Culture

In February 2020, a trio of bio-imaging experts were sitting amiably around a dinner table at a scientific conference in Washington, D.C., when the conversation shifted to what was then a worrying viral epidemic in China. Without foreseeing the global disaster to come, they wondered aloud how they might contribute.

Nearly a year and a half later, those three scientists and their many collaborators across three national laboratories have published a comprehensive study in Biophysical Journal that - alongside other recent, complementary studies of coronavirus proteins and genetics - represents the first step toward developing treatments for that viral infection, now seared into the global consciousness as COVID-19.

Their foundational work focused on the protein-based machine that enables the SARS-CoV-2 virus to hijack our own cells' molecular machinery in order to replicate inside our bodies.

From structure to function to solutions

"It has been remarked that all organisms are just a means for DNA to make copies of itself, and nowhere is this truer than in the case of a virus," said Greg Hura, a staff scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) and one of the study's lead authors. "A virus's singular task is to make copies of its genetic material - unfortunately, at our expense."

Viruses and mammals, including humans, have been stuck in this battle for millions of years, he added, and over that time the viruses have evolved many tricks to get their genes copied inside us, while our bodies have evolved counter defenses. And although viruses often perform a long list of other activities, their ability to harm us with an infection really does come down to whether or not they can replicate their genetic material (either RNA or DNA, depending on the species) to make more viral particles, and use our cells to translate their genetic code into proteins.

The protein-based machine responsible for RNA replication and translation in coronaviruses - and many other viruses - is called the RNA transcription complex (RTC), and it is a truly formidable piece of biological weaponry.

To successfully duplicate viral RNA for new virus particles and produce the new particles' many proteins, the RTC must: distinguish between viral and host RNA, recognize and pair RNA bases instead of highly similar DNA bases that are also abundant in human cells, convert their RNA into mRNA (to dupe human ribosomes into translating viral proteins), interface with copy error-checking molecules, and transcribe specific sections of viral RNA to amplify certain proteins over others depending on need - while at all times trying to evade the host immune system that will recognize it as a foreign protein.

As astounding as this sounds, any newly evolved virus that is successful "must have machines that are incredibly sophisticated to overcome mechanisms we have evolved," explained Hura, who heads the Structural Biology department in Berkeley Lab's Molecular Biophysics and Integrated Bioimaging Division.

He and the other study leads - Andrzej Joachimiak of Argonne National Laboratory and Hugh M. O'Neill at Oak Ridge National Laboratory - specialize in revealing the atomic structure of proteins in order to understand how they work at the molecular level. So, the trio knew from the moment they first discussed COVID-19 at the dinner table that studying the RTC would be particularly challenging because multitasking protein machines like the RTC aren't static or rigid, as molecular diagrams or ball-and-stick models might suggest. They're flexible and have associated molecules, called nonstructural and accessory proteins (Nsps), that exist in a multitude of rapidly rearranging forms depending on the task at hand - akin to how a gear shifter on a bike quickly adapts the vehicle to changing terrain.

Each of these Nsp arrangements give insights into the protein's different activities, and they also expose different parts of the overall RTC surface, which can be examined to find places where potential drug molecules could bind and inhibit the entire machine.

So, following their serendipitous convergence in Washington, the trio hatched a plan to pool their knowledge and national lab resources in order to document the structure of as many RTC arrangements as possible, and identify how these forms interact with other viral and human molecules.

Science during shutdowns

The investigation hinged on combining data collected from many advanced imaging techniques, as no approach by itself can generate complete, atomic-level blueprints of infectious proteins in their natural states. They combined small-angle X-ray scattering (SAXS), X-ray crystallography, and small-angle neutron scattering (SANS) performed at Berkeley Lab's Advanced Light Source, Argonne's Advanced Photon Source, and Oak Ridge's High Flux Isotope Reactor and Spallation Neutron Source, respectively, on samples of biosynthetically produced RTC.

Despite the extraordinary hurdles of conducting science during shelter-in-place conditions, the collaboration was able to work continuously for more than 15 months, thanks to funding for research and facility operations support from the Department of Energy's Office of Science National Virtual Biotechnology Laboratory (NVBL). During that time, the scientists collected detailed data on the RTC's key accessory proteins and their interactions with RNA. All of their findings were uploaded into the open-access Protein Data Bank prior to the journal article's publication.

Of the many structural findings that will help with drug design, one notable discovery is that assembly of the RTC subunits is incredibly precise. Drawing on a mechanical metaphor once more, the scientists compare the assembly process to putting together a spring-based machine. You can't put a spring in place when the rest of the machine is already in position, you must compress and place the spring at a specific step of assembly or the whole device is dysfunctional. Similarly, the RTC Nsps can't move into place in any random or chaotic order; they must follow a specific order of operations.

They also identified how one of the Nsps specifically recognizes the RNA molecules it acts upon, and how it cuts long strands of copied RNA into their correct lengths.

"Having the vaccines is certainly huge. However, why are we satisfied with just this one avenue of defense?" said Hura. Added Joachimiak: "This was a survey study, and it has identified many directions we and others should pursue very deeply; to tackle this virus we will need multiple ways of blocking its proliferation."

"Combining information from different structural techniques and computation will be key to achieving this goal," said O'Neill.

Due to the similarity of RTC proteins across viral strains, the team believe that any drugs developed to block RTC activity could work for multiple viral infections in addition to all COVID-19 variants.

Reflecting back to the beginning of their research journey, the scientists marvel at the lucky timing of it all. When we started to talk, said Hura, "we had no idea that this epidemic would soon become a pandemic that would change a generation."

African swine fever (ASF), first detected in Germany in domestic pigs on 15 July 2021, does not pose a health hazard to humans. "The ASF pathogen cannot be transferred to humans", explains Professor Dr. Dr. Andreas Hensel, President of the German Federal Institute for Risk Assessment (BfR). "No risk to health is posed by direct contact with diseased animals or from eating food made from infected domestic pigs or wild boar".

The ASF pathogen is a virus which infects domestic pigs and wild boar and which leads to a severe, often lethal, disease in these animals. It is transferred via direct contact or with excretions from infected animals, or through ticks. The ASF virus is endemic to infected wild animals in Africa, but there have also repeatedly been outbreaks in southern Europe. The pathogen has been spreading north-westwards since 2007 from Georgia through Armenia, Azerbaijan and Russia. Cases of ASF have been registered in wild boar along with outbreaks in domestic pigs in the Baltic states since 2014. The virus has also been detected in Romania, Hungary, Poland and the Czech Republic. In September 2018, the pathogen was also found in wild boars in Belgium and thus for the first time in Western Europe. On 10 September 2020, the ASF virus has been detected for the first time in Germany in a wild boar in Brandenburg. The first cases of ASF in domestic pigs in Germany were detected in two pig farms in Brandenburg on 15 July 2021.

The pathogen is very stable and can remain infectious in food over several months. If unheated food or food scraps from infected animals are fed to non-infected animals, the virus can therefore spread to previously ASF-free regions, thus infecting domestic pig herds too.

Although the ASF virus does not pose a hazard or a risk to humans, the meat of domestic pigs and wild boar should always be prepared under hygienic conditions, just like all other raw meats, as it can also contain other pathogens, advises the BfR. It should be kept refrigerated and prepared separately from other foods before cooking. When heating, a temperature of 70 degrees Celsius or higher should be reached at all parts of the food for at least two minutes, the BfR recommends.

The BfR has compiled some frequently asked questions about ASF for further information. They can be downloaded on the BfR website.

https://www.bfr.bund.de/en/frequently_asked_questions_about_african_swine_fever__asf_-205379.html

A coronavirus related to the virus that causes Covid-19 in humans has been found in UK horseshoe bats - according to new collaborative research from the University of East Anglia, ZSL (Zoological Society of London), and Public Health England (PHE).

However, there is no evidence that this novel virus has been transmitted to humans, or that it could in future, unless it mutates.

UEA researchers collected faecal samples from more than 50 lesser horseshoe bats in Somerset, Gloucestershire and Wales and sent them for viral analysis at Public Health England.

Genome sequencing found a novel coronavirus in one of the bat samples, which the team have named 'RhGB01'.

It is the first time that a sarbecovirus (SARS-related coronavirus) has been found in a lesser horseshoe bat and the first to be discovered in the UK.

The research team say that these bats will almost certainly have harboured the virus for a very long time. And it has been found now, because this is the first time that they have been tested.

Importantly, this novel virus is unlikely to pose a direct risk to humans, unless it mutates.

A mutation could happen if a human infected with Covid-19 passes it to an infected bat, so
anyone coming into contact with bats or their droppings, for example those engaged in caving or bat protection, should wear appropriate PPE.

Prof Diana Bell, an expert in emerging zoonotic diseases from UEA's School of Biological Sciences, said: "Horseshoe bats are found across Europe, Africa, Asia and Australia and the bats we tested lie at the western extreme of their range.

"Similar viruses have been found in other horseshoe bat species in China, South East Asia and Eastern Europe.

"Our research extends both the geographic and species ranges of these types of viruses and suggests their more widespread presence across more than 90 species of horseshoe bats.

"These bats will almost certainly have harboured this virus for a very long time - probably many thousands of years. We didn't know about it before because this is the first time that such tests have been carried out in UK bats.

"We already know that there are different coronaviruses in many other mammal species too," she said. "This is a case of 'seek and you will find'.

"Research into the origins of SARS-CoV-2, the virus that causes Covid-19 in humans, has focussed on horseshoe bats - but there are some 1,400 other bat species and they comprise 20 per cent of known mammals.

"Our findings highlight the need for robust genotype testing for these types of viruses in bat populations around the world. And it raises an important question about what other animals carry these types of viruses."

Prof Andrew Cunningham, from the Zoological Society of London, said: "Our findings highlight that the natural distribution of sarbecoviruses and opportunities for recombination through intermediate host co-infection have been underestimated.

"This UK virus is not a threat to humans because the receptor binding domain (RBD) - the part of the virus that attaches to host cells to infect them - is not compatible with being able to infect human cells.

"But the problem is that any bat harbouring a SARS-like coronavirus can act as a melting pot for virus mutation. So if a bat with the RhGB01 infection we found were to become infected with SARS-CoV-2, there is a risk that these viruses would hybridise and a new virus emerge with the RBD of SARS-CoV-2, and so be able to infect people.

"Preventing transmission of SARS-CoV-2 from humans to bats, and hence reducing opportunities for virus mutation, is critical with the current global mass vaccination campaign against this virus."

Prof Bell added: "The main risks would be for example a bat rehabilitator looking after a rescued animal and infecting it with SARS-CoV2 - which would provide an opportunity for genetic recombination if it is already carrying another sarbecovirus.

"Anyone coming into contact with bats or their droppings, such as bat rescuers or cavers, should wear appropriate PPE - in order to reduce the risk of a mutation occurring.

"We need to apply stringent regulations globally for anyone handling bats and other wild animals," she added.

The new virus falls within the subgroup of coronaviruses called sarbecoviruses which contains both SARS-CoV-2 (responsible for the current pandemic) and SARS-CoV (responsible for the initial 2003 SARS outbreak in humans).

Further analysis compared the virus with those found in other horseshoe bat species in China, South East Asia and Europe and showed that its closest relative was discovered in a Blasius's bat from Bulgaria in 2008.

The UK discovery was made by undergraduate ecology student Ivana Murphy, from UEA's School of Biological Sciences, who collected bat droppings as part of her final year research dissertation. Jack Crook conducted the genetic analyses in partnership with other researchers at PHE.

A total of 53 bats were captured, and their faeces collected in sterile bags. The research was conducted under strict Health and Safety protocols. Full PPE was worn and Ivana was regularly tested for Covid-19 to avoid any chance of cross contamination. The bats were released immediately after their droppings had been collected.

Ivana said: "More than anything, I'm worried that people may suddenly start fearing and persecuting bats, which is the last thing I would want and would be unnecessary. As like all wildlife, if left alone they do not pose any threat."

UK policymakers preparing trade deals post-Brexit can learn important lessons from New Zealand's 'unique drug agency' the Pharmaceutical Management Agency (PHARMAC), if prices for therapies and access to key drugs are to be protected, say researchers behind a new study.

Over two decades, New Zealand has managed to reduce spending on drugs significantly and consistently despite maintaining access for its population to key treatments. As such, it is an outlier among the world's richest nations: no other OECD country has managed to achieve this.

The investigation from researchers at the universities of Bath and Durham suggest New Zealand's success can largely be ascribed to its drug agency PHARMAC. PHARMAC is unique because it not only assesses drugs scientifically, but also negotiates their prices with pharma companies.

Its equivalent in England is NICE, however whereas NICE focuses on the scientific assessment of drugs, price negotiations with drug companies rest with NHS England. There is speculation that given the attractiveness of the UK as a market for multinational drug companies, new trade deals being agreed by the UK could undermine NICE's ability to assess new drugs and determine whether they represent value for money.

For example, the researchers argue that if trade deals grant pharmaceutical companies new powers to challenge NICE's decisions through new forms of appeals mechanisms this could be a 'game changer', providing companies with additional tactics to drive up prices.

Their study, which involved analysis of policy documents produced alongside New Zealand's trade talks with other countries, freedom of information requests and interviews with key experts and policymakers, points to what could go wrong with drug prices and drug access in the UK post-Brexit.

Researcher, Dr Piotr Ozieranski from the University of Bath's Centre for the Analysis of Social Policy explained: "The implications of this study are particularly important post-Brexit and especially in the context of trade policy because of the potential impact these new deals will have on drug prices. The key issue is whether NICE is sufficiently protected for the independent, expert analysis it gives to ensure value for money for the NHS.

"Another key lesson from the study is that not only is PHARMAC protected from commercial influence, it is also trusted with maximum flexibility in negotiating drug prices with manufacturers. Depending on the situation, it can negotiate prices before a drug even reaches the market or, conversely, stall negotiations until it is about to lose patent protection and become cheaper. It also encourages price competition among companies by setting up competitive tenders and play-offs, as well as negotiating with multiple applicants at the same time."

Ben Main from the University of Durham, commented: "New Zealand's success in ensuring continued access to drugs whilst consistently driving down prices is not by accident; even more so because, unlike the UK, New Zealand cannot use the argument of a large population to secure lower prices. PHARMAC is a brilliant negotiator and uses flexibility to achieve good deals. Healthcare policymakers in the UK can learn from this model.

"However, our work raises an important question for UK policymakers: Is it worth granting NICE extra powers that would allow it to emulate some of the tactics used by PHARMAC? While price negotiations are typically shrouded in secrecy, New Zealand's evident success suggests that experts can be trusted not only with evaluating drugs scientifically but also striking favourable deals with the industry."

The paper also highlights the importance of protecting NICE from political interference.

Ben Main added: "Crucially, PHARMAC wields much policy authority, which is bolstered by social and political support even though some of its decisions may at times deny access to promising drugs to some patients. This contrasts with NICE's position, which on occasions has been challenged by politicians and NHS officials wanting to secure funding for specific therapies which did not pass - or were unlikely to pass - NICE's evaluation criteria. By and large, PHARMAC is not part of party politics."

Main also draws attention to how the industry has sought legal changes to the way PHARMAC operates: "One key lesson surrounds the issue of transparency. In other institutional contexts a lack of transparency surrounding decision making is a criticism levelled at policymakers. What we see is that over the last decade in New Zealand there is 'transparency' on industry's terms - a weapon to offset PHARMAC's authority - and a lack of transparency on PHARMAC's terms which has enabled their spending model and offset industry's dominant market position."

New Zealand's policymakers have sought to insulate PHARMAC's power by legally exempting its decisions from being potentially challenged as 'anti-competitive' by drug companies (Section 53 of the New Zealand Public Health and Disability Act 2000). On top of this, after lengthy negotiations, New Zealand refused to sign a Trans-Pacific Partnership treaty with the US, whose 'transparency and disclosure requirements' included provisions which could be used to challenge PHARMAC's decisions.

Instead, it signed a Progressive Trans-Pacific Trade Treaty (CPPTP) with eight other countries. CPPTP is unlikely to affect PHARMAC, however to further safeguard this, New Zealand subsequently suspended the application of its procedural rules in relation to PHARMAC.

Proteins constitute an essential dietary component that help in the growth and repair of the body. Composed of long chains of amino acids, proteins promote the growth of skeletal muscles, the group of muscles that help us move. Humans have been aware of the benefits of proteins for long. However, recent studies have shown that having the right amount of protein at the right time of the day is essential for proper growth. This is called 'Chrononutrition,' in which when you eat is as important as what and how you eat.

The reason behind this is the body's internal biological clock, called the 'circadian rhythm.' This rhythm is followed by all cells and controls life functions like metabolism and growth. Interestingly, protein digestion and absorption have been found to fluctuate across day and night according to this clock. Moreover, earlier studies have reported that intake of protein at breakfast and lunch promotes skeletal muscle growth in adults. However, details on the effect of the time of protein intake on muscle growth and function have remained elusive till date.

Fortunately, researchers from Waseda University, led by Professor Shigenobu Shibata, recently endeavored to understand the effect of the distribution of protein intake through the day on muscles. They fed laboratory mice two meals per day containing either high (11.5% by proportion) or low (8.5% by proportion) protein concentrations. The researchers noted that protein intake at breakfast induced an increase in muscle growth, determined by assessing induced hypertrophy of the plantaris muscle in the leg, when compared with the effects of protein intake at dinner. Specifically, the ratio of muscle hypertrophy determined against the growth of the control muscle was 17% higher in mice fed 8.5% protein at breakfast, than that in mice fed 11.5% protein at dinner, despite the former group consuming a low proportion of protein overall. They also found that intake of a type of protein called the BCCA, short for branched-chain amino acids, early in the day increased the size of skeletal muscles specifically.

To confirm the association of these effects with the workings of the circadian rhythm, the researchers next engineered whole-body mutant ClockΔ19 or muscle-specific Bmal1 knockout mice lacking the genes that control the biological clock. They repeated diet distribution experiments on these mice but did not observe similar muscle change, which confirmed the involvement of the circadian rhythm in muscle growth in the context of protein intake.

Excited about the findings of their study published in a recent issue of the Cell Reports, Prof. Shibata emphasizes, "Protein-rich diet at an early phase of the daily active period, that is at breakfast, is important to maintain skeletal muscle health and enhance muscle volume and grip strength."

To check if their findings were applicable to humans, the team recruited women in their study and tested if their muscle function, determined by measuring skeletal muscle index (SMI) and grip strength, varied with the timing of the protein-rich diet consumed. Sixty women aged 65 years and above who took protein at breakfast rather than at dinner showed better muscle functions, suggesting the possibility of the findings to be true across species. Additionally, the researchers also found a strong association between SMI and the proportion of protein intake at breakfast relative to total protein intake through the day.

Prof. Shibata is hopeful that the findings of their study will lead to a widespread modification in the current diet regime of most people across the Western and Asian countries, who traditionally consume low amounts of protein at breakfast. He therefore stresses, "For humans, in general, the protein intake at breakfast averages about 15 grams, which is less than what we consume at dinner, which is roughly 28 grams. Our findings strongly support changing this norm and consuming more protein at breakfast or morning snacking time."

It seems, a simple change in our dietary regime can be our key to ensuring healthy muscles!

Chemical synapses transmit information within the nervous system. When a presynaptic cell is electrically excited, synaptic vesicles fuse with the presynaptic membrane causing messenger substances within the vesicles to be released into the synaptic cleft. These then bind to receptors in the postsynaptic cell where they trigger an electrical signal once again. The temporal and spatial sequence of the incoming signals determines how information is processed and transmitted in the brain. In order to sustain their function in the long term, chemical synapses need to recycle synaptic vesicles to make them available for renewed signal transmission. Professor Carsten Duch and Professor Martin Heine and their respective research groups at Johannes Gutenberg University Mainz (JGU) are investigating how the release and recycling of synaptic vesicles are coordinated. "Exocytosis and endocytosis rates at chemical synapses need to be coordinated to achieve reliable signal transmission in the brain," the biologists explained. Together with Dr. Ulrich Thomas, group leader at the Leibniz Institute for Neurobiology in Magdeburg, Duch and Heine have revealed in a PNAS paper how spatiotemporally separated presynaptic calcium signals independently regulate exocytosis and endocytosis of synaptic vesicles, i.e., their release and recycling.

Co-existence of different types of voltage-gated calcium channels at the presynapse

At chemical synapses, incoming electrical impulses are converted into chemical signals and relayed on to the next cell. The process entails calcium ions first flowing through voltage-dependent membrane channels into the presynapse, i.e., the upstream nerve cell that transmits the signal to the postsynaptic cell. This calcium influx is tightly constrained in both time and space and results in exocytosis of synaptic vesicles from a specialized vesicle reservoir. Presynaptic calcium signals also regulate synaptic vesicle recycling, but here the temporal and spatial requirements are different. One unresolved question is how presynaptic electrical activity can lead to calcium signals with different temporal and spatial profiles in the presynaptic terminal.

By combining genetic modifications with electrophysiological and optophysiological measurements at the neuromuscular synapse of the Drosophila melanogaster genetic model organism, the research team was able to demonstrate that the presynapse harbors two different types of voltage-gated calcium channels, Cav2 and Cav1. These, however, were found to be spatially segregated. Both types of channels open when electrical signals arrive, but only Cav2 channels, which reside in active zones of the presynapse, are required for exocytosis of synaptic vesicles. Cav1 channels are situated outside active zones and augment endocytosis of synaptic vesicles via activity-dependent calcium influx. Thus, knockdown of Cav2 by means of genetic manipulation prevents synaptic transmission, whereas knockdown of Cav1 decreases the rate of synaptic vesicle endocytosis, thereby enhancing synaptic depression during sustained activity. This is how calcium signals mediated by two different populations of largely independent voltage-gated calcium channels regulate two essential functions of the presynapse in response to neuronal activity, namely the release and recycling of synaptic vesicles.

Functional separation of Cav1 and Cav2 by means of a calcium pump

A key question was how calcium signals through different channels could be functionally separated at the nanometer scale of the presynaptic terminal, because calcium after all is a highly diffusible intracellular messenger. According to the researchers, different vital functions of calcium signals through Cav1 and Cav2 channels are separated by a membrane-anchored calcium buffer. Cav2 channels are found within presynaptic active zones at distances of 70 to 140 nanometers from readily releasable synaptic vesicles. This distinct localization of Cav2 results in the emergence of temporally and spatially tightly regulated calcium signals within so-called nano-domains during presynaptic electrical activity, and these are essential for temporally precise synaptic transmission. Cav1 localizes around active zones, in theory allowing calcium influx simultaneously through both types of channels to result in mixed signals with no measurable delay. However, mixed signals of this type are prevented by the plasma membrane calcium pump (PMCA). PMCA is located outside active zones and isolates them from the dynamic regulation of endocytosis achieved by Cav1-mediated calcium influx. Because Cav1, Cav2, and PMCA have been identified also at central synapses in the brains of mammals, these proteins may represent a conserved functional triad for separate activity-dependent regulation of exocytosis and endocytosis of synaptic vesicles.

Calcium channels and the regulation of essential synaptic functions

In the future, Duch's and Heine's research groups will continue to explore the interactions of calcium channels and their associated molecules at the presynapse. Calcium signals in the presynaptic terminal regulate other essential synaptic functions beyond exocytosis and endocytosis. These include the regulation of synaptic vesicle movements between distinct specialized reservoirs as well as the control of fixed synaptic transmission strengths, which are restored by compensatory mechanisms after perturbation. This homeostatic synaptic plasticity is essential for reliably processing information in the brain. As part of a project within Collaborative Research Center 1080 on Molecular and Cellular Mechanisms in Neural Homeostasis, Duch's and Heine's groups are investigating how spatiotemporally separated presynaptic calcium signals independently control exocytosis and endocytosis, the transport of vesicles between different reservoirs, and synaptic homeostasis. "Calcium signals are extremely well suited to precisely adapt a variety of vital synaptic functions to differing neuronal activities, but we are only just starting to work out the mechanisms that independently regulate these functions," Duch and Heine commented on their neurobiology research.

The economic and environmental pros and cons of melting Arctic ice creating shorter shipping routes through the polar region are weighed up in ground-breaking research from UCL experts in energy and transport.

They conclude that policy makers must properly assess the environmental trade-offs and costs in addition to the commercial benefits and opportunities in Arctic shipping. The authors also want to see more incentives to drive technological developments that will accelerate the uptake of green fuels and technologies.

The Arctic is the fastest-warming region on the planet.

Shorter Arctic shipping routes, which mean less fuel used are already used by a handful of ships, when areas of the Arctic ice melt during the summer. But the period when these routes are navigable is predicted to extend with increases in global warming and, if warming fails to remain within the 1.5?C/2?C limit set out in the Paris agreement, permanent Arctic ice may be a thing of the past.

The research, published in Transportation Research Part A: Policy and Practice, looked at the financial competitiveness of Arctic shipping, considering the impact of emissions from these vessels on the environment.

They looked at two policy scenarios, one being business-as-usual, where there is no policy on emissions, and the other operating under an Arctic specific zero-emissions policy, where ships which could run using energy from renewable sources were considered.

When environmental costs are ignored, fossil fuel based residual fuel oil is cheaper than alternative fuels. However, when the environmental impacts of accelerating climate change and the adverse effects of ship emissions on human health are considered, residual fuel ships are no longer feasible because of their contribution to greenhouse gas and air pollutant emissions.

The experts conclude that, in the second scenario, green ammonia fuel cell ships are the most commercially viable and that policies which facilitate the introduction of such zero carbon fuels and zero emission technologies should be encouraged. Green ammonia is an example of a fuel that can be emissions free in both its production and use, given a green electric infrastructure.

Lead author Joseph Lambert (UCL Energy Institute) said: "Significant change is under way in the Arctic region due to global warming and from a shipping perspective we should prepare for what this means through assessing all the opportunities, risks and trade-offs that aren't exclusively financial. These routes may become more financially competitive as global warming increases and Arctic ice retreats, but more factors must be considered. It is critical that the Arctic ice maintains its permanency - in order to stay within global warming targets and to protect the region's ecology."

Co-author Dr Tristan Smith (UCL Energy Institute), who supervised the research, said: "This is a novel work that shows the economic costs alongside the environmental costs for the Arctic route, as well as showing how certain technology choices, that could be incentivised through policy, could significantly reduce the environmental costs that would otherwise arise from Arctic shipping. The paper shows a clear justification for governments to intervene now to prevent a melting Arctic's enabling of a reduction in shipping costs because of further acceleration of the degradation of this crucial ecosystem."

The researchers say impacts that need to be explored include the effects of ecological damage, and how policy can be structured to address the environmental concerns.

Ishikawa, Japan - Powering everything from smartphones to electric cars, lithium-ion batteries (LIBs) have evolved markedly with advances in technology and revolutionized our world. The next step in the progress of technology is developing even better batteries to power electronic devices for longer durations. One promising technique for increasing battery performance involves the atomic substitution of positively charged ions or "cations" in the cathode material. However, doing so systematically for different substituent cations to determine the ideal ones experimentally is complex and expensive, leaving us with simulations as the only viable option for narrowing down the choices.

Several studies have reported an improved battery life and thermal stability based on their findings using a simulation-based approach. However, such improvements have, in turn, lowered the discharge capacity of the battery, which is the amount of energy that a battery can supply in a single discharge. As a result, an extensive search must be performed for the cation substituent that enhances the discharge capacity.

Against this backdrop, a team of scientists led by Prof. Ryo Maezono from Japan Advanced Institute of Science and Technology (JAIST) conducted an extensive screening of different cations for partial substitution of nickel in a nickel-based LIB with the intent of enhancing the battery discharge capacity.

"The discharge capacity can be determined using the discharge profile, which is the voltage change during the charge-discharge process," explains Prof. Maezono. "We used first-principles calculations to evaluate the discharge profiles of materials that, in turn, determines their discharge capacities. However, these calculations are computationally costly, so we integrated other methods to narrow down the candidates for cation replacement. To the best of our knowledge, this is the first study that successfully predicts cation substitution to increase battery capacity." The groundbreaking study has been published in a recent issue of The Journal of Physical Chemistry C.

A prominent strategy for successfully predicting the discharge voltage profile is the "strongly constrained and appropriately normed" (SCAN) functional. However, due to the large computing costs involved, such methods are impractical for extensive screening. So, the team began by using relatively inexpensive techniques such as density functional theory and cluster expansion to identify suitable candidates for cation replacement and then applied SCAN functional to the inferred candidates to assure reliability and accuracy in voltage predictions.

The screening process revealed that the highest discharge capacity was obtained when nickel was partially substituted with platinum and palladium in nickel-based LIB. These results were consistent with the experimental data, validating the proposed methodology.

While Prof. Maezono emphasizes the need for additional research, he is optimistic about the future of their low-cost screening process. "Our findings indicate that substituents such as rhenium and osmium offer high discharge capacities. However, these elements are rare and costly, and putting them to practical use would be challenging. Further study is needed to achieve the same effect with less substitution, multiple element substitution, or anion substitution," he says. "Having said that, our novel computational technique will accelerate the search for optimal materials that improve battery performance at lower costs, allowing us to replace the bulk of our current electricity sources with carbon-free alternatives."

Hopefully, such advances will bring humankind one step closer to becoming an environment-friendly species in the near future!

The final stage of cataclysmic explosions of dying massive stars, called supernovae, could pack an up to six times bigger punch on the surrounding interstellar gas with the help of cosmic rays, according to a new study led by researchers at the University of Oxford. The work will be presented by PhD student Francisco Rodríguez Montero today (19 July) at the virtual National Astronomy Meeting (NAM 2021).

When supernovae explode, they emit light and billions of particles into space. While the light can freely reach us, particles become trapped in spiral loops by magnetic shockwaves generated during the explosions. Crossing back and forth through shock fronts, these particles are accelerated almost to the speed of light and, on escaping the supernovae, are thought to be the source of the mysterious form of radiation known as cosmic rays.

Due to their immense speed, cosmic rays experience strong relativistic effects, effectively losing less energy than regular matter and allowing them to travel great distances through a galaxy. Along the way, they affect the energy and structure of interstellar gas in their path and may play a crucial role in shutting down the formation of new stars in dense pockets of gas. However, to date, the influence of cosmic rays in galaxy evolution has not been well understood.

In the first high-resolution numerical study of its kind, the team ran simulations of the evolution of the shockwaves emanating from supernovae explosions over several million years. They found that cosmic rays can play a critical role in the final stages of a supernova's evolution and its ability to inject energy into the galactic gas that surrounds it.

Rodríguez Montero explains: "Initially, the addition of cosmic rays does not appear to change how the explosion evolves. Nevertheless, when the supernova reaches the stage in which it cannot gain more momentum from the conversion of the supernova's thermal energy to kinetic energy, we found that cosmic rays can give an extra push to the gas, allowing for the final momentum imparted to be up to 4-6 times higher than previously predicted."

The results suggest that gas outflows driven from the interstellar medium into the surrounding tenuous gas, or circumgalactic medium, will be dramatically more massive than previously estimated.

Contrary to state-of-the-art theoretical arguments, the simulations also suggest that the extra push provided by cosmic rays is more significant when massive stars explode in low-density environments. This could facilitate the creation of super-bubbles powered by successive generations of supernovae, sweeping gas from the interstellar medium and venting it out of galactic discs.

Rodríguez Montero adds: "Our results are a first look at the extraordinary new insights that cosmic rays will provide to our understanding of the complex nature of galaxy formation."

Researchers at the RIKEN Center for Integrative Medical Sciences (IMS) have discovered that acetate, a major metabolite produced by some intestinal bacteria, is involved in regulating other intestinal bacteria. Specifically, experiments showed that acetate could trigger an immune response against potentially harmful bacteria. The findings, published in the scientific journal Nature, will lead to the development of new ways to regulate the balance of intestinal bacteria.

You may be surprised to know that 40 trillion important bacteria live in our intestines. They help keep us healthy by producing essential nutrients and eliminating foreign pathogens. On the other hand, these commensal bacteria can harm your health if they are out of control. Therefore, understanding the way the body regulates the balance of intestinal bacteria is important issue for staying healthy.

Immunoglobulin A (IgA) is the most abundant antibody produced in the human body, mostly secreted from the mucosal surfaces of the intestinal tract. IgA is thought to regulate the growth, colonization, and function of intestinal bacteria by binding to them. However, until now, we didn't know what could trigger IgA responses to bacteria in a dynamically changing intestinal environment.

Intestinal bacteria help us break down what we eat into smaller pieces called metabolites. Recent studies suggest that these metabolites have a significant impact on immune function in the intestinal tract. In particular, short-chain fatty acids (SCFAs), a major metabolite of intestinal bacteria, are known to be involved in creating and regulating immune-cell function. They are thought to increase IgA production, but until now, nobody knew what could trigger this behavior.

A research group led by Hiroshi Ohno at RIKEN IMS fed mice food that can specifically increase SCFAs locally in the large intestine. Analysis of the mice showed that acetate, a type of SCFA, increases both the number of IgA-producing cells and the amount of IgA, and also regulates how much IgA is bound to each intestinal bacterium. "SCFAs including acetate are easily absorbed in the stomach and proximal small intestine, so it was difficult to investigate the effects of orally administered SCFAs in the distal intestine such as the colon, where the intrinsic SCFA levels are high," says Ohno. "Our collaborators have developed a method that can efficiently deliver the metabolites into the distal intestine, which enabled us to analyze the effects of SCFAs on the immune system there." Other SCFAs, such as propionic acid or butyric acid did not affect IgA.

The researchers also found that the type of bacteria to which IgA binds depends on whether acetate is present or not. Normally, IgA binds mostly to common symbiotic bacteria, but in mice treated with acetate, it tended to bind to potentially harmful bacteria such as E. coli. More detailed analysis showed that when acetate leads to IgA production in the colon, the IgA binds to those potentially harmful bacteria and prevents them from settling in and invading the mucus layer.

These findings were somewhat unexpected. "At first we thought that acetate simply increases IgA equally against all commensal bacteria," explains Ohno. "It was rather surprising to see that it preferentially enhances production of IgA against certain microbes through collaboration with other immune cells." In fact, the experiments showed that acetate only increased IgA production when potentially harmful bacteria were present.

Overall, this study revealed that acetate produced by bacteria can change the balance of IgA in the intestines. The process involves enhancing IgA production together with bacterial components. By increasing IgA production, especially IgA that will attack potentially harmful bacteria, acetate can alter the bacterial makeup of the intestines.

"Accumulating evidence suggests the involvement of gut microbiota in many human diseases. IgA is one of the most efficient ways to control the microbiota, and therefore we think our findings are a basis for this regulatory mechanism. Since the functions of metabolites remain largely unknown, we will keep focusing on host-microbe interactions through these small molecules to reveal how they affect human pathophysiology," says Ohno.

The carbon-hydrogen bonds in alkanes--particularly those at the ends of the molecules, where each carbon has three hydrogen atoms bound to it--are very hard to "crack" if you want to replace the hydrogen atoms with other atoms. Methane (CH(4)) and ethane (CH(3)CH(3)) are made up, exclusively, of such tightly bound hydrogen atoms. In the journal Angewandte Chemie, a team of researchers has now described how they break these bonds while forming new carbon-nitrogen bonds (amidation).

If it were possible to easily break the C-H bonds in hydrocarbons, it would be possible to synthesize complex organic molecules, such as pharmaceuticals, much more conveniently and directly from petroleum. This strategy could also provide more pathways for recycling plastic waste. The formation of carbon-nitrogen bonds is of particular interest because these play an important role in natural products. For example, amide bonds link individual amino acids into proteins.

Although there has been some success in the functionalization of heavy hydrocarbons, even at the end positions, the particularly strong C-H bonds of light alkanes, especially methane, can hardly be split at all. The use of these primary components of natural gas as synthetic building blocks is especially desirable, as it would allow for the use of this often wasted side-product of oil extraction.

A team led by Ana Caballero and Pedro J. Pérez (Universidad de Huelva, Spain), as well as John F. Hartwig (University of California, Berkeley, USA) has now successfully coupled amides (nitrogen-containing organic compounds) to light alkanes with loss of a hydrogen atom. The products of these dehydrogenative amidations are known as N-alkyl amides.

The starting point for this approach was the amidation of C-H bonds in heavy alkanes with a copper-based catalyst and di-tert-butyl peroxide as an oxidizing agent, as developed several years ago by the Hartwig group. Variation of the catalyst led to success. If the copper has phenanthroline-type ligands (an aromatic, nitrogen-containing system of three six-membered rings), it is possible to produce high yields in the reaction of ethane with benzamide--as well as a number of other amides--using benzene as a solvent. The reaction also worked when supercritical carbon dioxide--a more environmentally friendly option--was used as a solvent. The reaction with ethane is an unusual C-N bond formation with a non-activated primary C-H bond.

Propane, n-butane, and iso-butane gave similar results. In the light alkanes, reactivity correlates significantly more strongly with the dissociation energy of the C-H bonds than in higher alkanes.

And methane? Even the toughest candidate--amidation of methane has never previously been observed--could be coupled to the amide. Isotopic experiments were used to prove that methane reacts to form N-methylbenzamide.

The climate crisis will lead to changes in distribution and habitat loss of stony corals in the tropical Atlantic, shows a new study published by the open access publisher Frontiers. The loss of such coral species could have devastating consequences for the marine ecosystems they inhabit. The results of the study highlight an urgent need for coral reef management in the Atlantic.

Researchers at the University of São Paulo projected current and future distributions of three key reef building corals of the tropical Atlantic (Mussismilia hispida, Montastraea cavernosa and the Siderastrea complex). They conclude that all three species will experience changes in range due to the climate crisis, which will elicit negative cascading effects on the biodiversity of reef ecosystems. The results are published in the journal Frontiers in Marine Science.

Nature's engineers are threatened

Mussismilia hispida, Montastraea cavernosa and the Siderastrea complex are stony corals of the eastern and western Atlantic. They are ecosystem engineers: much like beavers who contribute to the structure of their terrestrial habitats by building dams, stony corals help build reefs by depositing calcium carbonate. They are vital for the health and function of these reefs, which are among the most diverse ecosystems on Earth.

"Coral reefs provide essential ecosystem services such as food provision, coastal protection and nutrient cycling, that benefit millions of people - including those who live far from any coral reef," says lead author and PhD candidate Silas Principe of the University of São Paulo.

"If species that are important in structuring the coral reefs are lost, the provision of all those services is consequently also threatened."

Human activity has long harmed corals worldwide, and coral reefs are already some of the most threatened ecosystems on the planet. Intense and long-lasting mass bleaching events, ocean acidification, pollution, urbanization, fisheries, and tourism are all leading to reduction and loss of coral cover. Now, the climate crisis is adding to those threats.

Climate change leads to changes in coral distribution, with key coral species moving within the tropics or to temperate waters at higher latitudes. Changes in distributions of these key species may have unprecedented cascading effects on entire marine wildlife communities, such as drastic changes in the structural complexity of reef ecosystems.

Concerning findings

Researching possible changes in stony coral distribution is important for planning and management of coral reef conservation. The researchers collected data on M. hispida, M. cavernosa and the Siderastrea complex from different databases and used species distribution models to model their suitability on their current habitat. They also modeled future changes in range under three different climate change scenarios (most pessimistic, most optimistic, and moderate).

They found that, even in the most optimistic scenario, all three species could experience changes in their distributions. Especially in the western Atlantic, decreases in the abundance of stony corals are expected under all three scenarios. Several areas along the Brazilian coast and the Caribbean will lose habitat suitability. These projections are especially critical for the Brazilian coast, where there are fewer habitat-building coral species.

The researchers urge conservation and management efforts to be focused on regions such as the Abrolhos region, northeast coast of Brazil, western Caribbean, and the Gulf of Mexico. "We show that important reef builder species of the Atlantic will face shifts in its distribution due to climate change," Principe said.

"Certain areas, such as the Abrolhos region in the coast of Brazil, will completely lose at least one of its species in any of the future scenarios. Major areas in the Caribbean will also lose species in the future, although in the coast of Africa some species may expand their current range."

But the results also indicate that there is hope for Atlantic stony corals. "Although our results predict major negative impacts on Atlantic shallow reefs, we also identified several areas where none or less changes are predicted. Managers and policy makers can use this to support the planning process of conservation areas." Principe concludes: "Researchers and conservationists can use these results to focus research efforts on the so-called 'refuge areas' that may constitute safe areas for coral species in the future."

To prepare for the next pandemic and provide a coordinated approach to vaccination across the country, Canada should create Canadian Immunization Services based on the Canadian Blood Services model, authors propose in CMAJ (Canadian Medical Association Journal).

The authors, including a leading health policy and immunization expert, a blood system expert and a former federal minister of health, are Dr. Kumanan Wilson, professor, Department of Medicine and member of the Centre for Health Law, Policy and Ethics, University of Ottawa; Dr. Graham Sher, CEO, Canadian Blood Services; and Dr. Jane Philpott, Dean, Faculty of Health Sciences, Queen's University.

"If we want to be better prepared for the next pandemic, it is time to chart a bold new path forward," said Dr. Kumanan Wilson. "We propose intergovernmental collaboration through an arms-length entity, which was successful after the tainted blood scandal, one of Canada's biggest public health crises. We have done this before, emerging stronger from a public health crisis and creating a world-class blood system. We can do it again."

Various reports, including from the federal auditor general, have documented the problems with how Canada's federal, provincial and territorial governments work together. Different vaccination schedules for each province and territory, different terminology and variations in immunization tracking have made Canada's system fragmented.

"It is challenging to coordinate pan-Canadian disease surveillance and mass immunization responses without harmonized data and systems," said Dr. Wilson. "Our response to COVID-19 has been plagued by many of the challenges facing public health over the last 20 years."

As the responsibility for managing public health threats is largely the responsibility of the provinces and territories, unilateral federal mandates are difficult to implement.

The authors propose an independent not-for-profit corporation -- Canadian Immunization Services -- funded by participating provinces and territories, and potentially the federal government, based on the Canadian Blood Services model.

"Twenty-three years ago, Canadian Blood Services assumed full responsibility for the operation of the national blood supply outside Quebec, taking over a system that was unquestionably broken," said Dr. Graham Sher. "We were founded to restore confidence in the blood system, and over the past two decades, our journey has been one from tragedy to trust. We now have one of the safest blood systems in the world. We believe that Canada can effectively prepare for the next pandemic by establishing a world-class vaccination system based on this model as well."

Canadian Immunization Services would provide:

Ability to procure vaccines in bulk for Canada

Vaccine surveillance and supply chain management by single entity versus many

Common data standard to enable data sharing between provinces and territories

Ability to access expertise rapidly without government barriers to hiring

"If we hope for public health to be better prepared for the next pandemic, now is the time to implement needed changes," the authors conclude.

"Preparing for the next pandemic by creating Canadian Immunization Services" is published July 19, 2021.

Philadelphia, July 19, 2021 - University of Minnesota School of Public Health researchers recently completed a study to determine how food-insecure young (emerging) adults (18-29 years of age) adapted their eating and child feeding behaviors during the COVID-19 pandemic. The researchers also sought to identify barriers to food access and opportunities to improve local access to resources for emerging adults. Their study results are published in the Journal of the Academy of Nutrition and Dietetics.

The steep rise in food insecurity during the COVID-19 pandemic has disproportionately impacted Black, Indigenous, and persons of color across the United States. Emerging adulthood is a time of particular vulnerability for experiencing food insecurity and when young people may begin providing meals for their own children. It is a public health concern that food insecurity among emerging adult populations has the potential to negatively impact the health trajectories of multiple generations.

Researchers used data from the COVID-19 Eating and Activity over Time (C-EAT) study, which collected survey data from 720 emerging adults from April to October 2020 and included interviews with a diverse subset of 33 food-insecure respondents.

The study found:

Nearly one-third of emerging adults surveyed experienced food insecurity in the past year.
One Earth A disproportionately high prevalence of food insecurity and food insufficiency among emerging adults living with children and those who identified as Black, Indigenous, or a person of color.

Many food-insecure emerging adults made changes to their eating and feeding behaviors to cope during the pandemic -- and several of the changes, such as consuming more fast food and processed foods or increased sporadic eating, could lead to negative health consequences.

Food-insecure emerging adults reported concerns regarding the implementation of measures used to reduce COVID-19 transmission in food retail stores and other notable barriers to local food access (e.g., reduced store hours, neighborhood safety concerns).

Interview participants of diverse ethnic/racial backgrounds commented on how food access had been recently impacted by racial justice uprisings and reported several forms of discrimination experienced while shopping in food retail stores. Concerns about discrimination and xenophobia, including excessive monitoring and verbal harassment, influenced how households managed shopping for food.

Barriers to accessing food assistance were also themes among the comments made by food-insecure emerging adults. Most services were provided in line with guidance for preventing COVID-19 transmission, but factors limiting eligibility for benefits and access to emergency food assistance were identified along with some concerns about food quality, physical distancing, and physical safety at food pantries.

"Our findings show an urgent need for research to address how the processes of racism that are embedded in the policies and practices of society and institutions are directly contributing to food insecurity," said study lead Nicole Larson, PhD, MPH, RDN, Senior Research Associate, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. "The findings also support recent calls for expanding federal food assistance benefits for postsecondary students as the comments made by many emerging adult participants indicated that both students and workers were not eligible for adequate benefits to meet their food needs."

Dr. Larson remarked that even among households that reported receiving federal food assistance (e.g., SNAP), there were multiple emerging adults who reported needing to obtain food from local food pantries or distribution sites. The study results also highlighted the importance of ensuring that information about emergency food assistance sites is broadly distributed through multiple communication channels and varying the open hours of sites to address the needs of emerging adults who may need to visit outside of regular daytime hours.

"It is heartbreaking to learn about the high levels of food insecurity so close to home. It is incumbent upon all of us to work toward eliminating food insecurity and ensuring that all people have access to adequate amounts of healthful foods. As health care professionals, advocates, researchers, and members of society, we all have a role to play. We need to work now to prevent a widening of disparities following this global pandemic," added principal investigator Dianne Neumark-Sztainer, PhD, MPH, RD, Division Head and McKnight Presidential and Mayo Professor, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

Highlights

The results of a new study support the validity of a score that considers various patient-reported outcome measures and preferences for assessing health-related quality of life in individuals with kidney failure.

The score is calculated from assessments of cognitive function, depression, fatigue, pain interference, physical functioning, sleep disturbance, and ability to participate in social roles.

Washington, DC (July 16, 2021) -- Results from a new study support the validity of a score that considers various patient-reported measures and preferences for assessing health-related quality of life and promoting patient-centered care in individuals with kidney failure. The study appears in an upcoming issue of CJASN.

The score, called the Patient Reported Outcomes Measurement Information System (PROMIS®)-Preference (PROPr) Summary Score, is determined from 7 domains: cognitive function, depression, fatigue, pain interference, physical functioning, sleep disturbance, and ability to participate in social roles.

When investigators led by Istvan Mucsi, MD, PhD and Jing Zhang BSc, MPH (University Health Network and University of Toronto) correlated PROPr with other health-related measures, their findings supported the validity of PROPr among 524 patients who were undergoing hemodialysis or who had recently received kidney transplants.

"Up to 70% of patients with kidney failure experience persistent physical symptoms and emotional distress that substantially impair health-related quality of life. These concerns are under-reported, under-recognized and under-managed," said Dr. Mucsi. "Our results open the doors for the use of PROPr and PROMIS® tools in nephrology research and in the care of patients with kidney failure."