Tech

Performance test for neural interfaces

image: Analysis of characteristics of a microelectrode for receipt of electrical nerve cell signals at body temperature, photographed using a scanning electron microscope (left).

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Illustration: Maria Asplund

How can scientists measure and define the performance of neural electrodes if there are no uniform standards? Freiburg microsystems engineer Dr. Maria Asplund together with Dr. Christian Böhler and Prof. Dr. Thomas Stieglitz, as well as Prof. Dr. Luciano Fadiga and Dr. Stefano Carli from the Italian Institute of Technology at the University of Ferrara, Italy, have developed guidelines to standardize the testing of the performance of electrodes for neural interfaces and bioelectronic systems. The researchers have published their tutorial in Nature Protocols.

Implantable neural interface extensions increase opportunities for neuroscientists to study the nervous system including the brain, and to develop potential treatments for diseases such as epilepsy and multiple sclerosis as well as for neurological disorders such as paralysis and loss of speech after stroke. This gives the electrodes a key role, as they form the physical interface between the technical system and the biological cells. Nevertheless there is currently no general agreement on how best to assess and compare electrodes in the laboratory, or how to estimate and predict their efficiency when receiving and stimulating electrical signals after implantation.

In their tutorial the researchers present and critically discuss the key performance tests for characterizing neural interface electrodes. They also explain how they interpret the tests and implement them in scientific procedures, and the limits on this.

"Without generally accepted performance tests it's difficult to evaluate the many proposals for electrode materials in the literature and to determine where we should focus efforts," Asplund explains. "We're proposing a uniform standard, in order to enable transparent reporting on electrode performance and promote an efficient scientific process. In the end we want to speed up implementation in clinical practice."

Credit: 
University of Freiburg

An artificial cell on a chip

video: Elena dos Santos explains how the group created the artificial cell on a chip.

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Swiss Nanoscience Institute, University of Basel

Researchers at the University of Basel have developed a precisely controllable system for mimicking biochemical reaction cascades in cells. Using microfluidic technology, they produce miniature polymeric reaction containers equipped with the desired properties. This "cell on a chip" is useful not only for studying processes in cells, but also for the development of new synthetic pathways for chemical applications or for biological active substances in medicine.

In order to survive, grow and divide, cells rely on a multitude of different enzymes that catalyze many successive reactions. Given the complexity of processes in living cells, it is impossible to determine when specific enzymes are present at what concentrations and what their optimum proportions are relative to one another. Instead, researchers use smaller, synthetic systems as models in order to study these processes. These synthetic systems simulate the subdivision of living cells into separate compartments.

Close similarity to natural cells

Now, the team led by Professors Cornelia Palivan and Wolfgang Meier from the Department of Chemistry at the University of Basel has developed a new strategy for producing these synthetic systems. Writing in the journal Advanced Materials, the researchers describe how they create various synthetic miniature reaction containers, known as vesicles, which -- taken as a whole -- serve as models of a cell.

"Unlike in the past, this is not based on the self-assembly of vesicles," explains Wolfgang Meier. "Rather, we've developed efficient microfluidic technology in order to produce enzyme-loaded vesicles in a controlled manner." The new method allows the researchers to tweak the size and composition of the different vesicles so that various biochemical reactions can take place inside them without influencing one another -- like in the different compartments of a cell.

In order to manufacture the desired vesicles, the scientist feed the various components into tiny channels on a silicon-glass chip. On this chip, all of the microchannels come together at a junction. If the conditions are configured correctly, this arrangement produces an aqueous emulsion of uniformly sized polymer droplets that are formed at the point of intersection.

The researchers used the newly developed microfluidic platform to produce three different types of vesicles with a uniform size but different cargoes: β-galactosidase (red vesicle), glucose oxidase (green vesicle) or horseradish peroxidase (blue). The water-soluble enzymes gradually convert the starting product into the final colored product Resorufin, which -- like all of the intermediates -- enters the surrounding solution via selective channels in the vesicle membranes.

Precise control

The polymer membrane of the vesicles acts as an outer shell and encloses an aqueous solution. During production, the vesicles are filled with different combinations of enzymes. As first author Dr. Elena C. dos Santos explains, this technique provides some key advantages: "The newly developed method allows us to produce tailor-made vesicles and to precisely adjust the desired combination of enzymes inside."

Proteins incorporated into the membrane act as pores and allow the selective transport of compounds into and out of the polymer vesicles. The pore sizes are designed to allow the passage of only specific molecules or ions, thereby enabling the separate study of cellular processes that take place closely alongside one another in nature.

"We were able to show that the new system offers an excellent foundation for studying enzymatic reaction processes," explains Cornelia Palivan. "These processes can be optimized to boost the production of a desired final product. What's more, the technology allows us to examine specific mechanisms that play a role in metabolic diseases or that affect the reaction of certain drugs in the body."

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Swiss Nanoscience Institute, University of Basel

Mountain gorillas are good neighbours - up to a point

video: Dr Robin Morrison discusses the study

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Dr Robin Morrison / University of Exeter

Mountain gorilla groups are friendly to familiar neighbours - provided they stay out of "core" parts of their territory - new research shows.

Gorillas live in tight-knit groups, foraging, resting and sleeping together around a "core home range" and a wider "peripheral" range.

These groups sometimes split permanently, separating gorillas that may have lived together for years and may be closely related.

The new study - by the Dian Fossey Gorilla Fund (Fossey Fund) and the University of Exeter - shows groups that were previously united are more than four times as likely to be friendly to each other when they meet, even if they had split over a decade earlier.

Gorillas tend to react aggressively when another group strays into their core territory - regardless of whether the intruders are familiar. But in the peripheries of their home range, this heightened aggression only applies to less familiar groups, with groups that were previously united more tolerant of each other.

"Meetings of groups are fairly rare, and at first both groups are usually cautious," said Dr Robin Morrison, of the Fossey Fund and Exeter's Centre for Research in Animal Behaviour.

"They often beat their chests and show off their strength, but the interaction can then either become aggressive - with fighting and screaming - or 'affiliative'.

"In affiliative interactions, the initial tension passes and the groups intermingle. They may rest together, and younger gorillas will often play with youngsters from the other group."

Humans have an unrivalled capacity for cooperation based on the friendships that extend beyond our immediate group, and one theory for the evolutionary benefit of these wider friendships is that they allow shared access to space and resources with a reduced risk of aggression.

The new study is the first to test this theory beyond humans - and the findings suggest gorillas may indeed benefit in this way from maintaining "friendships" between groups.

"The pattern we found mirrors what we see in humans," Dr Morrison said.

"We also have concepts of public spaces outside our 'range' where we tolerate anyone, spaces like our homes where we tolerate certain individuals, and private spaces within those homes reserved for close family or just ourselves."

Understanding these patterns is also important for conservation.

"Mountain gorillas have less than 800 km2 of habitat remaining," said Jean Paul Hirwa, Gorilla Program Manager at the Fossey Fund and co-author on the study.

"As a result of extreme conservation efforts, the population has been growing over the last 30 years while their habitat has not."

"Understanding how groups interact and share their limited space is important for estimating future population dynamics and trends in this endangered species."

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University of Exeter

Scientists discover new organic compounds that could have helped form the first cells

image: A new study by scholars based at the Earth-Life Science Institute at Tokyo Institute of Technology showed that non-biological chemicals produce polymers and cell-like structures under primitive Earth-like settings.

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Kuhan Chandru

Chemists studying how life started often focus on how modern biopolymers like peptides and nucleic acids contributed, but modern biopolymers don't form easily without help from living organisms. A possible solution to this paradox is that life started using different components, and many non-biological chemicals were likely abundant in the environment. A new survey conducted by an international team of chemists from the Earth-Life Science Institute (ELSI) at Tokyo Institute of Technology and other institutes from Malaysia, the Czech Republic, the US and India, has found that a diverse set of such compounds easily form polymers under primitive environmental conditions, and some even spontaneously form cell-like structures.

Understanding how life started on Earth is one of the most challenging questions modern science attempts to explain. Scientists presently study modern organisms and try to see what aspects of their biochemistry are universal, and thus were probably present in the organisms from which they descended. The best guess is that life has thrived on Earth for at least 3.5 billion of Earth's 4.5 billion year history since the planet formed, and most scientists would say life likely began before there is good evidence for its existence. Problematically, since Earth's surface is dynamic, the earliest traces of life on Earth have not been preserved in the geological record. However, the earliest evidence for life on Earth tells us little about what the earliest organisms were made of, or what was going on inside their cells. "There is clearly a lot left to learn from prebiotic chemistry about how life may have arisen," says the study's co-author Jim Cleaves.

A hallmark of life is evolution, and the mechanisms of evolution suggest that common traits can suddenly be displaced by rare and novel mutations which allow mutant organisms to survive better and proliferate, often replacing previously common organisms very rapidly. Paleontological, ecological and laboratory evidence suggests this occurs commonly and quickly. One example is an invasive organism like the dandelion, which was introduced to the Americas from Europe and is now a common weed causing lawn-concerned homeowners to spend countless hours of effort and dollars to eradicate. Another less whimsical example is COVID-19, a virus (technically not living, but technically an organism) which was probably confined to a small population of bats for years, but suddenly spread among humans around the world. Organisms which reproduce faster than their competitors, even only slightly faster, quickly send their competitors to what Leon Trotsky termed the "ash heap of history." As most organisms which have ever existed are extinct, co-author Tony Z. Jia suggests that "to understand how modern biology emerged, it is important to study plausible non-biological chemistries or structures not currently present in modern biology which potentially went extinct as life complexified."

This idea of evolutionary replacement is pushed to an extreme when scientists try to understand the origins of life. All modern organisms have a few core commonalities: all life is cellular, life uses DNA as an information storage molecule, and uses DNA to make ribonucleic RNA as an intermediary way to make proteins. Proteins perform most of the catalysis in modern biochemistry, and they are created using a very nearly universal "code" to make them from RNA. How this code came to be is in itself enigmatic, but these deep questions point to their possibly having been a very murky period in early biological evolution ~ 4 billion years ago during which almost none of the molecular features observed in modern biochemistry were present, and few if any of the ones that were present have been carried forward.

Proteins are linear polymers of amino acids. These floppy strings of polymerised amino acids fold into unique three-dimensional shapes, forming extremely efficient catalysts which foster precise chemical reactions. In principle, many types of polymerised molecules could form similar strings and fold to form similar catalytic shapes, and synthetic chemists have already discovered many examples. "The point of this kind of study is finding functional polymers in plausibly prebiotic systems without the assistance of biology, including grad students," says co-author Irena Mamajanov.

Scientists have found many ways to make biological organic compounds without the intervention of biology, and these mechanisms help explain these compounds' presence in samples like carbonaceous meteorites, which are relics of the early solar system, and which scientists don't think ever hosted life. These primordial meteorite samples also contain many other types of molecules which could have formed complex folded polymers like proteins, which could have helped steer primitive chemistry. Proteins, by virtue of their folding and catalysis mediate much of the complex biochemical evolution observed in living systems. The ELSI team reasoned that alternative polymers could have helped this occur before the coding between DNA and protein evolved. "Perhaps we cannot reverse-engineer the origin of life; it may be more productive to try and build it from scratch, and not necessarily using modern biomolecules. There were large reservoirs of non-biological chemicals that existed on the primeval Earth. How they helped in the formation of life-as-we-know-it is what we are interested in," says co-author Kuhan Chandru.

The ELSI team did something simple yet profound: they took a large set of structurally diverse small organic molecules which could plausibly be made by prebiotic processes and tried to see if they could form polymers when evaporated from dilute solution. To their surprise, they found many of the primitive compounds could, though they also found some of them decomposed rapidly. This simple criterion, whether a compound is able to be dried without decomposing, may have been one of the earliest evolutionary selection pressures for primordial molecules.

The team conducted one further simple test. They took these dried reactions, added water and looked at them under a microscope. To their surprise, some of the products of these reaction formed cell-sized compartments. That simple starting materials containing 10 to 20 atoms can be converted to self-organised cell-like aggregates containing millions of atoms provides startling insight into how simple chemistry may have led to complex chemistry bordering on the kind of complexity associated with living systems, while not using modern biochemicals.

"We didn't test every possible compound, but we tested a lot of possible compounds. The diversity of chemical behaviors we found was surprising, and suggests this kind of small-molecule to functional-aggregate behavior is a common feature of organic chemistry, which may make the origin of life a more common phenomenon than previously thought," concludes co-author Niraja Bapat.

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Tokyo Institute of Technology

Reforestation plans in Africa could go awry

The state of mature ecosystems must be taken into account before launching massive reforestation plans in sub-Saharan Africa, according to geo-ecologist Julie Aleman, a visiting researcher in the geography department of Université de Montréal.

"The biomes of the region we studied, which includes all the countries south of the Sahara, are divided into two fairly distinct types: savannah at about 70 per cent and tropical forest for the rest," said Aleman, co-author of a major new study on African biomes.

Involving some 30 researchers, several from Africa itself, the study is published this week in the Proceedings of the National Academy of Science.

"When we analyze the assemblage of tree species in each biome, we find that each is extremely different," Aleman said. "Moreover, if we look closely at the history of these biomes, we realize that they have been fairly stable for 2,000 years. Reforestation with tropical forest species in areas that are more associated with savannahs would therefore be a mistake."

Without wanting to point the finger at countries that might make this mistake, Aleman pointed out that reforestation plans include the planting of billions of trees. Even the intention is good, countries must try to avoid artificially creating tropical forests where savannahs have dominated for several millennia, she said.

Moreover, the choice of species selected is decisive. Acacias are more associated with open environments, for example, whereas celtis trees are specific to forests. In some cases, eucalyptus plantations have proved to be "ecological disasters," according to Aleman.

Tracing the past

She does her work at UdeM's paleoecology laboratory, whose mission under director Olivier Barquez is to retrace the past of biomes. Aleman's main collaborator, Adeline Fayolle, a professor at the University of Liege, in Belgium, assembled the floristic data (lists of tree species) for the new study.

"To do this, we conducted a kind of old-fashioned data mining, in the sense that we analyzed a large amount of existing data, published and sometimes archived in forgotten documents, buried in dust, as well as data recently acquired in the field, to try to understand the history of the region," said Aleman.

The study takes taken equal account floristic, environmental and paleoecological data to better understand the ecological functioning of forests and savannas, helped by analysing 753 sites in both environments. The environmental factors having the greatest impact on these environments are rainfall and its seasonality, as well as temperature, the researchers found.

One of the most remarkable phenomena in the savannah is the frequency of disturbances that affect them. Brushwoods can flare up to three times a year in some places, for example. To protect public health, local governments sometimes want to limit these fires. These decisions are legitimate, but can have significant ecological consequences, the co-authors say.

That's because, for the most part, large trees are unaffected by the flames, and the ashes regenerate the soil.

Almost devoid of wildlife

The impact of human activity can be seen wherever the researchers carried out their research, but mainly in Tanzania, Congo and the Central African Republic. In some cases, some areas are almost devoid of wildlife.

As early as 2017, when she published an article in the African edition of the online platform The Conversation, Aleman has been steadily trying to alert public opinion to the threats to African ecosystems. The Conversation.

She believes that the situation is not desperate but that governments must be careful in how they intervene so as to not makes things worse. Aleman hopes that the new study will lead to a better understanding of the biological reality of the African continent.

"This is a rather theoretical contribution,: she said, "but I believe that we can use it to inform reforestation policies."

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University of Montreal

Yeast study yields insights into longstanding evolution debate

In the past two decades, researchers have shown that biological traits in both species and individual cells can be shaped by the environment and inherited even without gene mutations, an outcome that contradicts one of the classical interpretations of Darwinian theory.

But exactly how these epigenetic, or non-genetic, traits are inherited has been unclear.

Now, in a study published Oct. 27 in the journal Cell Reports, Yale scientists show how epigenetic mechanisms contribute in real time to the evolution of a gene network in yeast. Specifically, through multiple generations yeast cells were found to pass on changes in gene activity induced by researchers.

The finding helps shed light on a longstanding question in evolutionary biology; scientists have long debated whether organisms can pass on traits acquired during a lifetime.

"Do genetic mutations have to be the sole facilitator of gene network evolution or can epigenetic mechanisms also lead to stable and heritable gene expression states maintained generation after generation?" asked Yale's Murat Acar, associate professor of molecular, cellular & developmental biology, a faculty member at the Yale Systems Biology Institute, and senior author of the paper.

During much of the last half of the 20th century, biology students were taught that mutations of genes that helped species adapt to the environment were passed on through generations, eventually leading to tremendous diversity of life. However, this theory had a problem: advantageous mutations are rare, and it would take many generations for physiological changes caused by the mutation to take root in a population of any given species.

Scientists in the last century have found that certain regions of DNA do not code for genes but regulate gene activity in the face of environmental change. The concept of passing on stable gene expression states to offspring resurrected the once widely discredited theories of 18th century French scientist Jean-Baptiste Lamarck, who first proposed inheritance of traits acquired during a lifetime.

For the new study, Acar lab graduate students and co-first authors Xinyue Luo and Ruijie Song wanted to investigate the role of epigenetic inheritance in the evolution of gene network activity in individual yeast cells, which reproduce asexually about every 100 minutes. As their experimental model, they investigated a gene network known as the galactose utilization network, which regulates use of the sugar-like molecule galactose, in the yeast. Through daily cell-sorting, they segregated the cells that had lowest levels of gene expression in the population and grew these cells in the same environment over a period of seven days.

Ultimately, they found expression level reductions persisted for several days and multiple generations of reproduction after the 7-day segregation period. Genetic causes alone could not explain the expression reduction; inheritance of epigenetic factors contributed to the observed change, the Yale team found.

Acar said the findings show a clear Lamarckian epigenetic contribution to gene network evolution and the classic Darwinian interpretation of evolution alone cannot explain our observations. "The findings support the idea that both genetic and epigenetic mechanisms need to be combined in a 'grand unified theory of evolution,'" he said.

Credit: 
Yale University

The Grantecan finds the farthest black hole that belongs to a rare family of galaxies

image: Black-hole-powered galaxies called blazars are extremely rare. As matter falls toward the supermassive black hole at the galaxy's center, some of it is accelerated outward at nearly the speed of light along jets pointed in opposite directions. When one of the jets happens to be aimed in the direction of Earth, as illustrated here, the galaxy appears especially bright and is classified as a blazar.

Image: 
M. Weiss/CfA

Only a small fraction of the galaxies emits gamma rays, which is the most extreme form of light. Astronomers believe that these highly energetic photons originate from the vicinity of a supermassive black hole residing at the centers of these galaxies. When this happens, they are known as active galaxies. The black hole swallows matter from its surroundings and emits jets or, in other words, collimated streams of matter and radiation. Few of these active galaxies (less than 1%) have their jets pointing by chance toward Earth. Scientists call them blazars and are one of the most powerful sources of radiation in the universe.

Blazars come in two flavors: BL Lacertae (BL Lac) and flat-spectrum radio-quasars (FSRQs). Our current understanding about these mysterious astronomical objects is that FSRQs are relatively young active galaxies, rich in dust and gas that surround the central black hole. As time passes, the amount of matter available to feed the black hole is consumed and the FSRQ evolves to become a BL Lac object. "In other words, BL Lacs may represent the elderly and evolved phase of a blazar's life, while FSRQs resemble an adult," explains Vaidehi Paliya, a DESY researcher who participated in this program.

"Since the speed of light is limited, the farther we look, the earlier in the age of the Universe we investigate," says Alberto Domínguez of the Institute of Physics of Particles and the Cosmos (IPARCOS) at UCM and co-author of the study. Astronomers believe that the current age of the Universe is around 13.8 billion years. The most distant FSRQ was identified at a distance when the age of the universe was merely 1 billion years. For a comparison, the farthest BL Lac that is known was found when the age of the Universe was around 2.5 billion years. Therefore, the hypothesis of the evolution from FSRQ to BL Lacs appears to be valid.

Research Team On the left, Vaidehi S. Paliya. In the photo on the right: Cristina Cabello, Jesús Gallego, Alberto Domínguez, Armando Gil de Paz y Nicolás Cardiel.

Now, the team of international scientists has discovered a new BL Lac object, named 4FGL J1219.0+3653, much farther away than the previous record holder. "We have discovered a BL Lac existing even 800 million years earlier, this is when the Universe was less than 2 billion years old," states Cristina Cabello, a graduate student at IPARCOS-UCM. "This finding challenges the current scenario that BL Lacs are actually an evolved phase of FSRQ," adds Nicolás Cardiel, a professor at IPARCOS-UCM. Jesús Gallego, also a professor at the same institution and a co-author of the study concludes: "This discovery has challenged our knowledge of the cosmic evolution of blazars and active galaxies in general."

The researchers have used the OSIRIS and EMIR instruments, designed and built by the Instituto de Astrofísica de Canarias (IAC) and mounted on GTC, also known as Grantecan. "These results are a clear example of how the combination of the large collecting area of ??GTC, the world's largest optical-infrared telescope, together with the unique capabilities of complementary instruments installed in the telescope are providing breakthrough results to improve our understanding of the Universe," underlines Romano Corradi, director of Grantecan.

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Instituto de Astrofísica de Canarias (IAC)

TalTech chemists' new method is a significant step towards greener pharmaceutical industry

image: Professor at TalTech's Division of Chemistry Riina Aav

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TalTech

The rapid changes in the chemical industry are connected one hand with the depletion of natural resources and deepening of environmental concerns, on the other hand with the growth of environmental awareness. Green, environmentally friendly chemistry is playing an increasingly important role in the sustainable chemical industry.

The TalTech Supramolecular Chemistry Group led by Professor Riina Aav published a research article on the applications of mechanochemistry titled "Mechanochemical Synthesis of Amides with Uronium-Based Coupling Reagents: A Method for Hexa-amidation of Biotin[6]uril" in the journal ACS Sustainable Chemistry and Engineering.

Mechanochemistry is a branch of chemistry that studies the effects induced by mechanical action on chemical reactions. Since these reactions take place efficiently in the solid-state phase and do not require the use of solvents that generate toxic residues, it is becoming an increasingly important branch of chemistry, especially in the field of green and sustainable technology.

One of the authors of the article, TalTech Professor of Chemistry Riina Aav says, "Our Supramolecular Chemistry research group is currently one of the most active research groups in this field in Estonia, investigating in depth how to expand the possible applications of the mechanochemical method in the chemicals industry. As chemists, we see this method in particular as a good solution for environmentally friendly synthesis. This means that it is now possible to produce chemicals much faster and completely residue-free."

Twenty five per cent of pharmaceuticals produced in the chemical industry contain an amide bond. Such pharmaceuticals include e.g. drugs for the treatment of cardiovascular diseases (atorvastatin or Lipitor®), analgesics (Ibuprofen analogues), antibiotics (penicillin and chloramphenicol or Oftan Akvakol), as well as cancer drugs (methotrexate and, inter alia therapeutic peptides such as carfilzomib (KYPROLIS)). Until now, such drugs have conventionally been produced in the chemical industry using solvents. A mechanochemical process involves grinding of chemical substances without the need to use solvents. This means, however, that no toxic waste characteristic of solvent-based production is generated, and in addition, the whole process can take place tens of times faster (e.g. the required active ingredient is created within an hour, whereas the analogous solvent-based reaction requires 24-hours).

"I would like to point out that we were able to replace the organic catalysts used so far with an inorganic one to achieve the result, because dissolution of components is not necessary in mechanochemical synthesis. This further reduced our carbon footprint. We also studied the mechanism of the mechanochemical process, and the results show that the formation pathways of amides or peptides, which are essential for the manufacture of pharmaceutical products, are similar to the ones involved in protein formation in our bodies. The mechanochemical method developed by us is much simpler - the necessary elements are ground and the product obtained is washed with water," a co-author and senior researcher Dzmitry Kananovich, says.

It is a faster and and much more environmentally friendly chemical process compared to the solvent-based method. In addition, this method can be used to produce new molecular receptors biotin[6]urils, which scientists plan to apply as "chemical noses" upon developing residue capturing molecular containers.

"The developed method is great news for chemical and pharmaceutical industry, who are interested in sustainable and residue-free chemical technology solutions not only in the production of medicines, but also food supplements, detergents and other products. Our research group is a member of the European Cooperation in Science and Technology action "Mechanochemistry for Sustainable Industry", which will hopefully ensure practical application of the mechanochemical methods in the chemical industry in the near future," Riina Aav says.

Credit: 
Estonian Research Council

Sports science: quality wins games

image: KIT researchers identified the precision and efficiency of moves, home advantage, and the market value of players to be major criteria in winning a soccer game.

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(Photo: Amadeus Bramsiepe, KIT)

"Quality Wins Games" - this is the conclusion drawn by scientists of Karlsruhe Institute of Technology (KIT) in their study "Success Factors in Football: An Analysis of the German Bundesliga." The most important success criteria they identified is avoiding errors in the defense and efficiency in scoring goals especially after counter-attacks. In addition, the study empirically confirms that the market value of the team significantly affects win or loss. The study is based on data from 918 games of the Bundesliga. The findings are reported in the International Journal of Performance Analysis in Sport. (DOI: 10.1080/24748668.2020.1726157)

"We found that precision and efficiency in soccer are more important than the absolute number of moves," says Hannes Lepschy from KIT's Institute of Sports and Sports Science (IfSS). "This holds for shots at the goal as well as for passes and movement paths." In his doctoral thesis, Lepschy linked and analyzed player data of 918 Bundesliga games in the seasons from 2014 to 2017 from various sources. He evaluated games with a tight outcome, in which both teams showed about the same commitment. Together with his supervisors, Professor Alexander Woll and Dr. Hagen Wäsche, Lepschy checked 29 variables for their impact on win or loss. He also considered context factors, such as the market value of the team and the average age, with home and guest teams being analyzed separately.

On this basis, Hannes Lepschy identified the most and least important factors for win or loss. "Apart from expected results, some findings surprised us," says Alexander Woll, Head of IfSS. Avoiding errors in the defense as well as the number of shots at the goal and the efficiency in scoring goals have the strongest influence on the probability to win. Contrary to expectations, the chance to win does not increase with the number of hit crosses, but the risk of goals conceded. Neither ball possession nor running performance were found to influence the result of the game. "It is not important how many kilometers a player runs or how often he has the ball. It is the quality of the space opened that decides," Lepschy explains. Hagen Wäsche adds that context variables also have to be taken into account. The average age of the team has no game-deciding influence, but home advantage and market value of the players are of decisive importance.

Lepschy, Wäsche, and Woll recommend Bundesliga coaches to work on the quality of the actions of their teams. It is important to avoid errors in the defense and to train precise and quick moves in space. "And not least, you need a good purchasing strategy," Woll says. In the next stage, the scientists will develop their method further using network analysis methods. This will improve determination of relevant performance factors and practical training recommendations for soccer coaches in the Bundesliga.

Credit: 
Karlsruher Institut für Technologie (KIT)

Seasonal Forecasts Improve Food Supply

image: The Kilimanjaro dominates the landscape of East Africa. There, impacts of climate change can already be felt clearly.

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(Photo: Harald Kunstmann, KIT)

Developing more precise seasonal forecasts to improve food supply for a total of 365 million people in eleven countries in East Africa, this is the goal of the new CONFER project funded by the EU. In particular, more precise precipitation forecasts are deemed important to increase agricultural yields. Karlsruhe Institute of Technology (KIT) is one of nine partners of this international project that is funded by the European Union with a total amount of EUR 7 million.

In 2017, East Africa was affected by the most severe drought since more than half a century. In 2019, heavy precipitation produced widespread flooding within a short term. Entire regions were covered by a waist-high layer of water. Both events produced big damage in agriculture and infrastructure and represented existential threats to the population. "In East Africa, the impacts of climate change can already be felt clearly," says Professor Harald Kunstmann, Deputy Head of the Atmospheric Environmental Research Division of KIT's Institute of Meteorology and Climate Research (IMK-IFU), KIT's Campus Alpine in Garmisch-Partenkirchen. The Institute participates in the new EU project CONFER (Co-production of Climate Services for East Africa). The project started on September 01 and will have a duration of three and a half years. Research institutions, in close dialog with stakeholders and end users, will develop innovative climate services for energy, water, and food supply to support people in East Africa in coping with the challenges associated with climate change. A total of 365 million people in eleven countries in East Africa will profit from the findings.

Researchers Pool Data from Models, Satellites, and Measurement Stations

The international project coordinated by the Norwegian Research Centre (NORCE) is aimed at increasing the accuracy of forecasts for the next months and supplying various weather and climate data for the region. In countries like Kenya and Tanzania, where reservoirs and water power play an important role in irrigation and energy supply, improved control may contribute to increasing agricultural yields and reducing flooding risks.

"In CONFER, we use dynamic and statistical forecast models as well as methods of machine learning and pool data from models, satellites, and measurement stations," explains Kunstmann, who heads the "Regional Climate and Hydrology" Group of IMK-IFU. "Above all, we seek to improve seasonal forecasts, i.e. forecasts for several months. This will enable us to take measures in due time in order to reduce negative impacts of droughts or extremely wet periods."

Credit: 
Karlsruher Institut für Technologie (KIT)

Biomarkers could be used in a quick, inexpensive COVID-19 blood screening tool

image: Dr. Douglas Fraser, Researcher from Lawson Health Research Institute and Western University's Schulich School of Medicine & Dentistry

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Lawson Health Research Institute

LONDON, ONTARIO - A new study from Lawson Health Research Institute, Western University and University of Alberta suggests that COVID-19 affects the human body's blood concentration levels of specific metabolites - small molecules broken down in the human body through the process of metabolism. Three specific metabolites identified in this study could act as biomarkers and one day be measured through an inexpensive blood test to quickly screen patients for the disease and predict which patients will become most critically ill. The team also suspects those metabolites depleted by the virus could be delivered to patients as dietary supplements, acting as a secondary therapy. Published in Critical Care Explorations, the early findings add to the research team's growing body of evidence on the bodily changes caused by the SARS-CoV-2 virus.

"As the second wave progresses and COVID-19 cases rise, there is an overwhelming demand for testing," says Dr. Douglas Fraser, lead researcher from Lawson and Western's Schulich School of Medicine & Dentistry, and Critical Care Physician at London Health Sciences Centre (LHSC). "While our findings need to be confirmed in a larger group of patients, they could lead to a rapid, cost-effective screening tool as a first line of testing in the community and in-hospital."

The study was conducted by performing metabolomics profiling on blood samples from 30 participants at LHSC: 10 COVID-19 patients and 10 patients with other infections admitted to LHSC's ICU, as well as 10 healthy control participants. Samples were sent to The Metabolomics Innovation Centre (TMIC) at University of Alberta where a team measured plasma concentrations of 162 metabolites.

"Metabolites are the final breakdown products in the human body and play key roles in cellular activity and physiology. By studying them, we can understand chemical processes that are occurring at any given moment, including those that regulate biological functions related to health and disease," explains Dr. David Wishart, Codirector of TMIC and Professor of Biological Sciences, Computing Science and Laboratory Medicine & Pathology with the University of Alberta. "Because the human metabolome responds very quickly to environmental factors like pathogens, metabolomics can play an important role in early-stage disease detection, including for COVID-19."

The team discovered four metabolites of importance to COVID-19 disease detection. The concentration of one metabolite called kynurenine was elevated in COVID-19 patients while concentrations of the other three metabolites (arginine, sarcosine and lysophosphatidylcholines) were decreased. After further analysis, they discovered that by studying the concentrations of only two metabolites - kynurenine and arginine - they could distinguish COVID-19 patients from healthy participants and other critically ill patients with 98 per cent accuracy.

The team also discovered that concentrations of two metabolites (creatinine and arginine) could be used to predict which critically-ill COVID-19 patients were most at risk of dying. When measured on a patient's first and third day in ICU, these metabolites predicted COVID-19-associated death with 100 per cent accuracy.

"It's our hope these findings can be validated in larger patient populations and then used to develop a simple blood test that shows high likelihood of infection and disease severity, providing rapid results in as little as 20 minutes," explains Dr. Fraser. "This could ease the demand for current testing methods, perhaps being used as a portable, first-line screening tool in the community and for when undiagnosed patients present to hospital."

The team also notes the reduction of key metabolites reflects changes to biochemical pathways or functions in the body which are important to maintaining health and fighting disease. They suggest their findings warrant further study to determine whether certain metabolites could be boosted through dietary supplements. A precision health approach like this could lead to repaired biochemical pathways and improved disease outcomes.

"Providing dietary supplements could be a simple adjunctive or secondary therapy with meaningful outcomes," says Dr. Fraser. "For example, the metabolite arginine is essential to tissue repair while the metabolite sarcosine activates a process to remove damaged cells. Knowing that COVID-19 causes hyperinflammation that can damage cells and tissue, particularly in the lungs, supporting these processes may prove critical."

In an earlier study, the team was the first to profile the body's immune response to the SARS-CoV-2 virus and discover six potential therapeutic targets to improve outcomes. In other studies, they have discovered additional biomarkers that could be used to predict how severely ill a COVID-19 patient will become and uncovered a mechanism causing blood clots in COVID-19 patients and potential ways to treat them.

"We're working to uncover hard evidence about how the virus invades the body. Ultimately, we hope our combined findings can lead to faster diagnosis, ways to identify patients most at risk of poor outcomes and targets for novel treatments," notes Dr. Fraser.

Credit: 
Lawson Health Research Institute

Geologists simulate soil conditions to help grow plants on Mars

image: A rendering of a house beside a greenhouse on Mars

Image: 
NASA

Humankind's next giant step may be onto Mars. But before those missions can begin, scientists need to make scores of breakthrough advances, including learning how to grow crops on the red planet.

Practically speaking, astronauts cannot haul an endless supply of topsoil through space. So University of Georgia geologists are figuring out how best to use the materials already on the planet's surface.

To do that, they developed artificial soil mixtures that mimic materials found on Mars. In a new study published in the journal Icarus, the researchers evaluated the artificial soils to determine just how fertile Martian soil could be.

"We want to simulate certain characteristics of materials you could easily get on Mars' surface," said Laura Fackrell, UGA geology doctoral candidate and lead author on the study. Simulating the mineral makeup or salt content of these Martian mixtures can tell us a lot about the potential fertility of the soil. Things like nutrients, salinity, pH are part of what make a soil fertile and understanding where Mars' soils are at in that spectrum is key to knowing if they are viable and if not, are there feasible solutions that can be used to make them viable."

In the last decade, Martian surface exploration has expanded the understanding of the chemistry of the planet's surface. Using data taken from NASA's surface samples, the team studied regolith, or the loose material near the surface, to develop the simulants.

The materials used mimic mixtures of soil, clay minerals, salts and other materials obtainable from Mars' surface by scooping loose material or mining it from bedrock.

Despite its thin atmosphere, extreme cold and low oxygen, Mars' surface is known to contain the majority of plant essential nutrients, including nitrogen, phosphorus and potassium.

The presence of nutrients accomplishes one of the big hurdles, but there are still more challenges. "One problem is, their presence doesn't mean they are accessible to plants," Fackrell said. "If you actually put a plant in the ground--just because the iron or the magnesium is there doesn't mean the plant can actually pull it out of the soil."

Plus, the nutrients may or may not be present in sufficient quantity or they may be so high in concentration that they are toxic to plants.

Using simulated Martian soils, Fackrell and fellow researchers have found the textures of artificial simulants to be crusty and dried which may reflect some unexpected conditions of Mars soils that make them more difficult to use.

These challenges add up to a very difficult, though not impossible task. Looking to agricultural science, the group, which includes UGA faculty members Paul Schroeder, Mussie Habteselassie and Aaron Thompson, adapts solutions used on Earth, recommendations that range from rinsing the soil to adding inoculants like bacteria or other fungi to the soil to help the plants grow.

"Specific types of bacteria and fungi are known to be beneficial for plants, and may be able to support them under stress conditions like we see on Mars," said Fackrell, who began her studies in geomicrobiology with Schroeder while conducting her master's thesis research on extreme environments faced by microbes living in hot springs in the Kamchatka Peninsula, in the Russian Far East.

The scientists also see implications from their research for potential innovations in agricultural research for Earth. "Anything we learn about farming on Mars could help with farming in challenging environments on Earth that help us build to a sustainable future," Fackrell said.

Whatever the eventual solution, the prospect of a manned mission to Mars hinges on the ability to grow food.

"There are multiple ways you can look at it, but one option might be to use what's already there as a potting medium, and figure out if that's a viable way to do it or if you have to bring all the plant materials with you," Fackrell said. "The question of whether we can use Mars soil to provide that food will go a long way toward determining the feasibility of manned missions."

Credit: 
University of Georgia

Theoreticians show which quantum systems are suitable for quantum simulations

image: Ultracold atoms in an optical lattice have been considered for quantum simulations.

Image: 
arö/HZB

A joint research group led by Prof. Jens Eisert of Freie Universität Berlin and Helmholtz-Zentrum Berlin (HZB) has shown a way to simulate the quantum physical properties of complex solid state systems. This is done with the help of complex solid state systems that can be studied experimentally. The study was published in the renowned journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

"The real goal is a robust quantum computer that generates stable results even when errors occur and corrects these errors," explains Jens Eisert, professor at Freie Universität Berlin and head of a joint research group at HZB. So far, the development of robust quantum computers is still a long way off, because quantum bits react extremely sensitively to the smallest fluctuations in environmental parameters.

But now a new approach could promise success: two postdocs from the group around Jens Eisert, Maria Laura Baez and Marek Gluza have taken up an idea of Richard Feynman, a brilliant US-American physicist of the post-war period. Feynman had proposed to use real systems of atoms with their quantum physical properties to simulate other quantum systems. These quantum systems can consist of atoms strung together like pearls in a string with special spin properties, but could also be ion traps, Rydberg atoms, superconducting Qbits or atoms in optical lattices. What they have in common is that they can be created and controlled in the laboratory. Their quantum physical properties could be used to predict the behaviour of other quantum systems. But which quantum systems would be good candidates? Is there a way to find out in advance?

Eisert's team has now investigated this question using a combination of mathematical and numerical methods. In fact, the group showed that the so-called dynamic structure factor of such systems is a possible tool to make statements about other quantum systems. This factor indirectly maps how spins or other quantum quantities behave over time, it is calculated by a Fourier transformation.

"This work builds a bridge between two worlds," explains Jens Eisert. "On the one hand, there is the Condensed Matter Community, which studies quantum systems and gains new insights from them - and on the other hand there is Quantum Informatics - which deals with quantum information. We believe that great progress will be possible if we bring the two worlds together," says the scientist.

Credit: 
Helmholtz-Zentrum Berlin für Materialien und Energie

Scientists uncover prophage defense mechanisms against phage attacks in mycobacteria

image: Vassie Ware is a professor in Lehigh University's Department of Biological Sciences and is Co-Director of Lehigh's Howard Hughes Medical Institution (HHMI) Bioscience program
and Distance Education program

Image: 
Lehigh University

A phage is a virus that invades a bacterial cell. While harmless to human cells, phages are potentially deadly to bacteria since many phages enter a cell in order to hijack its machinery in order to reproduce itself, thus destroying the cell.

While this is bad news for bacteria, it may be good news for humans. There is a growing need to develop new treatments that effectively attack deadly strains of bacteria that have become resistant to other medicines. Already used with success in some parts of the world, phage therapy is gaining traction as a more widespread way to fight antibiotic-resistant bacterial infections and even, at some point, some viral infections including, according to a recent article, possibly COVID-19.

Among the challenges: a virus type known as a prophage. A phage enters a bacterial cell and, instead of destroying it, takes up residence. Called a "prophage," it fights off other viruses' attempts to invade. According to Vassie Ware, a professor in Lehigh University's Department of Biological Sciences, many bacterial strains contain prophages. These prophages, she says, may provide defense systems that would make therapeutic uses of phages more challenging. In order to eradicate a pathogen, phages may need to overcome an already-in-residence prophage's defense systems.

Ware and her team (former PhD student Catherine Mageeney, current PhD student Hamidu Mohammed and former undergraduate student Netta Cudkevich), collaborating with former Lehigh Chemical and Biomolecular Engineering and Bioengineering faculty member Javier Buceta and his team (former postdoctoral associate Marta Dies, recent PhD students Samira Anbari and Yanyan Chen), recently conducted a study that focused on a phage called Butters (discovered by Lena Ma in Lehigh's SEA-PHAGES Program in 2012) that attacks a bacterial strain related to mycobacteria that cause tuberculosis or other human infections.

The group uncovered a two-component system of Butters prophage genes that encode proteins that "collaborate" to block entry and subsequent infection of some phages, but not others. While the Butters prophage cannot protect the bacterial cell against all phage attacks, they discovered that more than one defense system is present in the Butters prophage defense repertoire. These weapons, they discovered, are specific for different types of phages. These findings were published in an article earlier this month in mSystems, a journal of the American Society for Microbiology.

"Previous findings by several members of our research team working with other collaborators showed that prophages express genes that defend their bacterial host from infection by some specific groups of phages. For Butters, no genes involved in defense against specific phages had been previously identified," says Ware. "With our experimental approach, we expected to identify genes involved in defense against infection by several phages, but were not expecting to uncover interactions between the two proteins that affected how one of the proteins functions in defense."

The Ware/Buceta team used a multidisciplinary approach to identify the genes and interactions. They utilized bioinformatics tools to predict structural features of proteins encoded by genes expressed by the Butters prophage and to probe databases for the presence of Butters genes within known bacterial strains. Molecular biology techniques were used to engineer mycobacterial strains to express phage genes from the prophage. Microbiology experiments included immunity plating efficiency assays for each engineered bacterial strain to determine if the gene in question would protect the engineered bacterial strain from infection by a particular phage type.

This strategy, says Ware, allowed identification of specific genes as part of the defense mechanism against specific viral attack.

They also conducted microscopy experiments for live-cell imaging to visualize the cellular location of phage proteins within engineered bacterial cells and to show a functional interaction between the phage proteins in question. Biochemical experiments determined that the phage proteins likely interact physically as part of the defense mechanism.

"Collectively, these approaches provided data that allowed the team to construct a model for how the Butters prophage two-component system may function in defense against specific viral attack," says Ware.

Adds Ware: "The diversity of defense systems that exists demonstrates that efforts to establish generic sets of phage cocktails for phage therapy to kill pathogenic bacteria will likely be more challenging."

In addition to advancing phage therapy development, the team's discovery may also be important for engineering phage-resistant bacteria that could be used in the food industry and in some biotechnology applications.

Credit: 
Lehigh University

What do breast cancer cells feel inside the tumour?

Using a new technique, a team of McGill University researchers has found tiny and previously undetectable 'hot spots' of extremely high stiffness inside aggressive and invasive breast cancer tumours. Their findings suggest, for the first time, that only very tiny regions of a tumor need to stiffen for metastasis to take place. Though still in its infancy, the researchers believe that their technique may prove useful in detecting and mapping the progression of aggressive cancers.

"We are now able to see these features because our approach allows us to take measurements within living, intact, 3D tissues," says Chris Moraes, from McGill University's Department of Chemical Engineering, a Canada Research Chair and senior author on a recent research paper in Nature Communications. "When tissue samples are disrupted in any way, as is normally required with standard techniques, signs of these 'hot spots' are eliminated."

"Smart" hydrogels provide information about cancer progression

The researchers built tiny hydrogel sensors that can expand on demand, much like inflating balloons the size of individual cells, and placed them inside 3D cultures and mouse models of breast cancer. When triggered, the expansion of the hydrogel can be used to measure very local stiffness inside the tumour.

This unusual technique, developed through a collaboration between McGill's Department of Chemical Engineering and the Rosalind and Morris Goodman Cancer Research Centre at McGill, allows the researchers to sense, from the perspective of a cancer cell, what is going on in their surrounding environment.

What cells sense drives their behaviour

"Human cells are not static. They grab and pull on the tissue around them, checking out how rigid or soft their surroundings are. What cells feel around them typically drives their behaviour: immune cells can activate, stem cells can become specialized, and cancer cells can become dangerously aggressive," explains Moraes. "Breast cancer cells usually feel surroundings that are quite soft. However, we found that cancer cells inside aggressive tumours experienced much harder surroundings than previously expected, as hard as really old and dried up gummy bears."

The researchers believe that their findings suggest new ways in which cell mechanics, even at the early stages of breast cancer, might affect disease progression.

"Developing methods to analyze the mechanical profiles in 3D tissues may better predict patient risk and outcome," says Stephanie Mok, the first author on the paper and a PhD candidate in the Department of Chemical Engineering. "Whether these 'hot spots' of stiffness are really causing cancer progression rather than simply being correlated with it remains an open, but critically important question to resolve."

Credit: 
McGill University