at its optimum temperature, then it might only manage 50 or 60 per cent, for example, if the temperature is higher than what's ideal."

Mr Sentinella said he was surprised to find that climate change would threaten so many tropical species.

"But our most unexpected discovery was that the hypothesis often used for animals - that those near the equator would struggle to survive the impact of climate change because they have narrower temperature tolerances - was not true for plants," he said.

"We found that regardless of latitude, plant species can germinate at roughly the same breadth of temperatures, which does not align with the animal studies."

The researchers also found 95 per cent of plant species at latitudes above 45 degrees are predicted to benefit from warming, because environmental temperatures are expected to shift closer to the species' optimal germination temperatures.

Findings to help target conservation efforts

Mr Sentinella said it was possible for some plants to slowly evolve to increasing temperatures, but it was difficult to predict which ones would survive.

"The problem with the quick change in temperatures forecasted, is that some species won't be able to adapt fast enough," he said.

"Sometimes plants can migrate by starting to grow further away from the equator or, up a mountain slope where it's cooler. But if a species can't do that it will become extinct.

"There are almost 400,000 plant species worldwide - so, we would expect a number of them to fail to germinate between now and 2070."

Mr Sentinella hopes the researchers' findings will help to conserve plant species under threat from climate change.

"Ideally, we would be able to conserve all ecosystems, but the funding is simply not there. So, our findings could help conservation efforts target resources towards areas which are more vulnerable," he said.

"We also hope our findings further strengthen the global body of research about the risks of climate change.

"Humans have known about dangers of climate change for decades and we already have the answers to tackle it. So, hopefully our study will help encourage people and policy makers to take action now."

Credit: 
University of New South Wales

A novel sperm selection technology to increase success rates of in vitro fertilization

image: LEFT: Mouse sperm collected by a conventional cell sorter. Motility cannot be maintained and sperm cannot advance.
RIGHT: Mouse sperm collected by a cell sorter using a microfluidic device. Motility is maintained and sperm remain active.
Video: https://youtu.be/e6SYnvHJz2g

Image: 
Professor Toru Takeo

Motile sperm are difficult to collect with a conventional cell sorter because they are vulnerable to physical damage. A research collaboration between Kumamoto and Kyoto Universities in Japan has developed a technique that uses a cell sorter with microfluidic chip technology to reduce cell damage and improve in vitro fertilization (IVF) rates. This research is expected to increase IVF rates to improve production of experimental animals and livestock, and could be used as a fertility treatment in human reproductive medicine.

It is important to select fertile sperm with good motility to obtain high IVF rates. Conventional cell sorters use flow cytometry to separate specific cells by type, and can be used to select sperm. However, since sperm cells are susceptible to physical damage, it is extremely difficult to separate them without effecting motility.

To reduce sperm cell damage, Professor Toru Takeo's research team at Kumamoto University tried to develop a sperm selection technique using a cell sorter with microfluidic chip technology that reduces detrimental effects to cells. Microfluidic devices have minute channel structures with a width and depth between several to several-hundreds of micrometers and are widely used in chemical and biotechnology research.

While investigating the optimum separation conditions of sperm from a culture medium with their device, the researchers successfully collected mouse sperm that maintained motility. Furthermore, IVF using sperm collected with this device produced fertilized eggs and the embryos developed into neonatal mice after being transplanted into female mice.

This new technology can also be used to improve IVF. At the end stage of maturation, before egg penetration and fertilization, sperm undergo morphological and physiological changes called the acrosome reaction that makes them ready to fertilize an egg. To test whether they could increase fertility, researchers prepared a fluorescent substance that binds to fertile sperm and used the device to sort them from non-fertile sperm. Comparison IVF experiments revealed that the fertile sperm had a higher fertilization rate than the non-fertile sperm.

"We expect that our research can be used to increase the success rate of IVF in animals, and for fertility treatments in human reproductive medicine," said Prof. Takeo. "Combined with techniques for labeling sex chromosomes in sperm, we may even be able to selectively breed males or females in experimental animals and livestock."

Credit: 
Kumamoto University

New drug reduces stroke damage in mice

image: Small protein drug TAT-DP-2 spares brain tissue after a stroke by disrupting potassium flow out of neurons.

Image: 
Anthony Schulien

PITTSBURGH, July 1, 2020 - Neuroscientists at the University of Pittsburgh Brain Institute have identified a novel drug that could protect the brain during and after a stroke.

The study, published today in Science Advances, shows that injured neurons can remain viable if they are prevented from following biochemical pathways that lead to cell death.

"No drugs exist in clinical practice that are capable of blocking the cell death that occurs following stroke," said Anthony Schulien, the study's first author and a medical student in Pitt's Physician Scientist Training Program. "These experiments provide exciting, early evidence of drug targets that we hope to one day translate to patients."

A stroke occurs because a clot clogs a brain blood vessel, blocking blood and oxygen from reaching neurons and killing them, explained Elias Aizenman, Ph.D., senior author and professor of neurobiology at Pitt's School of Medicine. Nearby neurons, in an area called the stroke penumbra, also can become dysfunctional and die hours or days later, even when their blood and oxygen supply was only mildly or transiently reduced.

"We are looking for ways to prevent these other neurons from dying, too," Aizenman said. "If we can do that, recovery might be improved, and we might be able to better help people who have strokes in which the clot is in an inaccessible blood vessel or who could not get to the hospital in time for early intervention. With the right drug, we also may be able to slow the progression of a known stroke before a patient reaches the hospital."

In previously published studies, Aizenman's research team showed that the interaction between a potassium channel in the cell membrane called Kv2.1 and a protein called syntaxin encouraged potassium ions to leak out of the neuron, triggering cell death. And they found that using an experimental compound called TAT-C1aB could prevent cell death by interfering with the interaction of syntaxin and Kv2.1.

For this new study, the researchers identified two types of Kv2.1 channels in the neuronal cell membrane. One channel is routinely involved in cell excitability, while the other allows entry of additional, new Kv2.1 channels into the membrane, promoting the release of potassium and ultimately neuronal cell death.

Armed with this knowledge, the scientists created a new small protein called TAT-DP-2 that disrupts the passage of these new channels into the cell membrane, keeping potassium in the cell and halting the biochemical pathway for cell death.

Mice that received an injection of TAT-DP-2 after a stroke had smaller areas of stroke damage, and their long-term neurological function was better than that of untreated animals.

"Two completely different approaches involving Kv2.1 led to better stroke outcomes, indicating the promise of neuroprotective drugs that target the channel," Aizenman said.

Credit: 
University of Pittsburgh

Researchers develop a new ultrafast insulin

image: Illustration depicting how fast different forms of insulin absorb in the bloodstream, and how the polymer developed by these researchers helps stabilize ultrafast-absorbing insulin in the vial.

Image: 
Joseph Mann and Caitlin Maikawa

Researchers at Stanford University are developing a new insulin formulation that begins to take effect almost immediately upon injection, potentially working four times as fast as current commercial fast-acting insulin formulations.

The researchers focused on so-called monomeric insulin, which has a molecular structure that, according to theory, should allow it to act faster than other forms of insulin. The catch is that monomeric insulin is too unstable for practical use. So, in order to realize the ultrafast potential of this insulin, the researchers relied on some materials science magic.

"The insulin molecules themselves are fine, so we wanted to develop a 'magic fairy dust' that you add into a vial that would help to fix the stability problem," said Eric Appel, assistant professor of materials science and engineering at Stanford. "People often focus on the therapeutic agents in a drug formulation but, by focusing only on the performance additives - parts that were once referred to as 'inactive ingredients' - we can achieve really big advancements in the overall efficacy of the drug."

After screening and testing a large library of additive polymers, the researchers found one that could stabilize monomeric insulin for more than 24 hours in stressed conditions. (By comparison, commercial fast-acting insulin stays stable for six to ten hours under the same conditions.) The researchers then confirmed the ultrafast action of their formulation in diabetic pigs. Their results were published July 1 in Science Translational Medicine. Now, the researchers are conducting additional tests in hopes of qualifying for clinical trials in humans.

One step back, two steps forward

Current commercial formulations of insulin contain a mix of three forms: monomers, dimers and hexamers. Scientists have assumed monomers would be the most readily useful in the body but, within vials, the insulin molecules are drawn to the surface of the liquid where they aggregate and become inactive. (Hexamers are more stable in the vial but take longer to work in the body because they first have to break down into monomers to become active.) This is where the "magic fairy dust" - a custom polymer that is attracted to the air/water interface - comes in.

"We focused on polymers that would preferentially go to that interface and act as a barrier between any of the insulin molecules trying to gather there," said Joseph Mann, a graduate student in the Appel lab and co-lead author of the paper. Crucially, the polymer can do this without interacting with the insulin molecules themselves, allowing the drug to take effect unimpeded.

Finding just the right polymer with the desired properties was a long process that involved a three-week trip to Australia, where a fast-moving robot created approximately 1500 preliminary candidates. This was followed by processing and testing individually by hand at Stanford to identify polymers that successfully exhibited the desired barrier behavior. The first 100 candidates didn't stabilize commercial insulin in tests but the researchers pressed on. They found their magic polymer only weeks before they were scheduled to run experiments with diabetic pigs.

"It felt like there was nothing happening and then all of the sudden there was this bright moment ... and a deadline a couple of months away," said Mann. "The moment we got an encouraging result, we had to hit the ground running."

In commercial insulin - which typically remains stable for about 10 hours in accelerated aging tests - the polymer drastically increased the duration of stability for upwards of a month. The next step was to see how the polymer affected monomeric insulin, which on its own aggregates in 1-2 hours. It was another welcome victory when the researchers confirmed that their formulation could remain stable for over 24 hours under stress.

"In terms of stability, we took a big step backward by making the insulin monomeric. Then, by adding our polymer, we met more than double the stability of the current commercial standard," said Caitlin Maikawa, a graduate student in the Appel lab and co-lead author of the paper.

With a seed grant from the Stanford Diabetes Research Center and the Stanford Maternal and Child Health Research Institute, the researchers were able to evaluate their new monomeric insulin formulation in diabetic pigs - the most advanced non-human animal model - and found that their insulin reached 90 percent of its peak activity within five minutes after the insulin injection. For comparison, the commercial fast-acting insulin began showing significant activity only after 10 minutes. Furthermore, the monomeric insulin activity peaked at about 10 minutes while the commercial insulin required 25 minutes. In humans, this difference could translate to a four-fold decrease in the time insulin takes to reach peak activity.

"When I ran the blood tests and started plotting the data, I almost couldn't believe how good it looked," said Maikawa.

"It's really unprecedented," said Appel, who is senior author of the paper. "This has been a major target for many big pharmaceutical companies for decades."

The monomeric insulin also finished its action sooner. Both beginning and ending activity sooner makes it easier for people to use insulin in coordination with mealtime glucose levels to appropriately manage their blood sugar levels.

A multifaceted success

The researchers plan to apply to the Food and Drug Administration for approval to test their insulin formulation in clinical trials with human participants (although no trials are planned yet and they are not seeking participants at this time). They are also considering other uses for their polymer, given how significantly it increased stability in commercial insulin.

Because their insulin formulation activates so quickly - and, therefore, more like insulin in a person without diabetes - the researchers are excited by the possibility that it could aid the development of an artificial pancreas device that functions without the need for patient intervention at mealtimes.

Additional Stanford co-authors include former visiting scholar Anton Smith (from Aarhus University in Denmark); graduate students Abigail Grosskopf, Gillie Roth, Catherine Meis, Emily Gale, Celine Liong, Doreen Chan, Lyndsay Stapleton and Anthony Yu; clinical veterinarian Sam Baker; and postdoctoral fellow Santiago Correa. Researchers from CSIRO Manufacturing in Australia are also co-authors. Appel is also a member of Stanford Bio-X, the Cardiovascular Institute, the Stanford Maternal and Child Research Institute and a faculty fellow at Stanford ChEM-H.

This research was funded by the National Institutes of Health, a Pilot and Feasibility seed grant from the Stanford Diabetes Research Center, the Stanford Maternal and Child Health Research Institute, the American Diabetes Association, the PhRMA Foundation, the U.S. Department of Defense, a Stanford Graduate Fellowship, the Natural Sciences and Engineering Research Council of Canada, the Stanford Bio-X Bowes Graduate Student Fellowship, the Novo Nordisk Foundation, Stanford Bio-X, and the Danish Council of Independent Research.

Credit: 
Stanford University