Thursday, April 01, 2021

Mystery of photosynthetic algae evolution finally solved

UNIVERSITY OF NEW SOUTH WALES

Research News

An evolutionary mystery that had eluded molecular biologists for decades may never have been solved if it weren't for the COVID-19 pandemic.

"Being stuck at home was a blessing in disguise, as there were no experiments that could be done. We just had our computers and lots of time," says Professor Paul Curmi, a structural biologist and molecular biophysicist with UNSW Sydney.

Prof. Curmi is referring to research published this month in Nature Communications that details the painstaking unravelling and reconstruction of a key protein in a single-celled, photosynthetic organism called a cryptophyte, a type of algae that evolved over a billion years ago.

Up until now, how cryptophytes acquired the proteins used to capture and funnel sunlight to be used by the cell had molecular biologists scratching their heads. They already knew that the protein was part of a sort of antenna that the organism used to convert sunlight into energy. They also knew that the cryptophyte had inherited some antenna components from its photosynthetic ancestors - red algae, and before that cyanobacteria, one of the earliest lifeforms on earth that are responsible for stromatolites.

But how the protein structures fit together in the cryptophyte's own, novel antenna structure remained a mystery - until Prof. Curmi, PhD student Harry Rathbone and colleagues from University of Queensland and University of British Columbia pored over the electron microscope images of the antenna protein from a progenitor red algal organism made public by Chinese researchers in March 2020.

Unravelling the mystery meant the team could finally tell the story of how this protein had enabled these ancient single-celled organisms to thrive in the most inhospitable conditions - metres under water with very little direct sunlight to convert into energy.

Prof. Curmi says the major implications of the work are for evolutionary biology.

"We provide a direct link between two very different antenna systems and open the door for discovering exactly how one system evolved into a different system - where both appear to be very efficient in capturing light," he says.

"Photosynthetic algae have many different antenna systems which have the property of being able to capture every available light photon and transferring it to a photosystem protein that converts the light energy to chemical energy."

By working to understand the algal systems, the scientists hope to uncover the fundamental physical principles that underlie the exquisite photon efficiency of these photosynthetic systems. Prof. Curmi says these may one day have application in optical devices including solar energy systems.

EATING FOR TWO

To better appreciate the significance of the protein discovery, it helps to understand the very strange world of single-celled organisms which take the adage "you are what you eat" to a new level.

As study lead author, PhD student Harry Rathbone explains, when a single-celled organism swallows another, it can enter a relationship of endosymbiosis, where one organism lives inside the other and the two become inseparable.

"Often with algae, they'll go and find some lunch - another alga - and they'll decide not to digest it. They'll keep it to do its bidding, essentially," Mr Rathbone says. "And those new organisms can be swallowed by other organisms in the same way, sort of like a matryoshka doll."

In fact, this is likely what happened when about one and a half billion years ago, a cyanobacterium was swallowed by another single-celled organism. The cyanobacteria already had a sophisticated antenna of proteins that trapped every photon of light. But instead of digesting the cyanobacterium, the host organism effectively stripped it for parts - retaining the antenna protein structure that the new organism - the red algae - used for energy.

And when another organism swallowed a red alga to become the first cryptophyte, it was a similar story. Except this time the antenna was brought to the other side of the membrane of the host organism and completely remoulded into new protein shapes that were equally as efficient at trapping sunlight photons.

EVOLUTION

As Prof. Curmi explains, these were the first tiny steps towards the evolution of modern plants and other photosynthetic organisms such as seaweeds.

"In going from cyanobacteria that are photosynthetic, to everything else on the planet that is photosynthetic, some ancient ancestor gobbled up a cyanobacteria which then became the cell's chloroplast that converts sunlight into chemical energy.

"And the deal between the organisms is sort of like, I'll keep you safe as long as you do photosynthesis and give me energy."

One of the collaborators on this project, Dr Beverley Green, Professor Emerita with the University of British Columbia's Department of Botany says Prof. Curmi was able to make the discovery by approaching the problem from a different angle.

"Paul's novel approach was to search for ancestral proteins on the basis of shape rather than similarity in amino acid sequence," she says.

"By searching the 3D structures of two red algal multi-protein complexes for segments of protein that folded in the same way as the cryptophyte protein, he was able to find the missing puzzle piece."

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Shining, colored LED lighting on microalgae for next-generation biofuel

Combined blue and red illumination enhances growth, biosynthesis of D. Salina microalgae

AMERICAN INSTITUTE OF PHYSICS

Research News

IMAGE

IMAGE: RESEARCHERS SHOW HOW A COMBINATION OF MONOCHROMATIC RED AND BLUE LED ILLUMINATION ON ONE TYPE OF MICROALGA CAN ENHANCE ITS GROWTH AND INCREASE THE BIOSYNTHESIS OF CRITICAL COMPONENTS. HERE, LED... view more 

CREDIT: XIAOJIAN ZHOU/YANGZHOU UNIVERSITY

WASHINGTON, March 30, 2021 -- As ethanol, biodiesel, and other biofuels continue to present challenges, such as competing with food security or lacking the technology for more efficient and low-cost production, microalgae are gaining momentum as a biofuel energy crop.

In their paper, published in the Journal of Renewable and Sustainable Energy, by AIP Publishing, Yangzhou University researchers in China show how a combination of monochromatic red and blue LED illumination on one type of microalga can enhance its growth and increase the biosynthesis of critical components, such as lipids, for microalgae feedstock development.

The researchers focused on Dunaliella salina (D. salina), typically extracted from sea salt fields and found in salt lakes. Easily cultivated and known for its bright pink color because of its high levels of carotenoid, D. salina is widely used in foods and cosmetics.

Microalgae tend to accumulate higher amounts of lipids (fatty acids that make up natural oils and waxes) than other biomass feedstocks do, which means a much higher percentage of the organisms can be turned into usable biofuel. In the case of D. salina, the lack of a cell wall could make algae biofuel production easier to pursue.

LEDs, as tunable single-color light sources, are already used to optimize plant growth, particularly in greenhouse cultivation. All parts of the visible spectrum are used in photosynthesis, but light also influences plant development. Adding more blue or red light, for instance, affects different plants in different ways. Optimal illumination conditions for microalgae growth and lipid production yield remain unknown.

In their study, the researchers applied red, blue, or combined red-blue illumination to D. salina culture. They found different intensities of blue light did not significantly enhance microalgae growth but boosted the lipid, protein, and carbohydrate levels. Red light, on the other hand, reduced algae growth and lipid formation, compared to blue and white light.

However, when red and blue lights were simultaneously applied in various ratios, the microalgae showed a major boost in growth and lipid productivity. The optimal 4-to-3 ratio of red and blue light significantly improved lipid productivity by more than 35% and increased dry biomass yield by more than 10% compared to the white light control.

The researchers are planning to analyze the composition of fatty acids synthesized in the algae under the favorable combined lighting for increased lipid production.

"Biodiesel performance is dependent on the composition of fatty acids, so we want to determine how the combined monochromatic lights would affect the quality of microalgae biodiesel," author Xiaojian Zhou said.

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The article "Impact of combined monochromatic light on the bio-component productivity of Dunaliella salina" is authored by Cuili Jin, Binqi Yu, Shouyuan Qian, Qing Liu, and Xiaojian Zhou. The article will appear in Journal of Renewable and Sustainable Energy on March 30, 2021 (DOI: 10.1063/5.0041330). After that date, it can be accessed at https://aip.scitation.org/doi/10.1063/5.0041330.

ABOUT THE JOURNAL

Journal of Renewable and Sustainable Energy is an interdisciplinary journal that publishes across all areas of renewable and sustainable energy relevant to the physical science and engineering communities. Topics covered include solar, wind, biofuels and more, as well as renewable energy integration, energy meteorology and climatology, and renewable resourcing and forecasting. See https://aip.scitation.org/journal/rse

Bottom-up' approach needed to study freshwater blooms

A national research team urges more complete study of harmful cyanobacteria

DARTMOUTH COLLEGE

Research News

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IMAGE: CYANOBACTERIA BLOOMS DAMAGE THE QUALITY OF LAKE WATER, AFFECT LAKE COMMUNITIES, AND CAN THREATEN HUMAN HEALTH. view more 

CREDIT: MIDGE ELIASSEN

HANOVER, N.H. - March 30, 2021 - Cyanobacteria living at the bottom of lakes may hold important, under-researched clues about the threat posed by these harmful organisms, according to a Dartmouth-led study.

The research, published in the Journal of Plankton Research, urges a more comprehensive approach to cyanobacteria studies in order to manage the dangerous blooms during a time of global climate change.

"Most studies of cyanobacteria focus on the times when they are visible in the water column," said Kathryn Cottingham, the Dartmouth Professor in the Arts and Sciences, and a professor of biology. "By concentrating on this part of the life cycle, we may be missing important clues about how these harmful organisms are responding to ongoing global change."

Also known as blue-green algae, blooms of cyanobacteria are increasing in many freshwater systems worldwide, damaging the quality of lake water and affecting lake communities. The blooms also threaten human health through toxins that can damage organ systems.

Cyanobacteria are complex, but researchers are bringing together clues on how they respond to changing seasons.

Freshwater cyanobacteria live either suspended in the water column or at the lake bottom depending, in part, on water temperature. During warmer months, suspended "pelagic" cyanobacteria thrive in warm, well-lit surface waters. In the fall, they sink to the bottom and spend the winter in a resting or fully dormant state.

The Dartmouth-led study focuses on how cyanobacteria behave around the bottom-dwelling "overwinter" period. The research stresses that the sediment-dwelling stage returns to the water column with higher water temperatures, often following the mixing of the water column. Climate change is decreasing some types of mixing but increasing others - such as that caused by extreme precipitation events.

According to the paper, if mixing is constrained and cyanobacteria are left at the bottom, blooms could decrease. "A more complete understanding of all stages of the cyanobacterial life cycle will enable plankton researchers to better predict how ongoing climate change will affect the frequency, intensity and duration of cyanobacterial blooms," the study said.

Land-use changes--such as deforestation, fertilizer use, and development--and climate change are considered the main drivers of cyanobacteria outbreaks. Although the precise causes of the blooms are still being studied, researchers believe that they come from ongoing increases in nutrient loading, temperature and precipitation.

"Our work indicates that cyanobacterial blooms could either increase or decrease as a result of climate change, necessitating preventative lake management to limit human health risks," said Cayelan Carey, associate professor of biological sciences at Virginia Tech and co-author on the study. "Avoiding fertilizer use and installing waterfront buffers can help decrease cyanobacteria, thereby providing 'insurance' against potential cyanobacteria increases due to warmer temperatures in the future."

The study focused on temperate lakes, but the research team stresses that other waterbodies should be include in the proposed research agenda.

Kathleen Weathers from the Cary Institute, and Holly Ewing and Meredith Greer from Bates College also contributed to the study.


STARE AT THE WHITE SPOT CLOSE YOUR EYES OPEN THEM TO SEE TRUE CYAN 

 

New early warning system for self-driving cars

AI recognizes potentially critical traffic situations seven seconds in advance

TECHNICAL UNIVERSITY OF MUNICH (TUM)

Research News

A team of researchers at the Technical University of Munich (TUM) has developed a new early warning system for vehicles that uses artificial intelligence to learn from thousands of real traffic situations. A study of the system was carried out in cooperation with the BMW Group. The results show that, if used in today's self-driving vehicles, it can warn seven seconds in advance against potentially critical situations that the cars cannot handle alone - with over 85% accuracy.

To make self-driving cars safe in the future, development efforts often rely on sophisticated models aimed at giving cars the ability to analyze the behavior of all traffic participants. But what happens if the models are not yet capable of handling some complex or unforeseen situations?

A team working with Prof. Eckehard Steinbach, who holds the Chair of Media Technology and is a member of the Board of Directors of the Munich School of Robotics and Machine Intelligence (MSRM) at TUM, is taking a new approach. Thanks to artificial intelligence (AI), their system can learn from past situations where self-driving test vehicles were pushed to their limits in real-world road traffic. Those are situations where a human driver takes over - either because the car signals the need for intervention or because the driver decides to intervene for safety reasons.

Pattern recognition through RNN

The technology uses sensors and cameras to capture surrounding conditions and records status data for the vehicle such as the steering wheel angle, road conditions, weather, visibility and speed. The AI system, based on a recurrent neural network (RNN), learns to recognize patterns with the data. If the system spots a pattern in a new driving situation that the control system was unable to handle in the past, the driver will be warned in advance of a possible critical situation.

"To make vehicles more autonomous, many existing methods study what the cars now understand about traffic and then try to improve the models used by them. The big advantage of our technology: we completely ignore what the car thinks. Instead we limit ourselves to the data based on what actually happens and look for patterns," says Steinbach. "In this way, the AI discovers potentially critical situations that models may not be capable of recognizing, or have yet to discover. Our system therefore offers a safety function that knows when and where the cars have weaknesses."

Warnings up to seven seconds in advance

The team of researchers tested the technology with the BMW Group and its autonomous development vehicles on public roads and analyzed around 2500 situations where the driver had to intervene. The study showed that the AI is already capable of predicting potentially critical situations with better than 85 percent accuracy - up to seven seconds before they occur.

Collecting data with no extra effort

For the technology to function, large quantities of data are needed. After all, the AI can only recognize and predict experiences at the limits of the system if the situations were seen before. With the large number of development vehicles on the road, the data was practically generated by itself, says Christopher Kuhn, one of the authors of the study: "Every time a potentially critical situation comes up on a test drive, we end up with a new training example." The central storage of the data makes it possible for every vehicle to learn from all of the data recorded across the entire fleet.

 

Association of Race/Ethnicity With Likeliness of COVID-19 Vaccine Uptake Among Health Workers and the General Population in the San Francisco Bay Area

JAMA Intern Med. Published online March 30, 2021. doi:10.1001/jamainternmed.2021.1445

Surveys have demonstrated racial differences in the public’s willingness to receive a COVID-19 vaccine1,2 but have not directly compared vaccine intentions among health workers and the general public.3 We investigated COVID-19 vaccine intentions among racially and ethnically diverse samples of health workers and the general population.

Methods

We conducted a cross-sectional survey from November 27, 2020, to January 15, 2021, nested within 2 longitudinal cohort studies of prevalence and incidence of SARS-CoV-2 infection in 6 San Francisco Bay Area counties. The general population cohort comprised 3935 community-residing adults sampled from randomly selected households, and the medical center employee cohort comprised 2501 employees of 3 large medical centers, who volunteered for biweekly to monthly COVID-19 testing. The main outcome measure was likeliness of vaccine uptake, derived from 2 survey items: (1) “How likely are you to get an approved COVID-19 vaccine when it becomes available?” (using a 1-7 Likert scale anchored at “not at all likely” and “very likely”), and (2) “How early would you ideally like to receive the COVID-19 vaccine?” (asked of respondents scoring ≥3 on the first item). The survey also included items asking about reasons to get, and to not get, vaccinated. Respondents self-identified race/ethnicity (see eMethods in the Supplement for details on sampling and the survey instrument). Crude results were compared using 2-tailed χ2 tests, with P < .05 considered significant. Logistic regression models stratified by cohort tested association of race/ethnicity with vaccine willingness, adjusting for age, gender, and level of education. All statistical analyses were performed using SAS, version 9.4 (SAS Institute). American Association for Public Opinion Research Response Rate 1 definition was used.

The University of California, San Francisco, and Stanford Institutional Review Boards designated the general population cohort study a public health surveillance study and approved the medical center employee cohort study protocol. Written electronic informed consent was obtained at enrollment.

Results

A total of 3161 of 3935 (80.3%) participants in the general population cohort and 1803 of 2501 (72.1%) participants in the medical center employee cohort responded to the vaccine survey (Table). Although a higher proportion of medical center employees than members of the general population reported likeliness of vaccine uptake, racial/ethnic differences in likeliness were comparable in both cohorts (Figure). In the medical center cohort, the adjusted odds ratio (aOR) (95% CI) of likeliness of vaccine uptake relative to White respondents was 0.24 (0.10-0.60) for Black respondents, 0.50 (0.31-0.79) for Latinx respondents, 0.37 (0.27-0.51) for Asian respondents, 0.28 (0.15-0.53) for respondents of other races, and 0.49 (0.29-0.82) for respondents of multiple races. In the general population cohort, the aOR (95% CI) relative to White respondents was 0.29 (0.20-0.43) for Black respondents, 0.55 (0.43-0.71) for Latinx respondents, 0.57 (0.47-0.70) for Asian respondents, 0.62 (0.38-1.02) for respondents of other races, and 0.65 (0.46-0.92) for respondents of multiple races. Ratings of reasons to get vaccinated were similar across racial/ethnic groups, but Black, Latinx, and Asian respondents were significantly more likely than White respondents to endorse reasons to not get vaccinated, especially less confidence in the vaccine preventing COVID-19 (aOR [95% CI] for Black, Latinx, and Asian respondents having low confidence relative to White respondents, 2.39 [1.58-3.61], 2.04 [1.58-2.64], and 1.85 [1.51-2.27], respectively); less trust in companies making the vaccine (aOR [95% CI] for Black, Latinx, and Asian respondents having low trust relative to White respondents, 3.08 [2.00-4.73], 1.85 [1.38-2.48], and 1.34 [1.04-1.72], respectively); and more worry that government rushed the approval process (aOR [95% CI] for Black, Latinx, and Asian respondents relative to White respondents, 2.10 [1.44-3.05], 1.68 [1.34-2.10], and 1.81 [1.53-2.15], respectively).

Discussion

In this survey study including a diversity of racial/ethnic groups, occupational immersion in a health care setting did not offset disparities in COVID-19 vaccination intentions. We found that Asian individuals, multiracial individuals, and those of other races were more similar to Black and Latinx individuals than White individuals in their likeliness of vaccine uptake. Limitations of this study include that the sample was drawn from people sufficiently concerned about their risk of COVID-19 and trusting of research to volunteer for a study involving repeated COVID-19 testing and the survey not including additional domains, such as perceived access, that might influence reported likeliness of vaccine uptake. However, it is striking that even among individuals motivated to participate in a longitudinal COVID-19 testing study, there were racial/ethnic differences in COVID-19 vaccination intentions and concerns about the vaccine.

Black, Latinx, Asian, and Native American communities have borne a disproportionate toll of the COVID-19 pandemic in the US4; inequities in vaccination would compound these disparities. Our survey was fielded at the time of the first emergency use authorization of COVID-19 vaccines in the US. Vaccination rollout since then has revealed barriers to accessing vaccination among historically marginalized populations who are highly motivated to be vaccinated.5 Vaccination intentions must be understood as a deliberative and dynamic process; a focus on intentions must not distract from the importance of ensuring equitable access to vaccination.5 Special effort is required to reach historically marginalized populations, including those in health occupations, to support informed vaccination decision-making and facilitate access. Efforts must acknowledge a history of racism that has degraded the trustworthiness of health and medical science institutions among historically marginalized populations,6 undermined confidence in COVID-19 vaccines, and perpetuated inequitable access to care.

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Article Information

Accepted for Publication: March 6, 2021.

Published Online: March 30, 2021. doi:10.1001/jamainternmed.2021.1445

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Grumbach K et al. JAMA Internal Medicine.

Corresponding Author: Kevin Grumbach, MD, San Francisco General Hospital, Department of Family and Community Medicine, University of California, San Francisco, 1001 Potrero Ave, Ward 83, Room 310, San Francisco, CA 94110 (kevin.grumbach@ucsf.edu).

Salt substitution -- an effective way to reduce blood pressure in rural India 

AND GLOBALLY 

GEORGE INSTITUTE FOR GLOBAL HEALTH

Research News

Replacing regular common salt consumed by hypertensive patients in rural areas with a salt substitute can have a significant impact in terms of lowering their blood pressure, a new study by The George Institute for Global Health has revealed.

Researchers found that substituting a small part of the sodium in salt with potassium without altering the taste led to a substantial reduction in systolic blood pressure in these patients, supporting salt substitution as an effective, low-cost intervention for lowering blood pressure in rural India.

The study entitled "Effects of reduced-sodium added-potassium salt substitute on blood pressure in rural Indian hypertensive patients: a randomized, double-blind, controlled trial" provides the first-of-its-kind evidence from rural India on the effectiveness of a salt substitute and has been published in the American Journal of Clinical Nutrition.

Excess salt intake causes high blood pressure, a leading risk for cardiovascular disease. Almost all adult populations worldwide consume more than the recommended level of salt including those living in rural India, where average salt intake is nearly double the World Health Organization (WHO) recommendations of less than 5 g/day (2 g/day sodium).

"A large proportion of dietary salt in India comes from salt added to food cooked at home, but whether reduced-sodium salt substitutes can help to lower blood pressure had not been tested thus far," said Dr Jie Yu, Research Fellow, Cardiovascular Program, The George Institute and lead author of the study. "Our study is the first to show that salt substitutes could make a real difference in these communities."

"The study was conducted in the Siddipet region of Telangana State, and 502 participants with hypertension from 7 villages were enrolled," She added, "Participants were randomized to receive either regular salt (100% sodium chloride) or the salt substitute (70% sodium chloride/30% potassium chloride blend) and advised to replace all home salt use with the substitute."

The primary outcome was the change in systolic blood pressure from baseline to 3 months in the salt substitute group compared to the regular salt groups. Secondary outcomes included the change in diastolic blood pressure, 24-hour urinary biomarkers, and self-reported use and satisfaction with the study salts provided.

"At 3 months, the salt substitute intervention significantly decreased average systolic blood pressure by about 4.6 units, an effect comparable to some commonly prescribed anti-hypertensive medications," said Sudhir Raj Thout, Research Fellow, The George Institute India, the study co-author who led the study's field operations.

"There was also a significant increase in the amount of potassium consumed in the salt substitute group. Participants reported that they used the study salt nearly every day of the week and rated the taste of the study salts similarly, indicating that the reduced-sodium salt substitutes are acceptable for home cooking for our study participants." he added.

The findings have policy implications. "Our data suggest that using reduced-sodium, added-potassium salt substitute to replace regular salt for home cooking will likely be an effective and scalable intervention for blood pressure control in rural India," said Jason Wu, Associate Professor and Scientia Fellow at The George Institute, and supervisor of the study.

"As none of the participants were aware of the existence of reduced-sodium salt at the beginning of the study, this suggests policymakers should consider supporting increased access to, and education about the use of such salt substitutes for hypertensive patients in India."

 THIS IS YOUR BRAIN ON SCIENCE

The egg in the X-ray beam

Innovative time-resolved method reveals network formation by and dynamics of proteins

DEUTSCHES ELEKTRONEN-SYNCHROTRON DESY

Research News

IMAGE

IMAGE: WHEN HEATED, THE PROTEINS IN THE ORIGINALLY TRANSPARENT CHICKEN EGG WHITE FORM A TIGHTLY MESHED, OPAQUE NETWORK. view more 

CREDIT: CREDIT: DESY, GESINE BORN

A team of scientists has been using DESY's X-ray source PETRA III to analyse the structural changes that take place in an egg when you cook it. The work reveals how the proteins in the white of a chicken egg unfold and cross-link with each other to form a solid structure when heated. Their innovative method can be of interest to the food industry as well as to the broad field of research surrounding protein analysis. The cooperation of two groups, headed by Frank Schreiber from the University of Tübingen and Christian Gutt from the University of Siegen, with scientists at DESY and European XFEL reports the research in two articles in the journal Physical Review Letters.

Eggs are among the most versatile food ingredients. They can take the form of a gel or a foam, they can be comparatively solid and also serve as the basis for emulsions. At about 80 degrees Celsius, egg white becomes solid and opaque. This is because the proteins in the egg white form a network structure. Studying the exact molecular structure of egg white calls for energetic radiation, such as X-rays, which is able to penetrate the opaque egg white and has a wavelength that is no longer than the structures being examined.

"To understand the structural evolution in detail, you have to study the phenomenon on the micrometre scale," explains Nafisa Begam, the lead author of the first study, who is an Alexander von Humboldt fellow in Schreiber's group. The scientists used so-called X-ray photon correlation spectroscopy (XPCS) with a specific geometry allowing them to determine the structure and the dynamics of the proteins in the egg white.

For their experiments on the P10 beamline at PETRA III the scientists used a chicken egg from a supermarket and filled the egg white into a quartz tube with a diameter of 1.5 millimetres. "Inside, the egg white was heated in a controlled manner while we analysed it with the help of the X-rays," explains DESY co-author Fabian Westermeier. "The X-ray beam was expanded to 0.1 by 0.1 millimetres, to keep the radiation dose below the damage threshold of the protein structures."

The measurements reveal the protein dynamics in the egg white over a period of about a quarter of an hour. During the first three minutes, the protein network grew exponentially, reaching a plateau after about five minutes, at which virtually no more protein links were formed. At this time, the average mesh size of the protein network was about 0.4 micrometres (thousandths of a millimetre).

In the second study, the team used the XPCS technique to investigate the self-organisation of protein solutions into domains with, respectively, high and low protein concentration, as an example of structure formation in cell biology. In the process, they were able to follow the temperature-dependent dynamics over time. "At high protein densities, mobility decreases, which slows down the phase separation. This is important for the special dynamics of the system," reports lead author Anita Girelli from Schreiber's group.

The studies, which were funded by the German Federal Ministry of Education and Research (BMBF), not only reveal new details about the structural changes occurring in egg whites, but also prove the experimental concept, which can be used for other samples too, as demonstrated by the second study. "Successfully applying X-ray photon correlation spectroscopy opens up a new way to study the dynamics of biomolecules, which is essential if we are to understand them properly," Schreiber comments.

DESY is one of the world's leading particle accelerator centres and investigates the structure and function of matter - from the interaction of tiny elementary particles and the behaviour of novel nanomaterials and vital biomolecules to the great mysteries of the universe. The particle accelerators and detectors that DESY develops and builds at its locations in Hamburg and Zeuthen are unique research tools. They generate the most intense X-ray radiation in the world, accelerate particles to record energies and open up new windows onto the universe. DESY is a member of the Helmholtz Association, Germany's largest scientific association, and receives its funding from the German Federal Ministry of Education and Research (BMBF) (90 per cent) and the German federal states of Hamburg and Brandenburg (10 per cent).

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References:

Kinetics of Network Formation and Heterogeneous Dynamics of an Egg White Gel Revealed by Coherent X-Ray Scattering; Nafisa Begam, Anastasia Ragulskaya, Anita Girelli, Hendrik Rahmann, Sivasurender Chandran, Fabian Westermeier, Mario Reiser, Michael Sprung, Fajun Zhang, Christian Gutt, and Frank Schreiber; Physical Review Letters, 2021; DOI: 10.1103/PhysRevLett.126.098001

Microscopic dynamics of liquid-liquid phase separation and domain coarsening in a protein solution revealed by XPCS; Anita Girelli, Hendrik Rahmann, Nafisa Begam, Anastasia Ragulskaya, Mario Reiser, Sivasurender Chandran, Fabian Westermeier, Michael Sprung, Fajun Zhang, Christian Gutt, and Frank Schreiber; Physical Review Letters, 2021 (accepted; in pri

Russian biologists discover a

transmissible cancer lineage in the 

Far Eastern mussels

The disease can have an adverse effect on the populations of these molluscs, which are extensively farmed in Russia.

ST. PETERSBURG STATE UNIVERSITY

Research News

IMAGE

IMAGE: CONFOCAL MICROSCOPY IMAGES OF HAEMOCYTES OF A DN-SUGGESTED MUSSEL (J54) STAINED WITH DAPI (BLUE) AND TRITC-LABELLED PHALLOIDIN (RED). IMAGES (A, B) ARE AT TWO DIFFERENT MAGNIFICATIONS (NOTE THE SCALE BARS).... view more 

CREDIT: SPBU

'A transmissible cancer was first discovered in dogs in the middle of the 19th century. It is transmitted sexually from a sick dog to a healthy one, the cancer cells themselves being the infective agent. In the 1990s, a contagious cancer was discovered in the Tasmanian devil. Since the cancer was found in only two species of mammals, scientists used to think that it is quite rare in the nature. However, time has come to reconsider this view. A transmissible cancer appears to be fairly widespread among bivalve molluscs,' says Maria Skazina, a research associate at the Department of Applied Ecology at St Petersburg University and the first author of the publication in Scientific Reports.

Disseminated neoplasia (DN) is a large-scale, fatal cancer disease of bivalve molluscs, which can be compared to leukemia in vertebrates. Diseased mussels have cancer cells, which circulate in the hemolymph, a functional analogue of blood. As neoplasia develops, they infiltrate all tissues and organs, disrupting their work.

The causes of this disease were described for the first time in 2016 in an article published by a group of scientists under the leadership of by Michael Metzger in Nature. The authors showed that disseminated neoplasia was a transmissible cancer lineage. Its cells have their own genotype, different from those of the molluscan hosts. In a way, they are parasites transmitted from sick individuals to healthy ones.

'A study proposing a mechanism of the transfer of cancer cells between individuals was published last year. When the mussel is under stress, the cells of its haemolymph can leave the body, exist for some time in the environment and then invade other mussels. This process has been observed in healthy molluscs. Cancer cells, it would seem, might use this mechanism too,' says Maria Skazina. 'However, this is only a hypothesis. To test it, sophisticated experimental research is necessary'.

Mussels Mytilus are important commercial invertebrates. Two genetic lineages of transmissible cancer are known in them: BTN1 and BTN2 (BTN stands for bivalve transmissible neoplasia). Both of them originated from the Pacific mussel Mytilus trossulus, which is also found in the Far Eastern and Northern seas of Russia.

'So far, BTN1 lineage has been found in a single mussel population at the Pacific coast of North America. BTN2 is much more widespread. Before our research, it had been found in several mussel species in Europe and South America, though not in the parental species Mytilus trossulus,' says Maria Skazina.

In 2019, marine biologists from St Petersburg University, A.V. Zhirmunsky National Research Centre of Marine Biology, and the University of Helsinki joined forces to search for transmissible cancer lineages in the mussels of the Russian seas. To diagnose the disease, they developed an integrated approach, which included cytological and molecular genetic tests, and applied it to the mussels Mytilus trossulus from the Sea of Japan, in which disseminated neoplasia had been previously shown.

In the haemolymph of molluscs from the Gaydamak Bay near the port city of Nakhodka, flow cytometry and immunocytochemistry methods revealed neoplastic cells. They are large, have polyploid nuclei and an abnormal cytoskeleton resembling the spines of a bristling hedgehog. Genotyping of the haemolymph and other tissues by nuclear and mitochondrial characteristics revealed genetic 'chimerism' of the sick mussels, that is, the presence of more than one individual genotype. Multiple alleles (different forms of the same gene that determine the development of a particular trait) were separated by molecular cloning. All diseased mussels were found to have 'additional' genotypes corresponding to BTN2. This means that the scientists from St Petersburg University and their colleagues proved, for the first time, the presence of BTN2 in Mytilus trossulus as well as the presence of transmittable cancer in mussels from the Sea of Japan and the Northwest Pacific.

At the next stage of the research, the scientists used molecular phylogenetic methods to compare the sequences of the mitochondrial BTN genes obtained by them with all the homologous sequences of the mussels themselves stored in the NCBI genetic bank. It turned out that the mitochondria of BTN2 are most similar to those of Mytilus trossulus from the Russian seas. It was probably there that 'patient zero' lived, the mussel that 'gave birth' to this transmissible cancer.

The Baltic Sea mussels were also shown to have BTN2. In 2014, Polish biologists found an unusual mitochondrial genotype in a Baltic mussel, which they interpreted as the genotype of Mytilus trossulus. It is now clear that this was not a mussel genotype, but a BTN2 genotype. It appears that the transmissible cancer that the scientists were looking for in the Far East could be found much closer to St Petersburg. Whether this disease is common among the molluscs of the Baltic Sea remains to be found out.

'This disease is so virulent for invertebrates because they do not have a developed immune system that can reliably distinguish alien cells from their own. Transmissible cancer of molluscs cannot harm humans in any way. However, the disease can be detrimental for the mussel marine culture. We do not yet know how widespread transmissible cancer is among mussels in Russia,' says Maria Skazina.

The scientists now continue to search for transmissible cancer in mussels in different seas of Russia. Preliminary evidence suggests that it is found not only in mussels in the Sea of Japan and the Baltic Sea and that its diversity is not limited to BTN2 lineage. They are also developing a method for rapid diagnosis of the disease in order to monitor it in natural and commercial populations of molluscs.

'Hopefully, our work might be of help for comparative oncology. I think that mussels, as a research model, can tell a lot about the mechanisms of the spread of cancer in different species, including humans,' notes Maria Skazina.

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