A new algorithm to predict information super spreaders in social media

SCIENCE CHINA PRESS

 

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NODES A AND B LOOK THE SAME WHEN ONLY CONSIDERING THEIR CLOSEST NETWORK CONNECTIONS (DIRECTED ARROWS IN THE GREEN REGION). THE TWO USERS A AND B INFLUENCE THREE USERS EACH (ORANGE NODES), AND THEY EXHIBIT THE SAME NUMBER OF INFORMATION PROPAGATION EVENTS (ARROWS’ THICKNESS). YET BY ANALYZING THE INFORMATION PROPAGATION PATTERNS TO THE SIX NODES INFLUENCED BY A AND B (INCLUDING ARROWS IN THE ORANGE REGION), THE INFLUENCE-SUSCEPTIBILITY ALGORITHM DETERMINES THAT THE NODES INFLUENCED BY B ARE MORE SUSCEPTIBLE TO INFLUENCE THAN THOSE INFLUENCED BY A AND, THEREFORE, A IS MORE INFLUENTIAL.

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CREDIT: ©SCIENCE CHINA PRESS

Understanding how information flows in social networks is critical to counteracting dangerous misinformation, promoting the spreading of news, and designing healthy online social environments. Scholars have long realized the role of information superspreaders – namely, users with the capability to rapidly spread messages and ideas to many others. A long-standing research tradition identifies the superspreaders through their position in the social network. This research, led by Prof. Linyuan Lü (University of Electronic Science and Technology of China) and Dr. Manuel S. Mariani (University of Zurich), challenges this long-standing paradigm. It shows that how users’ behavioral traits (i.e., how they tend to behave) provide more accurate early indicators of their spreading ability than where they sit in the social network.

The authors departed from traditional network approaches by starting from a model for how information flows from individual to individual. Motivated by previous empirical findings, the model assumes that the probability that a message is transmitted from a source to a target user is determined by both the source’s influence (namely, a parameter that captures her likelihood to transmit information to others) and the target’s susceptibility to influence. The users’ influence and susceptibility parameters are not known a priori. However, the authors derived a pair of coupled equations that connect the users’ influence and susceptibility with the structure of the underlying propagation network, which enables their computation on massive behavioral datasets.

 

Through these equations, the authors could measure the influence and susceptibility scores of millions of users in Weibo and Twitter, which improves our understanding of information superspreaders in two ways. First, the results by the authors challenge the paradigm that the network hubs – i.e., the users with many followers – are the most effective information spreaders. They show that, instead, the influence and susceptibility scores of the users provide more accurate predictors of being a superspreader than the users’ number of followers. Second, the superspreaders are characterized by more high-contagion links (i.e. the product between their influence and their audiences’ susceptibilities tends to be large), and they tend to influence more influential users. This suggests that explaining the superspreaders requires the integration of network structures and individual-level behavioral characteristics. 

These findings could open new directions in social network research. Within the realm of information spreading, the simplifying assumptions of the propagation model might be gradually relaxed. More refined models may include topic diversity, algorithmic influences, memory effects, all of which could lead to different equations for the users’ influence and susceptibility scores. The influence and susceptibility scores may also vary by topic, which could eventually lead to a multidimensional characterization of the users and their spreading capabilities.

On a more general note, the paradigm proposed by this study could also have implications for interventions aimed at large-scale behavioral change. Traditionally, these activities focus on persuading the social hubs to early adopt a new product or behavior. The authors’ findings suggest that a more effective approach might rely on identifying high-contagion links that connect highly-influential and highly-susceptible potential adopters. To this end, additional research is needed to adapt the algorithm to the spreading of behaviors, which will likely require different sets of equations compared to those obtained for information spreading. Field experiments will be needed to validate the resulting insights. Eventually, these efforts could reveal how to best integrate individuals’ position in their social networks with how they typically behave to design interventions for behavioral change, which is key for organizations and policymakers.

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JOURNAL

National Science Review

DOI

10.1093/nsr/nwae073 

 

Tiny plastic particles are found everywhere

UNIVERSITY OF BASEL

It’s not the first study on microplastics in Antarctica that researchers from the University of Basel and the Alfred-Wegener Institute (AWI) have conducted. But analysis of the data from an expedition in spring 2021 shows that environmental pollution from these tiny plastic particles is a bigger problem in the remote Weddell Sea than was previously known.

The total of 17 seawater samples all indicated higher concentrations of microplastics than in previous studies. “The reason for this is the type of sampling we conducted,” says Clara Leistenschneider, doctoral candidate in the Department of Environmental Sciences at the University of Basel and lead author of the study.

The current study focused on particles measuring between 11 and 500 micrometers in size. The researchers collected them by pumping water into tanks, filtering it, and then analyzing it using infrared spectroscopy. Previous studies in the region had mostly collected microplastic particles out of the ocean using fine nets with a mesh size of around 300 micrometers. Smaller particles would simply pass through these plankton nets.

The results of the new study indicate that 98.3 percent of the plastic particles present in the water were smaller than 300 micrometers, meaning that they were not collected in previous samples. “Pollution in the Antarctic Ocean goes far beyond what was reported in past studies,” Leistenschneider notes. The study appears in the journal Science of the Total Environment.

What role do ocean currents play?

The individual samples were polluted to different extents. The offshore samples, which were collected north of the continental slope and the Antarctic Slope Current, contained the highest concentrations of microplastics. The reasons for this are not conclusively known. It may be that the ice that tends to form near the coast retains the tiny plastic particles, and they are only released back into the water when the ice melts. It could also be the case that ocean currents play a role. “They might work like a barrier, reducing water exchange between the north and south,” suggests Gunnar Gerdts from the AWI in Heligoland, Germany.

What is certainly true is that ocean currents are an important factor and the subject of many open questions in the field. So far the researchers have only examined water samples from the ocean surface, but not from lower depths. This is primarily due to limited time on the ship expeditions for taking samples and to equipment with insufficient pumping capacity. “It would nonetheless be revealing to analyze such data, since the deep currents differ greatly from the surface currents and thermohaline circulation leads to exchange with water masses from northern regions,” Leistenschneider says.

It is also still unclear how the microplastics make their way to the Weddell Sea in the first place and whether they ever leave the region. The strong Antarctic Circumpolar Current, which flows all the way around the Antarctic Ocean at a latitude of about 60° south, might prevent their departure. The researchers are also not yet able to say conclusively where the microplastics originate. Possible sources include regional ship traffic from the tourism, fishing and research industries, as well as research stations on land. However, the microplastics might also make their way to Antarctica from other regions via ocean currents or atmospheric transport.

Research leads to awareness

Clara Leistenschneider plans to focus next on analyzing the sediment samples she collected during the same expedition. This should provide information about how microplastics are accumulating on the sea floor, which is home to unique and sensitive organisms and is a breeding ground for Antarctic icefish (Bovichtidae).

With the increase in tourism in the Antarctic Ocean, pollution may increase even more in the future, further impacting the environment and the food chain.

Nonetheless, Leistenschneider remains cautiously optimistic: “Research on the topic has dramatically increased awareness in recent years of the problems that microplastics cause for the environment and all living organisms.” Although there is no all-encompassing solution, she notes that a variety of stakeholders all over the world are working intensively to better understand the problem and develop innovative ideas to reduce plastic pollution. And, of course, “every individual who engages in environmentally-conscious behavior can bring about positive change.”

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JOURNAL

Science of The Total Environment

DOI

10.1016/j.scitotenv.2024.172124 

ARTICLE TITLE

Unveiling High Concentrations of Small Microplastics (11–500 μm) in Surface Water Samples from the Southern Weddell Sea off Antarctica.

ARTICLE PUBLICATION DATE

8-Apr-2024

Understanding the northward movement of the subtropical westerly jet in changing climates

 NEWS RELEASE 9-APR-2024

INSTITUTE OF ATMOSPHERIC PHYSICS, CHINESE ACADEMY OF SCIENCES

 

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FAST-MOVING AIR CURRENT WITH SWIRLING AIR PATTERNS CALLED EDDIES

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CREDIT: CHEN SHENG

The subtropical westerly jet is a high-altitude, fast-moving air current that flows from west to east in the subtropical region of the Earth's atmosphere. It's an important part of atmospheric circulation, influencing weather patterns and climate conditions globally. Scientists have noticed that this jet has been shifting northward under global warming. They've been trying to figure out why, focusing on two main factors: changes caused by temperature and those driven by swirling air patterns called eddies. But it's been hard to say which factor is more important.

A new study from the Institute of Atmospheric Physics at the Chinese Academy of Sciences, might have some answers. Researchers looked at data from the past 40 years and found that during winter in northern hemisphere, changes in temperature seem to be the main reason behind the jet's shift north. They think this happens because change in temperature structure is the fundamental rule governing how air moves around the globe. Their study suggests that about 72% of the jet's northward movement is because of changes in temperature, while about 28% is due to swirling air patterns.

 

"In the context of climate change, the northward shift of the zonal-mean SWJ in boreal winter results from the interplay of multiple mechanisms, but pinpointing the primary controlling factors is essential for refining our research thought," Dr. Chen Sheng, the lead author of the study published in the Journal of Geophysical Research-Atmospheres, explains, "Our research suggests that changes in how heat moves around the atmosphere are a big part of it. "

 

This study builds on the team’s previous research within the PVC (Potential Vorticity Circulation) framework, which explores how air movements affect weather patterns. The new findings suggest that the northward shift of the subtropical westerly jet likely indicates changes in how different parts of the Northern Hemisphere interact with each other in terms of air circulation and weather systems.

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JOURNAL

Journal of Geophysical Research Atmospheres

DOI

10.1029/2023JD039937 

ARTICLE TITLE

Roles of thermal forced and eddy-driven effects in the northward shifting of the subtropical westerly jet under recent climate change

A natural touch for coastal defense

Hybrid solutions which combine nature with common “hard” coastal protection measures may offer more benefits in lower-risk areas

UNIVERSITY OF TOKYO

 

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THIS ILLUSTRATION SHOWS NATURAL (CORAL REEF) AND SOFT (REPLANTED MANGROVE) MEASURES, FORMING A HYBRID DEFENSE WITH THE CONCRETE SEA WALL. NATURE-BASED SOLUTIONS WERE RECOGNIZED AS A KEY OPTION TO TACKLE THE “TRIPLE PLANETARY CRISIS” OF CLIMATE CHANGE, POLLUTION AND BIODIVERSITY LOSS AT THE MOST RECENT UNITED NATIONS CLIMATE CONFERENCE, COP28, HELD IN 2023. 

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CREDIT: 2024, NICOLA BURGHALL

Common “hard” coastal defenses, like concrete sea walls, might struggle to keep up with increasing climate risks. A new study shows that combining them with nature-based solutions could, in some contexts, create defenses which are better able to adapt. Researchers reviewed 304 academic articles on the performance of coastal defenses around the world, including: natural environments; soft measures (which support or enrich nature); hard measures (such as concrete sea walls); and hybrids of the aforementioned. Soft and hybrid measures turned out to be more cost-effective than hard measures, and hybrid measures provided the highest hazard reduction overall in low-risk areas. Although their comparative performance during extreme events that pose a high risk is not clear due to lack of data, these results still support the careful inclusion of nature-based solutions to help protect, support and enrich coastal communities. 

 

Japan’s dramatic natural coastline, with iconic views of Mount Fuji, wind-blown pines and rocky beaches, has been captured and admired in paintings and prints for hundreds of years. But take a walk by the ocean nowadays and it can be hard to find a stretch that retains its pristine natural seascape. By the early 1990s, a government survey found that around 40% of the coast had been altered with concrete sea walls, filled harbors, stacks of tetrapods and more, adding swaths of gray to the blue-green landscape. Sprawling coastal cities and towns have grown to house most of the population, so protecting homes and businesses from the dangers of tsunamis, typhoon swells and sea-level rise has become an ever-increasing challenge.

 

“Sea walls, dikes, dams and breakwaters, the so-called traditional hard measures, despite being the most popular coastal defenses globally and with proven track records, are facing challenges to keep pace with increasing climate risks”, explained Lam Thi Mai Huynh, a doctoral student from the graduate program in sustainability science at the University of Tokyo and lead author of a new study on coastal defenses. “These hard structures are expensive to build and require continuous upgrades and repairs as sea level rises and climatic hazards become stronger. Although they are good at mitigating certain coastal disaster risks, they can also cause significant disruption to coastal communities and have adverse environmental effects. Furthermore, they often significantly alter the seascape and sometimes alienate local communities from nature and the very environment we seek to protect.”

 

To better understand the performance and benefits of different hard and nature-based coastal defenses, an international team compared the results of 304 academic studies. Nature-based coastal defenses included: “natural” ecosystems, for example, existing mangroves and coral reefs; “soft” measures, which restore, rehabilitate, reforest or nourish natural ecosystems; and “hybrid” measures that combine both nature-based components and hard structures, such as placing concrete breakwaters in front of mangroves.

 

“By incorporating such natural components, we can create coastal defenses that reduce risk and also offer substantial environmental benefits. We believe that such strategies are very promising in many parts of the world, but they are also not a ‘fix-all’ solution,” said Professor Alexandros Gasparatos from the Institute for Future Initiatives at the University of Tokyo.

 

The researchers analyzed three key aspects of each type of defense: 1. risk reduction (how much the measure could reduce wave height and energy, and influence shoreline change); 2. climate change mitigation (including carbon storage and greenhouse gas emissions for nature-based measures); and 3. cost-effectiveness over a 20-year period. 

 

“Our results indicate that among all coastal defense options in lower-risk areas, hybrid measures provide the highest risk reduction. Hybrid measures can harness the advantages of both hard and soft measures. They provide the immediacy of an engineered barrier while largely maintaining the ecological functionality of a permeable vegetated zone,” said Huynh. “All nature-based solutions are found to be effective in storing carbon, while both soft and hybrid measures are relatively more cost-effective than traditional hard measures over a 20-year period, though all have positive economic returns.” 

 

These findings provide strong evidence for integrating and upscaling nature-based components into coastal defenses, but the team advised doing so with caution. “All types of coastal defenses have yet to be adequately tested through paired experiments in circumstances of extreme events and high-risk urgency,” warned Gasparatos. “Until there are many more such experiments focusing on this, we must caution against any universal assumptions about the comparative performance of coastal defense options, whether natural, soft or hybrid measures.” 

 

While acknowledging the limits imposed by the lack of available research on extreme and high-risk situations, Huynh and Gasparatos still believe that this study supports the idea of investing in nature-based solutions for coastal defense in lower-risk areas. Research like this has important implications for policymakers, coastal planners and communities looking to make evidence-based decisions.

 

“I firmly believe that we must think more carefully about the design and function of these barriers in this era of ever-accelerating climate change,” said Huynh. “Not only can nature-based solutions contribute to risk reduction and climate mitigation in many areas, but they can also help reconnect people with nature and support biodiversity. Greening our coastlines can create spaces which enhance quality of life, foster community well-being and inspire environmental stewardship.”

 

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Paper Title:

Lam T.M. Huynh, Jie Su, Quanli Wang, Lindsay C. Stringer, Adam D. Switzer, Alexandros Gasparatos. Meta-analysis shows hybrid engineering-natural coastal defences perform best for climate adaptation and mitigation. Nature Communications. April 9th 2024. Doi: 10.1038/s41467-024-46970-w

 

Funding:

L.H acknowledges the support of Grant-in-Aid Research Fellowship for young Scientist offered by the Japan Society for the Promotion of Science (23KJ0544). A.G is supported by a Grant-in-Aid for Scientific Research A offered by the Japan Society for the Promotion of Science (22H00567).  A.D.S. is supported by the Singapore Ministry of Education Academic Research Fund (MOE2019-T3-1-004 and MOET32022-0006).

 

Useful Links
Graduate Program in Sustainability Science - Global Leadership Initiative: https://www.sustainability.k.u-tokyo.ac.jp/en/

Graduate School of Frontier Sciences: https://www.k.u-tokyo.ac.jp/en/ 

Institute for Future Initiatives: https://ifi.u-tokyo.ac.jp/en/ 

Gasparatos Lab: https://www.gasparatos-lab.org/ 

 

Research Contact: 

Lam Thi Mai Huynh

Graduate School of Frontier Sciences, The University of Tokyo

5-1-5 Kashiwanoha, Kashiwa City 277- 8563, Japan.

Email: lam.huynh@s.k.u-tokyo.ac.jp

 

Professor Alexandros Gasparatos

Institute for Future Initiatives (IFI), The University of Tokyo

Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033

Email: gasparatos@ifi.u-tokyo.ac.jp 

 

Press contact:
Mrs. Nicola Burghall
Public Relations Group, The University of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654, Japan
press-releases.adm@gs.mail.u-tokyo.ac.jp

 

About the University of Tokyo
The University of Tokyo is Japan's leading university and one of the world's top research universities. The vast research output of some 6,000 researchers is published in the world's top journals across the arts and sciences. Our vibrant student body of around 15,000 undergraduate and 15,000 graduate students includes over 4,000 international students. Find out more at www.u-tokyo.ac.jp/en/ or follow us on X (formally Twitter) at @UTokyo_News_en.

 

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JOURNAL

Nature Communications

DOI

10.1038/s41467-024-46970-w 

METHOD OF RESEARCH

Literature review

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Meta-analysis shows hybrid engineering-natural coastal defences perform best for climate adaptation and mitigation.

ARTICLE PUBLICATION DATE

9-Apr-2024

 

Impact of climate change on marine life much bigger than previously known

Fish and invertebrate animals are far more affected by warmer and more acidic seawater than was previously known. This is the conclusion of a study co-led by NIOZ marine biologist Katharina Alter, based on a new analysis method

ROYAL NETHERLANDS INSTITUTE FOR SEA RESEARCH

 

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REDFIN NEEDLEFISH (STRONGYLURA NOTATA) "HIDING" BELOW THE SEA SURFACE NEAR THE CARRIBEAN ISLAND OF CURACAO. CREDIT: JULIETTE JACQUEMONT (CO-AUTHOR OF THE STUDY).

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CREDIT: JULIETTE JACQUEMONT

Fish and invertebrate animals are far more affected by warmer and more acidic seawater than was previously known. This is the conclusion of a study co-led by NIOZ marine biologist Katharina Alter, based on a new analysis method and published in the scientific journal Nature Communications.

Lead author Katharina Alter of the Royal Netherlands Institute for Sea Research (NIOZ) explains why it is essential to summarize and analyze the results of published studies addressing the effects of climate change: “To gain a better understanding of the overall worldwide impact of climate change, marine biologists calculate its effects on all fish or all invertebrate species lumped together. Yet, effects determined in different individual studies can cancel each other out: for example if invertebrate animals such as snails profit from a certain environmental change and other invertebrates, such as sea urchins, suffer from it, the overall effect for invertebrates is concluded to be zero, although both animal groups are affected.”

In fact, snails eat more due to climate change and sea urchins eat less. Alter: “Both effects matter and even have cascading effects: turf algae, the food for sea urchins, grow more while the growth of kelp, the food for gastropods, decreases. The difference in feeding in the two invertebrates causes a shift in the ecosystem from a kelp dominated ecosystem to a turf algae dominated ecosystem, consequently changing the living environment for all other animals living in this ecosystem.”

Important for understanding ecological shifts

Together with colleagues from Wageningen University and 12 other research institutions from the US, France, Argentina, Italy and Chile, dr. Alter developed the new research method that no longer cancels out seemingly contradictory results, but uses both to determine the consequences of climate change on animals’ fitness.

Before the use of this method, ocean warming and more acidic seawater was known to negatively affect fish and invertebrate animals in three general ways: their chance of survival is reduced, their metabolism is increased, and the skeletons of invertebrates are weakened.

Using the new method, the international group of marine researchers discovered that climate change has negative effects on additional important biological responses of fish and invertebrates: physiology, reproduction, behaviour and physical development. Alter: “Because this may result in ecological shifts impacting marine ecosystem structures, our results suggest that climate change will likely have stronger impacts than previously thought.”

Up to 100% of biological processes affected

Increasing levels of carbon dioxide in the air have been causing warmer and more acidic seawater for decades, a trend that is expected to continue in the future. However, it is unknown at which speed and to what extent.

Alter and her colleagues calculated the consequences of three projected scenarios of carbon dioxide increase, and thus of ocean warming and ocean acidification: extreme increase, moderate increase at the current speed and – due to possible measures – mitigated increase. Alter: “Our new approach suggests that if ocean warming and acidification continue on the current trajectory, up to 100% of the biological processes in fish and invertebrate species will be affected, while previous research methods found changes in only about 20 and 25% of all processes, respectively.”

Furthermore, the research shows that measures to mitigate atmospheric carbon dioxide levels will help reduce changes in biological processes: in the low carbon dioxide scenario, 50% of responses in invertebrates and 30% in fish will be affected.

Detect hidden impacts

The big gain of the new method, according to Alter, is that more details become known about effects of climate change on species. "The new calculation method weighs the significant deviation from the current state irrespective of its direction - be it beneficial or detrimental - and counts it as impact of warming and acidifying seawater. With our new approach, you can include the broadest range of measured responses and detect impacts that were hidden in the traditional approach."

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JOURNAL

Nature Communications

DOI

10.1038/s41467-024-47064-3 

METHOD OF RESEARCH

Meta-analysis

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Hidden impacts of ocean warming andacidification on biological responses ofmarine animals revealed through meta-analysis

ARTICLE PUBLICATION DATE

Are lab-grown brain tissues ethical? There is no no-brainer answer

Insights into ethical and legal ramifications of growing brain organoids from human fetal brain tissue

HIROSHIMA UNIVERSITY

Brain organoids, though often referred to as “mini brains,” are not truly human brains. But the concerns over these lab-grown brain tissues, especially when they are developed from human fetal tissues, can be very human indeed.

Researchers from the Graduate School of Humanities and Social Sciences at Hiroshima University offer valuable insights into the complexities inherent in brain organoid research, making significant contributions to the ongoing discourse surrounding this innovative biotechnology and paving the way for informed decision-making and legal and ethical stewardship in the pursuit of scientific advancement.

Their paper was published on March 4 in EMBO Reports.

Brain organoids are three-dimensional human brain tissues derived from stem cells, which are capable of developing into many different cell types. They replicate the complexity of the human brain in a laboratory setting, allowing researchers to study brain development and diseases in the hopes of acquiring vital insights and making innovative medical advancements.

Traditionally, brain organoids are grown from pluripotent stem cells, an especially potent sub-type that is typical of early embryonic development, but new technologies now make it possible to generate these organoids from human fetal brain cells. This method comes, however, with even more heated legal and ethical debates about brain organoids — debates that are already intense in conventional organoid research.

“Our research seeks to illuminate previously often-overlooked ethical dilemmas and legal complexities that arise at the intersection of advanced organoid research and the use of fetal tissue, which is predominantly obtained through elective abortions,” said Tsutomu Sawai, an associate professor at Hiroshima University and lead author of the study.

The study highlights the urgent need for a sophisticated and globally harmonized regulatory framework tailored to navigate the complex ethical and legal landscape of fetal brain organoid (FeBO) research. The paper emphasizes the importance of informed consent protocols, ethical considerations surrounding organoid consciousness, transplantation of organoids into animals, integration with computational systems, and broader debates related to embryo research and the ethics of abortion.

“Our plan is to vigorously advocate for the development of thorough ethical and regulatory frameworks for brain organoid research, including FeBO research, at both national and international levels,” said Masanori Kataoka, a fellow researcher at Hiroshima University.

“Rather than being limited to issues of consciousness, it’s imperative, now more than ever, to systematically advance the ethical and regulatory discussion in order to responsibly and ethically advance scientific and medical progress,” Sawai said.

Moving forward, the research duo plans to continue supporting the advancement of ethical and regulatory discussions surrounding brain organoid research. By promoting responsible and ethical progress in science and medicine, they aim to ensure that all research involving brain organoids, including FeBOs, is conducted within a framework that prioritizes human dignity and ethical integrity.

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About Hiroshima University

Since its foundation in 1949, Hiroshima University has striven to become one of the most prominent and comprehensive universities in Japan for the promotion and development of scholarship and education. Consisting of 12 schools for undergraduate level and 4 graduate schools, ranging from natural sciences to humanities and social sciences, the university has grown into one of the most distinguished comprehensive research universities in Japan. English website: https://www.hiroshima-u.ac.jp/en

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JOURNAL

EMBO Reports

DOI

10.1038/s44319-024-00099-5 

ARTICLE TITLE

The ethical and legal challenges of human foetal brain tissue-derived organoids: At the intersection of science, ethics, and regulation

 

Tiny brain bubbles carry complete codes

Scientists at Sanford Burnham Prebys demonstrated that vesicles traveling between cells in the brain carry more complete instructions for altering cellular function than previously thought.

Peer-Reviewed Publication

SANFORD-BURNHAM PREBYS

 

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THIS PORTRAIT OF EXTRACELLULAR VESICLES WAS TAKEN USING CONFOCAL LASER SCANNING MICROSCOPY. THE MEMBRANE WAS STAINED WITH FLUORESCENT DYE. IMAGE TITLED “Exosomes” COURTESY OF TOMAŽ EINFALT, UNIVERSITY OF BASEL, UNDER Creative Commons BY-NC-ND license.

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CREDIT: TOMAŽ EINFALT

In findings published in Cell Reports, senior author Jerold Chun, M.D., Ph.D., and team also discovered that the biological instructions within these vesicles differed significantly in postmortem brain samples donated from patients suffering from Alzheimer’s disease.

Researchers call the tiny brain bubbles under scrutiny in this study small extracellular vesicles (sEVs). These tiny biological water balloons are produced by most cells in the body to ferry a wide variety of proteins, lipids and byproducts of cellular metabolism, as well as RNA nucleic acid codes used by recipient cells to construct new proteins.

Because this biologically active cargo can easily elicit changes in other cells, scientists are interested in brain sEVs as a medium for passing along normal as well as bungled instructions for misfolded proteins that accumulate in the brain as neurodegenerative diseases such as Alzheimer’s disease progress.

To be a potential contributor to the buildup of unwanted proteins, sEVs would have to carry blueprints with sufficient information to enable other cells to produce the problematic proteins. Most previous research had indicated that the messenger RNA (mRNA) carrying plans for proteins were chopped into too many shorter fragments to allow recipient cells to change their construction patterns.

“We found quite the opposite to be true in our study,” says Chun, professor in the Center for Genetic Disorders and Aging Research at Sanford Burnham Prebys. “We identified more than 10,000 full-length mRNAs through the use of a relatively newer DNA sequencing technique called PacBio long-read sequencing.”

The team isolated sEVs from the prefrontal cortex of 12 postmortem brain samples donated from patients diagnosed with Alzheimer’s disease and 12 from donors without Alzheimer’s disease (or any other known neurological disease). Nearly 80% of identified mRNAs were full-length, allowing them to be transcribed by recipient cells into viable proteins.

“To corroborate the results of long-read sequencing in the human samples, we also looked at vesicles isolated from mouse cells,” says first author Linnea Ransom, Ph.D., postdoctoral fellow at Sanford Burnham Prebys. “We found similar averages of between 78% and 86% full-length transcripts in three brain cell types: astrocytes, microglia and neurons.”

In addition to analyzing and validating the results regarding the length of mRNAs in brain sEVs, the researchers compared the sequence of genes reflected in the sEV mRNA transcriptome. In Alzheimer’s disease samples, 700 genes showed increased expression whereas nearly 1500 were found to have reduced activity.

The scientists determined that the 700 upregulated genes are associated with inflammation and immune system activation, which fits within known patterns of brain inflammation present in neurodegenerative diseases such as Alzheimer’s disease. The researchers also found many genes associated with Alzheimer’s disease in prior genome-wide association studies also were present in Alzheimer’s disease sEVs.

“The changes in gene expression contained in these vesicles reveal an inflammatory signature that may serve as a window into disease processes occurring in the brain as Alzheimer’s disease progresses,” says Chun.

Following this study, Chun and team will dig deeper into how cells package sEVs and how the enclosed mRNA codes lead to functional changes in other brain cells affected in Alzheimer’s disease. Better understanding of sEVs and their mRNA contents may enable the discovery of biomarkers that could be used to improve early detection of Alzheimer’s disease and potentially other neurological conditions, while identifying new disease mechanisms to provide new therapeutic targets. 

“Additionally, sEVs naturally occur as a vehicle for transporting biologically active cargo between cells, so it also may be possible to leverage them as a targeted delivery system for future brain therapies” says Chun.

Additional authors on the study include Linnea S. Ransom, Christine S. Liu, Emily Dunsmore, Carter R. Palmer, Juliet Nicodemus, Derya Ziomek and Nyssa Williams, all at Sanford Burnham Prebys.

The study was supported by the National Institute on Aging (R01AG065541 and R01AG071465), National Institute of General Medical Sciences (T32GM007752) and Rotary International.

The study’s DOI is 10.1016/j.celrep.2024.114061.

Immunofluorescence was used to validate primary cell culture purity.  Image courtesy of the Chun lab.

Negative-stain transmission electron microscopy was used to confirm the isolation of small extracellular vesicles in mouse neurons (shown above), as well as in mouse astrocytes and microglia. Image courtesy of the Chun lab.

CREDIT

The Chun lab

JOURNAL

Cell Reports

DOI

10.1016/j.celrep.2024.114061 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Human tissue samples

ARTICLE TITLE

Human brain small extracellular vesicles contain selectively packaged, full-length mRNA

ARTICLE PUBLICATION DATE

4-Apr-2024

COI STATEMENT

J.C. has been or is a consultant or scientific advisory board member or has received research support for projects unrelated to the current work from the following: Aardvark Therapeutics, Aardwolf Therapeutics, Abbott/Abbvie, Amira Pharmaceuticals, Arena Pharmaceuticals, Autobahn Therapeutics, Biogen Idec, BrainStorm Cell Therapeutics, Bristol Myers Squibb, Celgene, GSK, Inception Sciences, Janssen Research and Development, Longboard Pharmaceuticals, MindX, Mitsubishi Tanabe, Neurocrine Biosciences, Novartis Pharmaceuticals, Ono Pharmaceuticals, Pfizer, Pipeline Therapeutics, RuiYi, ShouTi, Simulyve International, Structure Therapeutics, Taisho Pharmaceutical Co., Travecta Therapeutics, Trevena, and Vial. J.C. has an employment relationship with Neurocrine Biosciences, a company that may potentially benefit from the research results. J.C.’s relationship with Neurocrine Biosciences has been reviewed and approved by the Sanford Burnham Prebys Medical Discovery Institute in accordance with its conflict of interest policies.