A research team led by Professor Yong-Tae Kim from the Department of Materials Science and Engineering at Pohang University of Science and Technology (POSTECH), in collaboration with Professor Kyu-Young Park from the Graduate Institute of Ferrous & Eco Materials Technology and the Department of Materials Science and Engineering at POSTECH, and the research team of Dr. Woochul Jung from the Research Institute of Industrial Science and Technology (RIST), has discovered that the purity specifications for cathode materials, as set by cell manufacturers, are overly stringent. Their research demonstrates that streamlining the lithium refining process could substantially reduce the unit cost of batteries. The research findings are published in ‘Nature Communications’, one of international scientific journals.

In this research, the team delved into the impact of lithium raw material purity on the production and performance of secondary battery cathode materials. Conventionally, it’s assumed that impurities in lithium materials hamper secondary battery performance. Therefore, the goal is to manufacture lithium materials with purity of at least 99.5%. Nevertheless, the team uncovered that the presence of approximately 1% magnesium (Mg) impurity in the lithium raw material actually enhances process efficiency and prolongs the secondary battery’s lifespan. Through their experiments, they demonstrated that utilizing low-purity lithium, not entirely rid of impurities, could reduce secondary battery production costs and carbon dioxide emissions by up to 19.4% and 9.0%, respectively.

Professor Yong-Tae Kim who led the research stated, ” Secondary battery cell manufacturers need to reassess whether their current cathode material specifications are too stringent.” He further remarked, “Considering unconventional approaches could offer a fresh strategy against China’s aggressively low prices.”

In mammals, social behaviour and social status can substantially influence the survival, reproductive performance and health of individuals. However, it is not yet fully understood how the translation of social and environmental factors into the physiology of an organism is reflected in molecular processes. Now, scientists from the Leibniz-IZW Department of Evolutionary Genetics and the Serengeti Hyena Project at the Leibniz-IZW’s Department of Ecological Dynamics found that social status influenced epigenetic patterns, more specifically the methylation of DNA in both young and adult female spotted hyenas (Crocuta crocuta) which determines the activation of genes. They analysed DNA from gut epithelium cells from 18 adult female hyenas and 24 cubs with known social status from three clans in the Serengeti National Park, Tanzania. The scientists identified and validated 149 genome regions, where high-ranking and low-ranking individuals differed in the methylation of DNA (differentially methylated regions, DMRs). “We could, for the first time, provide evidence for epigenetic signatures of social inequalities in both young and adult spotted hyenas,” says Dr Alexandra Weyrich, head of the working group “Wildlife Epigenetics” in the Leibniz-IZW Department of Evolutionary Genetics and senior author of the paper.

The findings show that these epigenetic signatures are stable across life stages — and that they are linked to important physiological processes: Many of the identified DMRs were involved in the regulation of energy conversion, immune response, glutamate receptor signalling and ion transportation. “Especially the large number of DMRs in genes involved in energy conversion caught our eye,” says first author Colin Vullioud, data scientist in Weyrich’s working group. Co-author Dr Sarah Benhaiem, co-head of the Serengeti Hyena Project, explains: “We suspect that this may be driven by differences in behaviour and specifically the greater use of long-distance foraging trips by low-ranking than high-ranking females — the latter monopolising resources in their clan territory.” Interestingly, these genes were more methylated (or hypermethylated) in low-ranking adult females but not in cubs. This could indicate an adjustment of low-ranking adult females to higher energetic costs of frequent long-distance commuting, a behaviour not displayed by cubs. “Although the exact physiological consequences of the observed hypermethylation remain to be investigated, these findings are consistent with our observations and hint at the sought-after missing link between social and physiological factors,” Weyrich and Benhaiem conclude.

The analyses built on the expertise in epigenetics of the Leibniz-IZW as well as on the long-term research on spotted hyenas in the Serengeti, which started in 1987. The females in this investigation are individually known and their social status has been tracked for generations. This provided ideal conditions to study the links between behaviour, physiological factors, epigenetic modifications and fitness in terms of survival and reproduction in a wild population. “We collected our samples without invading the life of the hyenas,” say Dr Marion L. East and Professor Dr Heribert Hofer, founders of the Serengeti hyena project and co-authors of the paper. “We followed our study animals, collected super-fresh droppings immediately after they were produced and preserved gut epithelium samples from the surface of the faeces.” The use of samples collected in a non-invasive manner is one of the strengths of the investigation, the authors surmise. “The capture methylation method we used enriches methylated DNA as well as mammalian DNA, which improved the amount of hyena DNA over bacterial DNA and the quality of the sequencing data,” explains Weyrich.

DNA methylation is a chemical modification of the basic building blocks of a cell’s genetic material. This modification is enabled by the transfer of methyl groups to nucleobases at certain positions in the DNA. As the basic structure of the respective nucleobase is unaltered, DNA methylation is not a genetic mutation, but a modification which determines whether this part of the DNA is ‘being used’ (activated) or switched off. DNA methylation is the most important epigenetic modification and thus a pivotal part of making genetic information available to the physiological processes within a cell.

Spotted hyenas are highly social and a model for social status-related differences in life history traits that are accompanied by differences in physiological processes and health. In hyena clans, females and their offspring socially dominate all immigrant males, and social status is behaviourally “inherited” by cubs from mothers who gain privileges associated with maternal social status. “As in some primate species, young hyenas receive social support from their mothers during interactions with group members. From these they learn that they can dominate all individuals which are submissive to their mother, but have to submit to those which their mother is submissive to,” explains East. Therefore, social status is stable and predictable because it is determined by family relationships and behavioural conventions.

“Additionally, the effects of social status on life history trajectories and health are typically passed across generations,” adds Hofer. For example, high-ranking females have priority access to resources in the clan territory and do not need to commute as much as low-ranking females to find food. They are therefore much more often present at the communal den and more frequently nurse their young. The milk-dependent cubs disproportionally benefit at this early stage in their life — by growing faster, having a higher chance of surviving to adulthood and starting reproduction at an earlier age than the offspring of low-ranking females.

Researchers from the Wellcome Sanger Institute, and their collaborators at the University of Exeter and the University of Cambridge, were able to reassess genetic data from nearly 10,000 families from the Deciphering Developmental Disorders study.

In a new study, recently published in Genetics in Medicine, they show for the first time that using exome sequencing — which reads only protein-coding DNA — is as accurate, if not better, than standard microarrays at identifying disease-causing structural genetic variations.

Its adoption offers hope for faster and more accurate diagnoses of rare genetic diseases. It could also deliver substantial cost savings for the NHS, though more training is needed for specialists to generate and analyse the data, say researchers.

Changes in our genetic code can range from single letter changes to the deletion or duplication of larger stretches of DNA. These bigger changes — called copy number variations (CNVs) — can be harder for clinical teams to detect in sequencing data and understand, which is why microarrays are used. While usually harmless, making up one of the major sources of genetic diversity in humans, these large-scale variations can sometimes cause various neurodevelopmental disorders, including Angelman syndrome, DiGeorge syndrome, and Williams-Beuren syndrome.

Currently, children suspected to have genetic diseases arising from these large deletions or duplications of DNA go through a lengthy process of testing and waiting for results from multiple diagnostic approaches, starting with a microarray test before progressing to a broader genome-wide sequencing test (such as exome or genome sequencing). In this new study, scientists set out to develop a single approach to detect these structural changes, using data available from genome-wide exome sequencing assays.

Using data from the Deciphering Developmental Disorders study, the team developed a single-assay approach that combined four algorithms using machine learning methods to analyse exome sequencing data.

Comparison of the new single-assay approach with current standard clinical methods revealed it could reliably detect 305 large-scale pathogenic mutations, including 91 not previously detectable using standard clinical microarrays. The findings suggest it could replace the current methods.

Caroline Wright, Professor of Genomic Medicine at the University of Exeter, and author of the study, said: “Using exome sequencing data to detect clinically important large-scale changes, at the same time as small genetic variants, marks a significant step forward in making genetic testing simpler, cheaper and more accessible.”

Helen Firth, Professor of Clinical Genomics at the University of Cambridge, lead clinician and author of the study, said: “Under the current system, children often endure a lengthy, step-wise process of different genetic tests before reaching a diagnosis. This research brings hope that, in the near future, families might only need one test.”

Professor Matthew Hurles, Director of the Wellcome Sanger Institute and senior author of the study, said: “We are still learning how large-scale genetic variations impact human health. This study proves that with the right computational methods, a single test can accurately detect them. Our findings support its widespread adoption in NHS clinical practice, and the adequate bioinformatics training to support this.”

Led by researchers from NYU Grossman School of Medicine, the study revolves around brain cells called neurons that “fire” — or bring about swings in the balance of their positive and negative charges — to transmit electrical signals that encode memories. Large groups of neurons in a brain region called the hippocampus fire together in rhythmic cycles, creating sequences of signals within milliseconds of each other that can encode complex information.

Called “sharp wave-ripples,” these “shouts” to the rest of the brain represent the near-simultaneous firing of 15 percent of hippocampal neurons, and are named for the shape they take when their activity is captured by electrodes and recorded on a graph.

While past studies had linked ripples with memory formation during sleep, the new study, published online in the journal Science on March 28, found that daytime events followed immediately by five to 20 sharp wave-ripples are replayed more during sleep and so consolidated into permanent memories. Events followed by very few or no sharp wave-ripples failed to form lasting memories.

“Our study finds that sharp wave-ripples are the physiological mechanism used by the brain to ‘decide’ what to keep and what to discard,” said senior study author György Buzsáki, MD, PhD, the Biggs Professor of Neuroscience in the Department of Neuroscience and Physiology at NYU Langone Health.

Walk and Pause

The new study is based on a known pattern: mammals including humans experience the world for a few moments, then pause, then experience a little more, then pause again. After we pay attention to something, say the study authors, brain computation often switches into an “idle” re-assessment mode. Such momentary pauses occur throughout the day, but the longest idling periods occur during sleep.

Buzsaki and colleagues had previously established that no sharp wave-ripples occur as we actively explore sensory information or move, but only during the idle pauses before or after. The current study found that sharp wave-ripples represent the natural tagging mechanism during such pauses after waking experiences, with the tagged neuronal patterns reactivated during post-task sleep.

Importantly, sharp wave-ripples are known to be made up the firing of hippocampal “place cells” in a specific order that encodes every room we enter, and each arm of a maze entered by a mouse. For memories that are remembered, those same cells fire at high speed, as we sleep, “playing back the recorded event thousands times per night.” The process strengthens the connections between the cells involved.

For the current study, successive maze runs by study mice were tracked via electrodes by populations of hippocampal cells that constantly changed over time despite recording very similar experiences. This revealed for the first time the maze runs during which ripples occurred during waking pauses, and then were replayed during sleep.

Sharp wave-ripples were typically recorded when a mouse paused to enjoy a sugary treat after each maze run. The consumption of the reward, say the authors, prepared the brain to switch from an exploratory to an idle pattern so that sharp wave-ripples could occur.

Using dual-sided silicon probes, the research team was able to record up to 500 neurons simultaneously in the hippocampus of animals during maze runs. This in turn created a challenge because data becomes exceedingly complex the more neurons are independently recorded. To gain an intuitive understanding of the data, visualize neuronal activity, and form hypotheses, the team successfully reduced the number of dimensions in the data, in some ways like converting a three-dimensional image into a flat one, and without losing the data’s integrity.

“We worked to take the external world out of the equation, and looked at the mechanisms by which the mammalian brain innately and subconsciously tags some memories to become permanent,” said first author Wannan (Winnie) Yang, PhD, a graduate student in Buzsáki’s lab. “Why such a system evolved is still a mystery, but future research may reveal devices or therapies that can adjust sharp wave-ripples to improve memory, or even lessen recall of traumatic events.”

Along with Drs. Buzsáki and Yang, study authors from the Neuroscience Institute at NYU Langone Health were Roman Huszár and Thomas Hainmueller. Kirill Kiselev of the Center for Neural Science at New York University was also an author, as was Chen Sun of Mila, the Quebec Artificial Intelligence Institute, in Montréal. The work was supported by National Institute of Health grants R01MH122391 and U19NS107616.

The experts addressed setting standards for three key indoor pollutants — carbon dioxide (CO₂), carbon monoxide (CO), PM2.5 which are particles so small they can lodge deep in the lungs and enter the bloodstream — and ventilation rate.

Distinguished Professor Morawska, from the QUT School of Earth and Atmospheric Sciences, internationally known, among others, for leading the appeal to the WHO to recognise the airborne transmission spread of the Covid-19 virus early in the pandemic, has continued to raise the importance of adequate indoor air quality for public spaces.

“Most countries do not have any legislated indoor air quality (IAQ) performance standards for public spaces that address concentration levels of IA pollutants,” Professor Morawska said.

“To have practical value, IAQ standards must be implementable by designing new buildings that are built, operated and maintained to standard or retrofitted to meet the standards.

“While there is a cost in the short term, the social and economic benefits to public health, wellbeing and productivity will likely far outweigh the investment in cost in achieving clean indoor air.”

Professor Morawska said CO₂ sensors were readily available, inexpensive and robust and should be used as a proxy to measure pathogens and CO₂ during human occupancy in a public space.

“CO₂ can serve as a proxy for occupant-emitted contaminants and pathogens and to effectively assess ventilation quality,” she said.

“We propose a CO₂ concentration level of 800ppm with the proviso that outdoor concentration is used as a baseline and recognition of the fact that outdoor concentrations are increasing due to emissions to the atmosphere that outweigh removal.

“Another key indicator of air quality we addressed is the amount of PM2.5 and we propose the WHO air quality guidelines as a basis for indoor air quality standards but with a 1-hour averaging time, as the 24 hours of the WHO AQG is much longer than people usually spend in public places.”

Professor Morawska said mechanical ventilation systems should remove and dilute human-emitted and other indoor-generated pollutants at a higher rate than their production so that they would not accumulate in indoor air.

“The technologies for measuring ventilation already exist in most modern mechanically ventilated buildings but monitoring ventilation rates in terms of clean air delivered to the space requires us to consider the number of people and their activities in the space to ensure adequate IAQ.

“A practical ventilation standard could be air from outside (assumed to be clean), or clean recirculated air to the entire occupied zone and with airflow not directed from one person to another.

“Additional measures in support of ventilation, such as air cleaning and disinfection, could greatly reduce the need to increase the outdoor air supply, which carries a heavy energy demand.

“Filtering recirculated air is an effective way to reduce concentration of, and thus our exposure to, airborne particulate matter, allergens and pathogens.”

The research, led by the University of Cambridge and Penn State University, improves prospects for the elimination and control of bovine tuberculosis (TB), an infectious disease of cattle that results in large economic costs and health impacts across the world.

This is the first study to show that BCG-vaccinated cattle infected with TB are substantially less infectious to other cattle. This remarkable indirect effect of the vaccine beyond its direct protective effect has not been measured before.

The spillover of infection from livestock has been estimated to account for about 10% of human tuberculosis cases. While such zoonotic TB (zTB) infections are most commonly associated with gastro-intestinal infections related to drinking contaminated milk, zTB can also cause chronic lung infections in humans. Lung disease caused by zTB can be indistinguishable from regular tuberculosis, but is more difficult to treat due to natural antibiotic resistance in the cattle bacteria.

TB remains endemic in many countries around the world, including in Europe and the Americas, where its control costs farmers and taxpayers hundreds of millions of dollars each year.

The study is published today in the journal Science.

In the study, carried out in Ethiopia, researchers examined the ability of the vaccine, Bacillus Calmette-Guérin (BCG), to directly protect cattle that receive it, as well as to indirectly protect both vaccinated and unvaccinated cattle by reducing TB transmission. Vaccinated and unvaccinated animals were put into enclosures with naturally infected animals, in a novel crossover design performed over two years.

“Our study found that BCG vaccination reduces TB transmission in cattle by almost 90%. Vaccinated cows also developed significantly fewer visible signs of TB than unvaccinated ones. This suggests that the vaccination not only reduces the progression of the disease, but that if vaccinated animals become infected, they are substantially less infectious to others,” said Andrew Conlan, Associate Professor of Epidemiology at the University of Cambridge’s Department of Veterinary Medicine and a corresponding author of the study.

Using livestock census and movement data from Ethiopia, the team developed a transmission model to explore the potential for routine vaccination to control bovine tuberculosis.

“Results of the model suggest that vaccinating calves within the dairy sector of Ethiopia could reduce the reproduction number of the bacterium — the R₀ — to below 1, arresting the projected increase in the burden of disease and putting herds on a pathway towards elimination of TB,” Conlan said.

The team focused their studies in Ethiopia, a country with the largest cattle herd in Africa and a rapidly growing dairy sector that has a growing burden of bovine tuberculosis and no current control program, as a representative of similarly situated transitional economies.

“Bovine tuberculosis is largely uncontrolled in low- and middle-income countries, including Ethiopia,” said Abebe Fromsa, associate professor of agriculture and veterinary medicine at Addis Ababa University in Ethiopia and the study’s co-lead author. “Vaccination of cattle has the potential to provide significant benefits in these regions.”

“For over a hundred years, programs to eliminate bovine tuberculosis have relied on intensive testing and slaughtering of infected animals,” said Vivek Kapur, professor of microbiology and infectious diseases and Huck Distinguished Chair in Global Health at Penn State and a corresponding author of the study.

He added: “This approach is unimplementable in many parts of the world for economic and social reasons, resulting in considerable animal suffering and economic losses from lost productivity, alongside an increased risk of spillover of infection to humans. By vaccinating cattle, we hope to be able to protect both cattle and humans from the consequences of this devastating disease.”

Professor James Wood, Alborada Professor of Equine and Farm Animal Science in the University of Cambridge’s Department of Veterinary Medicine, noted that despite TB being more prevalent in lower-income countries, the United Kingdom, Ireland and New Zealand also experience considerable economic pressures from the disease which continues to persist despite intensive and costly control programmes.

Wood said: “For over twenty-years the UK government has pinned hopes on cattle vaccination for bovine tuberculosis as a solution to reduce the disease and the consequent costs of the controls. These results provide important support for the epidemiological benefit that cattle vaccination could have to reduce rates of transmission to and within herds.”

Their report, which will appear in Science, shows that an alternative medication, a viral papain-like protease inhibitor, inhibits disease progression in animals, a necessary step before human drug trials.

“COVID-19 remains the nation’s third leading cause of death, so there’s already a massive need for additional treatment options,” said Jun Wang, senior author of the study and an associate professor who runs a research lab at Rutgers’ Ernest Mario School of Pharmacy. “That need will grow more urgent when, inevitably, COVID-19 mutates in ways that prevent Paxlovid from working.”

The Rutgers team hoped to make a drug that interfered with viral papain-like protease (PLpro), a protein that performs important functions in all known strains of COVID-19.

Creating such a drug required detailed information about PLpro’s structure, which Wang’s team got from the Arnold Lab at Rutgers’ Center for Advanced Biotechnology and Medicine (CABM).

Precise knowledge of PLpro’s structure enabled Wang’s team to design and synthesize 85 drug candidates that would bond to – and interfere with — this vital protein.

“The PLpro crystal structures showed an unexpected arrangement of how the drug candidate molecules bind to its protein target, leading to innovative design ideas implemented by professor Wang’s medicinal chemistry team,” said Eddy Arnold, who is a professor at CABM and the Rutgers Department of Chemistry and Chemical Biology.

Laboratory testing established that the most effective of those drug candidates, a compound dubbed Jun12682, inhibited several strains of the SARS-CoV-2 virus, including strains that resist treatment with Paxlovid.

Subsequent testing on SARS-CoV-2-infected mice by the Deng lab at Oklahoma State University showed that oral treatment with Jun12682 reduced viral lung loads and lesions while improving survival rates.

“Our treatment was about as effective in mice as Paxlovid was in its initial animal tests,” said Wang, who added the experimental drug appears to have at least one major advantage over the older drug.

“Paxlovid interferes with many prescription medications, and most people who face the highest risk of severe COVID-19 take other prescription medicines, so it’s a real problem,” Wang said. “We tested our candidate Jun12682 against major drug-metabolizing enzymes and saw no evidence that it would interfere with other medications.”

Disclosure: Rutgers has submitted patent applications for Jun12682, along with the other 84 drug candidates, and is looking for partners to help move the drug candidate forward through further stages of testing and development.