Surprisingly simple model explains how brain cells organize and connect

ANARCHY IS IN YOUR HEAD

Scientists from UChicago, Harvard, and Yale propose a self-organizing model of connectivity that applies across a wide range of organisms and potentially other types of networks as well.

@ IS SELF ORGANIZATION

UNIVERSITY OF CHICAGO

A new study by physicists and neuroscientists from the University of Chicago, Harvard and Yale describes how connectivity among neurons comes about through general principles of networking and self-organization, rather than the biological features of an individual organism.

The research, published on January 17, 2024 in Nature Physics, accurately describes neuronal connectivity in a variety of model organisms and could apply to non-biological networks like social interactions as well.

“When you’re building simple models to explain biological data, you expect to get a good rough cut that fits some but not all scenarios,” said Stephanie Palmer, PhD, Associate Professor of Physics and Organismal Biology and Anatomy at UChicago and senior author of the paper. “You don’t expect it to work as well when you dig into the minutiae, but when we did that here, it ended up explaining things in a way that was really satisfying.”

Understanding how neurons connect

Neurons form an intricate web of connections between synapses to communicate and interact with each other. While the vast number of connections may seem random, networks of brain cells tend to be dominated by a small number of connections that are much stronger than most.

This “heavy-tailed” distribution of connections (so-called because of the way it looks when plotted on a graph) forms the backbone of circuitry that allows organisms to think, learn, communicate and move. Despite the importance of these strong connections, scientists were unsure if this heavy-tailed pattern arises because of biological processes specific to different organisms, or due to basic principles of network organization.

To answer these questions, Palmer and Christopher Lynn, PhD, Assistant Professor of Physics at Yale University, and Caroline Holmes, PhD, a postdoctoral researcher at Harvard University, analyzed connectomes, or maps of brain cell connections. The connectome data came from several different classic lab animals, including fruit flies, roundworms, marine worms and the mouse retina.

To understand how neurons form connections to one another, they developed a model based on Hebbian dynamics, a term coined by Canadian psychologist Donald Hebb in 1949 that essentially says, “neurons that fire together, wire together.” This means the more two neurons activate together, the stronger their connection becomes.

Across the board, the researchers found these Hebbian dynamics produce “heavy-tailed” connection strengths just like they saw in the different organisms. The results indicate that this kind of organization arises from general principles of networking, rather than something specific to the biology of fruit flies, mice, or worms.

The model also provided an unexpected explanation for another networking phenomenon called clustering, which describes the tendency of cells to link with other cells via connections they share. A good example of clustering occurs in social situations. If one person introduces a friend to a third person, those two people are more likely to become friends with them than if they met separately.

"These are mechanisms that everybody agrees are fundamentally going to happen in neuroscience,” Holmes said. “But we see here that if you treat the data carefully and quantitatively, it can give rise to all of these different effects in clustering and distributions, and then you see those things across all of these different organisms.”

Accounting for randomness

As Palmer pointed out, though, biology doesn’t always fit a neat and tidy explanation, and there is still plenty of randomness and noise involved in brain circuits. Neurons sometimes disconnect and rewire with each other — weak connections are pruned, and stronger connections can be formed elsewhere. This randomness provides a check on the kind of Hebbian organization the researchers found in this data, without which strong connections would grow to dominate the network.

The researchers tweaked their model to account for randomness, which improved its accuracy.

“Without that noise aspect, the model would fail,” Lynn said. “It wouldn’t produce anything that worked, which was surprising to us. It turns out you actually need to balance the Hebbian snowball effect with the randomness to get everything to look like real brains.”

Since these rules arise from general networking principles, the team hopes they can extend this work beyond the brain.

“That’s another cool aspect of this work: the way the science got done,” Palmer said. “The folks on this team have a huge diversity of knowledge, from theoretical physics and big data analysis to biochemical and evolutionary networks. We were focused on the brain here, but now we can talk about other types of networks in future work.”

The study, “Heavy–tailed neuronal connectivity arises from Hebbian self–organization,” was supported by the National Science Foundation, through the Center for the Physics of Biological Function (PHY–1734030) and a Graduate Research Fellowship (C.M.H.); by the James S. McDonnell Foundation through a Postdoctoral Fellowship Award (C.W.L.); and by the National Institutes of Health BRAIN initiative (R01EB026943).

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JOURNAL

Nature Physics

DOI

10.1038/s41567-023-02332-9 

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Heavy–tailed neuronal connectivity arises from Hebbian self–organization

ARTICLE PUBLICATION DATE

17-Jan-2024

Novel tissue-derived brain organoids could revolutionize brain research

Peer-Reviewed Publication

PRINCESS MÁXIMA CENTER FOR PEDIATRIC ONCOLOGY

 

IMAGE: 

AN IMAGE OF A WHOLE HUMAN FETAL BRAIN ORGANOID. STEM CELLS ARE MARKED BY SOX2 (GREY) AND NEURONAL CELLS (TUJ1) ARE COLOR CODED FROM PINK TO YELLOW BASED ON DEPTH.

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CREDIT: PRINCESS MÁXIMA CENTER, HUBRECHT INSTITUTE/B ARTEGIANI, D HENDRIKS, H CLEVERS

Press release – Princess Máxima Center for pediatric oncology

EMBARGO: 8 JANUARY 2024 AT 11:00 AM ET (US)

 

Scientists have developed 3D mini-organs from human fetal brain tissue that self-organize in vitro. These lab-grown organoids open up a brand-new way of studying how the brain develops. They also offer a valuable means to study the development and treatment of diseases related to brain development, including brain tumors.

Scientists use different ways to model the biology of healthy tissue and disease in the lab. These include cell lines, laboratory animals and, since a few years, 3D mini-organs. These so-called organoids have characteristics and a level of complexity that allows scientists to closely model the functions of an organ in the lab. Organoids can be formed directly from cells of a tissue. Scientists can also ‘guide’ stem cells – found in embryos or in some adult tissues – to develop into the organ they aim to study.

Until now, brain organoids were grown in the lab by coaxing embryonic or pluripotent stem cells to grow into structures representing different areas of the brain. Using a specific cocktail of molecules, they would try to mimic the natural development of the brain – with the ‘recipe’ for each cocktail taking a lot of research to develop.

Now, scientists at the Princess Máxima Center for pediatric oncology and the Hubrecht Institute, both based in Utrecht, the Netherlands, developed brain organoids directly from human fetal brain tissue. The study was published in the prestigious journal Cell today (Monday), and was part-funded by the Dutch Research Council.

The researchers, led by Dr. Delilah Hendriks, Prof. Dr. Hans Clevers and Dr. Benedetta Artegiani, were surprised to find that using small pieces of fetal brain tissue rather than individual cells was vital in growing mini-brains. To grow other mini-organs such as gut, scientists normally break down the original tissue to single cells. Instead working with small pieces of fetal brain tissue, the team found that these pieces could self-organize into organoids.

The brain organoids were roughly the size of a grain of rice. The tissue’s 3D make-up was complex, and it contained a number of different types of brain cells. Importantly, the brain organoids contained many so-called outer radial glia – a cell type found in humans and our evolutionary ancestors. This underlines the organoids’ close similarity to – and use in studying – the human brain.

The whole pieces of brain tissue also produced proteins that make up extracellular matrix – a kind of ‘scaffolding’ around cells. The team believes these proteins could be the reason why the pieces of brain tissue were able to self-organize into 3D brain structures. The presence of extracellular matrix in the organoids will allow further study of the environment of brain cells, and what happens when this goes wrong.

The researchers found that the tissue-derived organoids kept various characteristics of the specific region of the brain from which they were derived. They responded to signaling molecules known to play an important role in brain development. This finding suggests that the tissue-derived organoids could play an important role in untangling the complex network of molecules involved in directing the development of the brain.

Given the ability of the tissue-derived organoids to quickly expand, the team next investigated their potential in modeling brain cancer. The researchers used gene-editing technique CRISPR-Cas9 to introduce faults in the well-known cancer gene TP53 in a small number of cells in the organoids. After three months, the cells with defective TP53 had completely overtaken the healthy cells in the organoid – meaning they had acquired a growth advantage, a typical feature of cancer cells.

They then used CRISPR-Cas9 to switch off three genes linked to the brain tumor, glioblastoma: TP53, PTEN and NF1. The researchers also used these mutant organoids to look at their response to existing cancer drugs. These experiments showed the organoids’ potential for cancer drug research to link certain drugs to specific gene mutations.

The tissue-derived organoids continued to grow in a dish for more than six months. Importantly, the scientists could multiply them, allowing them to grow many similar organoids from one tissue sample. The mini-tumors with the glioblastoma gene changes – were also capable of multiplying, keeping the same mix of mutations. This feature means scientists can carry out repeat experiments with the tissue-derived organoids, increasing the reliability of their findings.

Next, the researchers aim to further explore the potential of their new tissue-derived brain organoids. They also plan to continue their work with bioethicists – who were already involved in shaping this research – to guide the future development and applications of the new brain organoids.

Dr. Benedetta Artegiani, research group leader at the Princess Máxima Center for pediatric oncology who co-led the research, says:

‘Brain organoids from fetal tissue are an invaluable new tool to study human brain development. We can now more easily study how the developing brain expands, and look at the role of different cell types and their environment.

‘Our new, tissue-derived brain model allows us to gain a better understanding of how the developing brain regulates the identity of cells. It could also help understand how mistakes in that process can lead to neurodevelopmental diseases such as microcephaly, as well as other diseases that can stem from derailed development, including childhood brain cancer.’

Dr. Delilah Hendriks, affiliated group leader at the Princess Máxima Center for pediatric oncology, postdoctoral researcher at the Hubrecht Institute and Oncode Investigator, who co-led the research, says:

‘These new fetal tissue-derived organoids can offer novel insights into what shapes the different regions of the brain, and what creates cellular diversity. Our organoids are an important addition to the brain organoid field, that can complement the existing organoids made from pluripotent stem cells. We hope to learn from both models to decode the complexity of the human brain.

‘Being able to keep growing and using the brain organoids from fetal tissue also means that we can learn as much as possible from such precious material. We’re excited to explore the use of these novel tissue organoids for new discoveries about the human brain.’

Prof. dr. Hans Clevers, pioneer in organoid research and former research group leader at the Hubrecht Institute and the Princess Máxima Center for pediatric oncology and Oncode Investigator, co-led the research. He says:

‘With our study, we’re making an important contribution to the organoid and brain research fields. Since we developed the first human gut organoids in 2011, it’s been great to see that the technology has really taken off. Organoids have since been developed for almost all tissues in the human body, both healthy and diseased – including an increasing number of childhood tumors.

‘Until now, we were able to derive organoids from most human organs, but not from the brain – it’s really exciting that we’ve now been able to jump that hurdle as well.’

The study was performed in collaboration with Leiden University Medical Center, Utrecht University, Maastricht University, Erasmus University Rotterdam, and National University of Singapore.

- ENDS -

Notes to editors

The human fetal tissue was derived from healthy abortion material, between gestational weeks 12-15, from fully anonymous donors. The anonymous women donated the tissue voluntarily and upon informed consent. They were informed that the material would be used for research purposes only, and that the research included the understanding of how organs normally develop, including the possibility to grow cells derived from the donated material.

About the Princess Máxima Center for pediatric oncology

When a child is seriously ill from cancer, only one thing matters: a cure.

Every year, 600 children in the Netherlands are diagnosed with cancer. Sadly, one in four of these children dies. That is why in the Princess Máxima Center for pediatric oncology, we work together with passion and without limits every day to improve the survival rate and quality of life of children with cancer. Now, and in the long term. Because children have their whole lives ahead of them.

The Princess Máxima Center is no ordinary hospital, but a research hospital. All children with cancer in the Netherlands are treated here, and it’s where all research into childhood cancer in the country takes place. This makes the Princess Máxima Center the largest pediatric cancer center in Europe. More than 900 healthcare professionals and 450 scientists work closely with Dutch and international hospitals to find better treatments and new perspectives for a cure.

In this way, we offer children today the best possible care, and we take important steps to improve survival for children who cannot not yet be cured.

A zoom-in image of a part of a human fetal brain organoid. Stem cells are marked by SOX2 (cyan) and neuronal cells (TUJ1) are color coded from pink to yellow based on depth.

Four zoom-in images of parts of different human fetal brain organoids. Different neural markers are stained, depicting their cellular heterogeneity and architecture.

CREDIT

Princess Máxima Center, Hubrecht Institute/B Artegiani, D Hendriks, H Clevers

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JOURNAL

Cell

DOI

10.1016/j.cell.2023.12.012 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Human embryos

ARTICLE TITLE

Human fetal brain self-organizes into long-term expanding organoids

ARTICLE PUBLICATION DATE

8-Jan-2024

Fastest swimming insect could inspire uncrewed boat designs

Peer-Reviewed Publication

CORNELL UNIVERSITY

ITHACA, N.Y. – Whirligig beetles, the world’s fastest-swimming insect, achieve surprising speeds by employing a strategy shared by speedy marine mammals and waterfowl, according to a new Cornell University study that rewrites previous explanations of the physics involved.

The centimeter-long beetles can reach a peak acceleration of 100 meters per second and a top velocity of 100 body lengths per second (or one meter per second).

Not only do the results explain the whirligig’s Olympian speeds, but they also offer valuable insights for bio-inspired designers of near-surface water robots and uncrewed boats.

Until now, researchers have believed that whirligigs attain their impressive speeds using a propulsion system called drag-based thrust. This type of thrust requires the insect’s legs to move faster than the swimming speed, in order for the legs to generate any thrust. For the whirligig beetle to achieve such fast swimming speeds, its legs would need to push against the water at unrealistic speeds.

“It could have well been questioned,” said Chris Roh, assistant professor of biological and environmental engineering. “The fastest swimmer and drag-based thrust don’t usually go together in the same sentence.”

In fact, fast-swimming marine mammals and waterfowls tend to forgo drag-based thrust in favor of lift-based thrust, another propulsion system. The finding was described in a study published Jan. 8 in the journal Current Biology.

Using two high-speed cameras synchronized at different angles, the researchers were able to film a whirligig and observe a lift-based thrust mechanism at play. Lift-based thrust works like a propeller, where the thrusting motion is perpendicular to the water surface, eliminating drag and allowing for more efficient momentum capable of greater speed.

Lift-based thrust has previously been identified in large-scale organisms, such as whales, dolphins and sea lions. “In this work, we extended the length-scale down to one centimeter, which means that whirligig beetles are by far the smallest organism to use lift-based thrust for swimming,” said Yukun Sun, a doctoral student in Roh’s lab and the paper’s first author.

“We’re hoping that this speaks to bio-inspired robotics and other engineering communities to first identify the right physics and then try to preserve that physics in creating the robotics,” Roh said.

The U.S. Navy has been developing uncrewed boats, as traditional ship design is constrained by the need to make boats hospitable to a crew. By eliminating a crew, boats can be much smaller and more flexible. Roh believes that the small size, ship-like shape and lift-generating propulsion mechanism of whirligigs translate well to inform robotic ship designs.

The study was funded by the National Science Foundation.

For additional information, see this Cornell Chronicle story.

Media note: Video of the whirligig beetle can be viewed and downloaded here: https://cornell.box.com/v/whirligigbeetles 

-30-

 

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JOURNAL

Current Biology

DOI

10.1016/j.cub.2023.11.008 

ARTICLE TITLE

Whirligig beetle uses lift-based thrust for fastest insect swimming

ARTICLE PUBLICATION DATE

8-Jan-2024

 

UC Study: Thirdhand smoke may harm children

UC researcher Ashley Merianos says toxic substances remain on surfaces, even in homes that ban indoor smoking

Peer-Reviewed Publication

UNIVERSITY OF CINCINNATI

 

IMAGE: 

ASHLEY MERIANOS, PHD, ASSOCIATE PROFESSOR IN UC’S SCHOOL OF HUMAN SERVICES.

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CREDIT: ANDREW HIGLEY/UC MARKETING + BRAND

It’s long been established that secondhand smoke is a detriment to health and linked to cancer.

Now, researchers are looking more closely at thirdhand smoke, which is the presence of toxic tobacco by-products that remain on surfaces such as furniture, décor, walls and floors.  

In a new study, published in the Journal of Exposure Science & Environmental Epidemiology, researchers tested the surfaces in smoking households where children reside and found troubling results, says Ashley Merianos, a tobacco researcher at the University of Cincinnati who led the study. 

Researchers found nicotine on surfaces in all of the children's homes and detected the presence of a tobacco-specific carcinogen (called NNK) in nearly half of the homes, she says.  

The study reported that the NNK levels on surfaces and vacuumed dust were similar, which Merianos says indicates that surfaces and dust can be similar reservoirs and sources of thirdhand smoke exposure for children.

“This is critically important and concerning, since NNK is considered the most potent carcinogen for tobacco-induced cancers,” says Merianos, an associate professor in UC’s School of Human Services.

Additional findings include:

• Children living in lower-income households had higher levels of NNK and nicotine found on home surfaces.
• Children living in homes that did not ban indoor smoking had higher levels of NNK and nicotine found on surfaces.

Merianos says that NNK and nicotine were still detected in homes with voluntary indoor smoking bans, which highlights the persistence of thirdhand smoke pollutants on surfaces in children's homes.

“This research highlights that home smoking bans do not fully protect children and their families from the dangers of tobacco,” she adds. 

Merianos is a prolific researcher and has extensive training and experience in the epidemiology and prevention of substance use with an emphasis on tobacco, as well as quantitative statistical methods and clinical and translational research in the pediatric health care setting. 

She is also a research affiliate member of Cincinnati Children’s Hospital Medical Center, the Thirdhand Smoke Research Consortium and the American Academy of Pediatrics Tobacco Consortium.

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JOURNAL

Journal of Exposure Science & Environmental Epidemiology

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Contamination of surfaces in children’s homes with nicotine and the potent carcinogenic tobacco-specific nitrosamine NNK

 

Unique framework of tin bimetal organic compound facilitates stable lithium-ion storage

Peer-Reviewed Publication

TSINGHUA UNIVERSITY PRESS

 

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THE SN-TI-EG ANODE MAINTAINED A CAPACITY OF 345 MAH G-1 (BLUE LINE) AT A CURRENT DENSITY OF 1.0 A G-1 AFTER 700 CHARGE-DISCHARGE CYCLES. THE METAL-ORGANIC FRAMEWORK (MOF) OF THE SN-TI-EG ANODE MITIGATES THE TYPICAL STABILITY ISSUES OF SN AND SN-ALLOY ANODES THAT OCCUR DUE TO EXPANSION DURING THE CHARGE-DISCHARGE CYCLE.

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CREDIT: ENERGY MATERIALS AND DEVICES, TSINGHUA UNIVERSITY PRESS

Battery capacity is one of the primary bottlenecks in efficient renewable energy storage and significant reductions in carbon emissions. As a battery anode that releases electrons in a lithium-ion battery (LIB), tin (Sn) and Sn-mixture alloys could theoretically store more energy at a higher density than more common carbon-based anodes. Pairing a Sn-Ti bimetal element with inexpensive ethylene glycol (Sn-Ti-EG) mitigated many of the challenges of using Sn as an anode material and produced an inexpensive LIB with excellent storage and performance characteristics.

 

Sn and Sn alloys, or mixture of another metal with Sn, could outperform other anode materials but suffer from poor stability due to the expansion of the metal during charging and discharging. One way to overcome this limitation is by creating a metal-organic framework (MOF) that maintains rapid electron transfer (energy flow) while providing good stability during charging and recharging. Materials scientists recently created a Sn-Ti-EG bimetal organic compound MOF that demonstrated high electricity conduction, energy capacity and stability through many charging and discharging cycles.

 

The researchers published their study in the journal Energy Materials and Devices on November 20.

 

“Significant efforts have been directed toward developing high-capacity cathode and anode materials for high energy-density LIBs. Because the capacities of well-known cathode materials, for example LiFePO4, Ni-rich layered oxides and LiMn2O4, have reached their theoretical limits, more attention is being focused on finding anode materials that have high energy densities as a substitute for the commonly used graphite anodes that have a relatively low theoretical capacity and tap density.” said Zhen-Dong Huang, senior author of the study and professor in the State Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors at Nanjing University of Posts and Telecommunications in Nanjing, China.

 

Specifically, anodes made from graphite, a crystalline form of carbon, have a theoretical capacity of 372 mAh g-1, which refers to the amount of electric charge (milliampere hours or mAh) the material can deliver per gram (g-1) of that material. In contrast, Sn, bismuth (Bi) and antimony (Sb) metals have higher theoretical capacities than graphite anodes. Sn anodes, for example, have a theoretical capacity of 994 mAh g-1, but suffer from stability issues due to expansion.

 

“To resolve the stability issues associated with Sn anodes, a myriad of strategies have been explored, including minimizing the particle size, introducing inert metals and assembling with carbon materials. Moreover, rationally designed structures, such as hollow, layered and

core–shell structures play an important role in alleviating volume expansion. Although these strategies helped the cyclic stability to a certain degree, the… energy densities of the nanostructured Sn-based anodes are normally low. In contrast, metal–organic frameworks have an intrinsically porous structure that not only provides a large number of active sites but also enables rapid electrolyte penetration and electron/ion transfer,” said Huang.

 

The research team created a unique MOF made up of Sn, Ti and EG that leveraged beneficial characteristics of each component to create a more stable anode material with high electrochemical performance. EG, for example, served as an organic bridge between positively charged Sn2+ and Ti4+ ions to complete the battery circuit. Ti additionally contributed to the improved structure and stability of the material. Sn contributed its higher theoretical capacity, improving the anode material’s electrochemical performance.

 

Ultimately, the team created a new, inexpensive LIB anode material that maintained a high specific capacity of 345 mAh g-1 at a current density of 1000 mA g−1 after 700 cycles, which demonstrates the stability of anode material. Scanning electron microscope pictures confirmed that the anode material had no cracks after 700 cycles.

 

Further analysis of the Sn-Ti-EG anode material revealed that the strong interaction between the Sn and carbon-oxygen species was responsible for the high specific capacity and excellent cyclic stability of the electrode, which may help future researchers design additional anode materials with similar characteristics. The research team sees this latest advance in anode specific capacity as a stepping stone to additional LIB materials that can improve battery storage capacity and be produced efficiently at large scale.

 

Other contributors include Yuqing Cai, Haoran Li, Qianzi Sun, Xiang Wang and Ziquan Li from the State Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors at the Institute of Advanced Materials in the Jiangsu National Synergetic Innovation Center for Advanced Materials at the Nanjing University of Posts and Telecommunications in Nanjing, China; Haigang Liu from the Shanghai Synchrotron Radiation Facility in the Shanghai Advanced Research Institute at the Chinese Academy of Sciences in Shanghai, China; and Jang-Kyo Kim from the Department of Mechanical Engineering at Khalifa University in Abu Dhabi, United Arab Emirates.

 

This research was supported by the National Natural Science Foundation of China (52277219, 61974072, 52032005), the Project of State Key Laboratory of Organic Electronics and Informa- tion Displays, Nanjing University of Posts and Telecommunications (GZR2022010024), Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX22_0992), Khalifa University financial support (FSU 2023-022, PD#8295), and the Shanghai Synchrotron Radiation Facility (BL07U).

 

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About Energy Materials and Devices

Energy Materials and Devices is launched by Tsinghua University, published quarterly by Tsinghua University Press, aiming at being an international, single-blind peer-reviewed, open-access and interdisciplinary journal in the cutting-edge field of energy materials and devices. It focuses on the innovation research of the whole chain of basic research, technological innovation, achievement transformation and industrialization in the field of energy materials and devices, and publishes original, leading and forward-looking research results, including but not limited to the materials design, synthesis, integration, assembly and characterization of devices for energy storage and conversion etc.

About SciOpen 

SciOpen is a professional open access resource for discovery of scientific and technical content published by the Tsinghua University Press and its publishing partners, providing the scholarly publishing community with innovative technology and market-leading capabilities. SciOpen provides end-to-end services across manuscript submission, peer review, content hosting, analytics, and identity management and expert advice to ensure each journal’s development by offering a range of options across all functions as Journal Layout, Production Services, Editorial Services, Marketing and Promotions, Online Functionality, etc. By digitalizing the publishing process, SciOpen widens the reach, deepens the impact, and accelerates the exchange of ideas.

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JOURNAL

Energy Materials and Devices

DOI

10.26599/EMD.2023.9370013 

ARTICLE TITLE

Strong coordination interaction in amorphous Sn-Ti-ethylene glycol compound for stable Li-ion storage

 

Nemours Children’s Health researchers find Zika virus is effective when used to treat a type of childhood cancer in mice

In models of neuroblastoma, Zika injection dramatically improved survival

Peer-Reviewed Publication

NEMOURS

ORLANDO, Fla. (Jan. 9, 2024) — Injecting neuroblastoma tumors with Zika virus shrank or eliminated those tumors in studies with mice, suggesting that the virus could someday serve as an effective cancer therapy, according to a study led by Nemours Children’s Health researchers and published today in Cancer Research Communications, a journal of the American Association for Cancer Research.

Neuroblastoma is a rare childhood cancer that typically develops in the sympathetic nervous system or the adrenal glands. Only 700 to 800 cases are diagnosed each year in the United States, accounting for 6% of childhood cancer diagnoses. However, high-risk neuroblastoma takes a disproportionate toll, causing 15% of childhood cancer deaths.

“More than half of patients with high-risk neuroblastoma do not respond to chemotherapy or radiation, or they respond initially, but develop a recurrence,” explained the study’s senior author, pediatric surgeon Tamarah Westmoreland, MD, PhD, Associate Professor of Surgery at Nemours Children’s in Orlando. “These patients are in urgent need of new treatment options.”

In recent years, researchers have discovered that Zika virus, which is carried by mosquitoes, can potentially be used to kill cancer cells. Zika virus infections in pregnant women can cause serious birth defects as the virus targets CD24, a developmental protein. Previous research has suggested that certain cancers that express the CD24 protein are also vulnerable to the Zika virus, opening the door for Zika virus to be used as a treatment. In this study, Westmoreland and first author Joseph Mazar, PhD, Research Scientist at Nemours Children’s, examined Zika’s potential against neuroblastoma.

The researchers studied mice with neuroblastoma tumors that express high levels of CD24. They injected half of the mice with a saline solution, and the other half with Zika virus. Tumor sizes were monitored three times a week thereafter.

The study showed that all mice injected with the Zika virus experienced a nearly total loss of tumor size. The highest dosage tested resulted in complete elimination of the tumor, which was confirmed by an independent Nemours Children’s pathologist. In four weeks of follow-up, there was no recurrence of the tumor. Furthermore, the mice did not develop any symptoms of Zika virus infection or any side effects.

To determine whether treatment with Zika virus is likely to help human patients survive longer, the researchers developed mouse models of human neuroblastoma tumors, treating them with either Zika virus or a saline solution. Twenty-eight days after the treatment, all tumors that received the saline solution had grown by as much as 800%. The tumor models that had received Zika had shrunk to approximately 12% of the original mass, which was confirmed to represent scar tissue rather than the tumor cells. After four additional weeks, no further tumor growth was detected, suggesting that patients treated with Zika virus would be more likely to survive.

The researchers cautioned that the use of Zika virus as a cancer therapy will require extensive additional studies encompassing safety and efficacy. They are currently testing Zika virus treatment in mouse adrenal glands growing neuroblastoma, mimicking neuroblastoma’s most typical location in humans. Routine use in the United States would require testing in clinical trials and ultimately approval by the U.S. Food and Drug Administration.

“With further validation, Zika virus could be an extremely effective bridge therapy for patients with high-risk neuroblastoma,” said Mazar. “We also see potential for Zika virus to be used to treat children and adults with other cancers that express high levels of CD24.”

“Neuroblastoma is often a very challenging diagnosis, especially for the patients who are unlikely to respond well to chemotherapy,” said Matthew M. Davis, MD, MAPP, Executive Vice-President, Enterprise Physician-in-Chief and Chief Scientific Officer of Nemours. “Dr. Westmoreland and Dr. Mazar are at the forefront of potentially lifesaving cancer treatment. We are hopeful that this study will pave the way toward improved survival for patients with neuroblastoma.”

Zika background

• Zika virus was first identified in monkeys in Uganda in 1947, and first identified in humans in 1952. Spread by the bite of an infected mosquito, Zika virus can be passed from a pregnant woman to her fetus as the virus targets CD24, a developmental protein. Infection during pregnancy can lead to birth defects, including a small head size and an underdeveloped brain.
• While Zika virus infection is most common in tropical regions, the United States experienced a rise in cases in 2016 and 2017, primarily in Florida and Texas.
• In most humans, Zika virus infection results in mild cold-like symptoms. Most people infected with the virus never develop symptoms.
• This study builds upon a 2018 study by Westmoreland, Mazar, and Kenneth Alexander, MD, PhD, Chief of the Division of Infectious Diseases at Nemours Children’s Health in Orlando. That research established the precedent that Zika virus could kill neuroblastoma cells.
• Zika virus has also been studied as a potential treatment for glioblastoma, a deadly brain cancer.

About Nemours Children’s Health
Nemours Children’s Health is one of the nation’s largest multistate pediatric health systems, which includes two free-standing children's hospitals and a network of more than 70 primary and specialty care practices. Nemours Children's seeks to transform the health of children by adopting a holistic health model that utilizes innovative, safe and high-quality care, while also caring for the health of the whole child beyond medicine. Nemours Children's also powers the world’s most-visited website for information on the health of children and teens, Nemours KidsHealth.org.

The Nemours Foundation, established through the legacy and philanthropy of Alfred I. duPont, provides pediatric clinical care, research, education, advocacy, and prevention programs to the children, families and communities it serves. For more information, visit Nemours.org.

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JOURNAL

Cancer Research Communications

Xidian University researchers develop optimal design method for microwave power transmission

Peer-Reviewed Publication

ENGINEERING

 

IMAGE: 

RR1: THE INNER RADIUS OF THE ANNULAR RECEIVING AREA; RR2: THE OUTER RADIUS OF THE ANNULAR RECEIVING AREA; RT: THE RADIUS OF THE TRANSMITTING ANTENNA; L: THE DISTANCE BETWEEN THE TRANSMITTING ANTENNA AND RECTENNA; Θ1, Θ2: THE ANGLES OF THE ANNULAR RECEIVING AREA.

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CREDIT: XUN LI ET AL.

A team of researchers from Xidian University in China has achieved a new result in the field of microwave power transmission. Their study, published in Engineering, introduces an optimal design method for antenna aperture illumination with an annular collection area, with the goal of maximizing the power radiated on the collection area.

The research, led by Professor Baoyan Duan from Shaanxi Key Laboratory of Space Solar Power Station System, Xidian University, focused on formulating the aperture amplitude distribution using a unique set of series. As a result, they were able to simplify the optimal design problem to maximize the ratio of two real quadratic forms. Leveraging matrix theory, the team identified the solution to the optimization problem as determining the largest characteristic value and its associated characteristic vector.

In addressing security concerns, the researchers also integrated additional constraints to account for peak radiation levels outside the receiving area. To address this constrained optimization problem, they developed a hybrid grey wolf optimizer and Nelder–Mead simplex method. The effectiveness of this novel approach was confirmed through numerical experiments using continuous apertures. Furthermore, the optimized results were validated using discrete arrays of isotropic elements, along with patch arrays.

The newly proposed method offers several advantages in the field of microwave power transmission. “Our optimal design method enables the achievement of maximum beam collection efficiency (BCE) while satisfying security requirements,” explained the team. “This method allows for the design of continuous aperture distributions to maximize BCE, with or without extra constraints, and facilitates the easy design of array antennas of various sizes.”

The impact of this research extends beyond annular collection areas. The team emphasized, “Our method is not only applicable to annular collection areas but also extends to microwave power transmission applications with circular collection areas, as the circular collection area is a special case of an annular collection area.”

This breakthrough in optimal design methods for antenna aperture illumination holds significant potential for advancing microwave power transmission technologies. It has the capacity to optimize power radiated on collection areas, leading to more efficient and effective transmission of microwave power.

The research conducted by the team at Xidian University represents a promising development in the field. Their approach introduces new possibilities for enhancing the design and performance of microwave power transmission systems. As the demand for wireless power transfer continues to grow, advancements like these are crucial.

The paper “Optimal Design of Aperture Illuminations for Microwave Power Transmission with Annular Collection Areas,” authored by Xun Li, Baoyan Duan, Yiqun Zhang, Yongxin Guo. Full text of the open access paper: https://doi.org/10.1016/j.eng.2023.07.016. For more information about the Engineering, follow us on Twitter (https://twitter.com/EngineeringJrnl) & like us on Facebook (https://www.facebook.com/EngineeringPortfolio).

 

About Engineering:

Engineering (ISSN: 2095-8099 IF:12.8) is an international open-access journal that was launched by the Chinese Academy of Engineering (CAE) in 2015. Its aims are to provide a high-level platform where cutting-edge advancements in engineering R&D, current major research outputs, and key achievements can be disseminated and shared; to report progress in engineering science, discuss hot topics, areas of interest, challenges, and prospects in engineering development, and consider human and environmental well-being and ethics in engineering; to encourage engineering breakthroughs and innovations that are of profound economic and social importance, enabling them to reach advanced international standards and to become a new productive force, and thereby changing the world, benefiting humanity, and creating a new future.

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JOURNAL

Engineering

DOI

10.1016/j.eng.2023.07.016 

ARTICLE TITLE

Optimal Design of Aperture Illuminations for Microwave Power Transmission with Annular Collection Areas

 

Study on lamprey embryos sheds light on the evolutionary origin of vertebrate head

Scientists study developing lamprey embryos to clarify the origin of vertebrate head, paving the way to a better understanding of ancestral vertebrates

Peer-Reviewed Publication

UNIVERSITY OF FUKUI

 

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THESE PRIMITIVE JAWLESS FISH COULD HOLD CLUES TO THE EVOLUTIONARY ORIGIN OF VERTEBRATE HEADS, AS EVIDENCED BY DETAILED EMBRYOLOGICAL ANALYSES.

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CREDIT: TAKAYUKI ONAI FROM UNIVERSITY OF FUKUI

The origin of the vertebrate skull is a topic of much debate among evolutionary biologists. Some believe that the vertebrate head has developed as a result of modification of the segmental elements of the trunk, such as the vertebrae and somites. On the other hand, others believe that the vertebrate head has evolved as a new, unsegment body part, unrelated to other widely observed embryonic segments somites. Interestingly, previous studies on embryos have revealed the presence of some vestiges of somites in the head mesoderm (e.g., head cavities and somitomeres). However, homology between trunk somites and such head segments has been controversial.

The failure to understand the evolutionary origins of the vertebrate head is also attributable to the lack of studies on extant species such as lampreys, which are known to share several traits with fossil jawless vertebrates and retain primitive traits related to the head mesoderm. While some studies have focused on the embryonic morphology of lampreys, they have often fallen short because of challenges like tissue destruction and acidic fixation during examination, making it difficult to observe the formation of head mesoderm and trunk somites.

Now, however, a research team led by Assistant Professor Takayuki Onai from the University of Fukui, Japan, has utilized advanced techniques like transmission electron microscopy and serial block-face scanning electron microscopy (SBF-SEM) to understand the development of the head mesoderm and somites in lamprey embryos. The researchers also analyzed the morphology and gene expression patterns of cephalochordate and hemichordate (both being invertebrates) to understand the origins of somites and head mesoderm from an evolutionary perspective. This paper was made available online in iScience on November 13, 2023, and is co-authored by Dr. Noritaka Adachi from Aix-Marseille Université, Dr. Hidetoshi Urakubo from the National Institute for Physiological Sciences (NIPS), Dr. Fumiaki Sugahara from Hyogo Medical University, Dr. Toshihiro Aramaki from Osaka University, Dr. Mami Matsumoto from NIPS and Nagoya City University, and Dr. Nobuhiko Ohno from NIPS and Jichi Medical University.

To clarify the presence or absence of somites in the head mesoderm during early stages of diversification, the researchers focused on rosettes, which are major somite patterns and are important for the subsequent development of vertebrae. Their initial observations of lamprey embryos showed that the tissue closely related to the formation of facial muscles and other elements of the skull, known as the head mesoderm, did have cell clusters with features similar to somite rosettes. To clarify if these cell clusters were indeed rosettes, they conducted ultrastructural experiments, including the SBF-SEM and gene expression analysis. This examination of the cellular morphology and gene expression revealed that the cell clusters were clearly distinct from rosettes. “The cell clusters we observed are likely lamprey-specific features, as they are not recognizable in the head mesoderm of both hagfish and shark embryos,” explains Dr. Onai.

Furthermore, gene expression analysis also revealed the absence of segmental expression of somitogenesis-related genes, indicating their distinctiveness from somites. These findings indicate that the rosette pattern typically seen in somites is not necessarily the essential or most basic feature that defines the process of bodily segmentation.

Moreover, the experiments provide evidence that the vertebrate head mesoderm diverged during the early phases of vertebrate evolution. Furthermore, comparison of embryos of hemichordates (a basal deuterostome), amphioxus (a basal chordate), and vertebrates revealed that the somites likely arose from the “endomesoderm” tissue of an ancient deuterostome ancestor. The evolutionary origin of somites has been the central question in zoology for more than 150 years, and in this study, Onai et al., revealed the enigma. Regarding the evolutionary mechanism for the emergence of head mesoderm, they found that the head mesoderm emerged upon the segregation of mesodermal genes between the front and back parts (rostro-caudal axis) of organisms.

“Taken together, our findings revealed a different evolutionary origin for the vertebrate head mesoderm, suggesting that it evolved from the repatterning of an ancient mesoderm and diversified even before the emergence of jawed vertebrates,” concludes Dr. Onai.

In summary, the finding that the cell clusters present in the head mesoderm are distinct morphologically and molecularly from somites, favors a new model where the vertebrate head mesoderm diverged during early evolution. This sheds more light on the age-old debate on the evolution of the vertebrate head and can help us advance the understanding of our own origins.

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JOURNAL

iScience

DOI

10.1016/j.isci.2023.108338 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Ultrastructure of the lamprey head mesoderm reveals evolution of the vertebrate head