Myelin Optimizes Information Processing In The Brain (Neuroscience)

Myelin-forming glial cells are crucial for the temporal processing of acoustic signals.

In a conversation, we can easily understand and distinguish individual words. In the brain, the temporal structure of speech with its rapid succession of sounds and pauses and its characteristic rhythm is encoded by electrical impulses. Researchers at the Max Planck Institute for Experimental Medicine in Göttingen and the Charité – Universitätsmedizin Berlin have discovered that nerve cells can only process the temporal sequence of acoustic signals if they cooperate with certain glial cells.

Oligodendrocytes wrap around the axon of a nerve cell. In this way, they form an electrical insulation layer around the axon and thus increase the conduction speed. The oligodendrocytes also supply the neuron with energy. ©MPI f. Experimantal Medicine/ de Hoz, Moore.

Nerve cells transmit electrical signals with the help of their axons. The speed and temporal precision required for processing in the brain is only achieved thanks to myelin – an electrical insulation of the axons formed by so-called oligodendrocytes. On the one hand, these glial cells increase the speed of nerve conduction. In addition, the oligodendrocytes supply the nerve cells with energy in the form of lactic acid (lactate).

Little is known about the role of myelin in the processing of sensory perceptions in the cerebral cortex. The researchers have therefore investigated the hearing system, which is specialized in the continuous transmission of information and therefore requires constant energy. To this end, they measured the neuronal activity of the cortex specialized for hearing using animal research in genetically modified mice that produce varying amounts of myelin. “Our results show that less myelin is associated with lower nerve cell activity on repeated acoustic stimuli,” says Livia de Hoz, who co-directed the study with Klaus-Armin Nave at the Max Planck Institute for Experimental Medicine.

Deficits in sound processing

The researchers also found that the nerve cells of mice with less or no myelin are less able to identify short pauses within a long-lasting sound. In humans, for example, this ability is an important prerequisite for speech recognition.

For their study, the researchers examined genetically modified mice that produce less myelin (red, orange) as normal (grey) as well as mice that produce the same amount of myelin, but in which the myelin does not supply the nerve cells with energy (purple). (Electron microscopic images: Ax: axon, M: myelin) © MPI f. Experimantal Medicine/ de Hoz

The scientists have also supplemented the electrophysiological experiments with learning and behavioral studies. Similar to neuronal activity, it was shown that the genetically modified mice are unable to perceive the pauses embedded in long tones as such. “Myelin is therefore important independently of the actual nerve conduction speed so that nerve cells can correctly decode the temporal sequence of acoustic stimuli,” explains Klaus-Armin Nave.

Could this be because oligodendrocytes provide energy to the axons? The researchers have examined a third mouse mutant in which only the energy supply of glial cells to the axons is reduced, but which otherwise has normal myelin levels. Interestingly, these animals show the same deficits in the temporal coding of acoustic signals. “This result makes it very likely that, even with loss of myelin, the reduced energy supply from glial cells is a key factor in the deficits in processing acoustic stimuli,” said Sharlen Moore, first author of the study.

Reference: Sharlen Moore, Martin Meschkat, Torben Ruhwedel, Andrea Trevisiol, Iva D. Tzvetanova, Arne Battefeld, Kathrin Kusch, Maarten H. P. Kole, Nicola Strenzke, Wiebke Möbius, Livia de Hoz, Klaus-Armin Nave, “A role of oligodendrocytes in information processing”, Nature Communications; 30 October, 2020.

Provided by Max Planck Gesellschaft

Cambrian Shrimp-Like Arthropod Had Five Eyes (Paleontology)

Paleontologists in China have uncovered exceptionally preserved fossils of a previously unknown genus and species of extinct arthropod, Kylinxia zhangi, that provides important insights into the phylogenetic relationships among early arthropods, the evolutionary transformations and disparity of their frontal appendages, and the origin of crucial evolutionary innovations in the phylum Euarthropoda.

Life reconstruction of Kylinxia zhangi. Image credit: Diying Huang.

Kylinxia zhangi swam in the Early Cambrian seas, approximately 518 million years ago.

The six specimens with well-preserved soft parts of this ancient creature were found in the Yu’anshan Formation in Yunnan province, southern China.

They show an unexpected mix of distinctive features of true arthropods as well as more ancient features.

Kylinxia zhangi had a fused head shield, a segmented trunk, and jointed legs.

But it also had raptorial frontalmost appendages and five stalked compound eyes, of which the anterior (forward-facing) two are at least twice as large as the posterior three.

“This configuration of eyes is reminiscent of the peculiar five eyes in Opabinia regalis,” the paleontologists said.

Kylinxia zhangi was a member of the Chengjiang biota, the most diverse assemblage of Early Cambrian marine fossils known.

“Among the Chengjiang fauna, the giant top predator Anomalocaris is considered the ancestral form of arthropod,” the researchers said.

“But huge morphological differences exist between Anomalocaris and true arthropods. There is a great evolutionary gap between the two that can hardly be bridged.”

“Our results indicate that the evolutionary placement of Kylinxia zhangi is right between Anomalocaris and the true arthropods,” said co-author Professor Maoyan Zhu, a paleontologist at the Nanjing Institute of Geology and Palaeontology.

“Therefore, our finding reached the evolutionary root of the true arthropods.”

The holotype of Kylinxia zhangi. Image credit: Han Zeng.

Kylinxia zhangi represents a crucial transitional fossil predicted by Darwin’s evolutionary theory,” added lead author Dr. Han Zeng, also from the Nanjing Institute of Geology and Palaeontology.

“It bridges the evolutionary gap from Anomalocaris to true arthropods and forms a key ‘missing link’ in the origin of arthropods, contributing strong fossil evidence for the evolutionary theory of life.”

The team’s paper was published in the journal Nature.

Reference : H. Zeng et al. An early Cambrian euarthropod with radiodont-like raptorial appendages. Nature, published online November 4, 2020; doi: 10.1038/s41586-020-2883-7

Originally published in sci-news

Ultraviolet Fluorescence Discovered in Platypus (Paleontology)

The fur of the platypus (Ornithorhynchus anatinus), one of only five extant species of monotremes (egg-laying mammals), absorbs ultraviolet light at wavelengths of 200-400 nm and re-emits visible light, making it fluoresce, according to new research from Northland College and the Warner College of Natural Resources at Colorado State University. This is the first observation of biofluorescence in a monotreme.

This image is a digital reproduction of a painting by John Lewin of a platypus in 1808.

Biofluorescence, in which short wavelengths of light are absorbed and longer wavelengths are re-emitted by living organisms, has been observed in a wide range of fishes, reptiles and amphibians and birds.

Within mammals, marsupial opossums and placental flying squirrels are known to have fur that biofluoresces under UV light.

“It was a mix of serendipity and curiosity that led us to shine a UV light on the platypuses,” said Northland College’s Professor Paula Spaeth Anich, lead author on the study.

“But we were also interested in seeing how deep in the mammalian tree the trait of biofluorescent fur went.”

“It’s thought that monotremes branched off the marsupial-placental lineage more than 150 million years ago. So, it was intriguing to see that animals that were such distant relatives also had biofluorescent fur.”

In the study, Professor Anich and colleagues examined three specimens of the platypus from Tasmania and New South Wales, Australia, housed in the Field Museum of Natural History and the University of Nebraska State Museum under visible and UV light.

The fur of the animals appeared uniformly brown under visible light and green or cyan under UV light, due to fluoresced wavelengths that peaked around 500 nm.

A male platypus (Ornithorhynchus anatinus) museum specimen collected from Tasmania, Australia, photographed under visible light and 385-395 nm UV light without and with a yellow camera lens filter. Cyan to green biofluorescence of 500 nm is seen in the middle panels. UV absorption is indicated by dark areas in the far right panel. Image credit: Anich et al., doi: 10.1515/mammalia-2020-0027.

“Like the marsupial opossum and the placental flying squirrel, platypuses are most active during the night and at dawn and dusk,” the researchers said.

“It may be that these mammals — and possibly others — developed biofluorescence to adapt to low light conditions.”

They suggest this may be a way for platypuses to see and interact with each other in the dark.

“The discovery of biofluorescence in the platypus adds a new dimension to our understanding of this trait in mammals,” they said.

“Biofluorescence has now been observed in placental New World flying squirrels, marsupial New World opossums, and the monotreme platypus of Australia and Tasmania.”

“These species, inhabiting three continents and a diverse array of ecosystems, represent the major lineages of Mammalia.”

“Biofluorescence in mammals is not restricted to a few closely related specialists; instead, it appears across the phylogeny, which begs the question: Is biofluorescence an ancestral mammalian trait?”

A paper on the findings was published in the journal Mammalia.

Reference: Paula Spaeth Anich et al. Biofluorescence in the platypus (Ornithorhynchus anatinus). Mammalia, published online October 15, 2020; doi: 10.1515/mammalia-2020-0027

Originally published in sci-news

New Remote Sensing Technique Could Bring Key Planetary Mineral Into Focus (Planetary Science)

The mineral olivine, thought to be a major component inside all planetary bodies, holds secrets about the early formation of the solar system, and a team of Brown University researchers has a new way to study it remotely.

A mountain peak at the center of the Moon’s Copernicus Crater has an abundance of olivine, a mineral that can help scientists understand the internal evolution of planetary bodies. A new technique developed by Brown University researchers can help to study olivine from afar. CREDIT: NASA/GSFC/Arizona State University.

Planetary scientists from Brown University have developed a new remote sensing method for studying olivine, a mineral that could help scientists understand the early evolution of the Moon, Mars and other planetary bodies.

“Olivine is understood to be a major component in the interiors of rocky planets,” said Christopher Kremer, a Ph.D. candidate at Brown University and lead author of a new paper describing the work. “It’s a primary constituent of Earth’s mantle, and it’s been detected on the surfaces of the Moon and Mars in volcanic deposits or in impact craters that bring up material from the subsurface.”

Current remote sensing techniques are good at spotting olivine from orbit, Kremer says, but scientists would like to do more than just spot it. They’d like to be able to learn more about its chemical makeup. All olivines have silicon and oxygen, but some are rich in iron while others have lots of magnesium.

Olivine (greenish crystals) is thought to be one of the most abundant minerals in interior of the Earth and other planetary bodies. ©Brown University

“The composition tells us something about the environment in which the minerals formed, particularly the temperature,” Kremer said. “Higher temperatures during formation yield more magnesium, while lower temperatures yield more iron. Being able to tease out those compositions could tell us something about how the interiors of these planetary bodies have evolved since their formation.”

To find out if there might be a way to see that composition using remote sensing, Kremer worked with Brown professors Carlé Pieters and Jack Mustard, as well as mountains of data from the Keck/NASA Reflectance Experiment Laboratory (RELAB), which is housed at Brown.

One method researchers use to study rocks on other planetary bodies is spectroscopy. Particular elements or compounds reflect or absorb different wavelengths of light to various degrees. By looking at the light spectra rocks reflect, scientists can get an idea of what compounds are present. RELAB makes high-precision spectral measurements of samples for which the composition is already determined using other laboratory techniques. By doing that, the lab provides a ground truth for interpreting spectral measurements taken by spacecraft looking at other planetary bodies.

In poring through data from olivine samples examined over the years at RELAB, Kremer found something interesting hiding in a small swath of wavelengths that’s overlooked by the kinds of spectroscopes that fly on orbital spacecraft.

“Over the past few decades, there’s been a lot of interest in near infrared spectroscopy and middle infrared spectroscopy,” Kremer said. “But there’s a small range of wavelengths between those two that’s left out, and those are the wavelengths I was looking at.”

Kremer found that those wavelengths, a band between 4 and 8 microns, could predict the amount of magnesium or iron in an olivine sample to within about 10% of the actual content. That’s far better than can be done when those wavelengths are ignored.

“With the instruments we have now, we could say maybe we have a little bit of this or a little bit of that,” Mustard said. “But with this we’re able to really put a number on it, which is a big step forward.”

The researchers hope that this study, which is published in Geophysical Research Letters, might provide the impetus to build and fly a spectrometer that captures these previously overlooked wavelengths. Such an instrument could pay immediate dividends in understanding the nature of olivine deposits on the Moon’s surface, Kremer says.

“The olivine samples brought back during the Apollo program that we’ve been able to study here on Earth vary widely in magnesium composition,” Kremer said. “But we don’t know how those differing compositions are distributed on the Moon itself, because we can’t see those compositions spectroscopically. That’s where this new technique comes in. If we could figure out a pattern to how those deposits are distributed, it could tell us something about the early evolution of the Moon.”

There’s the potential for other discoveries as well. The airplane-based SOFIA telescope is one of the few non-lab instruments that can look in this forgotten frequency range. The instrument’s recent detection of water molecules in sunlit lunar surfaces made use of those frequencies.

“That makes the idea of space-borne spectrometers that can see this range much more attractive, both for water and for rocky material like olivine,” Kremer said.

The research was supported through NASA SSERVI (NNA14AB01A) and a NASA FINESST grant.

Reference: Kremer, C. H., Mustard, J. F., & Pieters, C. M. (2020). Cross‐over infrared spectroscopy: A new tool for the remote determination of olivine composition. Geophysical Research Letters, 47, e2020GL089151.

Provided by Brown University

Combating Brain Inflammation: Investigating the Role of Phosphatases in Fungi (Neuroscience)

Scientists reveal the functions of 31 phosphatases that enable fungus Cryptococcus neoformans to survive while infecting its host.

Cell signalling is the process through which cells of human bodies, and those of other higher organisms or “eukaryotes” (including pathogens), respond appropriately to changes in the environment. Proteins called kinases and phosphatases control the on-off switches of signalling pathways: phosphorylation and dephosphorylation, respectively. It is known that almost 20-30% of eukaryotic proteins are regulated by this post-translational process. While biologists have studied kinases extensively, phosphatases are less well understood.

Now, in a new study, researchers from Yonsei University of Seoul, South Korea, including Prof. Yong-Sun Bahn (Biotechnology), decided to perform a large-scale investigation of phosphatases in a pathogenic fungus, Cryptococcus neoformans, the organism that causes the meningoencephalitis, or brain inflammation, which kills over 180,000 people a year.

The fungus Cryptococcus neoformans causes life-threatening brain inflammation, and new research on its signalling pathways could help develop more effective drugs to treat this fungal infection. (Photo courtesy: Prof. Yong-sun Bahn)

“There have been a few studies identifying the functions of phosphatases in other fungi that cause diseases, and this knowledge could help us uncover new drugs to treat those diseases,” explains Prof. Bahn. Phosphatases are important for maintaining steady conditions inside cells through their control of signalling pathways affecting metabolism and growth. So, disrupting those pathways by targeting and inhibiting phosphatases means you can stop the pathogen from infecting a host.

The research group created a “library” of C. neoformans strains that have been individually mutated in each of the 114 phosphatase genes. These mutant fungi were then grown under 30 different environmental conditions to see how they responded; this would give researchers an idea about what the different phosphatases did inside the fungi. For example, if a certain mutant strain was grown under higher temperatures, but did very poorly, that suggests the mutated phosphatase is involved in regulating heat response. The researchers also tested the mutant fungi on insects and mice to determine how infectious and virulent they were.

In total, Prof Bahn and colleagues identified 31 phosphatases involved in causing the disease. They helped C. neoformans survive high temperatures and tolerate other stressful environments. Other functions undertaken by the phosphatases included the production of melanin and capsule protein, which are important for protecting the fungus against the host defences. Importantly, the scientists also identified phosphatases that participate in pathways that allow C. neoformans to cross the blood-brain barrier and reach the brain, explaining how the fungus causes inflammation.

“This is a big discovery because of its medical implications,” suggests Prof. Bahn when asked about the societal impact of their findings. “Our research on phosphatases can be integrated with previous work characterizing other parts of fungal signalling pathways, such as kinases and transcription factors.” In essence, this study provides a clearer, more holistic understanding of the signalling pathways that allow pathogens like C. neoformans to successfully infect their hosts. The research team is also gaining new options for treatment of fungus-related infectious diseases, because the identified genes are potential targets for antifungal drug development.

References: Jin, J., Lee, K., Hong, J. et al. Genome-wide functional analysis of phosphatases in the pathogenic fungus Cryptococcus neoformans. Nat Commun 11, 4212 (2020).

Provided by Yonsei University

Breathing New Life into Old Cellphones Through a Smart Recollection System (Science And Technology)

Cellphones have undeniably become an important tool used by millions to stay connected in the current information era. However, despite being designed to last for about 10 years, most cellphones are replaced within the first two years. While many would not think about what happens to those older devices, they are becoming part of an ever-worsening problem.

Nearly 400 million cellphones are discarded yearly around the world, but only one percent of them are recycled properly. (Photo courtesy: Shutterstock)

A vast majority of cellphones in their end-of-life (EOL) end up in municipal waste and landfills, where they could pose environmental and health hazards because of certain toxic materials they contain. On the other hand, a large number of EOL cellphones are simply stored away in cupboards or drawers for years.

If we are to create a more environment-conscious society, all EOL cellphones should go through appropriate disposal channels and be refurbished, reused, recycled, or disposed of according to their state and quality. Unfortunately, experience has shown that users don’t go out of their way to dispose of their cellphones appropriately and that manufacturers think the problem is therefore out of their control.

Now, in a recent study published in the International Journal of Production Economics, a pair of researchers led by Prof. Biswajit Sarkar from Yonsei University, Korea propose a novel approach that could greatly increase the return rate of EOL cellphones. Their method is centered around the use of radio frequency identification (RFID) tags, which are small circuits embedded in all cellphones.

By strategically placing RFID readers, the precise location of old cellphones stored away in buildings can be narrowed down by subdividing the search area. (Photo courtesy: Biswajit Sarkar, Yonsei University)

The idea behind this approach is to allow manufacturers to locate EOL cellphones that were either stored away or discarded, by means of RFID tags that can be read remotely even after the cellphone has run out of battery through the “Internet of Things” technology. Prof. Sarkar explains his reasoning, “Traditionally, manufacturers consider the return rate as a variable that is out of their control, providing a way to skip their responsibilities regarding the collection of used devices. We have developed a system in which the return rate is directly under the manufacturer’s control by employing RFID technology, allowing for tracing and retrieving EOL cellphones.”

Detecting discarded cellphones in trash bags is fairly easy using large RFID gates. However, detecting EOL cellphones stored away is trickier. In the proposed system, these are found and bought back from users by scanning large areas using RFID readers—portable devices that emit signals and receive responses from RFID tags.

Moreover, the researchers designed a mathematical model that shows the potential economic benefits of the proposed system for both the users and the manufacturers. Refurbished cellphones, which will mostly be older models, can be sold in secondary markets, where people who cannot afford new cellphones will opt for a functional older device.

If properly implemented, this system could have a very positive economic and environmental impact. Prof. Sarkar remarks, “We propose an approach to achieve sustainable development. This fundamental concept is nowadays one of the main areas of research aimed at creating a circular economy.” Hopefully, this system will be adopted in future to bring new life to old cellphones and keep them away from landfill.

References: Mehran Ullah, Biswajit Sarkar, “Recovery-channel selection in a hybrid manufacturing-remanufacturing production model with RFID and product quality”, International Journal of Production Economics, vol 219, pp. 360-374, 2020. DOI : 10.1016/j.ijpe.2019.07.017

Provided by Yonsei University

Sea Sponge Unravels 700 Million-year-old Mystery (Paleontology)

In a discovery spanning millions of years, scientists have found that humans, and most likely other animals, share important genetic mechanisms with a prehistoric Great Barrier Reef sea sponge.

The University of Queensland’s Professor Bernie Degnan said some elements of the human genome – an organism’s complete set of DNA – functioned in the same way as the sponge.

“Incredibly, these elements have been preserved across 700 million years of evolution,” Professor Degnan said.

“This mechanism drives gene expression, which is key to species diversity across the animal kingdom.

“It’s an important piece of a puzzle over many millions of years, and will feed into future research studies across the medical, technology and life sciences fields.”

The significance of unravelling a mystery of this magnitude is not lost on former Degnan Lab researcher, Dr Emily Wong, now with the Victor Chang Cardiac Research Institute and UNSW Sydney.

“This is a fundamental discovery in evolution and the understanding of genetic diseases, which we never imagined was possible,” Dr Wong said.

“It was such a far-fetched idea to begin with, but we had nothing to lose so we went for it.

“We collected sea sponge samples from the Great Barrier Reef at UQ’s Heron Island Research Station, before extracting DNA samples from the sea sponge and injecting them into a single cell from a zebrafish embryo.

“Without harming the zebrafish, we then repeated the process at the Victor Chang Cardiac Research Institute with hundreds of embryos, inserting small DNA samples from humans and mice as well.

“What we found is despite a lack of similarity between sponge and human DNA, we identified a similar set of genomic instructions that controls gene expression in both organisms – we were blown away by the results.”

Scientists say the sections of DNA that are responsible for controlling gene expression are notoriously difficult to find, study and understand.

Even though they make up a significant part of the human genome, researchers are only at the beginnings of understanding this genetic “dark matter”.

“We are interested in an important class of these regions called ‘enhancers’,” Dr Wong said.

“Trying to find these regions based on the genome sequence alone is like looking for a light switch in a pitch-black room.

“And that’s why, up to this point, there has not been a single example of a DNA sequence enhancer that has been found to be conserved across the animal kingdom.”

Dr Wong’s husband and paper co-senior author, Associate Professor Mathias Francois, from the Centenary Institute, said the work was incredibly exciting.

“The team focused on an ancient gene that is important in our nervous system but which also gave rise to a gene critical in heart development, and the findings will also drive biomedical research and future healthcare benefits too,” Dr Francois said.

“The more we know about how our genes are wired, the better we are able to develop new treatments for diseases.”

Researchers on this study are affiliated with the University of Queensland, the Victor Chang Cardiac Research Institute, Centenary Institute, UNSW Sydney, Monash University, University of Melbourne and University of Sydney.

The research was funded by the Australian Research Council.

References: Emily S. Wong, Dawei Zheng, Siew Z. Tan, Neil L. Bower, Victoria Garside, Gilles Vanwalleghem, Federico Gaiti, Ethan Scott, Benjamin M. Hogan, Kazu Kikuchi, Edwina McGlinn, Mathias Francois, Bernard M. Degnan, “Deep conservation of the enhancer regulatory code in animals”, Science 06 Nov 2020: Vol. 370, Issue 6517, eaax8137 DOI: 10.1126/science.aax8137

Provided by University of Queensland

Scientists Uncover New Layer Of Complexity In How Our Bodies Respond To Drug Treatments (Medicine)

Scientists from the University of Glasgow have played an important role in understanding why some patients respond better to drug treatments than others.

©University of Glasgow

The study – published today in Nature and involving the University of Glasgow and a number of international partners – uncovers a new layer of complexity in how the body responds to medical treatments by using the power of data analysis on GPCRs.

GPCRs – or G protein-coupled receptors – are a family of proteins in the body and the molecular targets for many effective medicines (approximately 34% of approved drugs). However, there are individual responses to GPCR signalling in each of us, which could explain differences in receptor function and drug response.

These important drug target receptors exist in multiple structurally and functionally distinct versions distributed in a tissue-specific manner around our bodies.

By looking in detail at different isoform variants being produced from a single gene, the scientists in this study – led by Prof Madan Babu, St. Jude Children’s Research Hospital, Tennessee – have illustrated how this knowledge may be developed for the benefit of patients.

Scientists based at the Medical Research Council-funded Laboratory of Molecular Biology in Cambridge defined the expression patterns of sequence variant isoforms of all GPCRs in different tissues, and even single cell types of the human body. This gave the team a detailed understanding, on a tissue-by-tissue basis, of natural receptor activation and drug effects.

Analysis of the functional responses of such GPCR isoforms to medicines, conducted at University of Glasgow, as well as at the Universities of Cambridge and Michigan, illustrated how to take advantage of the glut of data available to understand these questions.

For the study, the collaborators integrated and analysed genomics, transcriptomics, proteomics, structural, and pharmacological data for more than 300 receptors in 30 different tissues from individual donors. This investigation created a vast amount of data that was used to generate a new resource in the GPCR database maintained at the University of Copenhagen. This resource will allow experts interested in particular GPCRs to determine if their receptor of interest can exist in one or multiple isoforms and get detailed information of receptor isoform structural and functional data on a tissue-by-tissue basis.

Professor Andrew Tobin, from the University of Glasgow’s Institute of Molecular, Cell and Systems Biology, said: “This research shines a light on why some patients respond well to medicines and others do not. If we can understand key genetic differences that determine why some patients respond better to drug treatment than others then we will be able to tailor medicines to the specific needs of patients – this will be of benefit to patients and save time and money for the health service.”

Professor Graeme Milligan, of the College of Medical, Veterinary and Life Sciences at University of Glasgow said: “Multidisciplinary approaches than link experimental laboratory studies to the analysis of large data sets offer fantastic opportunities to develop novel medicines with reduced side effects. The studies we have been part of provide an excellent example of how data and experimental scientists can and must collaborate to improve human health.”

The work was funded by UKRI MRC, Wolfson College, FEBS, Marie Skłodowska-Curie actions, Swiss National Science Foundation, NIH, NIDA Core Center of Excellence in Omics, Systems Genetics, and the Addictome, NSF, UKRI BBSRC, AstraZeneca, Lundbeck Foundation, Novo Nordisk Foundation, Lister Institute, ERC, and ALSAC.

Provided by University of Glasgow

Science Reveals Secrets Behind The Success Of Game of Thrones (Science)

Writing long novels is a pitfall for the unwary, as many an over-ambitious novelist has found to their cost. It’s very hard to maintain the reader’s interest even through 1000 pages of text, never mind keep this going over a series involving several books. Tolkien, of course, famously achieved it in the Lord of the Rings. And so has the American novelist and screenwriter, George R.R. Martin (once referred to as the American Tolkien) in A Song of Ice and Fire. As one of the most successful fantasy series of all time, it achieved iconic status when it was turned into the astonishingly successful TV series Game of Thrones. It has sold more than 90 million copies worldwide and has been translated into 47 languages.

Just consider the enormity of the task Martin set himself. In the five volumes published so far (we are still waiting for the promised sixth and concluding seventh), three separate main stories, with many subplots, are interwoven over the course of 343 chapters, more than 4000 pages and nearly two million words. There are more than 2000 characters who, between them, engage in over 41,000 interactions, with nearly 300 deaths – all crammed into the space of a mere handful of years of storytime. That’s more than enough to baffle and defeat even a Shakespeare – and Shakespeare was a master at tailoring his plays to suit the psychology of his audience.

The problem lies in the way the human mind has been designed by evolution to cope with the social world in which we typically live. That world is much smaller scale than most people realise. We can, for example, only hold four people in a conversation at the same time (and Shakespeare never breaks this rule onstage). Sixty percent of our social effort is devoted to just 15 core friends and family, and our entire personal social networks (the people we have meaningful relationships with) average just 150.

Yet, like Lord of the Rings, the Fire and Ice stories are gripping despite their size and have an enthusiastic international following. How did George Martin do it?

In a paper published in the Proceedings of the National Academy of Sciences of the USA, a team of physicists, mathematicians and psychologists from Coventry, Warwick, Limerick, Cambridge and Oxford Universities have used network science methods to unpack the secrets behind A Song of Ice and Fire.

It turns out that Martin has very carefully mapped the structure of his storyline to fit the psychology of his readers in two crucial respects. First, the team found remarkable similarities to real life in the way the interactions between the characters are arranged. So much so, in fact, that the sprawling narrative neatly fits into the type of societies for which evolution has designed the human mind. Second, although important characters are famously killed off seemingly at random as the story unfolds, the underlying chronology is not at all unpredictable. Instead, Martin uses the literary device of making each of the chapters an integrated story and then randomly intermingling the stories out of chronological sequence.

Despite the enormous cast of characters and the fact that new characters are added at a constant rate in each of the 343 chapters, the typical number of active characters in each chapter is just 35, about the same as Shakespeare has in each of his plays (and, incidentally, the size that optimises research productivity for English language and literature departments in UK universities). The average number of contacts that each character within a chapter has is stable at between 12-16, about the same number that we would have in our close social circle (our so-called sympathy group).

Each chapter revolves around a central character who provides the “point of view” for the chapter. By virtue of their function as point-of-view characters, of course, these individuals necessarily interact widely, but none of the point-of-view characters has a complete network across the volumes that is significantly above 150. This is the same number as the average human personal social network, known as the Dunbar Number.

In other words, Martin keeps his characters’ networks within the limits that his readers’ human minds were designed by evolution to cope with.

While matching mathematical motifs might, in the hands of a lesser writer, easily have resulted in a rather narrow script, Martin keeps the tale bubbling along by making deaths appear random as the story unfolds, thereby maintaining the suspense for the reader. But, as the team show, when the true chronological sequence of the chapters is reconstructed, the deaths are not random at all: rather, they reflect exactly how non-violent human activities in the real world are typically spaced in time.

Game of Thrones has invited all sorts of comparisons to history and myth. In this respect, the social structure of Game of Thrones is more akin to historical texts that describe real events, such as the Icelandic family sagas, and quite unlike fictional mythological stories like Beowulf or the Irish Táin Bó Cúailnge. Giving the story the characteristic of real life ensures that it stays within the cognitive limits of the reader, thereby making it easier for the reader to track the story without becoming confused. The trick in Game of Thrones, it seems, has been to mix realism and unpredictability in a psychologically engaging manner.

As part of the Coventry University-based Maths Meets Myths Project, the marriage of science and humanities in this paper opens exciting new avenues for comparative literary studies. The computational power of network science has not yet been applied to humanities projects of this kind. Nonetheless, as this project demonstrates it offers the prospect of probing behind the tsunami of detail to provide novel insights into the patterns that underlie stories. As such, it offers a potentially valuable addition to the literary scholar’s analytical toolkit.

Provided by University of Oxford