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Once you crush, cut or fracture a rock, there are no do-overs. It's a fact that means geoscientists have to be particularly careful about which rock samples they can sacrifice to physics experiments versus which ones should stay on the shelf.

A team of geoscience researchers from The University of Texas at Austin is working to change that with a new method for creating digital replicas of rock samples that is more accurate and simpler to use than other techniques.

The digital replicas can take the place of the real thing in certain experiments, allowing scientists to learn about rock samples without having to touch them. They also allow scientists to collect data from samples that are too small to run certain experiments on, such as cuttings brought up when drilling for oil.

"Now we don't have to take a rock into the lab," said Ken Ikeda, a graduate student at the UT Jackson School of Geosciences. "We don't have to risk a sample, there's no way to ruin it."

Ikeda is the lead author of a paper published in the Journal of Geophysical Research - Solid Earth on April 14, 2020, that describes the new method. The research was conducted entirely by Jackson School researchers in the Department of Geological Sciences, with the other two authors being graduate student Eric Goldfarb, and Nicola Tisato, an assistant professor in the Jackson School's Department of Geological Sciences.

In their study, the researchers tested their method against two others, comparing how the three techniques fared at calculating how fast seismic waves could move through a sample. The new method came closest to the speeds measured in the actual sample, with the calculation being off by 4.5%. The other methods were off by 4.7% and 29%.

Seismic velocity data is a fundamental tool used by geoscientists to learn about rock formations underground. But the researchers said that their method could be used for calculating a number of other important rock properties, such as permeability or electrical conductivity.

All digital rock replicas are built using data collected from a CT scan of a rock sample, which provides a high-resolution record of how the rock interacts with X-rays. By analyzing that information, researchers can determine physical properties about the sample.

The other two methods came with processing trade offs. One of these methods can account for pores and fractures in the rock sample - features that have a big influence on overall elasticity - but requires a target, a pure sample of the mineral that makes up the majority of the rock, to be scanned at the same time as the rock. The other method doesn't require a target, but can't account for the pores and fractures.

The new technique gets around these trade-offs by sampling itself for targets, using extremes in the X-ray data to find bits of pure mineral--something the researchers call a "pseudotarget"--as well as fractures and pores.

"A rock has certain areas that are pristine, grains of quartz that are pristine, and space, pores, that are totally empty," Tisato said. "So if you find those points, you have calibration points."

With no need for a pure mineral target to accompany a sample, the technique simplifies the CT scanning process. The study also shows that, when it comes to calculating seismic speed, the technique is more accurate than the other two methods.

Gary Mavko, a professor emeritus in geophysics at Stanford University who did not take part in the research, said that the study helps advance research in a rapidly growing field.

"This work represents a promising new approach for elastic digital rock physics -- the much studied problem of predicting effective elastic properties of porous Earth materials from high-resolution CT image," he said.

Currently, the new technique can only be applied to samples that are made mostly of a single mineral - such as the Berea Sandstone core used in the study. Nevertheless, there are plenty of fascinating rocks that fit the bill. Goldfarb said he has applied the technique to three Mars meteorites, samples currently being studied by fellow Jackson School graduate student Scott Eckley.

The meteorite example highlights the value of the technique as a way to make rare specimens more accessible for research, Goldfarb said. A high-quality rock replica means you don't need a meteorite in your lab to be able to study one.

DALLAS, JUNE 8, 2020 -- Taking blood pressure medication as prescribed helped even the frailest elderly people (65 and older) live longer, and the healthiest older people had the biggest survival boost, according to a large study in northern Italy published today in Hypertension, an American Heart Association journal.

"We knew that high blood pressure medication was protective in general among older people, however, we focused on whether it is also protective in frail patients with many other medical conditions who are usually excluded from randomized trials," said Giuseppe Mancia, M.D., lead study author and professor emeritus at the University of Milano-Bicocca in Milan, Italy.

Researchers reviewed data on almost 1.3 million people aged 65 and older (average age 76) in the Lombardy region of northern Italy who had 3 or more high blood pressure medication prescriptions in 2011-2012. Examining the public health care database, researchers calculated the percentage of time over the next seven years (or until death) that each person continued to receive the medications. Because almost all medications are free or low-cost and dispensed by the public health service, this corresponds roughly to people's adherence in using the medication in Italy.

To look separately at outcomes among older people with various medical conditions, researchers used a previously developed score that accounts for 34 different health factors and has a close relationship with mortality.

Researchers compared roughly 255,000 people who died during the 7-year follow-up with age-, gender-, and health-status-matched controls who survived and divided them into four groups of health status: good, medium, poor or very poor.

The probability of death over 7-years was 16% for people rated in good health at the beginning of the study. Mortality probability increased progressively to 64% for those rated in very poor health.

Compared with people with very low adherence to blood pressure medications (dispensed pills covered less than 25% of the time period), people with high adherence to blood pressure medications (more than 75% of the time period covered) were:

44% less likely to die if they started in good health; and

33% less likely to die if they started in very poor health.

A similar pattern was seen with cardiovascular deaths. The greatest survival benefit was among the people who started in good health, and the most modest survival benefit was in those who started in very poor health.

"Our findings definitely suggest that even in very frail people, antihypertensive treatment reduces the risk of death; however, the benefits may be smaller in this group," Mancia said.

No matter what a person's initial health status, survival benefits were greatest in those who received blood pressure medication to cover more than 75% of the follow-up period, compared with those with intermediate (25-75%) or low levels (less than 25%) of coverage, highlighting the importance of consistent use of blood pressure medications.

"Do your best to encourage and support patients to take their medications, because adherence is crucial to getting the benefits. Medications do nothing if people don't take them," Mancia said.

Prescription medications given to elderly people living in nursing homes or assisted-living homes in Italy are not included in the national database, so the study's results may only apply to elderly people living in the community. In addition, all data for this analysis are from Italy, where hospitalizations and blood pressure medications are available for free or at low cost, thus, the study's findings may not be generalizable to countries with a different health care system.

Biological tissues have evolved over millennia to be perfectly optimized for their specific functions. Take cartilage as an example. It's a compliant, elastic tissue that's soft enough to cushion joints, but strong enough to resist compression and withstand the substantial load bearing of our bodies: key for running, jumping, and our daily wear and tear.

Creating synthetic replacements which truly match the properties and behaviors of biological tissues hasn't been easy. But University of Colorado Denver scientists, led by mechanical engineer professor Chris Yakacki, PhD, are the first to 3D print a complex, porous lattice structure using liquid crystal elastomers (LCEs) creating devices that can finally mimic cartilage and other biological tissues.

The CU Denver team, including professor Kai Yu, PhD, postdoctoral fellow Devesh Mistry, PhD, and doctoral student Nicholas Traugutt, as well as scientists from the Southern University of Science and Technology in China, reported its findings this week in the journal Advanced Materials.

Revolution in the manufacturing of LCEs

Yakacki, who works out of CU Denver's Smart Materials and Biomechanics (SMAB) Lab, began working with LCEs in 2012. The soft, multifunctional materials are known for their elasticity and extraordinary ability to dissipate high energy. In 2018, Yakacki received an NSF CAREER award to revolutionize the manufacturability of LCEs and several rounds of funding to develop them as a shock absorber for football helmets. Even then, he knew its applications could go further.

"Everyone's heard of liquid crystals because you stare at them in your phone display," says Yakacki. "And you've likely heard of liquid crystal polymers because that's exactly what Kevlar is. Our challenge was to get them into soft polymers, like elastomers, to use them as shock absorbers. That's when you go down the layers of complexity."

LCEs are tricky to manipulate. Until now, most researchers could create either large objects with minimal detail or high detail in practically microscopic structures. But as with phone screens, big devices with high resolutions are where the future lies. Yakacki and his team's chemicals and printing process took the difficulty down to nearly zero.

Shining a light on honey-like resin

For their study, Yakacki and his team explored a 3D printing process called digital light processing (DLP). The team developed a honey-like LC resin that, when hit with ultraviolet light, cures--forming new bonds in a succession of thin photopolymer layers. The final cured resin forms a soft, strong, and compliant elastomer. When printed in lattice structures--levels of patterning akin to a honeycomb--that's when it began to mimic cartilage.

The group printed several structures, including a tiny, detailed lotus flower and a prototype of a spinal fusion cage, creating the largest LCE device with the most detail. The combination of the resin and printing process also led to 12 times greater rate-dependence and up to 27 times greater strain-energy dissipation compared to those printed from a commercially available photocurable elastomer resin.

From football helmets to the spine

Going forward, the structures have several applications, like shock-absorbing football helmet foam or even small biomedical implants for toes. Yakacki is most excited about its possibilities in the spine.

LCE spinal cage prototype

"The spine is full of challenges and it's a hard problem to solve," said Yakacki. "People have tried making synthetic spinal tissue discs and they haven't done a good job of it. With 3D printing, and the high resolution we've gotten from it, you can match a person's anatomy exactly. One day, we may be able to grow cells to fix the spine, but for now, we can take a step forward with the next generation of materials. That's where we'd like to go."

This work is supported by the U.S. Army Research Laboratory and U. S. Army Research Office, an NSF CAREER Award, and the Laboratory Directed Research and Development program at Sandia National Laboratories, for the U.S. Department of Energy's National Nuclear Security Administration.

Vaccines are notoriously difficult to transport to remote or dangerous places, as they spoil when not refrigerated. Formulations are safe between 2°C and 8°C, but at other temperatures the proteins start to unravel, making the vaccines ineffective. As a result, millions of children around the world miss out on life-saving inoculations.

However, scientists have now found a way to prevent warmed-up vaccines from degrading. By encasing protein molecules in a silica shell, the structure remains intact even when heated to 100°C, or stored at room temperature for up to three years.

The technique for tailor-fitting a vaccine with a silica coat - known as ensilication- was developed by a Bath team in collaboration with the University of Newcastle. This pioneering technology was seen to work in the lab two years ago, and now it has demonstrated its effectiveness in the real world too.

In their latest study, published in the journal Scientific Reports, the researchers sent both ensilicated and regular samples of the tetanus vaccine from Bath to Newcastle by ordinary post (a journey time of over 300 miles, which by post takes a day or two). When doses of the ensilicated vaccine were subsequently injected into mice, an immune response was triggered, showing the vaccine to be active. No immune response was detected in mice injected with unprotected doses of the vaccine, indicating the medicine had been damaged in transit.

Dr Asel Sartbaeva, who led the project from the University of Bath's Department of Chemistry, said: "This is really exciting data because it shows us that ensilication preserves not just the structure of the vaccine proteins but also the function - the immunogenicity."

"This project has focused on tetanus, which is part of the DTP (diphtheria, tetanus and pertussis) vaccine given to young children in three doses. Next, we will be working on developing a thermally-stable vaccine for diphtheria, and then pertussis. Eventually we want to create a silica cage for the whole DTP trivalent vaccine, so that every child in the world can be given DTP without having to rely on cold chain distribution."

Cold chain distribution requires a vaccine to be refrigerated from the moment of manufacturing to the endpoint destination.

Silica is an inorganic, non-toxic material, and Dr Sartbaeva estimates that ensilicated vaccines could be used for humans within five to 15 years. She hopes the technology to silica-wrap proteins will eventually be adopted to store and transport all childhood vaccines, as well as other protein-based products, such as antibodies and enzymes.

"Ultimately, we want to make important medicines stable so they can be more widely available," she said. "The aim is to eradicate vaccine-preventable diseases in low income countries by using thermally stable vaccines and cutting out dependence on cold chain."

Currently, up to 50% of vaccine doses are discarded before use due to exposure to suboptimal temperatures. According to the World Health Organisation (WHO), 19.4 million infants did not receive routine life-saving vaccinations in 2018.

Already in the 19th century Charles Darwin recognized that the number of male gametes - pollen for plants, sperm for animals - is highly variable among individuals and species. At first sight a high number of male gametes seems beneficial for the competition among males to produce more offspring. However, many domesticated species have a reduced number of male gametes. In theory it might be advantageous to reduce the cost of producing male gametes, for example when the rate of self-fertilization or inbreeding is high and fewer male gametes are necessary for successful reproduction.

Genome analysis of self-fertilizing plant

"So far there has been little evidence to support this idea, because the production of male gametes is a complex trait affected by many genes with small effects and its molecular basis remained unknown", says Kentaro Shimizu, Professor for Evolutionary Biology and Environmental Studies at the University of Zurich (UZH). An international study under his lead now provides such evidence and demonstrates that a reduction in pollen number is not necessarily deleterious but rather advantageous in a self-fertilizing species.

For their investigation the researchers used the well-characterized model plant Arabidopsis thaliana that is mainly self-fertilizing and has a reduced number of pollen grains compared to its relatives in the wild. They counted the pollen number of 144 plants with distinct genetic background and found variations from 2,000 to 8,000 pollen grains per flower. They then compared the entire genetic information of these variants, looking for differences between plants with higher and lower pollen numbers.

RDP1 gene controls pollen production

This computational analysis, a so-called genome-wide association study, revealed one gene that affects the number of pollen each plant produces, which was subsequently named REDUCED POLLEN NUMBER1 (RDP1) gene. Using the novel genome editing technology CRISPR-Cas9 the researchers created several mutant variants of the RDP1 gene, both in plants with high and low pollen number. They crossed the mutated plants with each other and counted the pollen the hybrid offspring produced. "These experiments confirmed the subtle but significant effect of the RDP1 gene", says co-author Misako Yamazaki, a technical staff of the Shimizu group. A comparison with other organisms revealed that the gene encodes a factor that promotes the building of ribosomes, the cellular factories for protein production.

Less pollen confers higher fitness

Next, the team investigated if the reduction in pollen number is positively selected for and did not happen incidentally. For this they used a statistical method to gain insight into the evolution of the RDP1 gene within model plants with different pollen production. The results showed that the trait for reduced pollen number has indeed been under positive selection.

Furthermore, the research team studied the evolution of the many genomic regions associated with pollen number. The selection on pollen number was very strong - in comparison to previous studies of more than 100 traits such as disease-resistance and environmental responses. This supports the importance of pollen number for reproductive success.

Optimizing fertilization in agriculture

"The evidence supports the theoretical prediction that reduced investment in male gametes is advantageous. This is not only important for evolutionary biology but also for the practice of plant breeding and domestication in general", explains Shimizu. "Many crop plants have a reduced number of pollen due to domestication. Lowering the cost of producing pollen may increase crop yield. On the other hand, too few pollen grains might be an obstacle to breeding and seed production. Our study opens the way for molecular breeding of the optimal pollen number."

Protected areas across the globe are effectively keeping invasive animals at bay, but the large majority of them are at risk of invasions, finds a China-UK research team involving UCL.

The research, led by the Chinese Academy of Science and published in Nature Communications, show that for most protected areas, there is an invasive animal species living less than 10km away that is well suited to the protected area's environment.

Co-author Professor Tim Blackburn (UCL Genetics, Evolution & Environment and the Institute of Zoology, ZSL) said: "One of the most harmful ways that people are impacting the natural environment is through the introduction of 'aliens' - species that do not occur naturally in an area, but have been taken there by human activities.

"These species may kill or compete with native species, or destroy habitats, amongst other impacts. Invasions by alien species are regarded as one of the top five direct drivers of global biodiversity loss, and aliens are establishing themselves in new areas at ever increasing rates. Protected areas are a cornerstone of biodiversity conservation, but aliens don't know where their boundaries lie. It's important to know whether these areas might protect against the spread of invasive species."

The researchers investigated 894 terrestrial animal species (including mammals, birds, reptiles and invertebrates) that are known to have established alien populations somewhere in the world.

They then assessed whether these species occurred within, or near, the boundaries of 199,957 protected areas across the globe, as defined by the International Union for Conservation of Nature (IUCN), including wilderness areas, national parks, and natural monuments or features.

The team found that less than 10% of the protected areas are currently home to any of the invasive species surveyed, suggesting that protected areas are generally effective in protecting against invasive species.

But almost all of those areas may be at risk of invasion, as an invasive species was found within 100km of the boundaries of 99% of the protected areas. For 89% of the protected areas, there was an alien species resident within 10km of the boundaries.

More than 95% of the protected areas were deemed to be environmentally suitable for the establishment of at least some of the alien species under investigation.

The researchers also investigated common factors among the protected areas that are already home to alien species. They found that protected areas tend to have more alien animal species if they have a larger human footprint index, due to factors such as transport links and large human populations nearby.

The researchers also found that larger, and more recently established protected areas, tend to have more alien species. Older protected areas tend to be in more remote areas, so they are less exposed to human impacts.

Senior author Dr Li Yiming (Institute of Zoology, Chinese Academy of Sciences) said: "At the moment most protected areas are still free of most animal invaders, but this might not last. Areas readily accessible to large numbers of people are the most vulnerable."

"We need to increase efforts to monitor and record invasive alien species that people may bring into protected areas, deliberately or by accident, especially damaging species like the American bullfrog, brown rat and wild boar."

The findings do not suggest that the rich existing biodiversity in protected areas acts as a barrier to invasions, as they found mixed evidence on the relationships between existing native biodiversity and presence of invasive species.

Professor Blackburn concluded: "If alien species continue to spread - and we would expect many to do that - many more protected areas will have their boundaries reached, and potentially breached, by these alien species."

Advances in the Production of Minor Ginsenosides Using Microorganisms and Their Enzymes - BIO Integration

https://bio-integration.org/wp-content/uploads/2020/05/bioi20200007.pdf

Announcing a new article publication for BIO Integration journal. In this review article the author Almando Geraldi from the Universitas Airlangga, Indonesia considers the advances in the production of minor ginsenosides using microorganisms and their enzymes.

In this review, various minor ginsenosides production strategies, namely utilizing microorganisms and recombinant microbial enzymes, for biotransforming major ginsenosides into minor ginsenoside, as well as constructing synthetic minor ginsenosides production pathways in yeast cell factories, are described and discussed. The present challenges and future research direction for producing minor ginsenosides using those approaches are considered.

Minor ginsenodes are of great interest due to their diverse pharmacological activities such as their anti-cancer, anti-diabetic, neuroprotective, immunomodulator, and anti-inflammatory effects. The miniscule amount of minor ginsenosides in ginseng plants has driven the development of their mass production methods. Among the various production methods for minor ginsenosides, the utilization of microorganisms and their enzymes are considered as highly specific, safe, and environmentally friendly.

BIO Integration is fully open access journal which will allow for the rapid dissemination of multidisciplinary views driving the progress of modern medicine.

As part of its mandate to help bring interesting work and knowledge from around the world to a wider audience, BIOI will actively support authors through open access publishing and through waiving author fees in its first years. Also, publication support for authors whose first language is not English will be offered in areas such as manuscript development, English language editing and artwork assistance.

Buried deep within the varied properties of metals, there is a fundamental question up for grabs: What makes it a metal? In other words, which properties are inherent to a metal and which are incidental?

Scientists at USC Dornsife College of Letters, Arts and Sciences, collaborating with an international group of researchers, have helped further define what constitutes a metal. In the process, they open the door for organic chemists to improve the synthesis of useful compounds.

The study appears on the cover of the journal Science on June 5.

Going full metal

Intuition suggests that metals are dense, and while that bears true for some (think gold or lead), it fails to hold up for others. For example, lithium -- commonly used in batteries -- floats on water. Some metals are hard, such as titanium, yet others yield easily to pressure, including indium and aluminium. How about melting temperature? Platinum melts at more than 1,700 degrees Celsius (3,200 F), but mercury is a liquid well below zero.

Many other definitions of 'metal-hood' suffer similar contradictions, but British physicist and Nobel laureate Sir Nevill Mott provided one inherent property: "I've thought a lot about 'What is a metal?' and I think one can only answer the question at T = 0. There a metal conducts, and a non-metal doesn't."

Only metals are able to conduct electricity at absolute zero, the temperature at which even molecular motion all but stops. Conduction, unlike density or hardness, is an inherent property of metals.

Seeking to further understand the intrinsic properties of metals, the USC Dornsife scientists, led by Stephen Bradforth, professor of chemistry and divisional dean for natural sciences and mathematics, and their colleagues used a trick first noted by chemist Sir Humphry Davy in 1809. In essence, they made a metal from scratch.

The scientists cooled ammonia -- normally a gas at room temperature -- to minus 33 C to liquify it and then added, in separate experiments, the alkali metals lithium, sodium and potassium.

In these solutions, electrons from the alkali metal initially become trapped in the gaps between ammonia molecules. This creates what scientists call 'solvated electrons,' which are highly reactive but stabilized in the ammonia. These solutions have a characteristic blue color. Given enough solvated electrons (by adding about 1% alkali metal to the ammonia) the whole liquid turns bronze and, in essence, becomes a metal while remaining liquid.

Solvated electrons have proven to be extremely important to organic chemists. Through a reaction called the "Birch reduction," named after chemist Arthur Birch, they were key to synthesizing many important compounds and led to the manufacture of oral contraceptives in the 1950s.

Beaming in on electrons

The scientists next measured the amount of energy needed to bump the solvated electrons out of metallic ammonia using an X-ray beam. In a first-ever experiment, they forced different concentrations of the metallic ammonia through a microjet, which creates a stream about the width of a human hair that then passes through a hair-thin X-ray beam. Electrons interacting with the X-rays become dislodged.

The results show that, at low concentrations, solvated electrons are more easily dislodged from the solution by the interaction with the X-rays, giving a simple energy pattern. At higher concentrations, though, the energy pattern suddenly develops a sharp band edge, indicating the solution is behaving as a metal would.

Most important, however, the experiment presents a way for researchers to assess the behavior of solvated electrons in ammonia when other compounds are introduced to the mix. This opens a new window for chemists to synthesize important organic compounds, going well beyond Birch's experiments.

"This is the sort of things that goes in textbooks, or at least changes how textbooks are written," Bradforth said, noting the potentially historic importance of the work.

The work allows scientists to understand exactly how chemicals react with metallic ammonia, in essence giving the researchers a frame-by-frame view of what's happening in the test tube. Armed with this information, chemists can alter conditions to ensure they produce exactly the desired end product.

A collaborative project between the Center for Genome Integrity, within the Institute for Basic Science (IBS, South Korea), and the Dundee School of Life Sciences, the EMBL's European Bioinformatics Institute (EMBL-EBI), and the Wellcome Sanger Institute (UK) have screened almost 163,000 DNA mutations in 2,700 C. elegans roundworms to shed light on DNA damage. The results, published in Nature Communications, lead to the conclusion that mutation patterns seen in cancer are more complicated than we previously thought.

Our genetic material is constantly exposed to possible sources of mutations, including UV light, tobacco smoke and carcinogenic chemicals. These genetic alterations are usually corrected by an army of DNA repair proteins that patrol the DNA and fix its mistakes. However, what happens when the policemen themselves are malfunctioning? They can overlook some DNA alterations, or even generate some mutations while trying to correct them. In this study, researchers looked at mutational signatures - patterns of mutations occurring in the genome - caused by the combined action of 11 known DNA damaging agents and inaccurate DNA repair mechanisms using C. elegans worms as a model system.

"Our paper is the first to use experimental approaches to systematically test, at a genome-wide scale, how DNA damaging agents cause mutations, and how this is prevented by DNA repair proteins," says Anton Gartner, Associate Director of the IBS Center for Genomic Integrity and co-leading author of this study.

While mutagens were thought to generate unique mutational signatures, the results showed a more intricate picture. DNA repair pathways are highly redundant: up to four different repair pathways act together to prevent mutagenesis caused by the same cancer inducing agents. Using roundworms with 53 different DNA repair deficits, the researchers found out that a single mutagen may leave a variety of mutational signatures depending on the faulty repair system.

This study is particularly important because unmended mutations in specific parts of the DNA can lead to cancer. Since fundamental processes, such as DNA repair, are conserved throughout evolution, the team was able to use data derived from C. elegans to scan through thousands of human cancer genome sequences and find possible evidence for mutagenic events linked to faulty DNA repair systems.

Over the past years, mutational signatures of cancer have been deduced from computational analyses. Some of these signatures could be associated with suspected mutagenic causes, such as the exposure to UV light for melanomas, or exposure to aflatoxin for liver cancer. However, the cause of the majority of these mutational signatures observed in cancer is not known. In most cases, it is unclear if there is a direct one-to-one relationship between the mutational signatures and a single mutagen. This paper reports that mutational signatures are due to a combination of factors, 'offending' DNA damaging agents and cellular policemen that properly do their job most of the time, but in some cases allow culprits to escape.

Genome-wide association studies (GWAS) analyse a genome-wide set of genetic variants in different individuals to see if any are associated with a trait or disease. Such studies are getting larger and larger and, in some cases, millions of participants are involved. This means that researchers can see smaller and smaller effects increasing the number of genes they can link to a disease or trait.

&laquoIt is good for us, because it allows us to understand much more about genetics influences our make-up, behaviour, and disease status, » says Dr Andrea Ganna, from the Institute for Molecular Medicine Finland, Helsinki, Finland, who will present his team's research to the 53rd annual conference of the European Society of Human Genetics, being held entirely on-line due to the Covid-19 pandemic, today [Monday]. &laquo But this good news comes with a downside. These large numbers mean that biases can creep in and affect our results. The most difficult of these to control is participation bias - when people who participate in a study are not from a random set but have something in common that is linked to their participation.

&laquoTo give an extreme example, if we were to use the participants in a professional basketball team to understand how tall or fit people are, the results would not be at all representative of the general population. But even low- level participation bias can skew results,» says Dr Ganna.

Recent studies looking at people who have participated more than once in a genetic study have shown a correlation with their level of educational attainment, for example. The researchers set out to characterise better what the consequences of this type of bias were. To do so, they needed a trait that they were certain was not determined genetically on the non-sexual chromosomes and about which they could be sure in advance that no association with those genes existed.
&laquoThe only area where we felt certain that genetics outside the sexual chromosomes was not involved was the genetic differences between males and females," commented co-author Dr Nicola Pirastu, from the University of Edinburgh, Edinburgh, United Kingdom. &laquoTherefore our analyses should have come out completely negative.»
The team carried out an association study of data from over three million individuals1 looking at which genetic variants showed differences in study participation frequencies between males and females. &laquoTo our surprise, we found over 150 loci with such differences. For example, we saw more body mass index-raising alleles2 among men than women, suggesting that genetically higher-weight women were less likely to participate in population studies than men. This can only have been related to differences in the characteristics that drive men and women to participate. And we saw a similar effect in different cohorts, which confirmed our hypothesis,» said Dr Pirastu.

These findings emphasise the importance of scientists' awareness of the necessity of careful study design and the meticulous choices of cases and controls when conducting genetic studies. In order to draw useful conclusions, the risk of participation bias should be minimised. If these kinds of bias exist in a study involving men and women, it will be far more difficult to distinguish between true results and those arising from biases when looking at disease. &laquoFor example, in the recent pandemic we know that those people who have been tested for Covid-19 were not chosen at random and share common characteristics, so making the right choice of controls to be used to understand if there are any genetic determinants involved is very important. I think our study shows what the risks are if this is not done,» says Dr Ganna.

At the moment, all the evidence is that participation biases are mild enough not to be a major problem. But it is important to take them into account when planning the collection of data from large cohorts and when data from participants is collected at multiple time points. Genotyping a random set of the population, for example, from the blood spots collected at birth, would be a good way of further verifying if these biases exist.
&laquoWe have shown that it would allow us to correct the statistical analyses. In addition, it would cost very little in comparison of what it has cost to date to create these studies. We really need to do this if we are to be able to draw the right conclusions from our analyses,» Dr Ganna will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Dean of the Biosciences Institute at Newcastle University, Newcastle upon Tyne, UK, said: "This fascinating study shows us how important it is to be aware of unexpected biases in participation in genetic association studies as well as other large scale 'population' studies, as this can significantly impact results if not properly corrected for."

An investigation into one of the current great mysteries of astronomy has come to the fore thanks to a four-year observing campaign conducted at the Jodrell Bank Observatory.

Using the long-term monitoring capabilities of the iconic Lovell Telescope, an international team led by Jodrell Bank astronomers has been studying an object known as a repeating Fast Radio Burst (FRB), which emits very short duration bright radio pulses.

Using the 32 bursts discovered during the campaign, in conjunction with data from previously published observations, the team has discovered that emission from the FRB known as 121102 follows a cyclic pattern, with radio bursts observed in a window lasting approximately 90 days followed by a silent period of 67 days. The same behaviour then repeats every 157 days.

This discovery provides an important clue to identifying the origin of these enigmatic fast radio bursts. The presence of a regular sequence in the burst activity could imply that the powerful bursts are linked to the orbital motion of a massive star, a neutron star or a black hole.

Dr Kaustubh Rajwade of The University of Manchester, who led the new research, said: "This is an exciting result as it is only the second system where we believe we see this modulation in burst activity. Detecting a periodicity provides an important constraint on the origin of the bursts and the activity cycles could argue against a precessing neutron star."

Repeating FRBs could be explained by the precession, like a wobbling top, of the magnetic axis of a highly magnetized neutron star but with current data scientists believe it may be hard to explain a 157-day precession period given the large magnetic fields expected in these stars.

The existence of FRBs was only discovered as recently as 2007 and they were initially thought to be one-off events related to a cataclysmic event such as an exploding star. This picture partly changed once FRB 121102, originally discovered with the Arecibo radio telescope on November 2 2012, was seen to repeat in 2016. However, until now, no one recognised that these bursts were in fact organised in a regular pattern.

Professor Benjamin Stappers, who leads the MeerTRAP project to hunt for FRBs using the MeerKAT telescope in South Africa said: "This result relied on the regular monitoring possible with the Lovell Telescope, and non-detections were just as important as the detections."

In a new paper published in Monthly Notices of the Royal Astronomical Society, the team confirm that FRB 121102 is only the second repeating source of FRBs to display such periodic activity. To their surprise, the timescale for this cycle is almost 10 times longer than the 16-day periodicity exhibited by the first repeating source, FRB 180916.J10158+56, which was recently discovered by the CHIME telescope in Canada.

"This exciting discovery highlights how little we know about the origin of FRBs," says Duncan Lorimer who serves as Associate Dean for Research at West Virginia University and, along with PhD student Devansh Agarwal, helped develop the data analysis technique that led to the discovery. "Further observations of a larger number of FRBs will be needed in order to obtain a clearer picture about these periodic sources and elucidate their origin," he added.

The first-ever detailed study of the diets of great white sharks off the east Australian coast reveals this apex predator spends more time feeding close to the seabed than expected.

"Within the sharks' stomachs we found remains from a variety of fish species that typically live on the seafloor or buried in the sand. This indicates the sharks must spend a good portion of their time foraging just above the seabed," said lead author Richard Grainger, a PhD candidate at the Charles Perkins Centre and School of Life and Environmental Sciences at the University of Sydney.

"The stereotype of a shark's dorsal fin above the surface as it hunts is probably not a very accurate picture," he said.

The study, published today on World Oceans Day in the journal Frontiers in Marine Science, is an important contribution towards understanding the sharks' feeding and migratory habits.

Dr Vic Peddemors a co-author from the NSW Department of Primary Industries (Fisheries), said: "We discovered that although mid-water fish, especially eastern Australian salmon, were the predominant prey for juvenile white sharks in NSW, stomach contents highlighted that these sharks also feed at or near the seabed."

Mr Grainger said: "This evidence matches data we have from tagging white sharks that shows them spending a lot of time many metres below the surface."

The study examined the stomach contents of 40 juvenile white sharks (Carcharodon carcharias) caught in the NSW Shark Meshing Program. The scientists compared this with published data elsewhere in the world, mainly South Africa, to establish a nutritional framework for the species.

"Understanding the nutritional goals of these cryptic predators and how these relate to migration patterns will give insights into what drives human-shark conflict and how we can best protect this species," said Dr Gabriel Machovsky-Capuska, an adjunct Senior Research Fellow at the Charles Perkins Centre and a co-author of the study.

Mr Grainger said: "White sharks have a varied diet. As well as east Australian salmon, we found evidence of other bony fish including eels, whiting, mullet and wrasses. We found that rays were also an important dietary component, including small bottom-dwelling stingrays and electric rays.

"Eagle rays are also hunted, although this can be difficult for the sharks given how fast the rays can swim."

The study found that based on abundance, the sharks' diet relied mostly on:

- Pelagic, or mid-water ocean swimming fish, such as Australian salmon: 32.2%

- Bottom-dwelling fish, such as stargazers, sole or flathead: 17.4%

- Reef fish, such as eastern blue gropers: 5.0%

- Batoid fish, such as stingrays: 14.9%

The remainder was unidentified fish or less abundant prey. Mr Grainger said that marine mammals, other sharks and cephalopods (squid and cuttlefish) were eaten less frequently.

"The hunting of bigger prey, including other sharks and marine mammals such as dolphin, is not likely to happen until the sharks reach about 2.2 metres in length," Mr Grainger said.

The scientists also found that larger sharks tended to have a diet that was higher in fat, likely due to their high energy needs for migration.

"This fits with a lot of other research we've done showing that wild animals, including predators, select diets precisely balanced to meet their nutrient needs," said co-author Professor David Raubenheimer, Chair of Nutritional Ecology in the School of Life and Environmental Sciences.

Tracking of white sharks shows that they migrate seasonally along Australia's east coast from southern Queensland to northern Tasmania, and the range of movement increases with age.

Protecting this species and safely managing its interactions with humans is a priority for scientists and the NSW Department of Primary Industries.

"This study will give us a lot of information to assist in this management process," Dr Peddemors said.

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inherited disorder that begins in childhood and adolescence. Various defects in the enzyme alanine-glyoxylate aminotransferase cause an overproduction of oxalate in the liver, which is excreted in the urine (hyperoxaluria). It leads to the formation of recurrent kidney stones, renal calcification (nephrocalcinosis) and kidney injury, even kidney failure; many such patients require dialysis even before they reach adulthood. It can be managed prophylactically by drinking large amounts of fluids (2-3 litres), but this is not tolerated by smaller children, especially. Hardly any effective therapies have been available so far. In some patients, the administration of vitamin B6 (pyridoxine) can reduce oxalate excretion. Another basic therapy is to administer alkali citrate, as this improves the solubility of oxalate in urine, but no currently available treatment addresses the cause of the disease.

Lumasiran, a subcutaneously administered investigational RNAi therapeutic, could close that gap. RNA interference (RNAi) is a natural biological gene silencing mechanism. Lumasiran silences the HAO1 gene that encodes the liver enzyme GO, thereby inhibiting hepatic production of oxalate - the metabolite that directly contributes to the clinical manifestations of PH1.

At the ERA-EDTA Congress today, the results of a randomized, double-blind, placebo-controlled Phase 3 study were presented. 39 patients (age?6 years, 24hr urinary oxalate (UOx)?0.70 mmol/24hr/1.73 m2, confirmed PH1 diagnosis, eGFR?30 mL/min/1.73 m2) were randomized (2:1) and received either the investigational RNAi therapeutic or placebo once a month for 3 months followed by dosing once every 3 months. Lumasiran led to a statistically significant percent reduction in 24hr UOx excretion compared to placebo: the LS mean change from baseline after 6 months was -65.4% with lumasiran and -11.8% with placebo (LS mean difference: ?53.5%; p=1.7×10?14). Lumasiran treatment also resulted in a majority of patients achieving near-normalization (84%) or normalization (52%) of urinary oxalate (versus 0% of those treated with placebo), and reductions in mean plasma oxalate relative to placebo. The most common adverse events related to lumasiran were injection-site reactions, all of which were mild and transient; no severe or serious adverse events were reported.

"Lumasiran resulted in rapid, sustained, and statistically significant reductions in urinary and plasma oxalate levels and had an encouraging safety profile", concluded Sander Garrelfs from the Emma Children's Hospital, Amsterdam UMC, University of Amsterdam.

"We were very impressed by these results", added Maria Jose Soler Romeo, Chair of the Paper Selection Committee of the 2020 ERA-EDTA Congress. "It is now necessary to demonstrate that the drug not only reduces the overproduction of oxalate effectively, but can also prevent long-term injury to the kidneys. If that is the case, we will finally have a treatment for children and young people who are affected by this rare disease that prevents them from needing dialysis."

A group of Japanese scientists has developed an ultrastable, selective catalyst to dehydrogenate propane - an essential process to produce the key petrochemical substance of propylene - without deactivation, even at temperatures of more than 600°C.

Propylene is an important raw material for plastics, synthetic rubber, surfactants, dyes and pharmaceuticals. In recent years, there has been an increased demand for propylene produced from cheaper, shale-originated propane. Reaction temperatures of more than 600°C are necessary to obtain sufficient propylene yields, but under these harsh conditions, severe catalyst deactivation is inevitable due to carbon deposition and/or sintering. Catalysts in practical use, therefore, must be regenerated either continuously or in short cycles, making the process inefficient and costly.

In the present study, the group, including a master's student Yuki Nakaya and Associate Professor Shinya Furukawa at Hokkaido University's Institute for Catalysis, focused on the intermetallics (PtGa) of platinum (Pt) and gallium (Ga), which have unique properties and structures. PtGa has a high thermal stability and its structure does not change even under high temperatures. It is also known to have two kinds of catalytic sites on its surface: a site with three Pt atoms (Pt3 site) and one with single-atom-like isolated Pt (Pt1 site).

The group hypothesized that if the Pt3 sites - which facilitates carbon deposition in addition to producing propylene - is disabled to allow only the Pt1 sites to function, the catalyst will be ultrastable and also able to prevent carbon deposition. The group tried various metals and catalyst synthesis methods to make only the Pt1 site function.

The newly developed catalyst (PtGa-Pb/SiO2), which is silica-supported and made by adding lead (Pb) to the surface of PtGa, exhibits no deactivation when dehydrogenating propane at 600°C. The catalyst maintained the initial conversion rate of 30 percent for 96 hours after the reaction started, which is significantly more stable than conventional catalysts. Propylene selectivity is as high as 99.6 percent with few side reactions, including carbon deposition. The results showed that this catalyst produces the world's best performance at temperatures of 580°C or higher. In particular, its life span is more than twice as long as the previous reported record longevity for such catalysts. Furthermore, the catalyst can be produced as cheaply as conventional catalysts. Their structural analysis confirmed Pt3 sites, not Pt1 sites, were covered and disabled by Pb, as they expected.

"Our finding could lead to a more efficient and cheaper industrial process to produce propylene from propane without the need for catalyst regeneration - which is far superior in selectivity and stability than conventional ones," says Furukawa. "Moreover, this method could be applicable to dehydrogenation of other lower alkanes such as ethane and isobutane, thus contributing to the petrochemical industry's development."