Culture

University of Bath research shows how to improve emergency service response to terrorist incident

video: Dr Olivia Brown of the University of Bath School of Management discusses her new research which shows flaws in the response of emergency services, such as those seen in the Manchester Arena bombing of 2017, that could be addressed with a new three-phase approach

Image: 
Olivia Brown

The Manchester Arena terrorist bomb attack in 2017 exposed flaws in the response of emergency services that could be addressed with a new three-phase approach, research by the University of Bath School of Management shows.

Current government guidelines outline a two-phase structure of 'response and recovery', which researchers discovered hampered effective communication between agencies, created over-reliance on centralised Police decision-making, and inhibited other services' ability to take initiative earlier in an emergency.

"To better prepare responders for emergencies we recommend a three?phase structure of 'response/resolve/recovery' is introduced in place of the current guidelines that outline a two?phase structure of response and recovery. Introducing the 'resolve' phase would allow and encourage other emergency services to act earlier and more effectively," said Dr Olivia Brown of the University of Bath.

Brown and her co-researchers from Lancaster University studied communication and coordination between emergency services during the response to a simulated terrorist incident. They worked with 30 commanders from 11 agencies, including the Police, Fire and Rescue, Ambulance, Military and local and central government.

They studied three phases: 1 - when the incident was ongoing; 2 - 48 hours after the incident; and 3 - three weeks after the incident.

Brown said communications were dominated by the Police in the first phase - a typical and sensible approach in the immediate aftermath of an incident where there remained a threat to life. However, they discovered that even after that threat had been resolved, other agencies became overly reliant on the Police to maintain the communication network, hampering the emergency response. And the Police struggled to act on important information from their emergency service partners.

"Our findings suggest that the Police were so focused on delivering the overall strategy of the response that they failed to attend to important information provided by other agencies and to manage the information flow across the network. This ultimately disrupted coordination and caused delay and uncertainty," she said.

Brown said a similar phenomenon was noted in the report reviewing the Manchester Arena attack, in which the demands placed on the Police commander to implement decisions and deal with the immediate aftermath of the explosion contributed to their lack of communication with the Fire Service located at a different site. This poor communication contributed to a two-hour delay in the deployment of the Fire Service to the site of the incident, which meant that their skills and expertise could be not be utilised until later on in the response.

Brown said decentralized communication structures should be introduced in the early phases of an emergency to improve decision?making across several specialised and diverse teams. Other agencies needed to be empowered to intervene on their own initiative once Police had addressed any immediate threat to life.

"Take the response to a terrorist incident as an example - the Police are tasked with mitigating any further threat, cordoning off the scene and collecting evidence, whereas the Ambulance service must quickly begin accessing and triaging casualties. An effective response to the incident cannot be achieved by one agency alone and instead rests on the ability of teams to work cohesively under immense pressure," she said.

Brown said the study showed that, as the incident evolved, the involvement of other agencies increased and communication became less centralised. That resulted in improved coordination, more joint decision-making, less uncertainty and a better use of the diverse expertise of all agencies.

Brown said their research showed the three-phase structure of 'response/resolve/recovery' more accurately described the behaviours of responders during emergencies than the existing 'response/recovery' structure outlined in government guidelines.

"Changing procedural guidelines to a three-phase structure may empower other agencies to get involved in decision making before the response transitions into the recovery phase," she said.

Brown suggested 'boundary spanners' - specially assigned team members tasked with managing the flow of communications across teams and having a comprehensive view of an emergency incident from its very beginning - may be one solution to the communication issue.

Credit: 
University of Bath

Skeletal muscle loss exacerbated by diabetes improved with oligo DNA

image: myoDN recovers the impaired muscle differentiation of patients with type 1 and type 2 diabetes

Image: 
Modified from Nakamura et al., Frontiers in Physiology (2021) 12: 679152

Skeletal muscle is the largest organ in the body that accounts for 30 to 40% of body weight and is responsible for multiple functions such as energy metabolism and heat production. However, skeletal muscle mass is reduced in some diabetics, and that muscle loss correlates with mortality. It has been reported that the differentiation of myoblasts, which are the muscle precursor cells, is reduced in diabetic patients, and this is thought to be one of the underlying causes of muscle loss.

Assistant Professor Tomohide Takaya of Shinshu University recently reported that oligo DNA derived from the genome sequence of lactic acid bacteria promotes differentiation into skeletal muscle by binding to the target protein nucleolin in myoblasts. This "muscle-forming oligo DNA" (myoDN) has potential for use in nucleic acid drugs for various muscle diseases. In this study, the group examined whether myoDN improves the differentiation of myoblasts, which is exacerbated by diabetes.

Myoblasts collected from healthy subjects, patients with type 1 diabetes, and patients with type 2 diabetes were used for this experiment. Compared to healthy subjects, diabetic myoblasts had a reduced ability to differentiate into skeletal muscle. Remarkably, administration of myoDN improved skeletal muscle differentiation exacerbated by diabetes. The group also found that glucose and fatty acids, which are increased in the blood of diabetic patients, induce an inflammatory response in myoblasts, and myoDN suppresses these inflammatory responses.

It is thought that myoDN is a nucleic acid molecule that is effective in reducing muscle mass associated with diabetics. Currently, there is no effective therapeutic agent for muscle wasting, and the action of myoDN, which promotes skeletal muscle differentiation, is unique. myoDN is effective for healthy subjects with various backgrounds and type 1 and type 2 patients. On the other hand, analysis using multiple myoblasts revealed that there are individual differences in the effects of myoDN, and issues for clinical application were also clarified.

In the future, it will be necessary to expand the scope and test in order to clarify the cause of individual differences. Diseases other than diabetes such as cancer and heart failure also cause muscle wasting. The group hopes to verify whether myoDN promotes skeletal muscle differentiation in these diseases as well. The ultimate goal is to apply myoDN as an effective nucleic acid drug for muscle wasting associated with various diseases.

Credit: 
Shinshu University

Geological riddle solved: Roof of the World has gotten higher

GEOLOGY There has long been controversy about whether the world's highest region, Tibet, has grown taller during the recent geological past. New results from the University of Copenhagen indicate that the 'Roof of the World' appears to have risen by up to 600 meters and the answer was found in underwater lava. The knowledge sheds new light on Earth's evolution.

Tibet is referred to as the Roof of the World for good reason. With an average altitude of 4,500 meters above sea level and the world's two highest peaks, Mount Everest and K2, the vast Himalayan mountain range towers higher than anywhere else on Earth.

But the Tibetan plateau's height has been the subject of academic controversy for many years. Some researchers believe that the area has been as high as it is today for most of its existence, while others believe that the area has increased in height over the past 20 - 30 million years. It is a riddle that until recently has stood and flickered unanswered in the wind.

With the help of new analyses of the Indian Ocean seabed and calculations of the movement of Earth's tectonic plates, a researcher from the Department of Geosciences and Natural Resource Management at the University of Copenhagen has contributed new answers to the disagreement.

"By looking at older data of Tibet's emergence and combining it with new geological data from the Indian Ocean, we are pretty certain that there was a major geological change in Tibet about 15-18 million years ago, one that caused the wide area to rise between 300 and 600 meters," explains Associate Professor Giampiero Iaffaldano, the study's main author.

A slow, head on collision between the India subcontinent and Eurasia

The change is due to a head on collision between what are today India and China. India was originally located much further south, but the tectonic plate upon which India lies gradually moved northwards over millions of years and closer to China, until they finally collided to form Tibet.

Using plant fossils and geochemical analyses of rocks found in the mountainous region, some scientific researchers have been quite sure that Tibet looked the way it does today as far back as 20-30 million years ago and that its altitude has not changed over time.

Other researchers have believed that the prolonged and decelerating collision between India and China was caused by Tibet shooting upwards as much as two kilometers over a few million years. But according to Associate Professor Giampiero Iaffaldano, the answer is found somewhere in between.

"What the study contributes to, is actually a combination of the two previous hypotheses, different data sets and conclusions. What I've done is take a closer look at the speed of the India-China collision using Indian Ocean geological data that has only recently become available to the public," he says.

Finding an answer at the bottom of the Indian Ocean

Continuously through time, hot stones and other material are spat from Earth's interior onto the ocean floor. They have much to reveal about the movements of Earth's tectonic plates. Encoded within these lavas are records of Earth's magnetic polarity - the direction of Earth's north and south poles.

Polarity has reversed several times in Earth's history, meaning that North has become South and vice-versa. And, scientific researchers know roughly when these flips occurred. As such, they can trace tectonic plates to specific places and times during Earth's history using their magnetization along a so-called geomagnetic timescale.

"A closer look at this type of data held the answer to the question of whether Tibet has gotten higher or not. It has proven tremendously useful to calculate the speed of India's collision with China from geomagnetic data. More and more of such data, often originally collected for purposes other than fundamental scientific research and thereby not publicly available, is now being released and used by scientists," explains Giampiero Iaffaldano and adds:

"This new knowledge about Tibet is important for better understanding of Earth's evolution and the metods used could turn out usefull in future studies."

Credit: 
University of Copenhagen - Faculty of Science

To sting or not to sting?

image: Alerted honey bee (Apis mellifera)

Image: 
Morgane Nouvian

When do bees sting and how do they organise their collective defence behaviour against predators? An interdisciplinary team of researchers from the Universities of Constance and Innsbruck has provided new insights into these questions. Their study, published in BMC Biology, combined behavioural experiments with an innovative theoretical modelling approach based on "Projective Simulation". It shows that individual bees decide whether to sting - or not - based on the presence and concentration of an alarm pheromone. The scientists suggest that each bee has a likelihood of stinging that is not constant, but shows at least two internal thresholds for the concentration of the pheromone: one to start stinging and one to stop stinging. The computational modelling also revealed how several environmental factors, such as the rate of predator attacks and predator diversity, likely drove the evolution of the honeybees' pheromone-based communication in their defensive behaviour.

High concentrations of alarm pheromone as a stop signal

When a honeybee colony is attacked by a predator or seriously disturbed by a human who - accidentally or intentionally - got too close to the hive, the bees of the colony launch a coordinated counterattack to defend the colony and to scare off the trespasser. An important stimulus for them to start chasing and stinging the intruder is the presence of an alarm pheromone, which the bees carry on their stinger. In the event of an attack, the pheromone is dispersed either actively - by guard bees - or automatically upon stinging - by recruited soldiers. Thus, it carries information not only about the presence of an attacker, but also about the extent of the colony's counterattack. "The more bees have stung the intruder, the more alarm pheromone has been released with each sting and the higher its local concentration," clarifies Dr Morgane Nouvian, a biologist from Konstanz and joint-lead author of the study together with Andrea López-Incera from Innsbruck.

To understand how individual bees from the hive may use this information to make the ultimate decision to sting for the good of the colony and possibly die as a result, the scientists observed individual stinging responses of Western Honeybees (Apis mellifera) from three colonies. Using different concentrations of natural and synthetic alarm pheromones and a dummy predator, they revealed that the aggressiveness towards the dummy - measured as the stinging likelihood - initially increases with the concentration of the alarm pheromones until it reaches a peak. However, at high concentrations, the aggressiveness drops back to a low level.

This is the first time decreasing aggressiveness at high pheromone concentrations has been demonstrated under controlled experimental conditions. "One possible function of this 'stopping' effect of high concentrations of the alarm pheromone could be to avoid over-stinging and unnecessary sacrifice when attacking an already defeated intruder," Nouvian suggests.

The "superorganism" as an evolutionary unit

In social insects, be they honeybees or other social species such as army ants, individuals often coordinate their actions for the benefit and survival of the colony. For this reason, evolutionary selection processes in these insects acts on the group rather than the individual level. "Normally, if an organism dies, it cannot pass on its genes to the next generation anymore. In a bee colony, however, it is the queen that is responsible for reproduction. If another bee dies defending the hive but saves the queen in the process, the colony will continue to reproduce," Nouvian exemplifies. Because the bee colony functions as a single 'superorganism,' the behaviours of the belonging individuals can only be understood through the collective outcome to which they contribute.

To further analyse their experimental results and address this peculiarity of the evolution of collective behaviours, the scientists used computational modelling based on so-called Projective Simulation, an approach originally developed by co-author Professor Hans Briegel and his colleagues from Innsbruck. In their agent-based model, each agent or "bee" has a very limited set of percepts - the concentration of the alarm pheromone and a signal that the predator is leaving - and actions - to sting or not to sting - relevant to the defence behaviour. "Our idea was to build a model that is realistic, yet minimal," explains Professor Thomas Müller, professor of philosophy at the University of Konstanz and co-author of the study. He continues: "We simulated a collective of these agents, which were called upon one after the other to perceive the current level of alarm pheromone at any given time. When a bee stings in response, the pheromone's concentration increases and the next bee's response depends on this new pheromone level."

A second important aspect of the model is that it includes a learning component: Neither the responses of individual bees nor the rules of interaction between them are predetermined. Instead, they "evolve" over many cycles of the simulation or, in other words, over many generations of the collective. "If the decisions of the individual agents are beneficial to the collective under certain environmental pressures, they are positively reinforced. This increases the likelihood that the next generation of agents will act similarly under identical conditions," Müller clarifies. Taken together, the agent-based approach with reinforcement learning at the group-level allowed modelling of the observed defensive behaviour of honeybees from the perspective of both, the individual bees and the collective.

Putting the model to the test

Using the model and different parameter combinations, predictions could be made about the possible influence of environmental pressures on the defensive behaviour of bees. For example, the simulations suggest that colonies adapt to the strongest predator they encounter. This means that colonies that primarily encounter weak predators, such as mice or toads, are less likely to sting at high pheromone concentrations than colonies that more frequently encounter strong and difficult-to-deter predators, such as bears. "For the survival of the colony, it makes perfect sense to be able to cope with the worst predator around, even if that means over-stinging some of the weaker predators," Nouvian describes.

The scientists also applied their model to the case of the notoriously aggressive "African bee", a subspecies of the Western honeybee. It has previously been suggested that the highly aggressive behaviour of this subspecies evolved in response to higher predation rates in the tropics and to highly specialised, hard-to-deter predators, such as honey badgers. Indeed, the simulation predicted that bee populations suffering from a high predation rate and predators that take a high number of stings before stopping their attack develop stronger defence responses than those that do not.

What's next?

"We were quite happy to see that our model supports the current hypotheses on how the higher aggressiveness of 'African bees' might have evolved. One of the next steps will be to collect empirical data from real bees in Africa to verify the results," Nouvian gives an outlook. Another step for the future is to model a more diverse population of bees. As mentioned before, there are at least two different types of bees involved in the defence attack of a real hive: guards and recruits. "In the current model, each bee in the collective followed the same decision-making process. Training a model with two different types of agents and comparing it with experimental data will be very interesting," Müller adds. In general, the modelling approach is highly versatile and can be applied to other tasks and species, providing a valuable new tool for studying the evolution of collective behaviour.

Credit: 
University of Konstanz

A plant-fungus partnership is at the origin of terrestrial vegetation

A long-standing theory assumes that terrestrial plants could only have developed by entering into a symbiosis with fungi, whereby the two organisms exchange resources in a mutually beneficial way. A new study by an international group of scientists has now confirmed this theory. By studying a liverwort species (a bryophyte related to mosses), the scientists succeeded in demonstrating that a lipid transfer takes place between the plant and the fungus similar to that already known to exist in plants with stems and roots - so called vascular plants. The study was led by French researchers from the Centre national de la recherche scientifique (CNRS) and the Université de Toulouse III - Paul Sabatier, in collaboration with the Institut national de la recherche agronomique (INRA) and has been published in Science on 21 May. Professor Dr Marcel Bucher from the Institute for Plant Sciences and the CEPLAS Cluster of Excellence on Plant Science in Cologne participated in the study and contributed essential genetic information at the beginning and experimental results on the molecular mechanism underlying the symbiotic exchange of lipids throughout the collaboration.

About 450 million years ago, the first plants left the freshwater to live on land. To do this, they had to adapt to the aridity and nutrient scarcity of the land. In the 1980s, the study of fossils led to the hypothesis that a plant-fungus alliance has been at the origin of plant vegetation. Previous studies have shown the existence of genes that are essential for the proper functioning of this symbiosis, particularly in vascular plants. In the present study, the scientists focused on a bryophyte resembling a succulent plant, for which such genes had not yet been studied: Marchantia paleacea. Validating this forty-year-old hypothesis allows the scientists to understand a stage that was crucial to the development of life on Earth.

By adapting the use of CRISPR, a molecular tool that allows DNA to be cleaved precisely, the team modified a gene predicted as 'symbiotic'. As in vascular plants, the interruption of lipid exchange between the plant and the fungus leads to symbiosis failure in the liverwort. 'The beauty of the work lies in the use of different complementary molecular genetic approaches which have shown that this "symbiotic gene" encodes a key regulator, a so-called transcription factor, which directly regulates the expression of other symbiosis genes, among them genes required for "feeding" the fungus,' Marcel Bucher remarked. These are involved in lipid metabolism and transport in cells in M. paleacea, leading to the transfer of valuable carbon derived from the photosynthetic plant host in the form of fatty acids as a building material and energy source to the fungal symbiotic partner.

The results of the study show that the common ancestor of liverworts and vascular plants, which colonised dry land, must therefore have exchanged lipids with the fungus, as do the plants of today. Thus, 450 million years later, one of the secrets of life's first steps on land has finally been elucidated.

Credit: 
University of Cologne

Can racial identity protect black teens from racism-related stress? It's complicated

A recent study finds that the vast majority of Black adolescents have experienced racism, that they experience anticipatory stress about experiencing racism again, and that their racial identity can influence that stress in a variety of ways.

"We know that racism is stressful," says Elan Hope, corresponding author of the study and an associate professor of psychology at North Carolina State University. "Part of that stress is anticipatory - waiting for the next racist thing to happen. But not everyone experiences this stress the same way. We wanted to know how racial identity may influence the way teens experience this stress. Can racial identity buffer them from this type of stress? Can it make it worse? The answer is complicated."

To that end, the researchers conducted an in-depth survey of 442 Black adolescents between the ages of 14 and 17. The survey included questions about each participant's experiences with racism; various aspects of their racial identity; and questions aimed at understanding the extent to which they experienced anticipatory racism-related stress.

The researchers focused on three aspects of racial identity: centrality, private regard and public regard. Centrality is how important being Black is to a study participant's sense of self. Private regard is how the participant feels about Black people in general. Public regard is how the participant thinks other people feel about Black people in general.

The researchers also examined four aspects of anticipatory stress: psychological stress; physiological stress; "perseverative cognition" - when you can't stop thinking about something; and "secondary appraisal" - which assesses the extent to which someone effectively evaluates their ability to prevent or reduce harm caused by a racism-related event.

Ninety-four percent of the study participants reported experiencing racism.

"We found that racial identity is a mixed bag when it comes to its relationship with anticipatory stress," Hope says.

For example, the higher study participants scored on private regard, the less psychological stress they reported in anticipation of experiencing racism. But private regard did not appear to have any protective effect against the other aspects of anticipatory stress.

Meanwhile, the higher participants scored on centrality, the more anticipatory stress they reported across the board.

"This is complicated, because while high centrality scores were associated with worse anticipatory stress, previous research makes clear that there are many reasons it is important for Black people to feel good about being Black," Hope says.

Researchers also found that higher public regard is associated with participants having less racism-related anticipatory stress. However, scoring high on public regard can pose challenges of its own. For example, there is some concern that Black teens who score high on public regard may be more likely to blame racist experiences on their personal characteristics, when they've done nothing wrong.

"This doesn't mean that we should lie to kids about the state of racism in the world, but it highlights the value of kids being exposed to environments where people care about Black communities and are committed to anti-racism," Hope says.

"Ultimately, the study highlights that while racial identity can help, there is a limit to what Black adolescents can do to protect themselves from the stresses associated with racism. And that, in turn, underscores the need for us, as a society, to address racism in a meaningful way.

"Racism is pervasive, and the vast majority of our study participants reported experiencing it," Hope says. "Adolescence is a period of development when people begin to come to terms with who they are and how they fit into the world.

"Parents, teachers and caregivers need to be proactive about supporting these youth as they navigate who they are in terms of their race and what that will mean for how they interact with the world."

Credit: 
North Carolina State University

Finnish biodiversity information management inspires globally

image: A digitised sample of Cucullia argentea

Image: 
Pekka Malinen / Luomus

The Finnish solution to include all types of biodiversity data and the whole data life cycle, from collection to use, in the same data infrastructure is unique. It is also rare for one infrastructure to be able to serve cutting-edge research, public administration, business and the civil society simultaneously.

This solution, the Finnish Biodiversity Information Facility “FinBIF” is described as a best-practice model in biodiversity informatics in a recent paper in the Nature Portfolio journal Scientific Data.

All data types and the whole data life cycle in a one-stop shop

FinBIF, which is coordinated and developed by the Finnish Museum of Natural History Luomus of the University of Helsinki:

digitises natural history specimens and produces digital DNA barcodes

collects born-digital observation records of professionals and amateurs alike

integrates data collated from different sources

distributes the data mass as open data

offers data management services, such as platforms for recording and publishing monitoring data and for reporting observations, to researchers, the environmental administration and the public

Typically, different types of species data and the different stages of the data life cycle, that is, digitisation, collection, integration, distribution, and facilitation of use, are managed by several separate data infrastructures. Scattered solutions are, however, not cost-effective, and they do not facilitate finding and using the services.

FinBIF currently has over 39 million observations of more than 40,000 species in its portal http://www.laji.fi/en. The data mass is compiled from 444 separate datasets. Most of these come from natural history museums, which have formed the core group in developing FinBIF. Part of their data are species observations, but 3.8 million records distributed by FinBIF are based on collection specimens, and 800,000 of these are accompanied by images. Eleven Finnish collection institutions share their data through FinBIF, but there are also significant observational datasets from governmental research institutes and citizen science projects. Recent observations are added through the iNaturalist Finland service and app, which are hosted by FinBIF.

"Ten years ago, we had a vision of an all-inclusive biodiversity data service. After building consensus among all actors in the field and acquiring funding through the national research infrastructure programme, the actual development work began in 2014. A great number of specialists have worked extremely hard to create the current, world-leading system. I am grateful for their efforts and proud of what they have achieved," says Professor Leif Schulman who led the development of FinBIF until last year.

Hun­dreds of thou­sands of users

As an open service, FinBIF has been adopted throughout society. More than 700,000 users have visited the portal at least once, even though it has only been available for just over four years. Registered users, that is, people who enter data into FinBIF or download citable data batches from it, now number over 10,000. At the end of 2019, 13% of these were from research and education institutions, 3% from state or municipal governments, and 4% from private companies, while 80% had used a private email address for registration.

"It is more challenging to monitor outputs of the use, since not all users remember to acknowledge the use of research infrastructures in publications, for instance. Based on our records, we estimate that FinBIF's services have been used for more than 700 published papers," says Dr Aino Juslén who has participated in the development of FinBIF from the start and been the Director of Luomus since the beginning of this year.

An Open Science Am­bas­sador

FinBIF is also a leader in open data distribution. Considerable effort has been put into implementing a data policy that is as open as possible. FinBIF has even received a national award for this work. However, not quite all the data can be openly shared, since the law prohibits the disclosure of occurrence data that could harm the conservation status of endangered species. The discoverability of the data is, nevertheless, important, and this has been a focus at FinBIF. The sensitive data, too, is findable and can be obtained for research upon request by using nationally agreed principles and a data request service.

"It required lengthy negotiations in a cross-sectoral working group to reach a common view on which data have to be restricted and on which grounds and, on the other hand, how officials nevertheless can share exact data among themselves to enable the protection of biodiversity," says Aino Juslén, who acted as chair of the working group.

A unique IT in­fra­struc­ture through agile de­vel­op­ment

The development of the FinBIF system has required repeated trial and error. A prerequisite for its success has been agile development and an in-house development team that has been in continuous interaction with the users of the service.

"It feels like we are now seeing how the solid foundations are paying dividends, since any new services created quickly reach the operative stage when built on the carefully designed base. This is impressive since basically everything we now do requires innovation in the absence of international benchmarks," says Director of the Biodiversity Informatics Unit of Luomus Kari Lahti, who joined FinBIF's development team as a project manager in 2015.

Credit: 
University of Helsinki

Scientists find a way to detect the spectral signals of amyloid fibrils

image: Data obtained in the Resource Centre 'The Centre for Molecular and Cell Technologies' of the St Petersburg University Research Park

Image: 
SPbU

Alzheimer's disease is the most common neurodegenerative disorder in which neurons gradually die off, leading to dementia. The exact mechanism and causes of this disorder have not yet been identified. However, it is known that amyloid plaques form in the brains of patients. Plaques consist of amyloid fibrils, which are special filamentous assemblies formed by amyloid proteins.

'The number of patients with neurodegenerative disorders will continue to grow in the future. Thanks to the success of humanity in the treatment of cancer and cardiovascular diseases, more and more people are living into their 80s. At this age, the risk of developing neurodegenerative disorders, including Alzheimer's disease, becomes very high. Unfortunately, no cures for these diseases have yet been found' says Nikolai Skrynnikov, a co-author of the research, Ph.D., Professor, Head of the Biomolecular NMR Laboratory at St Petersburg University.

According to Nikolai Skrynnikov, scientists have deciphered the structural features of amyloid deposits relatively recently. However, a more detailed study of amyloidogenesis is faced with a number of difficulties. In particular, this is because in brain tissues amyloid fibrils coexist with other structural forms of amyloidogenic protein. These are monomers, proteolytic fragments, and various oligomers, some of which serve as 'seeds' for building new fibrils. Analysing such a mixture is a major challenge. For example, when studying amyloidogenic samples by means of nuclear magnetic resonance (NMR) spectroscopy, one obtains a multitude of signals that originate not only from fibrils that are of interest to scientists, but also from other protein species. Experts are therefore looking for ways to separate the spectral signals of fibrils and other concomitant structural forms.

The most obvious and straightforward method to achieve this goal is the so-called 'diffusion filter'. This is a special NMR experiment that makes it possible to separate signals from heavy fibrils and other more mobile components of the sample. However, about ten years ago scientists from Oxford University published two articles in which the feasibility of such a filter for samples of amyloid fibrils has been put into question. After that, the research in this field has come to a halt.

'The motion of a fibril can be likened to random motion of a log on the surface of a lake, while the motion of a monomer is like that of a pine needle. The researchers from Oxford argued that the rotation of the log might be faster - while turning, the linear speed at the ends of the log proves to be sufficiently high. For this reason, according to the authors, it becomes impossible to distinguish between a rapidly turning log and a nimble needle,' explains Nikolai Skrynnikov. 'But this is far from the truth'.

The scientists from St Petersburg University put the assertion of their Oxford colleagues to a rigorous test, and not only disproved it, but also created a new theory of the diffusion NMR experiment. Moreover, the researchers described the essence of the effect by three methods: the analytical method, i.e. by deriving a compact formula that reflects the outcome of the experiment; the numerical method, i.e. by solving certain differential equation by means of a suitable numerical algorithm; and the Monte Carlo method, i.e. by using computer simulation to capture random fibril movements in solution. All three methods showed virtually identical results, thereby validating the new theory.

For the experimental verification of the new theory, the researchers have turned to yeast protein Sup35, which is known to have amyloidogenic properties. Scientists from St Petersburg University played a prominent role in the early studies of this protein. Professor Sergey Inge-Vechtomov, his students and followers were among the first investigators of Sup35. The research team from the Biomolecular NMR Laboratory at St Petersburg University together with the scientists from the University's Department of Genetics and Biotechnology used Sup35 as a model system to demonstrate that the use of a diffusion filter in samples containing amyloid fibrils is indeed possible. The researchers successfully obtained a spectrum of fibrils, 'cleared' from other spectral signals.

'Twenty to thirty years ago, scientists had little understanding of what happens in the human brain with the onset of dementia. Gradually, knowledge has been accumulated and new research methods have been developed. Thanks to these methods, we now know about the existence of amyloid deposits and have a fairly detailed idea of their structure,' notes Nikolai Skrynnikov. 'Our theory and its proof is a contribution to the body of fundamental knowledge that medicinal chemists rely on in their search for new drugs. In the future, our proposed diffusion filter for NMR experiments in amyloidogenic systems may help in this search.'

Credit: 
St. Petersburg State University

Dive bombing killer flies are so fast they lose steering control

video: Killer flies can reach accelerations of over 3g when aerial diving to catch their prey - but at such high speeds they often miss because they can't correct their course.

Image: 
S. Rossoni

Killer flies can reach accelerations of over 3g when aerial diving to catch their prey - but at such high speeds they often miss because they can't correct their course.

These are the findings of a study by researchers at the Universities of Cambridge, Lincoln, and Minnesota, published today in the Journal of the Royal Society Interface.

Killer flies (Coenosia attenuata) perform high-speed aerial dives to attack prey flying beneath them, reaching impressive accelerations of up to 36 m/s2, equivalent to 3.6 times the acceleration due to gravity (or 3.6g). This happens because they beat their wings as they fall, combining the acceleration of powered flight with the acceleration of gravity.

This is an impressive feat: diving Falcons, the fastest animals that predate in the air, achieve much lower accelerations of only 6.8m/s2. Falcons dive by folding their wings and simply letting gravity accelerate them towards their prey.

For the tiny Killer fly though, the high speeds achieved in aerial dives could come as a surprise - because the researchers think the fly doesn't take the effect of gravity into account when diving to intercept a target.

To get their results, the researchers built a transparent 'flight arena' and flew a dummy prey target through it at constant velocity. Killer flies were filmed with high speed video cameras as they attacked the target, and the researchers watched the footage back in slow motion - using this data to reconstruct the entire attack sequence in 3D.

The study found that Killer flies reached much higher accelerations in flight when taking off from the ceiling of the arena, compared to from the floor or walls. The flies beat their wings at a similar rate wherever they launched from, indicating that their flight speed is determined by a combination of wing power and gravity.

"When Killer flies took off from the floor or walls of the arena, they moved at the time when they could take the shortest path to the target. But they couldn't manage that when they took off from the ceiling because the high acceleration caused by gravity changed the expected flight path," said Sergio Rossoni, a PhD student in the University of Cambridge's Department of Zoology and first author of the paper.

By diving with super-high acceleration the Killer fly sometimes catches its target prey extremely quickly, but it often misses because its speed makes it challenging to change course mid-dive if the prey moves. But even if the fly doesn't land on target, the dive quickly reduces its distance from the prey so it can keep sight of it while making the final manoeuvers to catch it.

The researchers think the effect of not accounting for gravity during downward dives might be compensated by another advantage. High speed dives force the potential prey to change direction as the attacker approaches, but to do this the prey has to slow down - making it easier to catch.

Insects that hunt in the air usually attack their prey upwards, because the contrast of the prey against the sky makes it easier to see. Killer flies are unusual insect predators in this respect; hunting downwards against a visually cluttered ground, using eyes that have only coarse resolution, is more difficult.

"This research into miniature flies helps us understand what shortcuts are acceptable when survival depends on fast decisions and accurate actions, but the sensory capabilities and processing power of the predator are heavily constrained," said Professor Gonzalez-Bellido at the University of Minnesota, who led the study.

Credit: 
University of Cambridge

Similar states of activity identified in supermassive and stellar mass black holes

image: The figure illustrates how the population of active Seyfert-1 galaxies is typically dominated by the emission of the accretion disk ('soft' state), while the population of LINERs is much less luminous and is dominated by jets ('hard' state), which emit intensely in radio waves. The Seyfert-2 galaxies, on the other hand, do not show a homogeneous behaviour and while a good part behave in a similar way to the Seyfert-1, a large group of them are located in intermediate states. The latter are also observed in stellar black holes for short periods of time.

Image: 
Teo Muñoz Darias/Juan A. Fernández Ontiveros

The researchers Juan A. Fernández-Ontiveros, of the Istituto Nazionale di Astrofisica (INAF) in Rome and Teo Muñoz-Darias, of the Instituto de Astrofísica de Canarias (IAC), have written an article in which they describe the different states of activity of a large sample of supermassive black holes in the centres of galaxies. They have classified them using the behaviour of their closest "relations", the stellar mass black holes in X-ray binaries. The article has just been published in the journal Monthly Notices of the Royal Astronomical Society (MNRAS).

Black holes range in mass from objects which have only a few times the mass of the sun up to those with thousands of millions of solar masses. To understand their activity cycles from a global perspective has been the object of research for decades. Those of stellar mass are found in binary systems together with a companion star from which they suck out the gas which they need to sustain their activity, while the supermassive variety are found in the centres of the majority of galaxies and they feed on the gas, dust, and stars which are fall into the gravitational well of the galactic nucleus.

Stellar mass black holes evolve rapidly. Their activity cycles usually last a few months or years, during which they pass through different states, or phases. These are characterized by changes in the properties of their accretion discs (where the hot gas accumulates before falling into the black hole), their winds, and the jets of material which they produce. There are two principal states, the first dominated by the accretion disc, and the second by the jet. The 'soft' state is noted by the thermal emission by the plasma of the disc, while the jet is observed in the 'hard' state, when the disc cools down, and the emission at radio wavelengths becomes very intense.

Because they are much more massive, the supermassive black holes evolve much more slowly than their stellar mass equivalents. So, to show the presence of states and transitory phenomena in these would imply observing them for millions of years, because the changes during a human lifetime would be too small to measure. In addition, the nuclei of galaxies are regions with dense populations of stars, and the absorption of light by hydrogen and dust masks and hides the radiation from the accretion disc around the central black hole.

In this study Fernández-Ontiveros and Muñoz-Darias have used a sample of 167 active galaxies to be able to identify the possible accretions states of supermassive black holes with good statistics. The emission from the accretion disc cannot be detected directly, but the gas in the central region absorbs and processes the radiation in the form of spectral lines. Using the lines of oxygen and neon, which are observed in the mid-infrared, it is possible to test the presence of the disc in these object. "The study demonstrates the presence of accretion states in supermassive black holes, with properties very similar to those we know from stellar mass black holes, where the systems in the 'soft' state harbour a bright disc, and those in the 'hard' state show intense radio emission while the disc is very weak", explains Juan A. Fernández-Ontiveros, an INAF researcher who was trained at the IAC.

"This work opens a new window to understand the behaviour of material (gas) when it falls into black holes with a wide range of masses, and helps a more precise understanding of the activity cycles of the supermassive black holes which are in the centres of most galaxies", adds Teo Muñoz-Darias, a researcher at the IAC.

The figure illustrates how the population of active Seyfert-1 galaxies is typically dominated by the emission of the accretion disk ('soft' state), while the population of LINERs is much less luminous and is dominated by jets ('hard' state), which emit intensely in radio waves. The Seyfert-2 galaxies, on the other hand, do not show a homogeneous behaviour and while a good part behave in a similar way to the Seyfert-1, a large group of them are located in intermediate states. The latter are also observed in stellar black holes for short periods of time.

Credit: 
Instituto de Astrofísica de Canarias (IAC)

Proteomics reveals how exercise increases the efficiency of muscle energy production

Mitochondria are the cell's power plants and produce the majority of a cell's energy needs through an electrochemical process called electron transport chain coupled to another process known as oxidative phosphorylation. A number of different proteins in mitochondria facilitate these processes, but it's not fully understood how these proteins are arranged inside mitochondria and the factors that can influence their arrangement.

Now, scientists at the University of Copenhagen have used state-of-the-art proteomics technology to shine new light on how mitochondrial proteins gather into electron transport chain complexes, and further into so-called supercomplexes. The research, which is published in Cell Reports, also examined how this process is influenced by exercise training.

"This study has allowed for a comprehensive quantification of electron transport chain proteins within supercomplexes and how they respond to exercise training. These data have implications for how exercise improves the efficiency of energy production in muscle," says Associate Professor Atul S. Deshmukh from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.

Traditional methods provide too little detail

It is already well established that exercise training stimulates mitochondrial mass and affects the formation of supercomplexes, which allows mitochondria in skeletal muscle to produce energy more efficiently. But questions remain about which complexes cluster into supercomplexes and how.

To better understand supercomplex formation, particularly in response to exercise, the team of scientists studied two groups of mice. One group was active, and given an exercise wheel for 25 days, and the second group was sedentary, and was not provided the exercise wheel. After 25 days, they measured the mitochondrial proteins in skeletal muscle from both groups to see how the supercomplexes had changed over time.

When scientists typically analyze how supercomplexes form, they use antibodies to measure one or two proteins per electron transport chain complex. But as there can be up to 44 proteins in a complex, this method is both time consuming and provides limited information about what happens to the remainder of the proteins in each complex.

As a result, there is a lack of detailed knowledge in the field.

Proteomics helps supercomplexes give up their secrets

To generate much more detailed data, the team applied a proteomic technology called mass spectrometry to measure the mitochondrial proteins. By applying proteomics instead of antibodies, the scientists were able to measure nearly all of the proteins in each complex. This provided unprecedented detail of mitochondrial supercomplexes in skeletal muscle and how exercise training influences their formation. Their approach demonstrated that not all of the proteins in each complex or a supercomplex respond to exercise in the same manner.

"Mitochondrial protein content is known to increase with exercise, thus understanding how these proteins assemble into supercomplexes is crucial to decipher how they work. Our research represents a valuable and precious resource for the scientific community, especially for those studying how the mitochondrial proteins organize to be better at what they do best: produce energy under demand,", explains Postdoc Alba Gonzalez-Franquesa.

The interdisciplinary project was a collaboration between the Deshmukh, Treebak and Zierath Groups at CBMR, and the Mann Group at the Novo Nordisk Foundation Center for Protein Research.

Credit: 
University of Copenhagen - The Faculty of Health and Medical Sciences

Disease of the smallest heart blood vessels is important global health problem

image: Mechanisms of myocardial ischaemia, including the microvessels

Image: 
European Heart Journal

For the first time, a prospective, international study has shown that chest pain caused by problems with the very small vessels supplying blood to the heart is an important health problem that increases the risk of heart attacks, stroke and death due to cardiovascular reasons.

The study, which is published today (Thursday) in the European Heart Journal [1], recruited 686 patients from 14 institutions in seven countries on four continents [2] between July 2015 and December 2018 to investigate microvascular angina (MVA). Until now, MVA was widely thought to be a benign disease that mainly occurs in women. However, the study showed that during one to two years of follow-up until December 2019, events such as stroke, heart attack and hospitalisation for chest pain (angina) occurred in nearly 8% of patients each year. Men and women were almost equally affected and the prognosis was no different according to sex or ethnicity.

Until relatively recently, little was known about MVA and it can be difficult to diagnose, partly because diagnostic criteria were proposed only in 2018 by the COronary VAsomotor Disorders International Study (COVADIS) Group. Patients with MVA can experience chest pains similar to those of a heart attack and/or shortness of breath, which can lead to them being admitted to hospital. However, standard tests, such as electrocardiograms (ECGs), angiograms and echocardiography, do not detect significant problems with heart rhythm or the main coronary arteries, meaning that MVA is often not diagnosed.

First author of the study and member of the COVADIS Group, Professor Hiroaki Shimokawa, said: "Microvascular angina is an under-researched area, partly because no definite universal definition was available before the COVADIS definition and partly because cardiologists are mainly interested in the large coronary arteries but not the smaller vessels that are also part of the coronary circulation. The former are easily visible by coronary angiography, whereas the latter are not.

"Currently, many doctors are not aware of the importance of coronary microvascular dysfunction. As a result, many patients with MVA are misdiagnosed as having postmenopausal disorders or an imbalance of conscious and unconscious nervous system, for instance. However, previous research has suggested that the number of patients with MVA is three to four million in USA, which is equal to or greater than the number of patients with breast cancer, so it is an important global problem." [3]

Prof. Shimokawa, who is Vice Dean of the Graduate School at the International University of Health and Welfare (Narita, Japan) and Emeritus/Visiting Professor at the Graduate School of Medicine, Tohoku University (Sendai, Japan), and colleagues applied the COVADIS diagnostic criteria in the current study: 1) signs and symptoms suggesting reduced blood flow to the heart (myocardial ischaemia); 2) no evidence of the main coronary arteries being blocked; 3) objective evidence of myocardial ischaemia provided by non-invasive stress testing of the heart using ECGs or non-invasive imaging such as cardiac magnetic resonance; and 4) evidence of impaired coronary microvascular function showing, for instance, inability of the coronary arteries to increase blood flow under stress, heart microvascular spasms, indications of abnormal resistance to blood flow in the heart's tiny blood vessels, or delayed flow in the arteries of the contrast agent used for angiograms, indicating increased resistance to blood flow in more distant vessels (known as "coronary slow flow") but with no evidence of disease in the main coronary arteries.

During the follow-up period, there were 78 cases of death or hospitalisation due to major cardiovascular problems such as heart attack and stroke, heart failure or unstable angina (6.4% in men and 8.6% in women) - an annual incidence of 7.7% among all the patients in the study. Hospitalisation for unstable angina was the commonest event.

Analysis showed that high blood pressure, previous history of coronary artery disease and stable angina were all important and independent predictors of these major cardiovascular events. Although Caucasians had a higher risk than Asians (annual incidences of 9.3% versus 4.5%), there was no significant difference between the two ethnic groups after adjustments were made for factors that could affect the results, such as age, sex, high blood pressure, diabetes, smoking etc. Women had significantly worse quality of life than men, although they had a similar long-term prognosis; the researchers say this could be due to the effect of female hormones on pain perception.

Prof. Shimokawa said: "Angina is usually thought to be caused mainly by narrowing of the large coronary arteries. However, even after treatment of these arteries with stents or bypass surgery, approximately 40% of patients will still experience chest pains, suggesting problems with microvascular dysfunction are very common. In addition, it has been recently and convincingly demonstrated that the treatment of the large coronary arteries with stent or bypass surgery alone does not significantly improve the long-term prognosis of patients with coronary artery disease, again suggesting the prognostic importance of coronary microvascular dysfunction.

"Our international study demonstrates the importance of coronary microvascular dysfunction in patients with MVA. Considering the fact that coronary microvascular dysfunction is involved not only in MVA but also in other forms of cardiovascular disease, including large coronary artery disease and myocardial disease, we believe clinicians should pay closer attention to it."

The researchers say that the management and treatment of MVA represents a major unmet need and more research is needed. Patients are usually treated with drugs to prevent blood clotting, such as statins, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), or drugs to dilate blood vessels such as beta-blockers, calcium channel blockers and nitrates.

Editor-in-Chief of the European Heart Journal, Filippo Crea, Professor of Cardiology and Director of the Department of Cardiovascular and Pneumological Sciences at the Catholic University of the Sacred Heart (Rome, Italy), is a co-author of the study. He said: "It can be estimated that in most European countries, 20,000-40,000 people per million of the population suffer from angina. Thus, the total number of angina patients is about 21 million in Europe. As several studies have shown that about 50% of angina patients do not have coronary narrowing, this means that about ten million people in Europe have angina caused by functional alterations in either the large or small coronary arteries or both. The situation is similar in Asia and US. This huge number of patients deserves to be carefully identified and treated. In addition, these data should stimulate the development of drugs that specifically target coronary microcirculation. Last but not least, these functional alterations are frequent not only in angina patients but also in those who present with myocardial infarction."

Limitations of the study include the fact that it was an observational study with no reference group against which to compare results; there was a relatively small number of major cardiovascular events during the follow-up period, which may affect the statistical power of the study; the majority of these events were hospitalisation for unstable angina; patients with obstructive coronary artery disease diagnosed by conventional or coronary computed angiography were excluded from the study; and there are no data on changes or adherence to medical therapy, or on symptoms or quality of life during the follow-up period.

Credit: 
European Society of Cardiology

Long COVID places 'huge burden' on survivors' families, new research suggests

A new study by Cardiff University in collaboration with the University of Hertfordshire has revealed the huge "secondary burden" placed on those closest to people living with Long Covid.

The researchers surveyed more than 700 Covid-19 survivors along with their partners and close relatives to understand for the first time the impact of the disease on families as a whole.

The findings, published today in BMJ Open, suggest family quality of life is being "severely affected" and a major system of support is needed for both survivors - and those closest to them.

Survivors and their families spoke of the huge impact on their lives and backed calls for more support.

Billie-Jo Redman, 27, a mum from Essex, suffers from fatigue, brain fog and daily waves of pins and needles, and at times has such a high heart rate she has to wear a 24-hour heart monitor.

"My life feels like it's over. I used to go on adventures with my son Roman - now I have days where I can't even get him to school," she said.

Lead author Rubina Shah, a PhD student at Cardiff University's School of Medicine, said: "We have all seen the devastating impact Long Covid can have on survivors, but we have heard very little about how it can affect the lives of their nearest and dearest.

"Our study reveals a domino effect from the Covid patient themselves through to all those closest to them, affecting everything from how worried and frustrated they feel to their ability to enjoy family activities, or for partners the impact on their relationship and sex life.

"The impact of Covid can be profound and long lasting; there needs to be a holistic support system that is sensitive to the needs of both survivors and their families to help ease this burden."

About one in five people have symptoms of Long Covid five weeks after an initial infection and one in seven after 12 weeks, according to the Office for National Statistics. In the four weeks from 6 February, 1.1 million people in the UK were estimated to be affected.

The researchers carried out the study because there was so little information about what families go through when a member has Long Covid. They say it is vital to assess this to help understand what support they might need.

A global online survey to measure impact was carried out last summer and was completed by 735 Covid-19 survivors around 12 weeks after diagnosis and by 571 partners and 164 family members.

The biggest impact was found to be on "feeling worried" (94%), followed by family activities (83%), feelings of frustration (82%), feeling sad (78%), sleep (69%) and sex life (68%). Two-thirds (66%) reported impact on holidays, and more than half (56%) reported an increase in family expenses.

There was a significant gender difference among family members, with females feeling more sad, experiencing more impact on everyday travel and on their sleep. Impact on sex life was experienced by significantly more men than women.

The researchers said the findings suggested policymakers should consider developing and commissioning a range of support services, including needs-based mental health counselling and local support groups.

'Tragic effect on our lives'

Billie-Jo, who previously had no health issues, tested positive on 9 January with usual Covid symptoms. After 10 days she was fine but by the end of February she felt like she was "dying upon standing".

She moved from London to Essex before the first lockdown so has little family support because they live too far away and feels her illness has had a huge impact on life with her son.

"The hospital just doesn't know what to do with me. They can see my heart rate is way too high, but they don't know why," she said.

"Everything has changed. My life feels like it's over. I used to go on adventures with my son Roman - now I have days where I can't even get him to school. It's had a tragic effect on our daily lives. There needs to be more support for families."

Ms Shah said: "Our research is the first to look at the impact of this devastating disease on the partners and families of survivors.

"It is so important that we understand the needs of those closest to survivors to ensure the overall wellbeing of families."

The researchers said future work was needed to measure the persistence of the impact on family members and to find out whether there are differences in family impact between ethnic groups.

Further research could also include assessing the impact of interventions, carrying out local studies to inform policy and practice in planning of local support services.

Credit: 
Cardiff University

Study examines how pandemic-related changes affect college students' motivation

image: Despite concerns that the shift to distance learning during the pandemic would adversely impact at-risk college students' motivation and persistence, a study by educational psychology professor Jennifer Cromley and graduate student Andrea Kunze found that some biology students' interest in their studies and motivation increased.

Image: 
Photo by L. Brian Stauffer

CHAMPAIGN, Ill. -- When the worsening COVID-19 pandemic prompted colleges to shutter their campuses and shift to remote learning in spring 2020, concerns arose that many underrepresented students in science, technology, engineering and mathematics disciplines would be demotivated and drop out in even greater numbers.

However, a study of 182 undergraduate students in a biology course at one university found little evidence to support that belief. Instead, across all demographic groups, the impact varied: Some students were more motivated, some were less so, and some saw no changes in their level of interest in the subject matter, researchers at the University of Illinois Urbana-Champaign found.

"There's resilience and a lack of resilience across all groups," said educational psychology professor Jennifer Cromley, the first author of the study, which was co-written by graduate student Andrea Kunze.

Published in the Journal of Microbiology and Biology Education, the findings are a caution against making stereotypical assumptions about individuals' commitment and persistence based on their demographic characteristics such as socioeconomic status or being a first-generation student, according to the researchers.

"We shouldn't assume that they're going to be resilient or not resilient," Cromley said.

"We should check in with them and see how they're doing. Stereotyping people as downtrodden or resilient doesn't reflect the realities of the situation."

The students were participants in an introductory biology course that was traditionally taught with in-person lectures but changed to online instruction during the final eight weeks of the Spring 2020 Semester. When face-to-face instruction was suspended to mitigate the spread of COVID-19 on campus, most students moved back home.

At the time, the researchers had a semester-long study of changes in motivation among the biology students in progress. When instruction went online, they shifted their focus to examine how the motivation of at-risk students - specifically, women, students from underrepresented minority and ethnic groups, and first-generation students - was affected.

Students who agreed to participate in the study were surveyed monthly from January to April, repeatedly completing the same two of 10 possible questionnaires that examined various factors associated with motivation according to several theories.

For example, some of the questionnaires asked about students' goals, such as whether their aim was to thoroughly understand the concepts being taught or to just avoid performing worse than their classmates or failing. Other surveys explored whether the students believed they could master the material in the course or if they considered themselves good at biology.

Some surveys asked students whether they intended to remain in a STEM major and whether they believed the effort required would be worth it in the end. While 42% of the students indicated they were completely committed to remaining in STEM when surveyed in January, the researchers found that this declined as the semester progressed.

By April, changes in each of the motivational variables indicated more students were at risk of dropping out. However, the team found no significant differences between demographic groups, Cromley said.

Because the students experienced numerous changes concurrently - such as concerns about health, their finances and living at home with their families and away from social and academic supports they had on campus - changes in their motivation could not be ascribed to remote learning alone, Cromley said.

While the researchers had hypothesized that students' interest in the material would decline during the semester, they found that some students' interest increased instead. Media stories about scientists' efforts to decipher COVID-19 and develop effective vaccines promoted a greater appreciation for the utility and societal value of science for some students, Kunze said.

This effect was particularly significant among some first-generation students, who represented 24% of those surveyed, according to the study.

One of these students, who also was from an underrepresented minority or ethnic group, wrote that she was motivated every day to achieve her dreams of becoming a doctor "and helping to end disparities within the healthcare system."

Despite predictions that underrepresented students' achievement and persistence would be adversely affected by the challenges associated with remote learning, some "students weren't just giving up. Some were inspired and still trying," Kunze said.

Women showed greater declines in the self-oriented variables, and the researchers hypothesized that their separation from supportive friends on campus may have negatively affected their confidence and feelings of competence in the course.

Conversely, living at home may have been beneficial for some first-generation students, whose academic goal orientation shifted during the semester from failure avoidance to a focus on future achievement and economic mobility. Separation from the highly competitive academic environment and social milieu on campus may have helped these students focus on more positive goals, the researchers said.

Students were asked an open-ended question on the surveys about any factors in their lives that influenced their feelings about their courses that day, and their answers provided glimpses into the impact of family dynamics on the students' achievement.

For example, one student wrote about having to lock themselves in the bathroom to escape pressure from their family members and get their schoolwork done in peace, Cromley said.

Credit: 
University of Illinois at Urbana-Champaign, News Bureau

A COVID-fighter's guide to T cells

image: T cells target more than 1,400 sites on SARS-CoV-2

Image: 
CDC

LA JOLLA--In a new paper, scientists from La Jolla Institute for Immunology (LJI) bring together research findings from COVID-19 researchers around the world. The results are striking: human T cells can target more than 1,400 sites on the SARS-CoV-2 virus.

"Our lab and many others have shown this very broad and diverse T cell response," says LJI Research Assistant Professor Daniela Weiskopf, Ph.D., co-author of the Cell Host & Microbe review.

This kind of research review, called a "meta-analysis," pools the results of multiple studies, and the researchers give close consideration to how the studies were conducted.

In the case of COVID-19, a global meta-analysis of T cell response studies is especially helpful because different patient populations can have vastly different immune responses, based on their genetic differences and past disease history.

"This really highlights how the study of SARS-CoV-2 has been a global undertaking," says LJI Professor Alessandro Sette, Dr.Biol.Sci, senior author of the review and member of the LJI Center for Infectious Disease and Vaccine Research. "To combine information from all the different labs is a powerful thing."

Key points:

The researchers evaluated all 25 known human T cell response studies conducted between the beginning of the COVID-19 pandemic and March 15, 2021.

The studies show human T cell responses against 1,434 CD4 and CD8 epitopes. Epitopes are sites on SARS-CoV-2 that T cells can recognize.

Grouping these studies together for this larger analysis has revealed several "immunodominant" sites on the virus. These sites are where T cells are most prone to homing in on.

This broad T cell response makes it difficult for SARS-CoV-2 variants to acquire enough mutations to "escape" the body's response against the virus.

Sette adds that this analysis can help researchers monitor whether T cells are mounting effective responses as they encounter viral variants--and vaccines. "Knowing what the key sites on the SARS-CoV-2 spike protein are especially important for monitoring immune responses to COVID-19 vaccines," he says.

Despite these encouraging results, the review is limited. The researchers emphasize that current studies tend to include mainly Caucasian participants. By broadening this research to include many ethnic groups, the researchers can better understand disparities in COVID-19 mortality.

Specifically, the researchers want to understand how variations in the human leukocyte antigen (HLA) system affects T cell responses. The immune system's HLA molecules control which epitopes a T cell can "see." The frequency of different HLA molecule types varies between ethnic groups, so research need to consider how these differences affect T cell responses and potentially COVID-19 case severity.

"This is a global pandemic, so it is important that we expand our studies," says LJI Instructor Alba Grifoni, Ph.D., who served as first author of the review.

The new review also highlights the value of the Immune Epitope Database (IEDB), a free, LJI-run resource funded by the National Institute of Allergy and Infectious Diseases (NIAID). By adding the known epitope data to the IEDB, the researchers were able to see the different study results side-by-side.

"We know there is a strong T cell response to SARS-CoV-2," says Grifoni. "Now we are trying to identify where we have knowledge gaps."

Credit: 
La Jolla Institute for Immunology