Pathways to production

 Biologists at Sandia National Laboratories developed comprehensive software that will help scientists in a variety of industries create engineered chemicals more quickly and easily. Sandia is now looking to license the software for commercial use, researchers said.

Sandia’s stand-alone software RetSynth uses a novel algorithm to sort through large, curated databases of biological and chemical reactions, which could help scientists synthetically engineer compounds used in the production of biofuels, pharmaceuticals, cosmetics, industrial chemicals, dyes, scents and flavors.

A graphic illustration of the kind of retrosynthetic analysis conducted by RetSynth software developed at Sandia National Laboratories. Using a novel algorithm, the software identifies the biological or chemical reactions needed to create a desired biological product or compound.
(Graphic by Laura Hatfield)

The software platform uses retrosynthetic analysis to help scientists identify possible pathways to production — the series of biological and chemical reactions, or steps, needed to engineer and modify the molecules in a cell — to create the desired biological product or compound. By using the software to rapidly analyze all pathways, scientists can determine the production sequence with the fewest steps, the sequences that can be completed with available resources or the most economically viable process.

Synthetic biology involves redesigning organisms for useful purposes by engineering them to have new abilities. Researchers and companies around the world are using synthetic biology to harness the power of nature to solve problems in medicine — such as the development of vaccines, antibodies and therapeutic treatments — as well as in manufacturing and agriculture.

“Synthetic biology is becoming a critical capability for U.S. manufacturing. It has the potential to dramatically reduce waste, eliminate or curtail emissions and create next-generation therapeutics and materials,” said Corey Hudson, a computational biologist at Sandia. “That is where people will see RetSynth have the biggest impact.”

“The diverse functionality of RetSynth opens a lot of opportunities for researchers, giving them multiple options, including biological, chemical or hybrid pathways to production,” Hudson said. “All the while, the software is accelerating the research and development process associated with bioproduction. Traditionally, this process has been relatively slow and complex.”

RetSynth is designed to save researchers time and money by suggesting process modifications to maximize theoretical yield, or the amount of bioproduct that could be produced, Hudson said. All available pathways are rendered using clear visual images, enabling software users to quickly interpret results.

Commercial licensing for broader impact

The RetSynth software was originally developed as part of the Department of Energy’s Co-Optimization of Fuels & Engines initiative, a consortium of national lab, university and industry researchers who are creating innovative fuels and combining them with high-efficiency engines to reduce emissions and boost fuel economy.

Today, RetSynth has been expanded to support a variety of diverse applications, and Sandia is ready to license the software to an industry partner for commercial use, Hudson said.

Source / Credit: Sandia National Laboratories

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Carbon nanotube fibers woven into clothing gather accurate EKG.

 

Rice University graduate student Lauren Taylor
 shows a shirt with carbon nanotube thread that provides
constant monitoring of the wearer’s heart. Photo by Jeff Fitlow

There’s no need to don uncomfortable smartwatches or chest straps to monitor your heart if your comfy shirt can do a better job.

That’s the idea behind “smart clothing” developed by a Rice University lab, which employed its conductive nanotube thread to weave functionality into regular apparel.

The Brown School of Engineering lab of chemical and biomolecular engineer Matteo Pasquali reported in the American Chemical Society journal Nano Letters that it sewed nanotube fibers into athletic wear to monitor the heart rate and take a continual electrocardiogram (EKG) of the wearer.

The fibers are just as conductive as metal wires, but washable, comfortable and far less likely to break when a body is in motion, according to the researchers.

On the whole, the shirt they enhanced was better at gathering data than a standard chest-strap monitor taking live measurements during experiments. When matched with commercial medical electrode monitors, the carbon nanotube shirt gave slightly better EKGs.

“The shirt has to be snug against the chest,” said Rice graduate student Lauren Taylor, lead author of the study. “In future studies, we will focus on using denser patches of carbon nanotube threads so there’s more surface area to contact the skin.”

The researchers noted nanotube fibers are soft and flexible, and clothing that incorporates them is machine washable. The fibers can be machine-sewn into fabric just like standard thread. The zigzag stitching pattern allows the fabric to stretch without breaking them.

The fibers provided not only steady electrical contact with the wearer’s skin but also served as electrodes to connect electronics like Bluetooth transmitters to relay data to a smartphone or connect to a Holter monitor that can be stowed in a user’s pocket, Taylor said.

Pasquali’s lab introduced carbon nanotube fiber in 2013. Since then the fibers, each containing tens of billions of nanotubes, have been studied for use as bridges to repair damaged hearts, as electrical interfaces with the brain, for use in cochlear implants, as flexible antennas and for automotive and aerospace applications. Their development is also part of the Rice-based Carbon Hub, a multiuniversity research initiative led by Rice and launched in 2019.

The original nanotube filaments, at about 22 microns wide, were too thin for a sewing machine to

A Rice lab uses a custom device that weaves
carbon nanotube fibers into larger threads for sewing. Photo by Jeff Fitlow

handle. Taylor said a rope-maker was used to create a sewable thread, essentially three bundles of seven filaments each, woven into a size roughly equivalent to regular thread.

“We worked with somebody who sells little machines designed to make ropes for model ships,” said Taylor, who at first tried to weave the thread by hand, with limited success. “He was able to make us a medium-scale device that does the same.”

She said the zigzag pattern can be adjusted to account for how much a shirt or other fabric is likely to stretch. Taylor said the team is working with Dr. Mehdi Razavi and his colleagues at the Texas Heart Institute to figure out how to maximize contact with the skin.

Fibers woven into fabric can also be used to embed antennas or LEDs, according to the researchers. Minor modifications to the fibers’ geometry and associated electronics could eventually allow clothing to monitor vital signs, force exertion or respiratory rate.

Taylor noted other potential uses could include human-machine interfaces for automobiles or soft robotics, or as antennas, health monitors and ballistic protection in military uniforms. “We demonstrated with a collaborator a few years ago that carbon nanotube fibers are better at dissipating energy on a per-weight basis than Kevlar, and that was without some of the gains that we’ve had since in tensile strength,” she said.

“We see that, after two decades of development in labs worldwide, this material works in more and more applications,” Pasquali said. “Because of the combination of conductivity, good contact with the skin, biocompatibility and softness, carbon nanotube threads are a natural component for wearables.”

He said the wearable market, although relatively small, could be an entry point for a new generation of sustainable materials that can be derived from hydrocarbons via direct splitting, a process that also produces clean hydrogen. Development of such materials is a focus of the Carbon Hub.

“We’re in the same situation as solar cells were a few decades ago,” Pasquali said. “We need application leaders that can provide a pull for scaling up production and increasing efficiency.”

Co-authors of the paper are Rice graduate students Steven Williams and Oliver Dewey, and alumni J. Stephen Yan, now at Boston Consulting Group, and Flavia Vitale, an assistant professor of neurology at the University of Pennsylvania. Pasquali is director of the Carbon Hub and the A.J. Hartsook Professor of Chemical and Biomolecular Engineering and a professor of chemistry and of materials science and nanoengineering.

The research was supported by the U.S. Air Force (FA9550-15-1-0370), the American Heart Association (15CSA24460004), the Robert A. Welch Foundation (C-1668), the Department of Energy (DE-EE0007865, DE-AR0001015), the Department of Defense (32 CFR 168a) and a Riki Kobayashi Fellowship from the Rice Department of Chemical and Biomolecular Engineering.

NEWS RELEASE
Source/Credit: Rice University

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Space Weather Questions

 We'll be bringing back Space Weather to Scientific Frontline soon in a reduced version from the original web site. So for those that don't know much about space weather here is a very informative video.

Will it be safe for humans to fly to Mars?

 

Credit: NASA

Sending human travelers to Mars would require scientists and engineers to overcome a range of technological and safety obstacles. One of them is the grave risk posed by particle radiation from the sun, distant stars and galaxies.

Answering two key questions would go a long way toward overcoming that hurdle: Would particle radiation pose too grave a threat to human life throughout a round trip to the red planet? And, could the very timing of a mission to Mars help shield astronauts and the spacecraft from the radiation?

In a new article published in the peer-reviewed journal Space Weather, an international team of space scientists, including researchers from UCLA, answers those two questions with a “no” and a “yes.”

That is, humans should be able to safely travel to and from Mars, provided that the spacecraft has sufficient shielding and the round trip is shorter than approximately four years. And the timing of a human mission to Mars would indeed make a difference: The scientists determined that the best time for a flight to leave Earth would be when solar activity is at its peak, known as the solar maximum.

The scientists’ calculations demonstrate that it would be possible to shield a Mars-bound spacecraft from energetic particles from the sun because, during solar maximum, the most dangerous and energetic particles from distant galaxies are deflected by the enhanced solar activity.

A trip of that length would be conceivable. The average flight to Mars takes about nine months, so depending on the timing of launch and available fuel, it is plausible that a human mission could reach the planet and return to Earth in less than two years, according to Yuri Shprits, a UCLA research geophysicist and co-author of the paper.

“This study shows that while space radiation imposes strict limitations on how heavy the spacecraft can be and the time of launch, and it presents technological difficulties for human missions to Mars, such a mission is viable,” said Shprits, who also is head of space physics and space weather at GFZ Research Centre for Geosciences in Potsdam, Germany.

The researchers recommend a mission not longer than four years because a longer journey would expose astronauts to a dangerously high amount of radiation during the round trip — even assuming they went when it was relatively safer than at other times. They also report that the main danger to such a flight would be particles from outside of our solar system.

Shprits and colleagues from UCLA, MIT, Moscow’s Skolkovo Institute of Science and Technology and GFZ Potsdam combined geophysical models of particle radiation for a solar cycle with models for how radiation would affect both human passengers — including its varying effects on different bodily organs — and a spacecraft. The modeling determined that having a spacecraft’s shell built out of a relatively thick material could help protect astronauts from radiation, but that if the shielding is too thick, it could actually increase the amount of secondary radiation to which they are exposed.

The two main types of hazardous radiation in space are solar energetic particles and galactic cosmic rays; the intensity of each depends on solar activity. Galactic cosmic ray activity is lowest within the six to 12 months after the peak of solar activity, while solar energetic particles’ intensity is greatest during solar maximum, Shprits said.

Source / Credit: UCLA

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Exposure to air pollution linked with increased mental health issues

 

Exposure to traffic-related air pollution is associated with increased mental health service-use among people recently diagnosed with psychotic and mood disorders such as schizophrenia and depression, a study on data from over 13,000 people has found.

Increased use of mental health services reflects mental illness severity, suggesting that initiatives to lessen air pollution could improve outcomes for those with these disorders and reduce costs of the healthcare needed to support them.

The research was published in the British Journal of Psychiatry and funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre.

In 2019 119,000 people lived with illegal levels of polluted air in London. Previous research has found that adults exposed to high levels of traffic-related air pollution are more likely to experience common mental health disorders such as anxiety and mild depression but, until now, little was known about whether air pollution exposure contributes to the course and severity after the onset of more serious mental illness.

Researchers at King’s College London, University of Bristol and Imperial College London analyzed data from 13,887 people aged 15 years and over who had face-to-face contact with South London and Maudsley NHS Foundation Trust (SLaM) services between 2008 and 2012. Individuals were followed from the date of their first face-to-face contact for up to seven years.

Anonymized electronic mental health records were linked with quarterly average modelled concentrations of air pollutants (20x20 meter grid points) at the residential address of the participants. These included nitrogen dioxide and nitrogen oxides (NO2 and NOx) and fine and coarse particulate matter (PM2.5 and PM10).

The study found people exposed to higher residential levels of air pollutants used mental healthcare services more frequently in the months and years following their initial presentation to secondary mental healthcare services compared to those exposed to lower air pollution.

The researchers found that for every 3 micrograms per cubic meter increase in very small particulate matter (PM2.5) and 15 micrograms per cubic meter increase in nitrogen dioxide (NO2) over a one-year period there was an increased risk of having an inpatient stay of 11 per cent and 18 per cent. Results also showed increases in PM2.5 and NO2 were associated with a 7 per cent and 32 per cent increased risk of requiring community-based mental healthcare for the same period. These findings were also replicated over a seven-year period.

Dr Ioannis Bakolis, Senior Lecturer in Biostatistics and Epidemiology at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London and lead author of the study, said: ‘There is already evidence linking air pollution to the incidence of mental disorders, but our novel findings suggest that air pollution could also play a role in the severity of mental disorders for people with pre-existing mental health conditions.’

He continued: ‘Our research indicates that air pollution is a major risk factor for increased severity of mental disorders. It is also a risk factor that is easily modifiable which suggests more public health initiatives to reduce exposure such as low emission zones could improve mental health outcomes as well as reduce the high healthcare costs caused by long-term chronic mental illness.’

According to the researchers, if the UK urban population’s exposure to PM2.5 was reduced by just a few units to the World Health Organization's recommended annual limit (10 micrograms per cubic metre), this would reduce usage of mental health services by around two per cent, thereby saving tens of millions of pounds each year in associated healthcare costs.

Dr Joanne Newbury, Sir Henry Wellcome Research Fellow, Bristol Medical School (PHS), and the study’s first author, added: ‘We observed these findings for both mood disorders and psychotic disorders, as well as for both inpatient and community-based mental healthcare, and over seven years follow-up. This suggests that air pollution may contribute to a broad range of mental health problems, across a wide spectrum of clinical need, and over long periods of time.

‘We now plan to examine whether air pollution is associated with a broader range of mental health, neurodevelopmental, and educational outcomes, particularly among children, who might be especially vulnerable to air pollution.’

South London and Maudsley NHS Foundation Trust provides comprehensive secondary mental healthcare to approximately 1.36 million people within the London boroughs of Croydon, Lambeth, Lewisham and Southwark. These are inner-city areas with high-traffic flows and high average air pollution concentrations compared to other UK urban areas that reflect London’s diversity in terms of ethnicity and wealth.

The researchers controlled the analyses for a number of potential variables that could influence the association between air pollution and service-use association, such as deprivation, population density, age, season, marital status and ethnicity. However, they cautioned that the study does not prove cause and effect, and further research needs to demonstrate exactly how air pollution might increase severity of mental health problems.

Dr Adrian James, President of the Royal College of Psychiatrists, said: ‘The environmental and climate emergency is also a mental health emergency. Our health is fundamentally linked to the quality of our environment, whether that's about cleaner air, access to green spaces or protection from extreme weather.

‘If air pollution is exacerbating pre-existing serious mental illnesses, such as schizophrenia, bipolar disorder and major depression, then improving air quality could reduce the pressure on mental health services. As we look ahead to our post-pandemic future, it is vital that we find ways to build back greener and prevent poor health. This important research presents a clear example where these go hand-in-hand.’

The research was funded by the National Institute for Health Research (NIHR), the NIHR Maudsley Biomedical Research Centre, Wellcome, the Economic and Social Research Council, and the UK Medical Research Council.

Press Release
Source / Credit: University of Bristol

Rice lab dives deep for DNA’s secrets

 The poor bacteriophages in Yang Gao’s lab are about to have a lot of bad days.

Yang Gao

That’s all to the good for the structural biologist, who has received a prestigious Maximizing Investigators’ Research Award for New and Early Stage Investigators from the National Institutes of Health to make the lives of viruses harder so ours can be better.

The five-year grant for $1.9 million, administered by the National Institute of General Medical Sciences, will help Gao and his group detail the mechanisms of proteins that produce copies of genomic DNA, and what can go awry when they’re either subjected to stress or face other barriers.

A better understanding of the structural framework of DNA replication, stress response and repair at the atomic level could help find new ways to target processes involved in a host of diseases, including cancer.

“We’re interested in the basic question of how DNA is replicated,” said Gao, an assistant professor of biosciences who joined Rice in 2019 with the backing of a grant from the Cancer Prevention and Research Institute of Texas. “We’ve known for a long time that DNA is a fragile molecule and subject to many different assaults, environmental and physiological, like ultraviolet from sunlight and oxidative species.

“So many things damage DNA,” he said. “Despite that, DNA replication has to keep on going, even if there are errors, with an enzyme called DNA polymerase and a motor called the helicase.”

A study of stress on bacteriophage T7 will help Rice structural biologist Yang Gao and his team to reveal the atomic-scale mechanisms of DNA replication. (Credit: Yang Gao Lab/Rice University)

These are part of the replisome, a complex chain of proteins that carry out DNA replication and help repair DNA on the fly. Part of their normal function is to catch and fix coding errors. “When they see something bad they call for help, either before or after replication,” Gao said. “But how that works is still unknown, and we want to figure it out.”

The lab will start with the T7 bacteriophage, a virus whose infection mechanism in Escherichia coli bacteria is a good analog for what happens in humans.

“During my postdoc, we solved the first structure of T7 replisome to show how T7 comes together at a replication site,” he said. “We’ve continued that work at Rice, and we’re using the system to explore how it deals with different damages.”

The lab will then study the structure of mitochondria, the “power plants” inside cells, to see how DNA mutations produced there could lead to genetic diseases. “These two systems are mechanistically similar, and because we have experience with T7 and we’ve recently established a mitochondrial hub, we’re in a good position to start this investigation,” Gao said.

He noted he will continue to collaborate with Rice physicist Peter Wolynes and his group, which produces models that advance the theory of DNA replication. The lab also plans to make use of a new transmission electron microscope pegged for Rice’s BioScience Research Collaborative.

Press Release
Source / Credit: Rice University

Covid-19, not vaccination, presents biggest blood clot risks

Researchers from the University of Oxford have today announced the results of a study into

thrombocytopenia (a condition with low platelet counts) and thromboembolic events (blood clots) following vaccination for Covid-19, some of the same events which have led to restricted use of the Oxford-AstraZeneca vaccine in a number of countries.

1. Study compares risks of thrombocytopenia and thromboembolic events following ChAdOx1 nCov-19 (Oxford-AstraZeneca), BNT162b2 mRNA (Pfizer-BioNTech) vaccination, and SARS-CoV-2 (Covid-19) infection
2. Study shows increased risk of thrombocytopenia and venous thromboembolism with ChAdOx1 nCoV-19, and increased risk of arterial thromboembolism following BNT162b2 mRNA
3. Risks of these adverse events were however much higher following SARS-CoV-2 infection
4. Study authors fully independent from Oxford vaccine developers

Researchers from the University of Oxford have today announced the results of a study into thrombocytopenia (a condition with low platelet counts) and thromboembolic events (blood clots) following vaccination for Covid-19, some of the same events which have led to restricted use of the Oxford-AstraZeneca vaccine in a number of countries. 

Writing in the British Medical Journal (BMJ), they detail the findings from over 29 million people vaccinated with first doses of either the ChAdOx1 nCov-19 ‘Oxford-AstraZeneca’ vaccine or the BNT162b2 mRNA ‘Pfizer-BioNTech’ vaccine. They conclude that with both of these vaccines, for short time intervals following the first dose, there are increased risks of some hematological and vascular adverse events leading to hospitalization or death.

Julia Hippisley-Cox, Professor of Clinical Epidemiology and General Practice at the University of Oxford, lead author of the paper, said:

‘People should be aware of these increased risks after Covid-19 vaccination and seek medical attention promptly if they develop symptoms, but also be aware that the risks are considerably higher and over longer periods of time if they become infected with SARS-CoV-2’ 

The authors further note that the risk of these adverse events is substantially higher and for a longer period of time, following infection from the SARS-CoV-2 ‘coronavirus’ than after either vaccine.

All of the coronavirus vaccines currently in use have been tested in randomized clinical trials, which are unlikely to be large enough to detect very rare adverse events. When rare events are uncovered, then regulators perform a risk-benefit analysis of the medicine; to compare the risks of the adverse events if vaccinated versus the benefits of avoidance of the disease – in this case, Covid-19.

In this paper, the team of authors from the University of Oxford, University of Leicester, Guys and St Thomas’ NHS Foundation Trust, the Intensive Care National Audit & Research Centre, the London School of Hygiene and Tropical Medicine, the University of Cambridge, the University of Edinburgh and the University of Nottingham, compared rates of adverse events after vaccination with Pfizer-BioNTech and Oxford-AstraZeneca vaccines with rates of the same events after a positive SARS-CoV-2 test result.

For this, they used routinely collected electronic health records to evaluate the short-term risks (within 28 days) of hospital admission with thrombocytopenia, venous thromboembolism (VTE) and arterial thromboembolism (ATE), using data collected from across England between December 1, 2020 and April 24, 2021. Other outcomes studied were cerebral venous sinus thrombosis (CVST), ischemic stroke, myocardial infarction and other rare arterial thrombotic events.

Prof. Hippisley-Cox added:

‘This research is important as many other studies, while useful, have been limited by small numbers and potential biases. Electronic healthcare records, which contain detailed recording of vaccinations, infections, outcomes and confounders, have provided us with a rich source of data with which to perform a robust evaluation of these vaccines, and compare to risks associated with Covid-19 infection.’

The authors detail the following limitations to their study:

1. restricting the analysis to first vaccine dose only
2. a short vaccination exposure window
3. the lack of formal adjudication of routinely acquired outcomes, and the potential for misclassification of outcomes or exposures
4. admissions where patients were still in hospital by the study end date being excluded.
5. However, they believe that any bias, if present, is likely to not change with respect to each vaccine and so the comparisons between vaccines are unlikely to be affected.

Andrew Morris, Director, Health Data Research UK and Lead, Data and Connectivity National Core Study:

‘Congratulations to the team at Oxford who have worked with colleagues across the UK on this important research. This is truly health data science in action – the use of secure, large scale, linked datasets to develop real-world insights on the safety of COVID-19 vaccines. The analyses in this paper are a vital addition to all of the work enabled by HDR UK to enhance our understanding of the virus, and a key output from the Data and Connectivity National Core Study.’

Aziz Sheikh, Professor of Primary Care Research & Development and Director of the Usher Institute at The University of Edinburgh and a co-author of the paper, said:

‘This enormous study, using data on over 29 million vaccinated people, has shown that there is a very small risk of clotting and other blood disorders following first dose Covid-19 vaccination.  Though serious, the risk of these same outcomes is much higher following SARS-CoV-2 infection.

‘On balance, this analysis therefore clearly underscores the importance of getting vaccinated to reduce the risk of these clotting and bleeding outcomes in individuals, and because of the substantial public health benefit that Covid-19 vaccinations offer.’

Source / Credit: University of Oxford

Together, but still apart

 Social disconnection is a lack of social, emotional and physical engagement with other people. This

results in isolation and loneliness. Risk factors such as the shrinking of family sizes, lack of family support and declining health have made it hard for older adults to keep up with social and economic activities and maintain social connections, which ultimately results in social disconnection and isolation. The social distancing measures brought about by the ongoing COVID-19 pandemic have exacerbated social isolation, especially among the elderly.

In the Singapore Chinese Health Study done by a team led by Professor Koh Woon Puay, from the Healthy Longevity Translational Research Program at the NUS Yong Loo Lin School of Medicine and Associate Professor Feng Qiushi of the Faculty of Arts and Social Sciences showed that from 16,943 community-dwelling seniors, 78.8% of socially disconnected older adults are living with family, compared to 14.4% of socially disconnected adults who are living alone. Hence, although older adults living alone are more likely to be socially disconnected, in Singapore, the majority of socially isolated older adults still stay with their families. Among those living alone, men were twice as likely to experience social disconnection, compared to the women. This study was published in Gerontology on 16 June 2021.

In this cohort, the team also studied the factors associated with social isolation in this cohort, to see if they had similar effects among those living alone and those living with their families. The salient findings were:

Regardless of the living arrangements, factors such as low education level, cognitive impairment, fair or poor self-rated health, depression, and limitations with daily living activities were independently associated with social disconnection.

Among those living alone, men were twice as likely to experience social disconnection compared to women.

From these findings, Prof Koh recommends targeting community interventions to elderly men living alone, and extending its scope to older adults in poor health who live with their families. The Singapore Government has made much effort in the area of eldercare which has helped most older people to stay socially connected. Despite this, social alienation is increasingly present due to the demographic trends of population ageing and solo-living and extra effort is needed to help vulnerable individuals, especially older men. Interventions that encourage individual and personal productivity, such as paid work, volunteerism and learning new skills should be promoted among older adults to create opportunities for social interaction and maintenance of cognitive functions, Prof Koh adds.

In addition to social isolation, older adults are also at increased risk of chronic age-related diseases, as well as gradual loss of bodily functions and independence in activities of daily living. Prof Koh and Associate Professor Feng have collaborated with other scientists within NUS and other research institutions to establish the SG70 Towards Healthy Longevity cohort study, as the next study to examine the effects of biological, lifestyle and socioeconomic factors that prevent people from ageing healthily and productively. This cohort will recruit 3,000 participants, from the ages of 65 to 75 years old comprising of the three major ethnic groups in Singapore. This age group has been identified as the vulnerable period where the average Singaporean may transit from good health to poor health, and the research team will study this ageing process in the SG70 participants for the next 10 to 15 years.

The eventual aim of this SG70 cohort study is to gather scientific evidence that will form the basis for intervention studies in the near future that may slow, halt or reverse the ageing process, in order to help people age more healthily, avoid age-related diseases and maintain a good quality of life in their twilight years.

Source / Credit: NUS Yong Loo Lin School of Medicine

Plants evolved ability to actively control water-loss earlier than previously thought

 

Fern stomata Credit: University of Birmingham

New research has shed light on when plants first evolved the ability to respond to changing humidity in the air around them, and was probably a feature of a common ancestor of both flowering plants and ferns.

New research has shed light on when plants first evolved the ability to respond to changing humidity in the air around them, and was probably a feature of a common ancestor of both flowering plants and ferns.

Key to the regulation mechanism are tiny holes, or pores, on the surface of leaves, called stomata. These enable the plant to regulate the uptake of CO2 gas as fuel for photosynthesis, and the loss of water vapour – a constant balancing act that requires the pores to open and close according to changing conditions. This ability is important to agriculture because it helps crops to use less water to grow.

Plants first evolved stomata soon after they moved from water to land, some 450 million years ago, but scientists are still uncertain about the evolutionary pathway they took and the point at which plants became able to choose whether to open or close the pores in response to their environment.

In the most recently evolved plants – flowering plants – stomata closure in response to drought is actively triggered by a number of internal signals, including a hormone called abscisic acid (ABA), but scientists have been struggling to understand if this mechanism is also present in older groups of plants. In a new study, published in Current Biology, researchers at the University of Birmingham have found evidence that the fern species Ceratopteris richardii actively closes its stomata using similar signals.

This semi-aquatic tropical fern has recently become the first model for exploring genetic control of development in the fern family, and is now helping scientists to unpick the long evolutionary history between the earliest land-living plants (mosses, liverworts and hornworts) and the modern flowering plants that dominate today’s ecosystems.

The team used RNA sequencing technology to identify the genetic mechanisms behind different stomatal responses and was able to demonstrate the fern’s ability to close stomata in response to low humidity or in response to ABA involves copies of genes already known to control stomata in flowering plants.

The results suggest that both ferns and flowering plants evolved using similar stomatal closure methods. This indicates that these mechanisms were present – at least in some form – in the stomata of the last common ancestor of both groups.

Dr Andrew Plackett, of the University of Birmingham’s School of Biosciences, led the research in collaboration with groups at the University of Bristol and the University of Oxford. He said: “We know that plants have possessed stomata for most of their evolutionary history, but the point in evolution where plants became able to actively open and close them has been controversial.

“We’ve been able to show the same active closure mechanisms found in flowering plants are also present in ferns, a much older group of plants. Being able to better understand how these mechanisms have changed during plant evolution gives us useful tools to learn more about how they work. This will be important for helping our crops to adapt to future environmental changes.”

Prof Alistair Hetherington of Bristol’s School of Biological Sciences added: “This new work confirms that the earliest plants were able to actively control the water they lost through the microscopic valve like structures on the surfaces of leaves known as stomata. This is important because it shows that the intracellular machinery allowing stomata to open and close was present in the earliest land plants. The research also shows that, whether stomata respond actively or passively is dictated by the environment in which the plants lived. "

Source / Credit: University of Bristol

Farmed carnivores may become disease reservoirs posing human health risk

 Farming large numbers of carnivores, like mink, could allow the formation of undetected ‘disease reservoirs’, in which a pathogen could spread to many animals and mutate to become a risk to human health.

Research led by the University of Cambridge has discovered that carnivores have a defective immune system, which makes them likely to be asymptomatic carriers of disease-causing pathogens.

Three key genes in carnivores that are critical for gut health were found to have lost their function. If these genes were working, they would produce protein complexes called inflammasomes to activate inflammatory responses and fight off pathogens. The study is published today in the journal Cell Reports.

The researchers say that the carnivorous diet, which is high in protein, is thought to have antimicrobial properties that could compensate for the loss of these immune pathways in carnivores – any gut infection is expelled by the production of diarrhoea. But the immune deficiency means that other pathogens can reside undetected elsewhere in these animals.

“We’ve found that a whole cohort of inflammatory genes is missing in carnivores - we didn’t expect this at all,” said Professor Clare Bryant in the University of Cambridge’s Department of Veterinary Medicine, senior author of the paper. 

She added: “We think that the lack of these functioning genes contributes to the ability of pathogens to hide undetected in carnivores, to potentially mutate and be transmitted becoming a human health risk.”

Zoonotic pathogens are those that live in animal hosts before jumping to infect humans. The COVID-19 pandemic, thought to originate in a wild animal, has shown the enormous damage that can be wrought by a novel human disease. Carnivores include mink, dogs, and cats, and are the biggest carriers of zoonotic pathogens. 

Three genes appear to be in the process of being lost entirely in carnivores: the DNA is still present but it is not expressed, meaning they have become ‘pseudogenes’ and are not functioning. A third gene important for gut health has developed a unique mutation, causing two proteins called caspases to be fused together to change their function so they can no longer respond to some pathogens in the animal’s body.

“When you have a large population of farmed carnivorous animals, like mink, they can harbour a pathogen - like SARS-CoV-2 and others - and it can mutate because the immune system of the mink isn’t being activated. This could potentially spread into humans,” said Bryant.

The researchers say that the results are not a reason to be concerned about COVID-19 being spread by dogs and cats. There is no evidence that these domestic pets carry or transmit COVID-19. It is when large numbers of carnivores are kept together in close proximity that a large reservoir of the pathogen can build up amongst them, and potentially mutate.

This research was funded by Wellcome.

Source / Credit: University of Cambridge