Culture

Creating a lab mangrove helps to identify new bacteria

image: Using a pioneering cultivation strategy, KAUST researchers have identified several microorganisms in Red Sea mangroves that were previously unknown to science.

Image: 
© 2021 Morgan Bennett Smith

A pioneering cultivation strategy that recreates a mangrove environment in the lab has enabled identification of novel bacteria residing in Red Sea mangroves and will help improve understanding of mangrove ecosystem stability, resilience and sustainability.

Mangroves are highly productive, dominant coastal ecosystems that line between 60-70 percent of the world's tropical and subtropical coastlines. They harbor diverse microbial communities thought to make up 80 percent of the ecosystem's biomass. Many of the microbial species, families and taxa are unknown to science.

The cultivation strategy was developed by a team of KAUST researchers, including Fatmah Sefrji and Ramona Marasco.

"Red Sea mangroves are particularly interesting because they represent an extreme and unique version of mangrove environments that are exposed to stressful conditions, including high temperatures, salinity and oligotrophy," says Sefrji. "These environmental stresses exert a strong selective force on the mangrove's microbial communities and so favor the presence of unique species and families."

The team's key challenge was to recreate the mangrove environment in the lab so that they could grow the bacteria in their natural setting. They moved portions of the mangrove sediment and seawater to lab-based growth chambers because in artificial media, it is nearly impossible to reproduce all the molecules, such as nutrients and vitamins, and the molecular cross-communication that are necessary for healthy microbial growth.

"It is difficult to successfully cultivate so-called 'microbial dark matter'-- the environmental microorganisms that are unknown to science and have never been cultured before," says Marasco. "There are so many molecules and parameters important for the growth of a given microbial species from a particular setting."

Once the growth chambers were set up, the team cultivated the resident microbial communities by feeding them regularly with nutrients taken from the natural mangrove environment. They then analyzed the genotypes and phenotypes of selected bacterial isolates, discovering a series of new species, and even taxa. Two papers highlight the first two organisms new to science, the bacterium Mangrovivirga cuniculi (new family Mangrovivirgaceae) and a new bacterial strain called Kaustia mangrovi.

"Both organisms grow in the presence of relatively high salinity and temperature and in the pH range typical of mangrove sediment on the Red Sea," says Sefrji. "Despite their similar physiology, each bacterial isolate showed unique physical and biochemical characteristics, confirmed also by the analysis of their genomes."

The researchers hope the identification of these organisms will contribute to a wider understanding of mangroves and provide insight into effective ways of protecting these unique ecosystems, particularly in light of climate change. The ability to cultivate Red Sea mangrove bacteria at scale could have significant implications, and not just for mangroves themselves.

"Cultivating members of a microbial community adapted to the variable and harsh conditions of the Red Sea may represent an important source of metabolites and enzymes for future biotechnological applications," says Marasco. "For example, bacteria that promote plant growth could boost mangrove seedling establishment, while others could confer salt tolerance to cereal crops. We are actively characterizing our novel strains for such capacities."

Credit: 
King Abdullah University of Science & Technology (KAUST)

An astounding find reveals a rare cause of epilepsy

image: Nerve cells, also called neurons, project to one another to establish a connection and form a neural circuit, the activity of which is essential for brain function such as learning and memory.

Image: 
Queensland Brain Institute, The University of Queensland

Researchers at The University of Queensland, working to gain a better understanding of how brain cells work, have discovered the underlying mechanism of a rare genetic mutation that can cause epilepsy.

Dr Victor Anggono from UQ's Queensland Brain Institute said his team made the ground-breaking findings while researching nerve cell communications, which are an important process in normal brain function.

''We're both excited and astounded to make such an important contribution to the field of cellular and molecular neuroscience,'' Dr Anggono said.

He stressed that the mutation was extremely rare, with only one reported case in the world to date.

Dr Anggono's team studied protein structures, called receptors, that are attached to cell surfaces to make the discovery.

''It turns out that this particular mutation causes receptors in brain cells to behave differently, resulting in an imbalance in brain cell communication - and that can lead to disorders,'' he said.

''For example, cells that talk too much are associated with epilepsy and unwanted cell death - while cells that talk too little have negative impacts on learning and memory.

''There are also many examples of other mutations in the same gene that are known to be associated with epilepsy.

''What we know is that this receptor is critical for brain function and can lead to epilepsy when its function is misregulated.

''The findings point the way for further research to understand and potentially treat similar mutations.''

The imbalance in brain cell communications is also believed to be involved in neurological conditions including Alzheimer's disease and autism spectrum disorders.

Dr Anggono said the research provided a springboard for developing personalised medicines to target the mutation.

''Receptor blockers which have been approved by the US Food and Drug Administration (FDA), are already available for human treatment, but the challenge is to find the right ones and see how patients respond,'' he said.

Credit: 
University of Queensland

The Lancet: CoronaVac COVID-19 vaccine is safe and protects against disease, interim analysis

Interim data from a phase 3 trial of a COVID-19 vaccine developed in China (CoronaVac) suggests that two doses offer 83.5% protection against symptomatic COVID-19.

The preliminary findings, published in The Lancet and presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), indicate that CoronaVac induces a robust antibody response. No severe adverse events or deaths were reported among the more than 10,000 trial participants in Turkey, with most adverse events mild and occurring within 7 days of an injection. However, more research is needed to confirm vaccine efficacy in the long term, in a more diverse group of participants, and against emerging variants of concern.

CoronaVac uses an inactivated whole virus. When people receive the vaccine, their immune system attacks the harmless form of the virus by producing antibodies to fight it off, leading to immunity. Developed by Sinovac Life Sciences, the vaccine - which can be stored and transported at 2-8°C - has been approved for emergency use in 22 countries, and has been in phase 3 trials since mid-2020 in Brazil, Indonesia, Chile, and Turkey. In this trial, participants were given two 3μg doses of CoronaVac 14 days apart.

To date, interim efficacy and safety results of phase 3 trials have been reported for 8 COVID-19 vaccines: University of Oxford/AstraZeneca, Gam-COVID-Vac, Moderna, Pfizer, Janssen, Novavax, and two inactivated vaccines developed by Sinopharm. [1]

Lead author Professor Murat Akova, from Hacettepe University Medical School, Turkey, said: "In order to bring the COVID-19 pandemic under control, the world needs every single dose of safe and effective vaccines, and our results add important evidence of the safety and effectiveness of inactivated-virus vaccines. One of the advantages of CoronaVac is that it does not need to be frozen, making it easier to transport and distribute. This could be particularly important for global distribution, as some countries may struggle to store large amounts of vaccine at very low temperatures." [2]

Between September 14, 2020, and January 5, 2021, 10,218 adults between 18 and 59 years were randomly assigned to receive two doses of the vaccine (6,650) or a placebo (3,568). The trial was conducted across 24 centres in Turkey. The average age of the participants was 45 years and 5,907 (58%) were male.

After the first dose, 87 participants in the vaccine group and 98 in the placebo group were excluded. The most common reasons for exclusion in the vaccine group were returning a positive COVID-19 test (60) and withdrawing from the study (11). The most common reasons in the placebo arm were unblinding before the second dose (45) and returning a positive COVID-19 test (35). A further 4 participants in the vaccine group were excluded after the second dose as they were aged over 59 years.

In total, 10,029 participants (6,559 in the vaccine group and 3,470 in the placebo group) were included in the efficacy analysis, and 10,214 participants (not including the 4 excluded who were over 59 years) were included in the safety analysis.

In total, 150 COVID-19 cases were confirmed by PCR after an average follow-up of 43 days, an incidence rate of 123 cases per 1,000 people per year. From 14 days after the second dose, 9 cases of symptomatic COVID-19 were confirmed in the vaccine group, an incidence rate of 32 cases per 1,000 people per year. In the placebo group, 32 cases were reported, an incidence rate of 192 cases per 1,000 people per year. Following analysis, the authors estimate that this is equivalent to a vaccine efficacy of 83.5%.

Analysis of immune responses induced by the vaccine involved a sample of 1,413 participants (981 from the vaccine group and 432 from the placebo group). CoronaVac induced an antibody response among 90% (880/981) of those who received the vaccine. The authors note that antibody response decreased with increasing age in men and women.

Adverse reactions were analysed using data from 10,214 participants (6,646 in the vaccine group and 3,568 in the placebo group). The incidence of adverse events in those who received the vaccine was relatively low at 19% (1,259/6,646). The incidence in the placebo group was 17% (603/3,568).

A total of 3,845 adverse effects were reported in 1,862 participants. Most of the reported adverse effects (90% [3,469/3,845]) were mild, and included fatigue, pain at the injection site, and myalgia. No severe adverse events or fatalities were recorded during the study period, and only 6 participants (

The authors acknowledge that the analysis included a short follow-up period and involved a relatively young and low-risk population. Further data is needed on the duration of protection, and safety and efficacy of the vaccine in elderly people, adolescents and young children, and those with chronic diseases. Data on the effectiveness of CoronaVac against variants of concern is also required. Study participants received doses 14 days apart, whereas community immunisation has involved a 28-day interval. While it has been claimed that 28-day immunisation schemes lead to better immunogenicity, the longer the interval, the higher the chances of contracting COVID-19 before getting fully immunised.

The phase 3 trial results published today follows an earlier phase 1/2 trial that reported on the safety and immunogenicity of CoronaVac in healthy children and adolescents. [3]

Writing in a linked Comment, Dr Maheshi N Ramasamy and Dr Lucy Jessop of the University of Oxford, UK, and the National Immunisation Office of the Health Service Executive, Ireland, respectively (who were not involved in the study), said: "Tanriover and colleagues' findings suggest that two doses of CoronaVac have robust efficacy (within the WHO target product profile for SARS-CoV-2 vaccines) and acceptable tolerability when administered with a 14-day interval. CoronaVac is also available as single-dose vials, which improves ease of administration and reduces wastage." They continue, echoing the authors' acknowledgement that further research is needed, saying: "... CoronaVac is another useful tool in the global fight against COVID-19, although more data are needed on its efficacy against emerging variants and on its duration of protection across different age groups and geographical settings and in the presence of comorbidities."

Credit: 
The Lancet

Zoo amphibians were on display while humans were locked away

image: Common toad. Credit Jack Boultwood from WWT

Image: 
Jack Boultwood from WWT

While the UK was in lockdown, certain species of captive amphibians became more visible, a new study suggests.

The COVID-19 pandemic forced the closure of zoos across the UK for several months from March 2020, with gradual re-openings from summer into autumn and winter.

These closures provided a team of researchers, from the University of Exeter and WWT Slimbridge Wetland Centre, a unique opportunity to study the effect of visitor presence on several species of amphibian at Slimbridge.

The project assessed the number of individuals of six species - common toad, common frog, smooth newt, pool frog, golden mantella and golden poison dart frog - visible to observers while their exhibit was closed, when it partially reopened to more staff and when it reopened to visitors.

"Amphibians responded to the lack of people at the wetland centre differently," said lead author Dr Paul Rose.

"Some species of amphibian were more likely to be on view when there were smaller numbers of visitors at their enclosure.

"These differences are probably related to the specific camouflage or anti-predation tactics of certain species, with aposematic frogs (toxic, brightly coloured species) being less impacted by visitor presence but cryptic (camouflaged species) being less visible when the public were around."

For example, the study found the camouflaged species of common toads were most likely to be on view when the centre was in lockdown compared to when visitors returned. They also showed the most significant decline in visibility from lockdown to when more staff returned to the centre.

These findings show it may be beneficial to offer more cover and camouflage opportunities for captive common toads, in a way that allows the toads to feel hidden but can still be viewed by visitors.

The results of the study can also be used help inform husbandry, collection planning and provide a useful benchmark for further, more complex, welfare assessment measures.

Credit: 
University of Exeter

Nearly 8% of men who have sex with men estimated to have syphilis globally

Led by the London School of Hygiene & Tropical Medicine (LSHTM), in partnership with the World Health Organization (WHO) and Avenir Health, the research team carried out a systematic review and meta-analysis of syphilis prevalence among MSM between 2000 to 2020, drawing on data from 275 studies involving more than 600,000 study participants across 77 countries.

The worldwide prevalence of syphilis among MSM was 15x higher than most recent estimates for men in the general population (7.5% versus 0.5%). Researchers further estimated the prevalence across eight regions of the Sustainable Development Goals (SDG) and six regions of the WHO. Latin America and the Caribbean region had the highest prevalence of syphilis (10.6%), whereas Australia and New Zealand had the lowest (1.9%). There is, therefore, an urgent need to quantify the burden of syphilis in this high-risk group.

Syphilis is a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum. When diagnosed, syphilis is easily treated with penicillin. One study found that annual screening and treatment of at least 62% of sexually active MSM is necessary to achieve local elimination.

Dr Matthew Chico, Associate Professor at LSHTM and lead author, said: "Men tend to be disadvantaged when it comes to syphilis testing and treatment. Women are routinely screened for syphilis at their first antenatal care visit, and are offered testing at family planning services. Men in general do not have the same number of contacts with the health system as women, and MSM face additional barriers due to stigma and shaming.

"As diseases go, syphilis is terribly deceptive. In the primary and secondary stages of infection, skin lesions, such as chancre or rash, may present, only to then disappear as if the person has been cured. Unfortunately, without treatment, the bacterium will slowly invade internal organs, and can lead to physical deformity, loss of vision, dementia, and even death. There is no good reason for this to happen. We have effective treatment."

Dr Motoyuki Tsuboi, from LSHTM and the study's first author, said: "The Global Health Sector Strategy of the WHO has an ambitious target to reduce global syphilis incidence by 90% between 2018 and 2030. We hope our findings - the first global prevalence estimates of syphilis among MSM - will serve as a catalyst for action."

In this new study, pooled estimates of syphilis among MSM were highest (8.7%) in regions where HIV prevalence is more than 5%. Lower-middle income countries also had a high burden (8·7%). Countries with low-income status had the lowest syphilis prevalence estimates among MSM (3.8%). Syphilis prevalence estimates were high among studies exclusively involving male sex workers, transgender women, and transgender women sex workers.

Among studies conducted from 2000 to 2009 and 2010 to 2020, global syphilis prevalence was estimated to be 8·9% and 6·6% respectively. However, four of eight SDG regions - Europe and Northern America, Latin America and the Caribbean, Oceania [excluding Australia and New Zealand]) - showed higher estimates between 2015 and 2020 than 2010 and 2014.

Dr Tsuboi said: "Syphilis prevalence among MSM is unacceptably high at the global and SDG regional levels, particularly in lower-middle, upper-middle, and high-income countries, where cases appear to be increasing and where HIV prevalence is high. Urgent action is needed."

The researchers say that it is difficult to know if syphilis prevalence among MSM will be altered by the COVID-19 pandemic. While there is evidence the pandemic has impacted MSM sexual activity, there have also been reports that MSM have experienced difficulty accessing STI testing and treatment due to COVID-19, potentially translating into fewer syphilis cases being diagnosed, treated and removed from the MSM population.

Eloise Stonborough, Associate Director of Policy and Research at Stonewall, (she/her) said: "Sexually transmitted infections, including syphilis, can cause severe health problems if untreated. These figures provide an important insight into the increased prevalence of syphilis infections for men who have sex with men. It's important that everyone, including LGBTQ+ people and those at higher risk, is supported to understand how to protect themselves against syphilis and other sexually transmitted infections.

"It's also vital that healthcare services are inclusive and welcoming of all lesbian, gay, bi, trans and queer people, so everyone feels comfortable getting the help and support they need."

The authors acknowledge limitations of the study, including the fact that Eastern and South-Eastern Asia contributed 55% of the global data points, most of which were from China where the prevalence of syphilis among MSM was slightly higher than the overall global total. This has the effect of slightly skewing upward the pooled prevalence estimates. Another limitation is that one-third of the data points relied on convenience sampling.

Credit: 
London School of Hygiene & Tropical Medicine

Researchers use JUWELS for record-breaking simulations of turbulence's smallest structures

image: Researchers at CORIA - CNRS UMR 6614 (France) and RWTH Aachen University have used JSC computing resources to model internal and external intermittency in turbulent jet flows. This image shows the morphology of fully developed turbulence at the center of the jet.

Image: 
Michael Gauding

When you pour cream into a cup of coffee, the viscous liquid seems to lazily disperse throughout the cup. Take a mixing spoon or straw to the cup, though, and the cream and coffee seem to quickly and seamlessly combine into a lighter color and, at least for some, a more enjoyable beverage.

The science behind this relatively simple anecdote actually speaks to a larger truth about complex fluid dynamics and underpins many of the advancements made in transportation, power generation, and other technologies since the industrial era--the seemingly random chaotic motions known as turbulence play a vital role in chemical and industrial processes that rely on effective mixing of different fluids.

While scientists have long studied turbulent fluid flows, their inherent chaotic natures have prevented researchers from developing an exhaustive list of reliable "rules," or universal models for accurately describing and predicting turbulence. This tall challenge has left turbulence as one of the last major unsolved "grand challenges" in physics.

In recent years, high-performance computing (HPC) resources have played an increasingly important role in gaining insight into how turbulence influences fluids under a variety of circumstances. Recently, researchers from the RWTH Aachen University and the CORIA (CNRS UMR 6614) research facility in France have been using HPC resources at the Jülich Supercomputing Centre (JSC), one of the three HPC centres comprising the Gauss Centre for Supercomputing (GCS), to run high-resolution direct numerical simulations (DNS) of turbulent setups including jet flames. While extremely computationally expensive, DNS of turbulence allows researchers to develop better models to run on more modest computing resources that can help academic or industrial researchers using turbulence's effects on a given fluid flow.

"The goal of our research is to ultimately improve these models, specifically in the context of combustion and mixing applications," said Dr. Michael Gauding, CORIA scientist and researcher on the project. The team's recent work was just named the distinguished paper from the "Turbulent Flames" colloquium, which happened as part of the 38th International Symposium on Combustion.

Starts and stops

Despite its seemingly random, chaotic characteristics, researchers have identified some important properties that are universal, or at least very common, for turbulence under specific conditions. Researchers studying how fuel and air mix in a combustion reaction, for instance, rely on turbulence to ensure a high mixing efficiency. Much of that important turbulent motion may stem from what happens in a thin area near the edge of the flame, where its chaotic motions collide with the smoother-flowing fluids around it. This area, the turbulent-non-turbulent interface (TNTI), has big implications for understanding turbulent mixing.

While running their DNS calculations, Gauding and his collaborator, Mathis Bode from RWTH Aachen, set out to specifically focus on this some of the subtler, more complex phenomena that take place at the TNTI.

Specifically, the researchers wanted to better understand the rare but powerful fluctuations called "intermittency" - an irregular process happening locally but with very high amplitude. In turbulent flames, intermittency enhances the mixing and combustion efficiency but too much can also extinguish the flame. Scientists distinguish between internal intermittency, which occurs at the smallest scales and is a characteristic feature of any fully developed turbulent flow, and external intermittency, which manifests itself at the edge of the flame and depends on the structure of the TNTI.

Even using world-class HPC resources, running large DNS simulations of turbulence is computationally expensive, as researchers cannot use assumptions about the fluid motion, but rather solve the governing equations for all relevant scales in a given system--and the scale range increases with the "strength" of turbulence as power law. Even among researchers with access to HPC resources, simulations oftentimes lack the necessary resolution to fully resolve intermittency, which occurs in thin confined layers.

For Bode and Gauding, understanding the small-scale turbulence happening at the thin boundary of the flame is the point. "Our simulations are highly resolved and are interested in these thin layers," Bode said. "For production runs, the simulation resolution is significantly higher compared to similar DNS simulations to accurately resolve the strong bursts that are connected to intermittency."

The researchers were able to use the supercomputers JUQUEEN, JURECA, and JUWELS at JSC to build a comprehensive database of turbulence simulations. For example, one simulation was run for multiple days on the full JUQUEEN module, employing all 458,752 compute cores during the centre's "Big Week" in 2019, simulating a jet flow with about 230 billion grid points.

Mixing and matching

With a better understanding of the role that intermittency plays, the team takes data from their DNS runs and using it to improve less computationally demanding large eddy simulations (LES). While still perfectly accurate for a variety of research aims, LES are somewhere between an ab initio simulation that begins with no assumptions and a model that has already baked in certain rules about how fluids will behave.

Studying turbulent jet flames has implications for a variety of engineering goals, from aerospace technologies to power plants. While many researchers studying fluid dynamics have access to HPC resources such as those at JSC, others do not. LES models can often run on more modest computing resources, and the team can use their DNS data to help better inform these LES models, making less computationally demanding simulations more accurate. "In general, present LES models are not able to accurately account for these phenomena in the vicinity of the TNTI," Gauding said.

The team was able to scale its application to take full advantage of JSC computing resources partially by regularly participating in training events and workshops held at JSC. Despite already being able to leverage large amounts of HPC power, though, the team recognizes that this scientific challenge is complex enough that even next-generation HPC systems capable of reaching exascale performance--slightly more than twice as fast as today's fastest supercomputer, the Fugaku supercomputer at RIKEN in Japan--may not be able to fully simulate these turbulent dynamics. However, each computational advancement allows the team to increase the degrees of freedom and include additional physics in their simulations. The researchers are also looking at using more data-driven approaches for including intermittency in simulations, as well as improving, developing, and validating models based on the team's DNS data.

Credit: 
Gauss Centre for Supercomputing

Protein crop's potential unlocked by deciphering anti-nutrient biosynthesis

image: Researchers have identified the VC1 gene as responsible for the production of anti-nutrients vicine and convicine that make people sensitive to the faba bean (credit: Frederick Stoddard, University of Helsinki)

Image: 
Frederick Stoddard, University of Helsinki

Faba beans are an excellent source of food protein, but about 4% of the world's population are afflicted by favism, which renders them sensitive to the faba bean anti-nutrients vicine and convicine. Now, an international research team has identified the VC1 gene as responsible for the production of these compounds.

Faba beans have actually been a source of food protein since pre-historic times, but a fraction of the population, mostly from warm southern regions, cannot tolerate them. Pythagoras and his followers avoided them, and Roman priests of Jupiter associated them with death. Today, we know that faba beans produce the anti-nutrients vicine and convicine, which cause a risk for favism - a condition arising from damage to red blood cells - for susceptible individuals.

Among legumes - the pod-producing family of plants to which pea, chickpea and soybean also belong - faba beans have the second-highest yield globally. They also have the highest seed protein content of the starch-containing legumes and out-perform soybean in cool climates. Faba beans are consequently a prime protein source for facilitating a global switch to a plant-based diet, considered necessary for significant reductions in carbon emissions.

The VC1 gene is responsible for vicine-convicine content

However, when people deficient in a specific enzyme eat a large portion of uncooked faba beans, vicine and convicine can induce abnormal breakdown of red blood cells. The resultant hemolytic anemia, known as favism, has inevitably limited the potential use of faba beans. Although there are a number of faba bean varieties with low levels of vicine and convicine, the gene responsible for this trait was previously unknown.

Now, the scientists have identified the gene responsible for vicine-convicine content. What is more, they have identified the specific mutation within this gene that causes the reduction in synthesis. They found that all faba bean varieties with a low vicine-convicine content, descended from a single accession found in a genebank, had two nucleotides - the "letters" that make up DNA - inserted within the VC1 gene. This insertion disrupts the VC1 function and is the only known genetic source of low vicine and convicine content.

Stig U. Andersen, one of project leaders, says, "Working across disciplines to integrate biochemical and molecular genetic data was key to finally unveiling the genetic source of low vicine and convicine."

The work has been published in Nature Plants and it paves the way for the complete description of the biosynthetic pathway of vicine and convicine, and ultimately for breeding, production and commercial use of faba bean varieties totally free from these anti-nutritional compounds.

The team, comprising leading scientists from Denmark, Finland, Germany, the UK and Canada, are already looking to the future. Fernando Geu-Flores, who led the work, says:

"Now that we understand where these anti-nutrients come from, we can attempt to breed them out completely, thus contributing to food safety and sustainability."

Credit: 
University of Copenhagen - Faculty of Science

Hybrid enzyme catalysts synthesized by a de novo approach for expanding biocatalysis

image: Synthesizing hybrid enzyme catalysts in situ to improve and expand enzymatic catalysis is an important way to address challenges of industrial biocatalysis. In this account, the construction principles, the structure-function relationship, the integration of biocatalysis and metal catalysis, and other key factors are introduced regarding the rational design of hybrid enzyme catalysts. This account sheds light on the development of rationally structurally designed hybrid enzyme catalysts for expanding biocatalysis in more chemical manufacturing processes.

Image: 
Chinese Journal of Catalysis

The two major challenges in industrial enzymatic catalysis are the limited number of chemical reaction types that are catalyzed by enzymes and the instability of enzymes under harsh conditions in industrial catalysis. Expanding enzyme catalysis to a larger substrate scope and greater variety of chemical reactions and tuning the microenvironment surrounding enzyme molecules to achieve high enzyme performance are urgently needed.

Recently, a research team led by Prof. Jun Ge from Tsinghua University, China reviewed their efforts using the de novo approach to synthesize hybrid enzyme catalysts that can address these two challenges and the structure-function relationship is discussed to reveal the principles of designing hybrid enzyme catalysts. The results were published in Chinese Journal of Catalysis.

In 2012, they first reported a coprecipitation method to prepare enzyme-inorganic-crystal composites. The coprecipitation method is general for preparing hybrid enzyme catalysts with various inorganic crystals, including MOFs. In 2014, they first proposed a coprecipitation strategy for directly synthesizing protein-embedded MOFs. The coprecipitation strategy for synthesizing enzyme-MOF composites is widely used in different types of MOFs, enzymes, proteins, DNA, siRNA, antibodies, and even cells. The mechanisms of enhancement of activity and stability of enzymes in the confined environment of MOFs were discussed. In addition to this, they constructed multienzyme-MOF composites to enhance the cascade reaction in a confined scaffold and developed a coarse-grained, particle-based model to understand the origin of the activity enhancement.

The apparent activity of enzymes in MOFs with a limited pore size is usually compromised when the enzyme substrate has a relatively high molecular weight. By introducing defects within the MOF matrix to generate larger pores, diffusional restrictions can be alleviated. Therefore, they developed methods for introducing defects into MOFs during coprecipitation. Tuning the concentration of precursors of MOFs, defected and even amorphous MOFs can be synthesized. These defects created mesopores in the composites, facilitated access of the substrates to the encapsulated enzymes and improved the apparent enzyme activity. The mechanism of defect generation was thoroughly studied and understood.

Moreover, instead of enzyme encapsulation, small inorganic crystals can grow in situ in a confined environment on the surface of an enzyme to combine enzymatic catalysis and chemocatalysis. They demonstrated how to construct an enzyme-metal hybrid catalyst to efficiently combine enzyme catalysis and metal cluster catalysis. Single lipase-polymer conjugates as confined nanoreactors were utilized for the in situ generation of Pd nanoparticles/clusters to accomplish chemoenzymatic dynamic kinetic resolution (DKR) of amines. The distinct size-dependent activity of Pd nanoparticles was observed. Experiments and simulations suggested that the engineering of the oxidation state of Pd plays an important role in the activity of Pd in the hybrid catalyst. This strategy for constructing enzyme-metal hybrid catalysts with excellent compatibility between enzymatic and metal-catalytic activities leads to many potential applications in chemical industry.

Credit: 
Dalian Institute of Chemical Physics, Chinese Academy Sciences

Highly fit teenagers coped better with COVID-19 later in life

image: Agnes af Geijerstam, Sahlgrenska Academy, University of Gothenburg.

Image: 
Photo: University of Gothenburg

Of the Swedish men in their late teens who performed well in the physical fitness tests for military conscription, a relatively high proportion were able to avoid hospital care when they became infected with COVID-19 during the pandemic up to 50 years later. This has been shown by University of Gothenburg researchers in a register study, with results now published in the BMJ Open.

The study is based on the Swedish Conscription Register, which contains particulars of over 1.5 million young Swedish men who began their military service in the years 1969-2005. Almost all of these men then underwent both a bicycle test and a strength test. Some 2,500 of the men included in the Conscription Register were later, in spring 2020, hospitalized with COVID-19.

For their study, the scientists divided the men into three groups based on their results in the fitness and strength tests. The data were merged with three other Swedish registers: the National Inpatient Register (IPR, also known as the Hospital Discharge Register), Intensive Care Register, and Cause of Death Register. The findings show a clear association between fitness and strength in youth and the risk of needing hospital care for COVID-19 infection 15-50 years after conscription.

"At the population level, we can see that both good fitness and good muscle strength in the late teens are protective factors for severe COVID. For those with good fitness at the time of conscription, the risk of dying in spring 2020 was half as high as for the least fit. For those whose strength was good back then, too, we see a similar protective effect," says Agnes af Geijerstam, PhD student at the University of Gothenburg's Sahlgrenska Academy, who is the lead author of the study.

However, since the oldest men in the study had not reached age 70, deaths from COVID-19 were uncommon in the study.

The Conscription Register also contains data on the young men's height and weight.

"Previous studies have shown that obesity is a risk factor for severe COVID. But we see that good fitness and strength are protective factors for everyone, including men with overweight or obesity," says Professor Lauren Lissner, senior coauthor of the study.

Moreover, the study showed a link between the men's height to the risk of COVID-19 infection.

"The taller the men were, the greater their risk of needing advanced care when they had gotten COVID; but per centimeter this increase in risk is very small. Also, unlike fitness and strength, there is no way to influence our height" af Geijerstam says.

There have already been many studies showing the protective effect of good physical fitness in numerous medical conditions, including infections. It has been established that the immune system is strengthened and the propensity to inflammation is reduced by physical activity. Fitness in adolescence is also likely to be associated with active and otherwise healthy lifestyles throughout adult life.

"It's interesting to see that the high fitness and strength levels those men had so many years ago can be linked to protection against severe COVID. Today, young people are becoming ever more sedentary, and that means there's a risk of major problems arising in the long term -- including a reduced resistance to future viral pandemics. Children and adolescents must get ample scope to move around," af Geijerstam says.

Credit: 
University of Gothenburg

Sample preparation in forensic toxicological analysis may have huge impacts

(Boston)--As analytical instrumentation (gas- and liquid-chromatographs coupled with mass spectrometers) increase in sensitivity and speed, forensic scientists may find themselves still hindered by the process of preparing samples (blood, urine, etc.) for analysis and seeking more efficient approaches.

In an article in WIRES Forensic Science, researchers from Boston University School of Medicine's (BUSM) Biomedical Forensic Sciences program, provide an overview of sample preparation techniques and information on routine sample types that may be encountered in forensic toxicology cases.

Forensic toxicology encompasses a large variety of scenarios including drug-facilitated crimes, understanding the role alcohol or other drugs may have played in an individuals' deaths, as well as complex polydrug use in driving under the influence cases. As variable as the cases, so too are the composition of biological matrices in addition to how to identify drugs or other compounds in biological samples. This has provided a vast array of sample preparation approaches that scientist have in their 'toolbox.' "Our work highlights the variability in sample types that toxicological analysis encompasses as well as vast array of sample preparation techniques that are currently available," said corresponding author Sabra R. Botch-Jones, MS, MS, MA, assistant professor of anatomy and neurobiology at BUSM.

According to the researchers, the choice of biological matrix is dependent on the anticipated answer the toxicologist is trying to get. Is suspected drug use recent? If so, a blood or oral fluid sample may be best to assess the drugs present and how much is in the sample. In cases of driving while impaired, it is essential to obtain a sample that is appropriate to assess if the drug effected the driver's ability to operate the vehicle safely. When drugs are used, the human body will break down, or metabolize, the drug and eventually excrete it. Drugs and their metabolites may be excreted or removed from the body over a course of hours and even days. For example, if there has been a delay in obtaining a sample or reporting a crime in which drugs are suspected, a urine sample may be best. If extensive amounts of time have elapsed, a hair sample may be a viable option to determine exposure to a suspected drug or other compound.

As with the instrumentation, sample preparation tools have also advanced over time. Solid phase and, more recently supported liquid extraction, allows the unwanted materials in the biological sample to be retained on a solid surface composed of natural materials such as silica or diatomaceous earth. These extraction tools can provide clean extracts containing the drugs of interest and help to recover a large variety of drugs, which can aid in laboratory efficiency when dealing with poly-drug cases.

"Researchers have a number of biological samples to choose from when trying to identify what substances may be in the human body, however it important that they choose the right one to help answer their research question. As equally important is the choice of how to prepare the sample for analysis. This work provides an overview of the routine biological samples, their components, and ways to process them for downstream analysis," explains Botch-Jones.

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Boston University School of Medicine

Handwriting beats typing and watching videos for learning to read

video: Though writing by hand is increasingly being eclipsed by the ease of computers, a new study finds we shouldn't be so quick to throw away the pencils and paper: handwriting helps people learn certain skills surprisingly faster and significantly better than learning the same material through typing or watching videos.

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Johns Hopkins University

Though writing by hand is increasingly being eclipsed by the ease of computers, a new study finds we shouldn't be so quick to throw away the pencils and paper: handwriting helps people learn certain skills surprisingly faster and significantly better than learning the same material through typing or watching videos.

"The question out there for parents and educators is why should our kids spend any time doing handwriting," says senior author Brenda Rapp, a Johns Hopkins University professor of cognitive science. "Obviously, you're going to be a better hand-writer if you practice it. But since people are handwriting less then maybe who cares? The real question is: Are there other benefits to handwriting that have to do with reading and spelling and understanding? We find there most definitely are."

The work appears in the journal Psychological Science.

Rapp and lead author Robert Wiley, a former Johns Hopkins University Ph.D. student who is now a professor at the University of North Carolina, Greensboro, conducted an experiment in which 42 people were taught the Arabic alphabet, split into three groups of learners: writers, typers and video watchers.

Everyone learned the letters one at a time by watching videos of them being written along with hearing names and sounds. After being introduced to each letter, the three groups would attempt to learn what they just saw and heard in different ways. The video group got an on-screen flash of a letter and had to say if it was the same letter they'd just seen. The typers would have to find the letter on the keyboard. The writers had to copy the letter with pen and paper.

At the end, after as many as six sessions, everyone could recognize the letters and made few mistakes when tested. But the writing group reached this level of proficiency faster than the other groups - a few of them in just two sessions.

Next the researchers wanted to determine to what extent, if at all, the groups could generalize this new knowledge. In other words, they could all recognize the letters, but could anyone really use them like a pro, by writing with them, using them to spell new words and using them to read unfamiliar words?

The writing group was better - decisively - in all of those things.

"The main lesson is that even though they were all good at recognizing letters, the writing training was the best at every other measure. And they required less time to get there," Wiley said.

The writing group ended up with more of the skills needed for expert adult-level reading and spelling. Wiley and Rapp say it's because handwriting reinforces the visual and aural lessons. The advantage has nothing to do with penmanship - it's that the simple act of writing by hand provides a perceptual-motor experience that unifies what is being learned about the letters (their shapes, their sounds, and their motor plans), which in turn creates richer knowledge and fuller, true learning, the team says.

"With writing, you're getting a stronger representation in your mind that lets you scaffold toward these other types of tasks that don't in any way involve handwriting," Wiley said.

Although the participants in the study were adults, Wiley and Rapp expect they'd see the same results in children. The findings have implications for classrooms, where pencils and notebooks have taken a backseat in recent years to tablets and laptops, and teaching cursive handwriting is all but extinct.

The findings also suggest that adults trying to learn a language with a different alphabet should supplement what they're learning through apps or tapes with good old-fashioned paperwork.

Wiley, for one, is making sure the kids in his life are stocked up on writing supplies.

"I have three nieces and a nephew right now and my siblings ask me should we get them crayons and pens? I say yes, let them just play with the letters and start writing them and write them all the time. I bought them all finger paint for Christmas and told them let's do letters."

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Johns Hopkins University

Populist anti-foreign aid rhetoric has an impact on the public - but only among fans of populist politicians, study shows

Populist anti-foreign aid rhetoric works - but only fans of populist politicians are convinced by hostile messages about charity abroad, a new study shows. Those who distrust populist politicians are significantly less susceptible to these messages.

The research shows international aid institutions and non-populist politicians should not be unduly worried about the impact of populism on global development cooperation.

Those wanting to convince the public about the importance of foreign aid should focus on communicating their message transparently and clearly, and using local partnerships.

The research, by A. Burcu Bayram from the University of Arkansas and Catarina Thomson from the University of Exeter, is published in the International Studies Quarterly.

Dr. Thomson said: "Populists are not converting pro-aid individuals with their rhetoric; they are preaching to those predisposed to be converted. Populist parties and politicians continue to portray overseas aid spending as the enemy of prosperity "at home", and this has an impact on public attitudes.

"We have found those most likely to be swayed by anti-foreign aid populist rhetoric are those who have favourable views of populist leaders. This means the situation for those wanting to make the case for foreign aid isn't necessarily as bleak as many fear. The Conservative Party backlash to cuts is a good example of this.

"The effect of negative comments about foreign aid is moderated by whether people think populist leaders stand up for the little guy or scapegoat those in other nations. The future of global development might not be as bleak as previously feared in the age of populism."

Dr Bayram said: "We found people who trust populist leaders are more persuaded by populist rhetoric against aid than those who are suspicious of populists. Populist rhetoric against foreign development aid has a larger impact on the willingness to provide such aid when people think populist leaders represent the will of the people than when they think populist leaders scapegoat others."

Academics surveyed 1,600 American and 1,200 British adults during 2017 and 2018. First they measured their political views, asking if they saw populist leaders as the kind of leaders who "stand up for the little guy" or "scapegoat out-groups" for America or Britain's problems. Participants were asked to read a hypothetical scenario showing how leaders had handled multilateral development aid in different ways. One group were told the U.S. President or Prime Minister had said people prefer to help children in their country first; another were told the President or Prime Minister blamed elites for exaggerating the situation of global poverty and manipulating the people and another were told the President or Prime Minister said it was not their country's responsibility to help. A control group was told the President or Prime Minister had called for a congressional or parliamentary committee to evaluate a request from UNICEF's for more funding.

Participants were then asked about their willingness to contribute funds to UNICEF, and if the American or British government should provide additional funds to UNICEF.

In the UK, among the participants exposed to anti-aid populist rhetoric, those who believe that populist leaders scapegoat others were 31 percentage points less likely to want to reduce aid funding compared to those who believe populist leaders stand up for "the little guy". They find similar results in the U.S..

About 12 per cent of British respondents expressed strong support for funding UNICEF while about 22 percent said they were strongly opposed. Around 16 percent of Americans were strongly in favour of funding UNICEF and 23 percent were strongly opposed.

Those in the UK told their leader wanted to help children in their country first, global poverty was exaggerated or it was not their country's responsibility to help, were 6 percentage points more likely to say funding should definitely not be given to UNICEF, compared with those told their leader would get an outside body to consider the charity's request.

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University of Exeter

Icequakes likely rumble along geyser-spitting fractures in Saturn's icy moon Enceladus

image: Ice shelves floating on Earth's Southern Ocean rise and fall with tides, causing rifts, fractures. Icequakes occur most frequently when falling tides pull the rifts apart. Models suggest seismic activity on Enceladus likely correspond to the tides inside the moon. From figure 1 of the new study.

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AGU/ JGR: Planets

WASHINGTON--Tidal stresses may be causing constant icequakes on Saturn's sixth largest moon Enceladus, a world of interest in the search for life beyond Earth, according to a new study. A better understanding of seismic activity could reveal what's under the moon's icy crust and provide clues to the habitability of its ocean.

Enceladus is about 500 kilometers in diameter and almost entirely covered in ice. The moon is nearly 10 times as far away from the Sun as Earth and its bright surface reflects most sunlight, making it very cold, yet researchers have long speculated that the ice encases an underlying liquid ocean.

The moon likely experiences massive tidal forces caused by Saturn and the planet's other, larger moons--similar to the way Earth's Moon causes tides on Earth. These tidal motions inside Enceladus warm its interior, crack the surface and sometimes squeeze tall geysers of water vapor through notable cracks called the tiger stripe fractures.

The new study used observations of Antarctic ice shelves to suggest tides on Enceladus may also cause small quakes in the ice at the moon's fractures, like icequakes observed on Antarctica's floating ice sheets.

"[Moons like] these are places that are exciting because they might have life," said Kira Olsen, a geophysicist at NASA's Goddard Space Flight Center. She said that since life is thought to have first developed in our oceans, liquid oceans under the ice of other worlds could be a good place to search for life. The icy crust of Enceladus might also protect the water below from radiation, making it more habitable.

The new study was published in the Journal of Geophysical Research: Planets, AGU's journal for research on the formation and evolution of the planets, moons and objects of our solar system and beyond.

"We have ideas of how thick the ice could be, but we don't have direct observation. Studying ice quakes is a way to get at that information," Olsen said.

Internal tides

To learn more about how Enceladus' tiger fractures might be moving, Olsen and her colleagues turned to floating ice shelves in Antarctica as the closest analogue on Earth for the types of activity they were seeing on Enceladus. They could then use their knowledge about how certain surface features on our planet produce seismic activity to estimate what kind of seismic activity is happening on the distant moon.

The researchers analyzed data collected by seismometers along the Ross Ice Shelf in the southern continent between 2014 and 2016 and compared these to satellite images of the area. They paid particular attention to two seismometers placed next to large rifts on the ice slab.

They related the seismic activity to the stress occurring along these rifts. The majority of icequakes on the Ross Ice Shelf occurred when the rifts were pulling apart, which happens when tides are falling.

We have no measurements of seismic activity on Enceladus, but Olsen and her colleagues created models that compared the types of fractures they saw on the moon's surface with those on the Ross Ice Shelf.

These models showed that the largest amount of seismic activity on Enceladus likely corresponded to the tides. Peak seismic activity there occurs when Enceladus is 100 degrees past the nearest approach to Saturn during its orbit. The ocean underneath the ice at this point acts something like water inside a sloshing balloon. The ice fractures are created at the points of highest stress, where the balloon would break apart.

The icequakes aren't massive along these cracks, even at the peak periods of stress. Olsen describes them more like "almost continuous little pops and fractures.

Mark Panning, a research scientist at NASA's Jet Propulsion Laboratory who was not involved in the new study, said that while the Cassini spacecraft revealed the moon is geologically active, it's difficult to tell how that translates to seismic activity. "The study represents a really key way of investigating what seismicity on Enceladus and other tidally activated icy worlds may look like by looking at the best analogs we can find on Earth," he said.

Olsen said scientists should aim to place seismometers within 10 kilometers of these fractures in any future missions to Enceladus to learn more about what's going on below.

"It's not a quiet out of the way place, but it's a pretty good place to study," she said.

More information about the seismic activity could then teach us more about the thickness of the ice crust on Enceladus. For now, no missions to Enceladus have been planned, but the European Space Agency is planning the JUICE mission to one of Jupiter's icy moons, Europa.

Olsen said that similar work could then be conducted on Titan, Saturn's largest moon, a world also covered with ice that may conceal liquid oceans and is another top pick for potential extraterrestrial life. NASA's Dragonfly mission is scheduled to visit Titan in 2036.

"This kind of work is one of the best ways to try to get an idea of what behaviors we may see on a planetary body that would be an incredible place to do more science," Panning said.

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American Geophysical Union

Advocacy for a digital oral health that leaves no one behind

demic have already had a dramatic impact on the prevailing oral health care model and will continue to do so. The paper "Advocacy for a Digital Oral Health That Leaves No One Behind," published in the JDR Clinical & Translational Research (JDR CTR), promotes the use of digital tools to offer opportunities to improve healthy behavior, lower risk factors common to oral diseases and other noncommunicable diseases and contribute to reducing oral health inequalities.

To mitigate the impact of the COVID-19 pandemic lockdowns, systems were quickly put in place in most countries to respond to dental emergencies, giving priority to distance screening, advice to patients by remote means and treatment of urgent cases while ensuring continuous care. Digital health was widely adopted as a central component of this new approach, leading to new practices and tools that, in turn, demonstrated their potential, limitations and possible excesses.

Authors Nicolas Giraudeau, University of Montpellier, France, and Benoit Varenne, World Health Organization (WHO), Oral Health Programme, Geneva, Switzerland, believe that digital tools can accelerate the implementation of universal health coverage and help achieve the World Health Organization 2030 Sustainable Development Agenda, leaving no one behind. TheWHO mOralHealth program is structured in four modules (literacy, training, early detection, and surveillance). "Digital oral health should be one of the pillars of oral healthcare post-COVID-19. Universal access to digital oral health should be promoted globally. The WHO's mOralHealth programme aims to do that."

"The use of digital health has led to a new way of understanding both general and oral health," said JDR CTR Editor-in-Chief Jocelyne S. Feine, McGill University, Montréal, Quebec, Canada. "This paper calls for political leaders to be made aware of the universal availability of digital technology and make use of it as a safe and equitable means of delivering oral health care to the public."

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International Association for Dental, Oral, and Craniofacial Research

Protein supplements work for women and not men, during fasted carb-restricted training

Consuming a protein supplement, specifically protein hydrolysate, during carbohydrate-restricted training was helpful for improving training intensity in women, but not in men.

That's according to new research which will be part of a presentation this week at The Physiological Society's Annual Conference Physiology 2021.

Most nutrition guidelines for athletes are based on research in men only. This study, by Tanja Oosthuyse and her colleagues, emphasizes that this shouldn't be the case, because nutritional research findings in men don't always apply to women.

While the protein supplement helped training intensity in women, it did not improve training intensity and instead resulted in modest negative effect in men. It made exercise feel harder for them because their bodies were working harder to break down the supplement, as compared to when they were drinking just plain water.

The conclusion from this research is that women should ingest protein supplements during fasted carbohydrate-restricted exercise, while men should be aware that it will increase their perception of effort.

Future studies need to determine whether ingesting protein hydrolysate supplements during carbohydrate-restricted training over a longer time frame of weeks or months will be beneficial.

In this study, the researchers did not consider menstrual phase. Follow up studies are needed to determine whether the improved training intensity when ingesting a protein hydrolysate compared with placebo-water is specific to menstrual phase.

Commenting on the study, first author Tanja Oosthuyse said,

"The application of the findings from our study are purely for the specialised training tactic of overnight fasted carbohydrate-restricted exercise that aims to enhance training.

Racing nutrition, however, is very different and at the moment guidelines are standard for both men and women. We need to specify potential differences so that both men and women can train and race at the highest possible calibre."

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The Physiological Society