Culture

Lung cancer in non-smokers likely to respond differently to treatment

Lung cancer in non-smokers is a diverse and distinct disease from that in smokers, and is likely to respond differently to targeted treatments, a major new study shows.

Scientists studied a population in Taiwan with high rates of lung cancer among non-smokers - and found a range of genetic changes which varied depending on a patient's age or sex.

Many non-smokers with lung cancer had signs of DNA damage from environmental carcinogens, with young women in particular having particular genetic changes which are known to drive cancer to evolve aggressively.

The study - which was co-led by scientists at The Institute of Cancer Research, London, alongside colleagues in Taiwan - could lead to new treatments for non-smokers with lung cancer tailored to the newly identified genetic changes.

The research, published in the prestigious journal Cell today (Thursday), is the most comprehensive ever study of the biology of lung cancer in non-smokers. It was funded by Cancer Research UK and various institutions in Taiwan including the Ministry of Science and Technology.

Scientists at The Institute of Cancer Research (ICR) worked with colleagues at the Academia Sinica and the National Taiwan University to analyse tumour samples from 103 lung cancer patients from Taiwan - the majority of whom were non-smokers.

Around 10-15 per cent of lung cancers in the UK occur in people who have never smoked - but in East Asia, the proportion of lung cancers that occur in non-smokers is much higher, especially among women.

The researchers conducted a detailed analysis of genetic changes, gene activation, protein activity and cellular 'switches' in lung cancer to develop the most comprehensive overview of the biology of disease in non-smokers to date.

Looking at the genetics and the related proteins produced by cancer cells in the tumour samples, scientists found that some early-stage lung tumours in non-smokers were biologically similar to more advanced disease in smokers.

Tumours in women often had a particular fault in the well-known lung cancer gene EGFR, whereas in men the most common faults were in the KRAS and APC genes. These differences could affect the response to targeted drugs in men and women.

Picking out people with 'late-like' early-stage lung tumours could help guide treatment decisions, and patients could be monitored more closely for signs of their disease progressing.

The study found a pattern of genetic changes involving the APOBEC gene family in three-quarters of tumours of female patients under the age of 60, and in all women without faults in the EGFR gene.

APOBEC proteins play an important role in the function of the immune system - but they can be hijacked by cancers, speeding up evolution and the emergence of drug resistance, a key area of study in the ICR's new Centre for Cancer Drug Discovery.

Patients without EGFR faults tend to do better on immunotherapy, and so testing for APOBEC could help pick out women more likely to respond to this form of treatment.

The team also picked out groups of patients - particularly among older women - whose cancers had mutation patterns linked to cancer-causing substances in their environment such as pollutants.

Finally, the team identified 65 proteins that were overactive in lung tumours that matched with existing candidate drugs. They found that one protein that cuts away at the surrounding tissue, called MMP11, was linked to poorer survival - and could be explored as a marker for early detection.

While the new study looked at patients treated in Taiwan, the researchers believe that many of their findings could be applicable to UK patients. Next, they will be validating their findings in larger studies and beyond Asia.

Dr Jyoti Choudhary, Team Leader in Functional Proteomics at The Institute of Cancer Research, London, said:

"We carried out the most comprehensive study ever conducted into the biology of lung cancers in an East-Asian population with a high proportion of non-smokers, and found that their disease is molecularly diverse, and distinct from what we classically see in smokers.

"We found distinct patterns of genetic faults in non-smokers and between women and men, which suggest that a woman who has never smoked, for example, is likely to respond differently to treatment than a male smoker.

"Some early-stage lung tumours had molecular features that are much more like that typically seen in later-stage disease - which could help us more accurately diagnose patients with aggressive disease, and inform treatment strategies."

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"This new study offers a deep dive into the biology of lung cancer in people who have never smoked. It reveals new ways of telling apart patients with different tumour characteristics that could be exploited with tailored treatment strategies.

"Lung cancer is the biggest cancer killer in the UK, and much of what we know about the disease comes from studies in smokers. I'm hopeful that the new insights gleaned in this new study will really step up precision medicine in lung cancer for non-smokers, so they can be offered smarter, kinder treatment options."

Dr Emily Armstrong, research information manager at Cancer Research UK, said:

"In order to beat cancer, we need to understand all the ways it can develop. This research highlights just how much cancers can vary between people depending on their lifestyle and environment. Understanding the difference between lung cancers in smokers and non-smokers could be vital for providing patients with the most appropriate treatment."

Credit: 
Institute of Cancer Research

Global wildlife surveillance could provide early warning for next pandemic

image: A juvenile saddleback tamarin is measured as part of an annual health check of a population of three primate species in southeastern Peru. In a perspective article published July 9 in Science, a team of wildlife biologists, infectious disease experts, and others propose a decentralized, global wildlife biosurveillance system to identify - before the next pandemic emerges - animal viruses that have the potential to cause human disease.

Image: 
Ishaan Raghunandan

The virus that causes COVID-19 probably originated in wild bats that live in caves around Wuhan, China, and may have been passed to a second animal species before infecting people, according to the World Health Organization. Many of the most devastating epidemics of recent decades - including Ebola, avian influenza and HIV/AIDS - were triggered by animal viruses that spilled over into people. Despite the ever-present danger of a new virus emerging and sparking a worldwide pandemic, there is no global system to screen for viruses in wild animals that eventually may jump to humans.

In a perspective article published July 9 in Science, a diverse group of infectious disease experts, ecologists, wildlife biologists and other experts argue that a decentralized global system of wildlife surveillance could - and must ­- be established to identify viruses in wild animals that have the potential to infect and sicken people before another pandemic begins.

"It's impossible to know how often animal viruses spill over into the human population, but coronaviruses alone have caused outbreaks in people three times in the last 20 years," said co-author Jennifer A. Philips, MD, PhD, referring to the SARS, MERS and COVID-19 epidemics. Philips is an associate professor of medicine and co-director of the Division of Infectious Diseases at Washington University School of Medicine in St. Louis. "Even a decade ago it would have been difficult to conduct worldwide surveillance at the human-wildlife interface. But because of technological advances, it is now feasible and affordable, and it has never been more obvious how necessary it is."

Every animal has its own set of viruses, with some overlap across species. Often, an animal species and its viruses have lived together for so long that they've adapted to one another, and the viruses cause either no symptoms or only mild to moderate disease. But when different animal species that don't normally have much contact are brought together, viruses have the opportunity to jump from one species to another. Most viruses don't have the genetic tools to infect another species. But viruses with such tools can be lethal to a newly infected species with no natural immunity.

Human activity is making such spillover events more and more likely. As the population of the world continues to grow, the demand for natural resources skyrockets. People push into wild areas to make space for new homes and businesses, and to access resources to fuel their economies and lifestyles. Wild animals are caught and sold for consumption, or as exotic pets at wildlife markets, where diverse species are jumbled together under crowded and unsanitary conditions. Wild-animal parts are shipped around the world as trinkets or ingredients for traditional or alternative medicines.

And yet there is no international system set up to screen for disease-causing viruses associated with the movement of wildlife or wildlife products.

"In the lead up to this article, I spoke with friends and colleagues around the world who do wildlife research in Madagascar, Indonesia, Peru, Ecuador and asked them, 'Where do you take your samples for screening?'" said co-author Gideon Erkenswick, PhD, a postdoctoral research associate in Philips' lab. Erkenswick is also the director of Field Projects International, a nonprofit organization dedicated to the study and conservation of tropical ecosystems. "In almost every situation, the answer was 'Nowhere.' Locally, there is nobody with dedicated time and resources to do this work. To find new disease-causing viruses, we have to find willing foreign collaborators, then get samples out of the country, which is difficult and expensive."

Philips, Erkenswick, and colleagues in the Wildlife Disease Surveillance Focus Group that authored the Science paper, suggest the establishment of a global surveillance network to screen wild animals and their products at hotspots such as wildlife markets. The idea would be to have local teams of researchers and technicians extract viral genomes from animal samples, rapidly sequence them on site and upload the sequences to a central database in the cloud. The cost and size of the necessary scientific equipment has dropped in recent years, making such screening affordable even in resource-limited settings where most such hotspots are located.

"There's now a genetic sequencer available that is literally the size of a USB stick," Erkenswick said. "You could bring that and a few other supplies into a rainforest and analyze a sample for sequences associated with disease-causing viruses on site in a matter of hours. I mean, if you do chance upon something like the virus that causes COVID-19, do you really want to be collecting it, storing it, transporting it, risking further exposure, sample degradation, and adding months or years of delay, before you figure out what you've got? There are people with the expertise and skills to do this kind of work safely pretty much everywhere in the world, they just haven't been given the tools."

Once viral sequences are uploaded, researchers around the world could help analyze them to identify animal viruses that may be a threat to people and to develop a better understanding of the universe of viruses that thrive in different environments. By comparing genomic sequence data, researchers can identify what family an unknown virus belongs to and how closely it is related to any disease-causing viruses. They can also identify whether a virus carries genes associated with the ability to cause disease in people.

"By knowing the diversity out there, and tracking its evolution, we can ensure that we stay ahead of what's in wildlife populations and at the wildlife-human interface," Philips said. "In the past, before modern transportation, spillover events would have been local and spread slowly, giving people elsewhere time to respond. But now the world is so small that an event in one place puts the whole world at risk. This is not someone else's problem. It's everyone's problem."

Credit: 
Washington University School of Medicine

Arctic Ocean 'regime shift'

Scientists at Stanford University have discovered a surprising shift in the Arctic Ocean. Exploding blooms of phytoplankton, the tiny algae at the base of a food web topped by whales and polar bears, have drastically altered the Arctic's ability to transform atmospheric carbon into living matter. Over the past decade, the surge has replaced sea ice loss as the biggest driver of changes in uptake of carbon dioxide by phytoplankton.

The research appears July 10 in Science. Senior author Kevin Arrigo, a professor in Stanford's School of Earth, Energy & Environmental Sciences (Stanford Earth), said the growing influence of phytoplankton biomass may represent a "significant regime shift" for the Arctic, a region that is warming faster than anywhere else on Earth.

The study centers on net primary production (NPP), a measure of how quickly plants and algae convert sunlight and carbon dioxide into sugars that other creatures can eat. "The rates are really important in terms of how much food there is for the rest of the ecosystem," Arrigo said. "It's also important because this is one of the main ways that CO2 is pulled out of the atmosphere and into the ocean."

A thickening soup

Arrigo and colleagues found that NPP in the Arctic increased 57 percent between 1998 and 2018. That's an unprecedented jump in productivity for an entire ocean basin. More surprising is the discovery that while NPP increases were initially linked to retreating sea ice, productivity continued to climb even after melting slowed down around 2009. "The increase in NPP over the past decade is due almost exclusively to a recent increase in phytoplankton biomass," Arrigo said.

Put another way, these microscopic algae were once metabolizing more carbon across the Arctic simply because they were gaining more open water over longer growing seasons, thanks to climate-driven changes in ice cover. Now, they are growing more concentrated, like a thickening algae soup.

"In a given volume of water, more phytoplankton were able to grow each year," said lead study author Kate Lewis, who worked on the research as a PhD student in Stanford's Department of Earth System Science. "This is the first time this has been reported in the Arctic Ocean."

New food supplies

Phytoplankton require light and nutrients to grow. But the availability and intermingling of these ingredients throughout the water column depend on complex factors. As a result, although Arctic researchers have observed phytoplankton blooms going into overdrive in recent decades, they have debated how long the boom might last and how high it may climb.

By assembling a massive new collection of ocean color measurements for the Arctic Ocean and building new algorithms to estimate phytoplankton concentrations from them, the Stanford team uncovered evidence that continued increases in production may no longer be as limited by scarce nutrients as once suspected. "It's still early days, but it looks like now there is a shift to greater nutrient supply," said Arrigo, the Donald and Donald M. Steel Professor in Earth Sciences.

The researchers hypothesize that a new influx of nutrients is flowing in from other oceans and sweeping up from the Arctic's depths. "We knew the Arctic had increased production in the last few years, but it seemed possible the system was just recycling the same store of nutrients," Lewis said. "Our study shows that's not the case. Phytoplankton are absorbing more carbon year after year as new nutrients come into this ocean. That was unexpected, and it has big ecological impacts."

Decoding the Arctic

The researchers were able to extract these insights from measures of the green plant pigment chlorophyll taken by satellite sensors and research cruises. But because of the unusual interplay of light, color and life in the Arctic, the work required new algorithms. "The Arctic Ocean is the most difficult place in the world to do satellite remote sensing," Arrigo explained. "Algorithms that work everywhere else in the world - that look at the color of the ocean to judge how much phytoplankton are there - do not work in the Arctic at all."

The difficulty stems in part from a huge volume of incoming tea-colored river water, which carries dissolved organic matter that remote sensors mistake for chlorophyll. Additional complexity comes from the unusual ways in which phytoplankton have adapted to the Arctic's extremely low light. "When you use global satellite remote sensing algorithms in the Arctic Ocean, you end up with serious errors in your estimates," said Lewis.

Yet these remote-sensing data are essential for understanding long-term trends across an ocean basin in one of the world's most extreme environments, where a single direct measurement of NPP may require 24 hours of round-the-clock work by a team of scientists aboard an icebreaker, Lewis said. She painstakingly curated sets of ocean color and NPP measurements, then used the compiled database to build algorithms tuned to the Arctic's unique conditions. Both the database and the algorithms are now available for public use.

The work helps to illuminate how climate change will shape the Arctic Ocean's future productivity, food supply and capacity to absorb carbon. "There's going to be winners and losers," Arrigo said. "A more productive Arctic means more food for lots of animals. But many animals that have adapted to live in a polar environment are finding life more difficult as the ice retreats."

Phytoplankton growth may also peak out of sync with the rest of the food web because ice is melting earlier in the year. Add to that the likelihood of more shipping traffic as Arctic waters open up, and the fact that the Arctic is simply too small to take much of a bite out of the world's greenhouse gas emissions. "It's taking in a lot more carbon than it used to take in," Arrigo said, "but it's not something we're going to be able to rely on to help us out of our climate problem."

Credit: 
Stanford's School of Earth, Energy & Environmental Sciences

Movement ecology bears fruits: ATLAS supports map-based navigation of wild bats

image: Researcher attaches ATLAS tracking collar to bat

Image: 
Courtesy of David Shohami

(Jerusalem, July 10, 2020) -- When wild Egyptian fruit bats set out at night to forage in Israel's Hula Valley, they do so using advanced spatial memory and a flexible cognitive mapping of the fruit trees and other goals scattered in their foraging area. They seldom search randomly and their foraging patterns cannot be explained by simpler navigation mechanisms, a research team headed by Hebrew University of Jerusalem's Professor Ran Nathan has found.

The groundbreaking study, co-authored with Tel Aviv University Prof. Sivan Toledo, Hebrew U doctoral candidate David Shohami and other members of Nathan's group, is featured as the cover story for the current issue of Science magazine. It details the bats' cognitive map - the animals' mental representation of their own position relative to the surrounding environment - that helps them to move efficiently from any location to any of the many goals within their foraging area, even if the goal is out of their sight or smell range.

The existence of a cognitive map allows the bats to remember and return to favorable fruit trees, roosting caves and other goals. They use mapping and memory skills, rather than relying on path "directions" following numerous landmarks, specific cues originating from these goals, or simply finding these targets by chance.

To track the animals, the researchers had to overcome the limitations of GPS and other available wildlife tracking technologies. Although scientists have achieved key insights into animals' navigational capabilities from experiments on rats and other laboratory animals, limited battery size and the need to remotely retrieve data from GPS trackers prevented researchers from collecting large sets of data on wild animals in their natural habitats.

Alternative tracking methods such as radio telemetry have been used to track small wild animals, but they do not provide sufficiently detailed, long-term information on the movements, leaving researchers at an impasse.

"Up to now the technologies we had could not be used to track small wild animals in their natural habitats with enough detail required to test the existence of a cognitive map," says Prof. Nathan.

To solve the dilemma, Nathan teamed up with Toledo to develop an advanced "reverse-GPS" tracking system they called ATLAS. After a few years of development and refinement, Shohami used the system to collect a large dataset of 172 foraging Egyptian fruit bats comprising more than 18 million localizations collected over 3449 bat-nights across 4 years.

ATLAS movement data provided the means for detailed track analysis combined with translocation experiments and mapping of all fruit trees in the study area, spanning 88,200 hectares. The system provided researchers with detailed, accurate information from many individuals for relatively long periods at relatively low cost, showing that wild bats seldom search for food randomly, but instead repeatedly forage in goal-directed, long, and straight flights that include frequent shortcuts.

The team also ruled out alternative, non-map-based strategies by analyzing simulated tracks, time-lag embedding, and other analyses of the trajectory data.

The results present the most comprehensive evidence for a cognitive map from any wild animal studied since scientists first hypothesized the existence of a human-style cognitive map in 1948, says Nathan. Furthermore, the study marks a landmark for movement ecology, the academic discipline that Nathan pioneered in 2008 to study life on the move.

"Movement ecology has benefited from advances in tracking technology, but new ideas and novel insights have lagged behind. ATLAS has given us the keys to unlock previously unanswerable questions and will continue to shed light on a range of enigmatic natural phenomena," he says.

Credit: 
The Hebrew University of Jerusalem

Fine-tuning excited state of Ru(II)-photosensitizers for boosting CO2-to-CO conversion

image: Photocatalytic CO2 reduction with Ru-1-Ru-4 PSs and their photocatalytic mechanism.

Image: 
©Science China Press

Solar-driven reduction of CO2 into energy-rich fuels, such as CO, HCOOH, and CH3OH, has been conceived as a highly promising approach to solve energy crisis and environmental pollution. Throughout the molecular photocatalytic systems, numerous catalysts, such as complexes of Re, Ru, Fe, Co and Ni, have been developed with detail study of their catalytic mechanism. In light of their relative mature study, more and more attention has begun to shift to accelerate electron transfer between catalyst and antenna molecules to promote CO2 reduction. At present, the research in this field focuses on the formation of composite systems between photosensitizers and catalysts through chemical bonds, hydrogen bonds, etc. This system shortens the distance between photosensitizers and catalysts, thus improving the electron transport capability between them. However, these studies still have many disadvantages, such as lack of flexibility and great influence from external factors. Accordingly, it's highly necessary yet remains great challenging to develop alternative strategy for dramatically boosting photocatalytic CO2 reduction.

At present, improving photosensitization ability of PSs for enhancing photocatalytic performance for CO2 reduction is still in its infancy. In this field, the frequently used PSs are confined to prototypical MLCT (metal-to-ligand charge transfer) complexes, such as Ru(bpy)32+ and Ru(phen)32+ (Phen = 1,10-phenanthroline), where their excited state lifetime was usually less than 1 μs (τ= 600 ns for Ru(bpy)32+ and 360 ns for Ru(phen)32+ in CH3CN). It will be a promising way to boost CO2 reduction via adjusting excited state population and lifetime of these PSs to improve their sensitizing ability.

In the present work, researchers put forward a new strategy to greatly boost photocatalytic CO2 reduction by improving photosensitization ability of PSs. A family of Ru(II)-based PSs Ru-2, Ru-3, and Ru-4 were prepared by selective addition of pyrene / pyrenyl ethynylene to 3- and 5-positions of Phen in Ru(Phen)32+ (Ru-1) (Fig. 1). As the triplet state energy level gradually decreased from Ru-1 with 3MLCT state to Ru-4 with 3IL state, the triplet lifetimes of these complexes were gradually prolonged and their excited state oxidation potentials became less negative, providing a platform to compare the effect of PSs with different sensitizing ability on photocatalytic CO2 reduction.

The photocatalytic process was dominated by oxidation mechanism for Ru-1 - Ru-4-containing system (Fig. 2). From the view of kinetics, long-lived triplet state of PSs greatly contributed to intermolecular electron transfer / energy transfer. Thus stern-volmer quenching constants of PSs by C-1 were in the order of 4.4 × 103 M-1 for Ru-4 > 3.2 × 103 M-1 for Ru-3 > 9.6 × 102 M-1 for Ru-2 > 3.8 × 102 M-1 for Ru-1, which was proportional to their excited state lifetimes (Fig. 2D). From the thermodynamics viewpoint, excited state oxidation potentials of PSs determine the driven force of electron transfer from excited PSs to C-1. As shown in Fig. 2F, the absolute value of excited state oxidation potential was in the order of Ru-4

This work provides a new insight for dramatically boosting photocatalytic CO2 reduction via improving photosensitization.

Credit: 
Science China Press

How vaping companies are use Instagram to market to young people

image: Samples of the images scraped from Instagram.

Image: 
Aqdas Malik, Aalto University

E-cigarettes are highly addictive nicotine products with unclear health impacts, particularly on young people. Instagram is a visual social media platform which is wildly popular, particularly with young people. Researchers interested in public health at Aalto university in Finland studied how vaping is represented on the platform. By using artificial intelligence, they were able to analyse hundreds of thousands of posts from a 6-month period last year, and found that a large portion of posts are promoting controversial flavoured e-liquids to young audiences.

The research worked by downloading every image on Instagram that had a caption including "#vaping" on the network for June to November 2019. 'We knew this would be predominantly promotional material,' said Dr Aqdas Malik from the department of computer science who studies public health and the internet, 'but we were interested in what types of images these would be, and who was posting them.' In the end, they generated a database of over half a million pictures, which they then sorted using a neural network, which grouped the images into categories of pictures with similar features.

What the neural network showed was that 40% of the images - the largest proportion out of the 6 categories - were of vaping e-liquids. These were predominantly posted by Instagram profiles listed as business accounts. The prominence of posts about e-liquids is interesting from a public health perspective because, although many e-cigarette brands market themselves as "smoking cessation" devices, it has been shown by other studies that flavoured liquids are strongly linked to adolescent users taking up vaping in the first place. The USA banned the sale of flavoured liquids at the beginning of this year specifically to help tackle the huge growth of teenage vaping, and other countries are looking to do the same.

'While print and broadcast media has clear rules and regulations about what can and cannot be advertised, and what constitutes advertising, we don't see this on social media,' said Dr Malik. 'I think we need stricter laws and rules on how we allow these products to be seen on these networks. Any 12-year-old with a phone can get an account and bypass the age-rules for seeing what's posted here, and the potential health implications are significant.' 60% of all the posts using the #vaping hashtag were from business accounts. Over 70% of Instagram users are under 35, and over 35% of its users are under 24 years old. 'It's a huge grey area in terms of advertising regulations, especially regarding promotion towards younger audiences' Dr Malik said.

Credit: 
Aalto University

Structural analysis of COVID-19 spike protein provides insight into its evolution

Researchers at the Francis Crick Institute have characterised the structure of the SARS-CoV-2 spike protein as well as its most similar relative in a bat coronavirus. The structures provide clues about how the spike evolved and could help inform vaccine design.

A characterising feature of SARS-CoV-2, the virus that causes COVID-19, is the protein spikes which cover the surface, which the virus uses to bind with and enter human cells.

Analysing the structure of these spikes could provide clues about the virus' evolution. It is not yet known how SARS-CoV-2 evolved to infect humans and whether this happened directly from coronaviruses in bats or via an intermediary species.

In their study, published in Nature Structural & Molecular Biology, the researchers characterised the spike protein in high resolution using a technique called cryo-electron microscopy, which allowed them to achieve a greater level of detail than previously reported structures. They then compared this structure to the spike protein of a bat coronavirus, RaTG13, which has the most similar spike to that of SARS-CoV-2.

While the spikes as a whole were over 97% similar, the researchers found a number of significant differences at the location where SARS-CoV-2 binds with a receptor on human cells, called ACE2, and at the surfaces that keep the subunits of the spike together.

These differences mean the spike of SARS-CoV-2 is more stable and is able to bind around 1,000 times more tightly to a human cell than this bat virus.

Based on their findings, the researchers suggest it is unlikely that a bat virus similar to RaTG13 could infect human cells. This supports the theory that SARS-CoV-2 is the result of different coronaviruses coming together and evolving over time, potentially also through several host species.

Antoni Wrobel, co-lead author and postdoctoral training fellow in the Structural Biology of Disease Processes Laboratory at the Crick, says: "The spike is the entry key that allows SARS-CoV-2 into human cells. Changes in the virus' genome, which affect the spike's structure, therefore have potential to make the virus either more or less able to enter the host's cell."

"At some point in the evolution of this virus, it seems to have picked up changes, like the differences we found, which made it able to infect humans."

Donald Benton, co-lead author and postdoctoral training fellow in the Structural Biology of Disease Processes Laboratory at the Crick, says: "The exact process of how SARS-CoV-2 evolved remains unclear and is something many researchers are trying to piece together. Our work provides a piece of this puzzle, as it suggests that the virus did not come straight from the bat coronaviruses currently known."

Steve Gamblin, group leader of the Structural Biology of Disease Processes Laboratory at the Crick says: "The world was caught off guard by SARS-CoV-2. Examining the structure of this virus, and its likely precursor, helps us understand where it came from, and how it interacts with human cells."

The Crick researchers will continue to study the structure of the virus, with a view to finding further clues as to its evolutionary path.

The spike protein structures are open-access, so other researchers can use these in their work and to aid with drug discovery and vaccine design.

Credit: 
The Francis Crick Institute

Sodium found to regulate the biological clock of mice

A new study from McGill University shows that increases in the concentrations of blood sodium can have an influence on the biological clock of mice, opening new research avenues for potentially treating the negative effects associated with long distance travel or shift work.

The findings, published in Nature by former McGill PhD student Claire Gizowski and Charles Bourque, a professor in McGill's Department of Neurology-Neurosurgery, are the first to show that injecting mice with a salt solution leads to the activation of neurons associated with the brain's master circadian clock - the suprachiasmatic nucleus (SCN).

Our biological clock - or circadian rhythm - adapts our body's cells and organs to changing requirements at different times of day. Prolonged disruption of these rhythms because of jetlag or shift work can lead to adverse health effects.

Though it is well established that light is the primary factor regulating our body's biological clock, it was unknown if or how physiological factors could regulate the SCN.

"Our study is the first to show that the SCN is listening to physiological signals and that such signals can in fact regulate clock time," says Bourque.

Gizowski and Bourque were able to show that salt-sensitive neurons found in a specific region of the brain - the organum vasculosum of the lamina terminalis - are capable of activating the brain's master circadian clock at a time of day when it is normally silent.

"This suggests that there could be ways by which we could speed up the clock, which could be useful to adapt more quickly to the time change associated with long distance travel, or when our work schedule is shifted by several hours," explains Gizowski.

The researchers now hope to establish if natural increases in blood sodium levels - through eating - have the same effect and whether or not these also occur in humans.

"One concern is that although ingestion of small amounts of salt is pleasant and not dangerous, it can be toxic when consumed in large amounts," Bourque adds. "Much more work is needed to examine if this finding is applicable to humans in a safe and practical way."

Credit: 
McGill University

Desert island discs: Music listened to in younger years defines us forever, research finds

Researchers at the University of Westminster and City University of London analysing the music record choices of guests on BBC Radio 4's Desert Island Discs programme has found that the music we listen to between the age of 10 and 30 define us for the rest of our lives.

Music from this time which the researchers call 'self-defining period' connects an individual to the people, places, and times that are significant to their identity. The study reveals that people imagining themselves in isolation not only prefer music reminding them of a time when they were aged between 10 and 30, but also they are most likely to choose music that reminds them of an important person playing to the sense that someone is with them, or an important turning point in their life as a powerful way to strengthen their sense of self.

In Britain's longest running radio programme guests are invited to imagine they are being cast away to a desert island and are asked to choose eight records to take with them. The researchers analysed the responses of 80 Desert Island Discs guests to reveal how people choose music that is important to them and whether they are more likely to select music from a particular time in their life if they can choose anything they like.

Half of all musical choices were seen to be important between the ages of 10 and 30, a period that has been commonly known as the 'reminiscence bump'. However, this new study reveals that it is more helpful to think of this period as a 'self-defining period' because it is characterised by enduring memories that support our sense of who we are. They suggest that listening to music is typically a key feature of this age and that music is also intrinsically linked to the developing self.

The power of music in identity formation is well-demonstrated through the reasons why people select certain records on Desert Island Discs. The most frequent reason for choosing a song (17%) was that it reminded the guest of their relationship with a specific person, such as a parent, partner or a friend, followed by a memory of a period of time (16.2%) such as reminding someone of their childhood or "remembering playing this at home over and over again". The third most popular explanation for choosing a record was the song's connection to specific memories relating to the formation of identity through life-changing moments (12.9%). Such reason was given by Bruce Springsteen, who said that the Beatles song "I want to hold your hand" had inspired him to pick up the guitar and start a band.

Professor Catherine Loveday, Neuropsychologist at the University of Westminster and Lead Researcher, said: "Guests frequently chose songs because they were related to important memories that occurred during teenage years. This extends previous findings by showing that music from this time has particular meaning, primarily because it relates to memories from this very important developmental period of our life. Unlike previous studies, this study shows that this occurs even in a completely naturalistic setting, where people are not constrained by experimental settings and have a completely free rein on their musical choices.

"Because the premise of the programme is that people imagine themselves in isolation, this research has relevance to anyone who becomes isolated, including during lockdown measures in the current coronavirus pandemic, or who becomes displaced from their everyday environment, such as residents in care homes, refugees or hospital patients."

Working with an international team, the researchers are now working on a new study that invites people to create and share their own Deserts Island Disc experience. The survey will provide important new insights into the benefits of music and reminiscence and can be accessed from http://instrumentaljourneys.com/diy-desert-island-discs

Credit: 
SAGE

Distorted passage of time during the COVID-19 lockdown

A survey conducted in the U.K. suggests that social and physical distancing measures put in place during the Covid-19 pandemic significantly impacted people's perception of how quickly time passed compared to their pre-lockdown perceptions. Ruth S. Ogden of Liverpool John Moores University, U.K., presented these findings in the open-access journal PLOS ONE on July 6, 2020.

Previous research suggests that one's perception of how quickly time passes can vary according to one's emotions, the number of daily tasks one must perform, and other factors. However, most of that research has been limited to normal day-to-day life. Social and physical distancing measures put in place during the Covid-19 pandemic provide a unique opportunity to examine how significant changes to life's daily routine impact time perception.

Ogden prepared an online questionnaire asking participants to rate on a sliding scale how quickly they felt time was passing compared to normal, both over the course of a single day and over a full week. The questionnaire also evaluated people's emotional state, task load, and satisfaction with levels of social interaction. The final analysis included 604 participants in the U.K. who answered the questionnaire between April 7 and April 30, 2020.

Ogden found that more than 80 percent of participants experienced changes to how quickly they perceived time passing during lockdown compared to pre-lockdown. Those who were older or less satisfied with their current levels of social interaction were more likely to experience slower passage of time over the course of a day or week. Slower passage of time over the course of a day was also associated with higher stress and a lower task load.

These findings suggest that significant changes to life's daily routine distort perception of time. Future research could look deeper into the effects of specific factors, such as whether social satisfaction influences perception of time during normal daily life, or if its significance in this study is due to the unique social impacts of the Covid-19 lockdown.

Author Ruth Ogden notes: "80% of people experienced distortion to the passage of time during the lockdown. Lockdown passing more slowly than normal was associated with older age and reduced satisfaction with social interactions."

Credit: 
PLOS

Surprisingly many peculiar long introns found in brain genes

image: In a recent study of genes involved in brain functioning, their previously unknown features have been uncovered by bioinformaticians from the Moscow Institute of Physics and Technology and the Institute of Mathematical Problems of Biology, RAS.

Image: 
MIPT Press Office

In a recent study of genes involved in brain functioning, their previously unknown features have been uncovered by bioinformaticians from the Moscow Institute of Physics and Technology and the Institute of Mathematical Problems of Biology, RAS. The findings are reported in PLOS One.

DNA is the molecule that stores information about the structure and functioning of living organisms. This "book of life" is a carefully arranged nucleotide-by-nucleotide record on every protein and RNA synthesized in a cell. Each DNA fragment corresponding to a particular protein is called a gene, and the pattern for translating a DNA sequence into the amino acid sequence of the associated protein is known as the genetic code.

Back in the 1960s, biologists discovered the basic properties of the genetic code, including its so-called triplet nature: Each amino acid is encoded by a codon -- a sequence of three nucleotides. For example, the sequence adenine-thymine-guanine encodes the amino acid called methionine, which usually begins the proteins of all living beings at the stage of synthesis.

Since the genetic code was discovered, scientists have learned a lot about gene structure. For example, they found that a kind of fragmentation was characteristic for the genes of eukaryotes -- organisms whose cells have a nucleus. Namely, genes contain noncoding regions referred to as introns. They are removed from the sequence in a process called splicing. The remaining regions that actually encode parts of the protein are termed exons.

Researchers have proposed a number of hypotheses as to how long ago and in what way introns originated, and what their functions are. For one thing, introns enable alternative splicing. This refers to the selective joining of certain exons but not others. The consequence is that more than one protein sequence can be produced based on the template of a single gene. As a result, the number of distinct proteins in cells is far greater than the number of genes.

Another intron-enabled process important for gene evolution is exon shuffling. This involves a kind of atypical recombination, where a foreign exon can become incorporated into a gene where it does not belong, giving rise to a new gene.

The currently available full-genome sequences of many organisms have made it possible to study the evolution of introns in detail. They are now known to vary in length from several dozen pairs to 10,000 times as many. Introns are also distinguished by phase, depending on where they occur relative to a codon. Phase 0 introns are found in between codons, whereas phases 1 and 2 occur immediately after the first or second nucleotide in the codon, respectively.

Now a team of bioinformaticians from MIPT and IMPB RAS has examined the relation between intron phase and length in humans and mice.

"No one had thought of investigating a potential link between intron length and phase before us. Common sense says there shouldn't be any connection at all, similarly to how a person's height has nothing to do with their eye color," commented Eugene Baulin, a researcher at the Applied Mathematics Lab at IMPB RAS, and the Algorithms and Programming Technologies Department at MIPT.

To their surprise, the study's authors identified a group of genes containing an unusually large number of phase 1 introns that were over 50,000 nucleotide pairs long. Moreover, these turned out to be genes involved in nerve impulse transmission in the brain.

A detailed analysis of numerous scientific publications enabled the team to put the fragments of knowledge together and arrive at a unified understanding. It turned out that in most cases, the phase 1 introns in the group of genes in question resulted from the presence of a particular amino acid sequence at the beginning of the protein. This so-called signal peptide serves to direct the protein to where it should perform its function. In the case of nerve cell receptors, that means to the plasma membrane.

As for the introns being fairly long, this also indirectly has to do with the signal peptide. In such proteins, the signal peptide is always located at the beginning of the molecule, and the DNA region encoding it is found at the start of the gene. And it is precisely there, at the beginning of a gene, that long introns tend to occur, because they contain regulatory DNA sequences important for the protein's synthesis.

The study reveals a clear and complete picture of how exon shuffling works and what role long phase 1 introns play in it. "That mechanism speeds up the evolution of intercellular and membrane proteins in animals, particularly the younger ones [evolutionary speaking], and these are the proteins that enable nerve impulse transmission in brain cells," Baulin added.

Credit: 
Moscow Institute of Physics and Technology

Sensation seekers, risk-takers who experience more bitterness apt to drink IPAs

image: A lager beer and two pale-ale-style beers were chosen as the test stimuli. The specific beer samples were selected by research staff following benchtop tasting of various commercial pale-ale-style beers sold in Pennsylvania. To represent the range of bitterness in commercial pale ales, researchers selected one pale ale that was strongly bitter and one that was moderately bitter.

Image: 
Molly Higgins, Penn State

People who seek novel and powerful sensations and are more prone to taking risks -- and who perceive bitter tastes more intensely -- are more likely to prefer bitter, pale-ale-style beers and drink them more often, according to Penn State sensory researchers, who conducted a study that involved blind taste tests and personality assessments.

The results of the study, which involved more than 100 beer consumers, were unexpected, explained researcher John Hayes, associate professor of food science, because previous research typically indicates that greater perceived bitterness leads to decreased intake of bitter foods and drinks.

"Traditionally, most researchers find that people who experience bitterness more intensely avoid bitter food or drink -- so with heightened bitterness, they like it less, and therefore consume it less," he said. "But here, we find that people who seek higher sensations and are more risk-taking, they like bitter beer such as India pale ales, if they also have greater bitter taste perception."

The connection between food liking and personality has been seen before, noted Hayes, director of Penn State's Sensory Evaluation Center. In a study spearheaded by one of his former doctoral students, his research group in the College of Agricultural Sciences found robust links between the liking of spicy foods and the high-sensation-seeking, risk-taking personality traits. Studies done in Mexico and Italy also have revealed similar findings.

These results highlight the importance of considering personality traits such as sensation seeking when considering the relationship between bitterness perception and the liking and intake of bitter food and beverage products, said lead researcher Molly Higgins, who will receive her doctoral degree in food science this August.

"Our data contradict the classic view that bitterness is merely an aversive sensation that limits intake. We found that increased bitterness perception does not always lead to decreased liking and intake -- rather, it's a positive attribute in some products for some consumers."

In Higgins' study, 109 beer consumers rated liking and intensity of two pale ales and a lager, and the intensity of two bitter solutions -- quinine, the compound that makes tonic water bitter, and hops extract Tetralone -- under blind laboratory conditions. Participants also completed intake and personality questionnaires. A liking ratio for each beer was calculated from each participant's liking for that specific beer and their total liking for all beers.

Participants, about half men and half women, most in their 30s, were classified as weekly, monthly or yearly pale-ale consumers using intake data. Using intensity ratings, personality measures and other parameters, the researchers developed models to predict liking ratios and beer-intake frequency.

A lager beer and two pale-ale-style beers were chosen as the test stimuli. The specific beer samples were selected by research staff following benchtop tasting of various commercial pale-ale-style beers sold in Pennsylvania. To represent the range of bitterness in commercial pale ales, researchers selected one pale ale that was strongly bitter and one that was moderately bitter.

To represent a lager-style beer with low bitterness, research staff selected Budweiser. The pale-ale-style beers used in the study were Founder's All-Day IPA Session Ale as the moderately bitter ale, and Troeg's Perpetual IPA Imperial Pale Ale, as the strongly bitter ale.

A significant interaction between sensation seeking and quinine bitterness was found for the liking ratio of the imperial pale ale, Higgins pointed out. But the relationship was not straightforward.

"The interaction revealed liking of the pale ale increased with sensation seeking but only if quinine bitterness was also high," she said. "Intake models showed increased odds of frequent pale-ale intake with greater quinine bitterness and lower liking for lager beer. These data suggest liking and intake of pale ales is positively related to sensation seeking and bitter taste perception."

The findings, recently published in Food Quality and Preference, suggest that further research on the relationship between personality traits and the liking and intake of bitter foods and beverages may lead to new strategies to promote consumption of healthy bitter foods, Higgins contended.

"Avoidance of bitter foods can impact health negatively, because bitter foods such as cruciferous vegetables, green tea and grapefruit contain healthy compounds like flavonols, which are reported to have antioxidant and anticarcinogenic properties," she said.

Alyssa Bakke, staff sensory scientist in food science, also was involved in the research.

Credit: 
Penn State

Contracting COVID-19, lifestyle and social connections may play a role

Summary: Current research indicates that unhealthy lifestyle choices, including smoking and lack of exercise, along with emotional stressors like social isolation and interpersonal conflicts are important risk factors for developing upper respiratory infections. It is possible these same factors also increase the risk of contracting COVID-19.

Unhealthy lifestyle choices, like smoking and avoiding exercise, are known risk factors for certain cancers and cardiovascular disease. A growing body of research reveals that these risk factors and a lack of supportive social connections can also increase the risk of developing respiratory infections, like the common cold and influenza.

A new article published in the journal Perspectives on Psychological Science explores how lifestyle, social, and psychological factors also may increase the risk of contracting COVID-19.

"We know little about why some of the people exposed to the coronavirus that causes COVID-19 are more likely to develop the disease than others," said Sheldon Cohen, a professor of psychology at Carnegie Mellon University and one of the authors on the paper. "Our research on psychological factors that predict susceptibility to other respiratory viruses may provide clues to help identify factors that matter for COVID-19."

Through a series of studies spanning more than 30 years, Cohen and his team examined how lifestyle, social, and psychological factors affect whether or not healthy adults exposed to respiratory viruses become ill. This work focused on eight viral strains that cause the common cold and two that cause influenza.

"In our work, we intentionally exposed people to cold and influenza viruses and studied whether psychological and social factors predict how effective the immune system is in suppressing infection, or preventing or mitigating the severity of illness," said Cohen. "We found a strong correlation between social and psychological stressors and increased susceptibility."

Intriguingly, the researchers also found that social integration and social support offer a protective shield against respiratory infection and illness.

Until now, the only tactics to slow the spread of coronavirus have been behavioral changes that reduce the probability of being exposed to the virus, such as stay-at-home measures and social-distancing requirements. These same behaviors, however, are often associated with interpersonal stressors, like loneliness, loss of employment, and familial conflict. According to the researchers, these stressors may be powerful predictors of how a person will respond if exposed to coronavirus because of the stressors' direct physiological effects on immunity and their psychological factors, which are thought to have their influence through the mind-body connection.

Cohen's work demonstrates that psychological and social stressors are associated with an overproduction of proinflammatory chemicals known as cytokines in response to cold and influenza viruses. In turn, this excess of inflammation was associated with an increased risk of becoming ill.

Similarly, research on COVID-19 has shown that producing an excess of proinflammatory cytokines is associated with more severe COVID-19 infections, suggesting that a stress-triggered excessive cytokine response might also contribute to excessive inflammation and symptoms in COVID-19 patients.

Cohen and his colleagues acknowledge that, as of now, there are no firmly established links between behavioral and psychological factors and the risk for disease and death in persons exposed to the corona virus that causes COVID-19. However, their prior body of research may be relevant to the current pandemic because, they note, the most potent predictors of disease, interpersonal and economic stressors, are the types of stressors that are commonly experienced among those who are isolated or in quarantine.

"If you have a diverse social network (social integration), you tend to take better care of yourself (no smoking, moderate drinking, more sleep and exercise)," said Cohen. "Also if people perceive that those in their social network will help them during a period of stress or adversity (social support) then it attenuates the effect of the stressor and is less impactful on their health."

Credit: 
Association for Psychological Science

Born to be a cannibal: Genes for feeding behavior in mandarin fish identified

image: Young S. chuatsi preying on a live fish.

Image: 
HZAU

Some mandarin fish species (Sinipercidae) are pure fish-eaters, which feed exclusively on living juvenile fish - also of their own species. A research team led by the Chinese Huazhong Agricultural University (HZAU) and the Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB) has described the genome of four mandarin fish species and thus also identified genes for cannibalistic eating behaviour. Knowledge of the connections between the genome and feeding behaviour is of interest for sustainable aquaculture.

Most fish larvae feed on easily digestible, small zooplankton. Not so some species of mandarin fish. These are pure "fish-eaters" already after hatching and feed on young fish of other fish species and on conspecifics. This cannibalism leads to a high mortality rate of juvenile fish and to economic losses in aquaculture.

32 genes make the difference to cannibals

The researchers compared the genome sequences of different species of mandarin fish and were thus able to trace the evolution of 20,000 genes over a period of 65 million years. They were able to link many genes with species-specific characteristics. "For 32 of these evolving genes, we were able to experimentally demonstrate different gene expression in mandarin fish species that are common to other food and in pure fish-eating species," explains Ling Li, one of the first authors of the study and guest scientist from HZAU at the IGB.

Rapid evolutionary adaptation in predatory behaviour

Mandarin fish are aggressive predators. During the complex genome analysis, the researchers identified so-called candidate genes that are associated with particularly high aggression and affect behaviour. "Our genome analyses show the evolutionary development of mandarin fish. They have adapted rapidly to changing environmental conditions, especially with regard to their feeding behaviour. Today, some mandarin fish species are more aggressive predators than others due to their genetic predisposition," says Prof. Xu-Fang Liang from HZAU.

"Research on the relationship between the genetic code and feeding behaviour is an important basis for the sustainable aquaculture of these fish. In future, fish farmers will be able to use marker based selection to choose fish for breeding where the genome indicates less predatory behavior - and thus reduce losses," summarises Dr. Heiner Kuhl, leading bioinformatician of the project from the IGB.

High-throughput genome research at IGB

The reference genome for Siniperca chuatsi is one of the highest quality fish genomes to date. It was analysed using third-generation sequencing techniques and has very high sequence continuity and almost complete reconstruction of the 24 chromosomes. The high-quality reference genome enabled the cost-efficient sequencing of three other species from the Sinipercidae family by means of comparative genomics. This approach to create genome sequences for entire taxonomic families of organisms could serve as a blueprint for large-scale genomic projects.

Credit: 
Forschungsverbund Berlin

About half of health care workers positive for COVID-19 by serology have no symptoms

image: Wesley Self, MD, associate professor of Emergency Medicine at Vanderbilt University Medical Center and lead investigator for the IVY Network.

Image: 
Vanderbilt University Medical Center

The IVY Research Network has completed initial studies evaluating the epidemiology of COVID-19 in health care workers and patients.

Among 249 front-line health care workers who cared for COVID-19 patients during the first month of the pandemic in Tennessee, 8% tested positive for COVID-19 antibodies by serology testing, suggesting they had contracted COVID-19 in the first several weeks of taking care of COVID-19 patients. Among these health care workers with positive serology results, 42% reported no symptoms of a respiratory illness in the prior two months. This suggests that front-line health care workers are at high risk for COVID-19 and that many health care workers with the virus may not have typical symptoms of a respiratory infection. These results were published in the journal Clinical Infectious Diseases on July 6.

"Our results suggest that screening health care workers for COVID-19 even when they don't have any symptoms could be important to prevent the spread of the virus within hospitals," said Wesley Self, MD, associate professor of Emergency Medicine at Vanderbilt University Medical Center and lead investigator for the IVY Network.

Investigator Bo Stubblefield, MD, instructor of Emergency Medicine, added, "We are continuing to study COVID-19 in front-line health care workers across the country to better understand what may be done to decrease their risk of infection, such as using specific types of personal protective equipment."

In a separate study, the IVY investigators studied 350 patients across 11 medical centers in the U.S. who tested positive for COVID-19; 54% of these patients reported no close contact with another person known to have COVID-19 in the two weeks before getting sick.

"With over half of COVID-19 patients not identifying a clear source of their infection, this study reinforces the need for practical measures to reduce the spread of the virus, such as social distancing and the use of face coverings when out in public," Self said.

Additionally, 40% of COVID-19 patients in the study remained symptomatic two weeks after a positive COVID-19 test, showing that patients with COVID-19 tend to remain ill longer than with other respiratory infections, such as influenza. The results were published by the journal Morbidity and Mortality Weekly Report on June 30.

The IVY Network is a collaborative research group of multiple medical centers in the U.S led by Vanderbilt University Medical Center. It is funded by Centers of Disease Control and Prevention (CDC) to conduct research on severe respiratory infections, including COVID-19 and influenza.

Credit: 
Vanderbilt University Medical Center