Culture

Maize (Zea mays ssp. mays) was initially domesticated by Native Americans over 10.000 years ago. Nowadays, America's "favourite corn" is cultivated throughout the world and is used in varying ways, ranging from animal feed to biofuel. Maize has been able to adapt to different climates and conditions around the world, indicating that the genetic variability between lines must be large. And when considering that maize also is one of the plants which can reproduce via self- as well as cross-pollination, it becomes evident that sequencing the genome of only one maize line is insufficient, when attempting to fully understand the genetics of maize. Instead, for genetically diverse crops, researchers aim towards establishing the species' pangenome - the entire sequence of all lines of a species.

Scientists from plant breeding and research institutions throughout Germany recently picked up this challenge in maize and published their contribution to the maize pangenome in the journal Nature Genetics.

Dent and flint corn are the two classes of maize with the greatest commercial importance. As such, it is unsurprising that the complete genome sequence of a dent maize line B73 was established as the go to reference for maize breeding and research. However, within their recent project, the researchers led by Dr. Klaus Haberer from the Helmholtz Center in Munich, concentrated on the investigation of four European flint lines. As Dr. Haberer let us know: "Whilst the dent line B73 is a high-quality reference sequence, very high diversity at the sequence level has been found between different maize lines. This indicates that the sequence of the line B73 captures only a portion of the maize pangenome."

Within their research, the scientists utilised a complementary approach which combined modern sequencing techniques and bioinformatics with cytogenetic technologies. Whilst the sequencing techniques delivered the main share of information on the maize genomes, cytogenetic methods such as FISH (Fluorescence in situ hybridization) facilitated the researchers to test for misinterpretations of the sequenced genomes at the chromosomal level. But more importantly, it enabled the scientists to spot differences between the maize lines by looking through the microscope.

Prof. Dr. Andreas Houben, who led the cytogenetic tests at the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) in Gatersleben, told us: "Flint and dent maize have a high similarity on the gene level. However, both maize types have a large number of non-coding sequences, for example, so-called knob repeats, which vary between different lines. We were able to show these differences on the chromosomal level."

The study of the flint lines is an important addition to the current maize pangenome. And maybe even more importantly, the findings show that while the overall conservation of the gene content within a species might be high, differences in the non-coding genome fraction exist. And these small differences help us to truly understand and utilize maize biology.

The Yellow River (YR) is the fifth-longest and the most sediment-laden river in the world. Although the YR accounts for only 3% of China's water resources, it irrigates 13% of its cropland.

Since the 1960s, an increasing number of large-scale dams and reservoirs have been built in the main YR channel, and water consumption by agricultural irrigation along the YR middle course has risen sharply. In recent decades, YR runoff and sediment load have fallen sharply.

The earliest observational record of YR runoff began in 1919 at the Shanxian gauge station, which is too short to study centennial-scale variability. Researchers led by Prof. LIU Yu from the Institute of Earth Environment of the Chinese Academy of Sciences and their collaborators reconstructed natural runoff history for the middle reach of the YR from 1492 to 2013 CE to assess the effects of human activities.

The study was published in Proceedings of the National Academy of Sciences of the United States of America (PNAS) on July 20.

Tree rings, with the merits of accurate dating and annual resolution, have been widely used in runoff reconstruction worldwide. In this study, the researchers collected 31 moisture-sensitive tree-ring width chronologies, including 860 trees and 1707 cores, within the upper-middle YR basins.

They found that the YR runoff in 1781 is the highest, and prior to anthropogenic interference that started in the 1960s, the lowest natural runoff over the past 500 y occurred during 1926 to 1932 CE. These two extreme values could be regarded as a benchmark for future judicious planning of YR water allocation.

Since the late 1980s, the low observed YR runoff has exceeded the natural range of runoff variability, which is caused by the combination of decreasing precipitation and increasing water consumption by direct and indirect human activities, particularly agricultural irrigation.

"This reduced runoff has resulted in an estimated 58% reduction of the sediment load in the upper reach of the YR and 29% reduction in the middle reach," said Prof. LIU.

Human activities, mainly expansive agricultural irrigation in the upper course, have contributed to reduced runoff and sediment load in the upper-middle course of the YR. If these human activities continue to intensify, future YR runoff will be further reduced, and this will negatively impact agriculture, human lives, and socioeconomic development in the middle and lower basins of the YR.

To reduce the risk of recurring cutoff of stream flow in the YR lower basin, water should be allocated judiciously. Policies should balance water allocation among the needs of agriculture, industry and ecosystems.

In addition, the study also provides an important model of how to distinguish and quantify anthropogenic influence from natural variability in global change studies.

Osteoporosis, a disease which leads to bone fragility and an increased risk of fractures, is very common among postmenopausal women, affecting around one in three over the age of 50 worldwide. However, as osteoporosis and related fragility fractures are rare in younger women, there is far less research, and consequently a lack of consensus and guidance on its diagnosis and management in this population group.

A newly published narrative review by a working group of the ECTS and IOF provides an updated review of literature published after 2017 on premenopausal osteoporosis (1). Based on the latest evidence, the authors outline key information on factors affecting peak bone mass and distinguishing low bone mass from proper osteoporosis with increased fracture risk at a young age, including causes of secondary osteoporosis versus idiopathic osteoporosis, as well as pregnancy-and lactation-associated osteoporosis. They also provide an update on the management and treatment of this condition (including a helpful flow-chart as general guidance).

Professor Serge Ferrari, Vice-Chair of the IOF Committee of Scientific Advisors and Head of the Service and Laboratory of Bone Diseases, Geneva University Hospital, Switzerland, stated:

"Premenopausal women with known causes of secondary osteoporosis have been found to have a high prevalence of bone fragility. As well, those with prior fracture have a 35% to 75% higher risk of having a fracture in their postmenopausal years, compared to premenopausal women without fracture. It is therefore important that physicians are aware of the latest evidence and best practice in diagnosis and clinical management of osteoporosis in younger women, especially in that specific therapy of the underlying disease in many cases can significantly improve bone mineral density and bone microarchitecture."

For example, in celiac disease, an increase of 9% in radius trabecular volumetric density was achieved after one year of gluten-free diet. Similarly, in amenorrhea, including anorexia nervosa, appropriate estrogen replacement therapy can also improve bone mineral density (BMD).

The Working Group experts conclude:

Fragility fractures are rare in premenopausal women and mostly due to secondary osteoporosis (typically underlying hormonal, inflammatory or digestive disorders);

Treating the disorders which cause secondary osteoporosis benefits both BMD and bone microstructure. In case treatment of the underlying cause is not successful, and/or in the presence of severe osteoporosis , antiresorptive and bone-forming drugs can be used;

In absence of an underlying disorder, BMD together with fragility fractures, qualifies as idiopathic osteoporosis;

Low BMD alone does not necessarily represent osteoporosis in the absence of bone microarchitectural abnormalities;

Further clinical trials are needed - especially those focused on fracture risk reduction as primary outcome, as well as on safety of bisphosphonates and other osteoporosis drugs in women of childbearing age.

Professor Bente L. Langdahl, ECTS Past-President and Chief Physician, Department of Endocrinology and Internal Medicine at Aarhus University Hospital, Denmark, added:

"With this review of the latest literature, the ECTS and IOF Working Group aims to provide a succinct overview of current best practice and general guidance on clinical management which can be of help to a wide range of practitioners. The review also points to the areas where future clinical studies are needed, including, first and foremost, the prevention of osteoporosis in women suffering from conditions known to negatively affect bone and the potential impact of osteoporosis-specific treatments on fracture reduction."

The maize genome tells an intriguing story about domestication and the shaping of the genome by human selection. Around 10,000 years ago, Native Americans started to domesticate maize in what is Mexico today. They created the basis for one of today's most important sources of food for both humans and livestock. After the discovery of the "new world" by Columbus, maize was brought from the Americas to Europe. Maize adapted to new growing and climate regimes through directed breeding and selection and finally spread around the globe.

Due to its history, today's maize lines do not only differ in appearance, their genome contains many differences (presence and absence of genes as well as structural variations). In 2009, researchers decoded the genome of the North American maize accession "B73". This reference sequence, however, only covers a small part of the global maize genome (pan-genome) and is of limited use as a benchmark for European lines. In order to improve maize breeding and adapt to climate change, basic research on the genome of other maize lines is needed.

European maize genome decoded for the first time

German researchers now succeeded in decoding the European maize genome. They analyzed four different European maize lines using modern sequencing technologies and bioinformatics approaches. In comparison with two lines from North America, they found significant differences in the genetic content and genome structure of these lines - after a few hundred to a thousand years of genetic separation only.

Moreover, so-called "knob" regions (condensed chromatin regions in the maize DNA) vary substantially in those maize lines. Knob regions are known to affect adjacent genes. In areas where knobs tend to be more pronounced, surrounding genes cannot be read. This results in a loss of genetic function.

Potential cause for heterosis

„We hypothesize that differences in gene content, gene regulation and the influence of knob regions might cause the heterosis effect," says Prof. Klaus Mayer, genomicist at Helmholtz Zentrum München and honorary professor of TUM School of Life Sciences at the Technical University of Munich.

Heterosis occurs when the descendants of crossbreeds are significantly larger and produce higher yields than their parents. If specific genes of a parental generation, e.g. those which determine the height of the maize plant, are not present in a certain region or cannot be read, this will affect the height of the offspring as well. Through crossbreeding with a plant that contains the necessary genetic factor, the defect can be compensated in the next generation. "This results in larger plants with higher yields - without the parents showing these characteristics. In some crossings, this effect can even result in doubling the yield. Although it has been exploited in breeding for a long time, the genetic and molecular basis of heterosis is not yet fully understood," says Prof. Chris-Carolin Schön, professor of Plant Breeding at TUM.

"In a next step, we will test our hypothesis. To this end, we will not only analyze the genomes of the different maize lines, but focus on potential epigenetic processes that may affect the functionality of particular genes," adds Klaus Mayer.

If the researchers' hypothesis proves right, heterosis could be applied even more effectively in future maize breeding. Areas with low yields could benefit from heterosis. Furthermore, these findings could become highly relevant in view of a growing world population and climate change, which poses increasing challenges onto agricultural production.

Humans have a hard time identifying individual birds just by looking at the patterns on their plumage. An international study involving scientists form the CNRS, Université de Montpellier* and the University of Porto in Portugal, among others, has shown how computers can learn to differentiate individual birds of a same species. The results are published on 27 July 2020 in Methods in Ecology and Evolution.

Differentiating between individuals of a same species is essential in the study of wild animals, their processes of adaptation and behaviour. Scientists from the CEFE research centre in Ecology and Evolutionary Ecology (CNRS/ Université de Montpellier/ Université Paul-Valéry-Montpellier/ IRD/ EPHE) and the Research Centre in Biodiversity and Genetic Resources (CIBIO) at Porto University** have for the very first time identified individual birds with the help of artificial intelligence technology.

They have developed a technique that enables them to gather a large number of photographs, taken from various angles, of individual birds wearing electronic tags. These images were fed into computers which used deep learning technology to recognise the birds by analysing the photographs. The computers were able to distinguish individual birds according to the patterns on their plumage, something humans can't do. The technology was able to identify specimens from populations of three different species: sociable weavers, great tits and zebra finches.

This new technique could not only result in a less invasive method of identification but also lead to new insights in ecology, for example, by opening ways of using AI to study animal behaviour in the wild.

An international team of scientists has collated all known bacterial genomes from the human gut microbiome into a single large database. Their work, published in Nature Biotechnology, will allow researchers to explore the links between bacterial genes and proteins, and their effects on human health.

This project was led by EMBL's European Bioinformatics Institute (EMBL-EBI) and included collaborators from the Wellcome Sanger Institute, the University of Trento, the Gladstone Institutes, and the US Department of Energy Joint Genome Institute.

More microbes than human cells

Bacteria coat the human body, inside and out. They produce proteins that affect our digestion, our health, and our susceptibility to diseases. They are so prevalent that the body is estimated to contain more cells in its microbiome - the bacteria, fungi, and other microbes - than it has human cells.

To understand the role that bacterial species play in human biology, scientists usually isolate and culture them in the lab before they sequence their DNA. However, many bacteria thrive in conditions that are not yet reproducible in a laboratory setting.

To obtain information on such species, researchers take another approach: they collect a single sample from the environment - in this case, the human gut - and sequence the DNA from the whole sample. They then use computational methods to reconstruct the individual genomes of thousands of species from that single sample. This method, called metagenomics, offers a powerful alternative to isolating and sequencing the DNA of individual species.

Biodiversity in the human gut

"Last year, three independent teams, including ours, reconstructed thousands of gut microbiome genomes. The big questions were whether these teams had comparable results, and whether we could pool them into a comprehensive inventory," says Rob Finn, Team Leader at EMBL-EBI.

The scientists have now compiled 200 000 genomes and 170 million protein sequences from more than 4 600 bacterial species in the human gut. Their new databases, the Unified Human Gastrointestinal Genome collection and the Unified Gastrointestinal Protein catalogue, reveal the tremendous diversity in our guts and pave the way for further microbiome research.

"This immense catalogue is a landmark in microbiome research, and will be an invaluable resource for scientists to start studying and hopefully understanding the role of each bacterial species in the human gut ecosystem," explains Nicola Segata, Principal Investigator at the University of Trento.

The project revealed that more than 70% of the detected bacterial species had never been cultured in the lab - their activity in the body remains unknown. The largest group of bacteria that falls into that category is the Comantemales, an order of gut bacteria first described in 2019 in a study led by the Bork Group at EMBL Heidelberg.

"It was a real surprise to see how widespread the Comantemales are. This highlights how little we know about the bacteria in our gut," explains Alexandre Almeida, EMBL-EBI/Sanger Postdoctoral Fellow in the Finn Team. "We hope our catalogue will help bioinformaticians and microbiologists bridge that knowledge gap in the coming years."

A freely accessible data resource

All the data collected in the Unified Human Gastrointestinal Genome collection and the Unified Human Gastrointestinal Protein catalogue are freely available in MGnify, an EMBL-EBI online resource that allows scientists to analyse their microbial genomic data and make comparisons with existing datasets.

The project already has a number of users in the scientific community. As new datasets emerge from research teams around the world, the catalogue might expand to include the microbiomes of other body parts, like the skin or inside the mouth.

"This catalogue provides a very rich source of information for microbiologists and clinicians. However, we will likely discover many more novel bacterial species in under-represented geographical areas like South America, Asia, and Africa. We still don't know much about the variation in bacterial diversity across different human populations," explains Almeida.

Relaxing on the sofa or savoring a delicious meal: Enjoying short-term pleasurable activities that don't lead to long-term goals contributes at least as much to a happy life as self-control, according to new research from the University of Zurich and Radboud University in the Netherlands. The researchers therefore argue for a greater appreciation of hedonism in psychology.

We all set ourselves long-term goals from time to time, such as finally getting into shape, eating less sugar or learning a foreign language. Research has devoted much time to finding out how we can reach these goals more effectively. The prevailing view is that self-control helps us prioritize long-term goals over momentary pleasure and that if you are good at self-control, this will usually result in a happier and more successful life.

"It's time for a rethink," says Katharina Bernecker, researcher in motivational psychology at the University of Zurich. "Of course self-control is important, but research on self-regulation should pay just as much attention to hedonism, or short-term pleasure." That's because Bernecker's new research shows that people's capacity to experience pleasure or enjoyment contributes at least as much to a happy and satisfied life as successful self-control.

Distraction disrupts pleasure

Bernecker and her colleague Daniela Becker of Radboud University developed a questionnaire to measure respondents' capacity for hedonism, i.e. their ability to focus on their immediate needs and indulge in and enjoy short-term pleasures. They used the questionnaire to find out whether people differ in their capacity to pursue hedonic goals in a variety of contexts, and whether this ability is related to well-being.

They found that certain people get distracted by intrusive thoughts in moments of relaxation or enjoyment by thinking about activities or tasks that they should be doing instead. "For example, when lying on the couch you might keep thinking of the sport you are not doing," says Becker. "Those thoughts about conflicting long-term goals undermine the immediate need to relax." On the other hand, people who can fully enjoy themselves in those situations tend to have a higher sense of well-being in general, not only in the short term, and are less likely to suffer from depression and anxiety, among other things.

More isn't always better

"The pursuit of hedonic and long-term goals needn't be in conflict with one another," says Bernecker. "Our research shows that both are important and can complement each other in achieving well-being and good health. It is important to find the right balance in everyday life."

Unfortunately, simply sitting about more on the sofa, eating more good food and going to the pub with friends more often won't automatically make for more happiness. "It was always thought that hedonism, as opposed to self-control, was the easier option," says Bernecker. "But really enjoying one's hedonic choice isn't actually that simple for everybody because of those distracting thoughts."

Conscious planning of downtime

This is currently a topical issue with more people working from home, as the environment where they normally rest is suddenly associated with work. "Thinking of the work you still need to do can lead to more distracting thoughts at home, making you less able to rest," says Bernecker.

So what can you do to enjoy your downtime more? More research is needed, but the researchers suspect that consciously planning and setting limits to periods of enjoyment could help to separate them more clearly from other activities, allowing pleasure to take place more undisturbed.

Thanks to optical tweezers, a new study reveals unexpected properties of the neurons responsible for the transduction of light signals. The research has been published in PLOS Biology.

"We thought we knew almost everything about photoreceptors, but we have proved that is not the case." With these words, Vincent Torre, Professor of neurobiology of SISSA - Scuola Internazionale Superiore di Studi Avanzati, comments the results of a new study that, thanks to a multidisciplinary approach and to the use of optical tweezers, reveals for the first time the sensitivity of nerve cells present on the retina to mechanical stimuli and opens up new questions on how they function. The work has been published in PLOS Biology.

Cones and rods, also known as photoreceptors. It is thanks to them that the light that reaches our eyes transforms into information. They are cells with a characteristic shape, as the names suggest, mutually complementary. If the cones are principally involved in daytime vision and colour recognition, the rods on the other hand are very sensitive to light and allow to see even in low-light conditions.

The mechanisms for transduction of light signals have been known for some time, but the development of new experimental methodologies inspired by nanotechnology has allowed a group of researchers of SISSA, the National Research Council (CNR) and the Australian National University to better understand the complexity of their functioning.

In particular, scholars have investigated the mechanical sensitivity of frog rods using optical tweezers. "This highly innovative technique uses an infrared laser beam to trap particles of very small dimensions and handle biological systems with extreme precision without damaging them" explains Dan Cojoc, head of the Optical Manipulation Laboratory of the 'Istituto Officina dei Materiali' of CNR. In this way the scientists could apply a slight pressure to the surface of isolated rods, while monitoring the response with calcium imaging techniques, which allows to detect the concentration of intracellular calcium through the presence of fluorescent molecules. They observed consistent variations in fluorescence thus showing an unexpected sensitivity of the photoreceptors to the mechanical stimuli.

In line with this interpretation, the research team, which included SISSA PhD students Ulisse Bocchero, Fabio Falleroni, Simone Mortal and Yunzhen Li, ascertained the presence in photoreceptors of specific molecules sensitive to mechanical stress. They detected a variation in electrical signals in the presence of drugs able to block the functionality of some of these molecules and, then, analysed their distribution in the retina through specific fluorescent markers. Finally, they demonstrated the existence in vertebrates of an association between the genes connected to phototransduction and some genes connected instead to mechanical transduction.

What are the physiological mechanical stimuli able to activate the photoreceptors? "It is still an open question," answers Torre. "Thanks to the optical tweezers we have shown the sensitivity of the rods to mechanical stimuli. However, we have also been able to observe a reduction in the length of their external segment when subjected to particularly intense light flashes, a phenomenon known as phototropism. In situations like these, it is more than plausible to think that mechanical stimulations are involved."

Undoubtedly, there are still many steps to understand: "We believe that sensitivity to mechanical stimuli is necessary to guarantee both cell integrity and optimal functioning of phototransduction," concludes Torre. "Once again, biology shows that there is always a greater complexity and it is incredible how the development of new technologies allows us to discover new things all the time."

Hokkaido University researchers have found a soft and wet material that can memorize, retrieve, and forget information, much like the human brain. They report their findings in the journal Proceedings of the National Academy of Sciences (PNAS).

The human brain learns things, but tends to forget them when the information is no longer important. Recreating this dynamic memory process in manmade materials has been a challenge. Hokkaido University researchers now report a hydrogel that mimics the dynamic memory function of the brain: encoding information that fades with time depending on the memory intensity.

Hydrogels are flexible materials comprised of a large percentage of water -- in this case about 45% -- along with other chemicals that provide a scaffold-like structure to contain the water. Professor Jian Ping Gong, Assistant Professor Kunpeng Cui, and their students and colleagues in Hokkaido University's Institute for Chemical Reaction Design and Discovery (WPI-ICReDD) are seeking to develop hydrogels that can serve biological functions.

"Hydrogels are excellent candidates to mimic biological functions because they are soft and wet like human tissues," says Gong. "We are excited to demonstrate how hydrogels can mimic some of the memory functions of brain tissue."

In this study, the researchers placed a thin hydrogel between two plastic plates; the top plate had a shape or letters cut out, leaving only that area of the hydrogel exposed. For example, patterns included an airplane and the word "GEL." They initially placed the gel in a cold water bath to establish equilibrium. Then they moved the gel to a hot bath. The gel absorbed water into its structure causing a swell, but only in the exposed area. This imprinted the pattern, which is like a piece of information, onto the gel. When the gel was moved back to the cold water bath, the exposed area turned opaque, making the stored information visible, due to what they call "structure frustration." At the cold temperature, the hydrogel gradually shrank, releasing the water it had absorbed. The pattern slowly faded. The longer the gel was left in the hot water, the darker or more intense the imprint would be, and therefore the longer it took to fade or "forget" the information. The team also showed hotter temperatures intensified the memories.

"This is similar to humans," says Cui. "The longer you spend learning something or the stronger the emotional stimuli, the longer it takes to forget it."

The team showed that the memory established in the hydrogel is stable against temperature fluctuation and large physical stretching. More interestingly, the forgetting processes can be programmed by tuning the thermal learning time or temperature. For example, when they applied different learning times to each letter of "GEL," the letters disappeared sequentially.

The team used a hydrogel containing materials called polyampholytes or PA gels. The memorizing-forgetting behavior is achieved based on fast water uptake and slow water release, which is enabled by dynamic bonds in the hydrogels. "This approach should work for a variety of hydrogels with physical bonds," says Gong.

"The hydrogel's brain-like memory system could be explored for some applications, such as disappearing messages for security," Cui added.

Chromatin Biology group aims to define the mechanisms involved in the cellular response to different types of stress such as metabolic, oxidative and genotoxic stress. In particular, they focus their studies on the impact of a family of enzymes, Sirtuins (responsible of the cellular stress response) in the maintenance of genome stability under these conditions and their impact in aging and different types of cancers, with a special focus on hematologic malignancies.

Dr. Vaquero's group has just published an article at Science Advances journal in which they have identified and characterized a new enzymatic activity of the Sirtuin SIRT7 that provides new evidence to understand its regulatory capacity in the cellular response to different types of stress damaging cellular integrity.

The regulation of this response acquires special relevance since these types of stress can produce alterations in the DNA and instability at cell's energy flow, and are directly involved in the appearance of pathologies such as cancer, neurodegenerative diseases or a number of endocrine pathologies.

The regulatory mechanism identified may represent an important advance towards new therapeutic targets in the treatment of cancer, particularly in hematological cancers, since previous studies have shown that both genome instability and metabolic stress contribute significantly to the development of leukemias and lymphomas.

Other groups have also collaborated in this multidisciplinary study, whose first author is Dr. Nicolas Simonet, including the research groups led by Dr. Manel Esteller and Dr. Marcus Buschbeck (both from the Josep Carreras Leukaemia Research Institute),the Proteomics Unit of this Inste, led by Dr. Carolina de la Torre, as well as groups from Pompeu Fabra University, the Centre for Genomic Regulation, Rutgers University (USA) and the Max Plank Institute (Germany).

This research has been funded by the Ministry of Economy and Competitiveness, the Agency for the Management of University and Research Grants (AGAUR) of the Government of Catalonia and co-financed by FEDER funds.

In terms of its structure and organization, the cryptocurrency market is a rather young and a very specific financial market. Due to its relatively short history, it is difficult to fully analyze the cryptocurrency market (it appeared only in 2009), which makes this task even more attractive for researchers.

However, even at this point we can trace some stages of its evolution, including those related to the development of cryptocurrency market institutions. Obviously, these processes were accompanied by the transformation of behavior patterns of the cryptocurrency market players. The study of these models makes it possible to test a number of theories of behavioral finance, and to determine the general and specific features of the cryptocurrency market functioning in comparison with other financial markets.

According to Marina Malkina, Professor at the Department of Economic Theory and Methodology of the Lobachevsky University's Institute of Economics and Entrepreneurship, of special interest for researchers is the degree of players' reaction to positive or negative news during different periods of market development (upward or downward price rally), manifestation of players' herd instincts in the transition from steady development to market boom, as well as the effects of learning when bullish and bearish trends repeat.

"We analyzed the dynamics of the cryptocurrency market in relation to significant institutional changes and the accompanying news background. The inclusion in the study of a long chronological period (from November 2014 to November 2019) allowed us to cover in our study different stages of the development of the cryptocurrency market. We also assessed its later fluctuations that occurred, as a rule, with negative news background, which was not fully taken into account in previous studies," Marina Malkina explains.

Nizhny Novgorod scientists pay special attention to the effect of asymmetry in the reaction of the cryptocurrency market to news. They attempt to answer the question whether it is the good or bad news background that is more likely to form the fluctuations of the cryptocurrency market and how this is related to the stages of its development.

"We used a combination of methodological techniques - from the sliding autocorrelation function of returns and statistics of search queries in Google Trends and Wikipedia Page Views to quite advanced models of conditional volatility with switching of market modes (Markov-Switching GARCH-models)," comments Vyacheslav Ovchinnikov, lecturer at the Department of World Economy and Customs of the UNN Institute of Economics and Entrepreneurship.

"We have also analyzed the transformation of herd instincts of cryptocurrency market participants, trying to answer the question of how small investors are inclined to borrow the trading practices of larger agents during the hype, and whether they are able to revise their behavior as they accumulate practical experience and knowledge. In this case, we used heterogeneous autoregressive models of realized volatility (HAR-RV-J-models) as our tool", Vyacheslav Ovchinnikov continues.

As a result of the research, Lobachevsky University scientists have proved the dependence of the asymmetry effect on the direction of market movement (upward or downward trend) and the amplitude of its fluctuations (high or low volatility).

In particular, with the rapid growth in the value of cryptocurrencies and the formation of a bullish trend, investors ignored the bad news and underestimated the risks of losses. During this period, there was an effect of inverse (as accepted on the stock market) asymmetry of market reaction. With a bearish trend and falling market, investors became overly sensitive to bad news (there was a traditional asymmetry in this case). However, when the market started intensive movements in principle (as manifested in the growth of volatility), there was practically no asymmetry in the reaction to good and bad news.

According to the researchers, small investors' behavior also varied at different intervals of the study period. It follows from the results of the study that before January 2017 (before the market boom or hype) small speculators were more likely to follow their own trading strategies, during the hype they borrowed the trading practices of "heavyweight" players.

In the course of the research, scientists observed some signs of small investors' learning in the course of trading. Over time, the small investors were already less susceptible to provocations by major players, and this is what prevented the 2019 small market rally from surpassing its counterpart in 2017 in terms of both return oscillations and duration.

Lobachevsky University researchers have proved that both the asymmetric reaction of the cryptocurrency market to the news that changes depending on the market conditions, and the pronounced herd behavior of the participants testify to the inefficiency of the cryptocurrency market (especially during its immaturity), thus confirming a number of basic concepts of behavioral finance.

The results obtained in the course of the research may prove useful for financial markets' participants in building their own strategies for trading in cryptocurrency assets.

BOSTON - (July 27, 2020) - Type 1 diabetes occurs when a person's own immune system destroys insulin-producing beta cells in the pancreas. In recent years, scientists have learned how to grow large volumes of replacement beta cells, but the researchers are still trying out many options to protect these cells against the immune attack. Joslin Diabetes Center researchers now have found an unusual strategy that eventually may help to guard such transplanted beta cells or to slow the original onset of the disease.

Research in mouse models and in human cells has shown that targeting a protein called renalase may protect beta cells against autoimmune attack by strengthening them against stress, says Stephan Kissler, an investigator in Joslin's Section on Immunobiology, associate professor of medicine at Harvard Medical School, and co-senior author on a paper describing the work in Nature Metabolism.

Kissler, co-senior author Peng Yi, PhD, and their colleagues also demonstrated that an existing FDA-approved drug inhibits renalase and increases the survival of beta cells in those lab models.

The Joslin study joins a growing set of evidence suggesting that functional problems with beta cells themselves may help to trigger the autoimmune attack in type 1 diabetes, say Kissler and Yi, who is an assistant investigator in the Islet Cell and Regenerative Biology Section. "You might have genes that make the beta cell a little bit dysfunctional and more prone to becoming a target of the immune system," Kissler explains.

The research began with a casual hallway conversation between Kissler and Yi about potential ways to protect beta cells from autoimmune attack. The two ended up launching a bold gamble to try inhibiting genes across the genome, one at a time, using a screening technique based on the CRISPR gene-editing method with a beta cell line from a "non-obese diabetic" (NOD) mouse that models type 1 diabetes. "Whole genome CRISPR screening is a powerful tool for new target discovery and we hoped that it would help us find any mutations that protect the beta cell," Yi says.

The CRISPR screen for surviving beta cells produced a dozen genes of interest. The most striking was the gene for renalase, which previous research had shown is associated with type 1 diabetes.

Next, the researchers created NOD mouse beta cells, some with the renalase gene functionally "knocked out" and some not. They transplanted these cells to NOD mice with autoimmune diabetes.

Intact beta cells died off--but the renalase knock-out cells survived. "This was a very black-and-white research model," Kissler comments. "If the cells aren't protected, they're gone."

The investigators then looked to see if the cells that lacked the renalase gene provoked a diminished response from T immune cells (which spearhead the autoimmune assault) in a dish. The scientists found that one type of T cell was less likely to attack these knockout cells than to attack normal beta cells.

But what was slowing this autoimmune assault?

In earlier work to analyze beta cell survival, Yi had analyzed how the cells respond to a condition called endoplasmic reticulum (ER) stress. Now when the team tried three ways of introducing ER stress to mouse beta cells in a dish, the researchers saw that the renalase mutation was protecting against this condition.

In the next step, to see if the same mechanisms were at work in human cells, the team joined up with Douglas Melton of the Harvard department of Stem Cell and Regenerative Biology to create human beta cells for similar tests in a dish. "Again, we saw that the renalase knockout protected cells against ER stress," Kissler says.

The functions of renalase are not well understood, but Yi and Kissler knew that the protein is an enzyme (which often can be targeted by drug compounds) and that other scientists had produced a three-dimensional crystal structural map of the protein.

Wondering if this map would give clues to uncover a compound that could target renalase, the Joslin investigators began working with Celia Schiffer of the University of Massachusetts Medical School. Structural biologists at the university's structure-based drug design core facility soon noticed that renalase is very similar to another enzyme that is inhibited by existing drugs--including one drug known as pargyline that was approved by the Food & Drug Administration almost 60 years ago to treat hypertension.

Testing pargyline in their mouse transplant model, the Joslin researchers found that the drug protected beta cells extremely well, says Kissler. Studying it in the mouse beta cells themselves, the scientists demonstrated that pargyline indeed was protecting against ER stress. In experiments with human cells, pargyline also displayed a protective effect.

Kissler and Yi hope to test pargyline in a pilot clinical trial to see if it slows the progress of new onset type 1 diabetes in a small number of patients. "Since it's FDA-approved and the drug is safe, this would be the best approach to test if the protection we observed in mice and human cells will hold true in people," Kissler remarks. If research results continue to be positive, their next goal will be to find industry backing to develop a small molecule drug that provides even better protection than pargyline.

In a study published in Nature Astronomy, an international team of researchers has presented a new, detailed look inside the "central engine" of a large solar flare accompanied by a powerful eruption first captured on Sept. 10, 2017 by the Owens Valley Solar Array (EOVSA) -- a solar radio telescope facility operated by New Jersey Institute of Technology's (NJIT) Center for Solar-Terrestrial Research (CSTR).

The new findings, based on EOVSA's observations of the event at microwave wavelengths, offer the first measurements characterizing the magnetic fields and particles at the heart of the explosion. The results have revealed an enormous electric current "sheet" stretching more than 40,000 kilometers through the core flaring region where opposing magnetic field lines approach each other, break and reconnect, generating the intense energy powering the flare.

Notably, the team's measurements also indicate a magnetic bottle-like structure located at the top of the flare's loop-shaped base (known as the flare arcade) at a height of nearly 20,000 kilometers above the Sun's surface. The structure, the team suggests, is likely the primary site where the flare's highly energetic electrons are trapped and accelerated to nearly the speed of light.

Researchers say the study's new insight into the central engine that drives such powerful eruptions may aid future space weather predictions for potentially catastrophic energy releases from solar flares -- the solar system's most powerful explosions, capable of severely disrupting technologies on Earth such as satellite operations, GPS navigation and communication systems, among many others.

"One of the major goals of this research is to better understand the fundamental physics of solar eruptions," said Bin Chen, the paper's lead author and professor of physics at NJIT. "It has been long suggested that the sudden release of magnetic energy through the reconnection current sheet is responsible for these major eruptions, yet there has been no measurement of its magnetic properties. With this study we've finally measured the details of the magnetic field of a current sheet for the first time, giving us a new understanding of the central engine of the Sun's major flares."

"The place where all the energy is stored and released in solar flares has been invisible until now. ... To play on a term from cosmology, it is the Sun's 'dark energy problem,' and previously we've had to infer indirectly that the flare's magnetic reconnection sheet existed," said Dale Gary, EOVSA director at NJIT and co-author of the paper. "EOVSA's images made at many microwave frequencies showed we can capture radio emissions to illuminate this important region. Once we had that data, and the analysis tools created by co-authors Gregory Fleishman and Gelu Nita, we were able to start analyzing the radiation to enable these measurements."

Earlier this year in the journal Science, the team reported it could finally provide quantitative measurements of the evolving magnetic field strength directly following the flare's ignition.

Continuing their investigation, the team's latest analysis combined numerical simulations performed at Center for Astrophysics | Harvard & Smithsonian (CfA) with EOVSA's spectral imaging observations and multiwavelength data -- spanning radio waves to X-rays -- collected from the X8.2-sized solar flare. The flare is the second largest to have occurred from the past 11-year solar cycle, occurring with a fast coronal mass ejection (CME) that drove a large-scale shock in the upper solar corona.

Among the study's surprises, the researchers found that the measured profile of the magnetic field along the flare's current sheet feature closely matched predictions from the team's numerical simulations, which were based on a well-known theoretical model for explaining solar flare physics, first proposed in the 1990s with an analytical form.

"It surprised us that the measured magnetic field profile of the current sheet beautifully matched the theoretical prediction made decades ago," said Chen.

"The force of the Sun's magnetic field plays a key role in accelerating plasma during an eruption. Our model was used for computing the physics of the magnetic forces during this eruption, which manifests as a highly twisted 'rope' of magnetic field lines, or magnetic flux rope," explained Kathy Reeves, astrophysicist at CfA and co-author of the study. "It is remarkable that this complicated process can be captured by a straightforward analytical model, and that the predicted and measured magnetic fields match so well."

The simulations, performed by Chengcai Shen at CfA, were developed to numerically solve governing equations for quantifying the behavior of electrically conducting plasma throughout the flare's magnetic field. By applying an advanced computational technique known as "adaptive mesh refinement," the team was able to resolve the thin reconnection current sheet and capture its detailed physics at superfine spatial scales to below 100 kilometers.

"Our simulation results match both the theoretical prediction on magnetic field configuration during a solar eruption and reproduce a set of observable features from this particular flare, including magnetic strength and plasma inflow/outflows around the reconnecting current sheet," Shen noted.

Shocking Measurements

The team's measurements and matching simulation results revealed that the flare's current sheet features an electric field that produces a shocking 4,000 volts per meter. Such a strong electric field is present over a 40,000-kilometer region, greater than the length of three Earths placed together side by side.

The analysis also showed a huge amount of magnetic energy being pumped into the current sheet at an estimated rate of 10-100 billion trillion (1022-1023) joules per second -- that is, the amount of energy being processed at the flare's engine, within each second, is equivalent to the total energy released by the explosion of about a hundred thousand of the most powerful hydrogen bombs (50-megaton-class) at the same time.

"Such an enormous energy release at the current sheet is mind-blowing. The strong electric field generated there can easily accelerate the electrons to relativistic energies, but the unexpected fact we found was that the electric field profile in the current sheet region did not coincide with the spatial distribution of relativistic electrons that we measured," said Chen. "In other words, something else had to be at play to accelerate or redirect these electrons. What our data showed was a special location at the bottom of the current sheet -- the magnetic bottle -- appears to be crucial in producing or confining the relativistic electrons."

"While the current sheet seems to be the place where the energy is released to get the ball rolling, most of the electron acceleration appears to be occurring in this other location, the magnetic bottle. ... Similar magnetic bottles are under development for confining and accelerating particles in some laboratory fusion reactors." added Gary. "Others have proposed such a structure in solar flares before, but we can truly see it now in the numbers."

Approximately 99% of the flare's relativistic electrons were observed congregating at the magnetic bottle throughout the duration of the five-minute-long emission.

For now, Chen says the group will be able to apply these new measurements as a comparative baseline to study other solar flare events, as well as explore the exact mechanism that accelerates particles by combining the new observations, numerical simulations and advanced theories. Because of the breakthrough capabilities of EOVSA, NJIT was recently selected to participate in a joint NASA/NSF DRIVE Science Center Collaboration on Solar Flare Energy Release (SolFER).

"Our goal is to develop a full understanding of solar flares, from their initiation until they finally spray out highly energized particles into the solar wind, and eventually, into the space environment of Earth," said Jim Drake, professor of physics at the University of Maryland and principal investigator of SolFER who was not involved in this study.
"These first observations are already suggesting that relativistic electrons might be trapped in a large magnetic bottle produced as the magnetic fields of the corona 'reconnect' to release their energy. ... The EOVSA observations will continue helping us unravel how the magnetic field drives these energetic electrons."

"Further investigating the role of the magnetic bottle in particle acceleration and transport will require more advanced modeling to compare with EOVSA's observations," said Chen. "There are certainly huge prospects out there for us to study that address these fundamental questions."

The differing immune system responses of patients with COVID-19 can help predict who will experience moderate and severe consequences of disease, according to a new study by Yale researchers published July 27 in the journal Nature.

The findings may help identify individuals at high risk of severe illness early in their hospitalization and suggest drugs to treat COVID-19.

Researchers examined 113 patients admitted to Yale New Haven Hospital, and analyzed the varying immune system responses they exhibited during their hospital stay, from admittance to discharge or death. They found that all patients shared a common COVID-19 "signature" in immune system activity early in the course of disease. But those who experienced only moderate symptoms exhibited diminishing immune system responses and viral load over time. Patients who went on to develop severe cases of the disease showed no decrease in viral load or immune system reaction, and many of the immune signals in these patients accelerated.

But even in the early course of treatment, researchers found indicators that predicted which patients were at greatest risk of developing severe forms of the illness.

"We were able to pull out signatures of disease risk," said senior author Akiko Iwasaki, the Waldemar Von Zedtwitz Professor of Immunobiology and Molecular, Cellular and Developmental Biology and investigator for the Howard Hughes Medical Institute.

Researchers had known that the immune system unleashed a massive and damaging "cytokine storm" in severe cases of COVID-19. But the specific elements of the immune system response most responsible for the damage were unknown.

The Yale analysis found some intriguing links to poor outcomes. Curiously, said researchers, one risk factor was the presence of alpha interferon, a cytokine mobilized to combat viral pathogens such as the flu virus. However, COVID-19 patients with high levels of alpha interferon fared worse than those with low levels.

"This virus just doesn't seem to care about alpha interferon," Iwasaki said. "The cytokine appears to be hurting, not helping."

Another early prognosticator of poor outcomes is activation of the inflammasome, a complex of proteins that detects pathogens and triggers an inflammatory response to infection. Inflammasome activation was linked to poor outcomes and death in several patients.

Researchers found that people who respond better to the infection tend to express high levels of growth factors, a type of cytokine that repairs tissue damage to the linings of blood vessels and lungs.

Taken together, the data can help predict patients at high risk of poor outcomes, the authors said.

They also said drugs that target specific causes of inflammation identified in the study could help treat patients at risk of developing severe cases of COVID-19.

COLUMBUS, Ohio - Concrete sewer pipes around the world are most likely to fail either because their concrete is not strong enough or because they can't handle the weight of trucks that drive over them, a new study indicates.

The study used a statistical analysis to show that those two factors were the most likely to trigger a problem among 16 common causes of sewer pipe failure they examined.

The study was published online earlier this year in the journal Structure and Infrastructure Engineering.

"There is a vast array of pipes underground that is working every day and if there is disruption - leakage or collapsing in a pipe, for example - not only will there be discomfort for the residents, but also economic, health and environmental consequences," said Abdollah Shafieezadeh, senior author on the study and an associate professor of civil, environmental and geodetic engineering at The Ohio State University. "The losses can be significant."

And so can the cost of repairs and maintenance: In 2017, the American Society of Civil Engineers estimated the cost to fix and maintain the U.S. sewer system at $150 billion.

For this study, researchers gathered data and analyzed buried sewer pipes, which, in the United States, are commonly made of concrete. Then, they identified the most likely causes of sewer pipe failure. Those causes included things like the density of soil surrounding sewer pipes, the elasticity and strength of the concrete materials and the weight of trucks that regularly drive over them.

They then built a statistical model that could evaluate the stress caused to the pipes by each variable individually and in combinations, and conducted several statistical analyses using the Ohio Supercomputer Center.

The analyses showed that, statistically, cracks that will eventually influence the structural integrity of sewer pipes are most likely to form when the concrete is made from weak components and not maintained properly, or when heavy trucks regularly drive on roads above the pipes. Cracks that influence structural integrity, the researchers say, are the first signs that a sewer pipe is on its way to collapse.

"It's a worldwide problem, and part of the issue is that, for many cities around the world, these sewer systems have been installed long ago, and the challenge now is to maintain these old systems," Shafieezadeh said.

Systems can be complex and expensive to maintain. Cities often have tens of thousands of miles of sewer pipes running beneath them. And, because they are underground, spotting issues is not as simple as finding issues with above-ground infrastructure like roads or power lines, said Soroush Zamanian, a graduate research associate in civil, environmental and geodetic engineering at Ohio State and lead author of the paper.

"In 2017, the American Society of Civil Engineers gave the United States' overall sewer system a D+ rating," Zamanian said. "And that's part of why we are looking at this question and seeing if we could help predict where lines might fail."

The researchers said future studies should examine the way aging and corrosion of pipes affects the way in which system operators can repair them. And, they said, future studies could analyze other pipe configurations, or analyze more details about the types of soil that surround those pipes.

"The big picture is if we want to design sewer pipes for the future, or if we want to assess the current condition and predict future conditions of these pipes, one key element is to know the important factors contributing to their failures - and how do those factors play out in the real world," Zamanian said.

CONTACTS: Abdollah Shafieezadeh, shafieezadeh.1@osu.edu

Soroush Zamanian, zamanian.2@osu.edu

Written by: Laura Arenschield, arenschield.2@osu.edu

Journal

Structure and Infrastructure Engineering

DOI

10.1080/15732479.2020.1762674