Culture

Sugar turns brown algae into good carbon stores

image: The brown algae Fucus vesiculosus grows on stones almost everywhere along the North Sea and Baltic Sea. For the study the researchers also examined fucoidan of these algae like those at the coast of Heligoland.

Image: 
Max Planck Institute for Marine Microbiology/M. Schultz-Johansen

You may like them or not, but almost everyone knows them: brown algae such as Fucus vesiculosus, commonly known as bladderwrack, grow along the entire German coast. Giant kelp like Macrocystis or Sargassum grow closely together along the coasts but can also form floating aggregates that can cover the Atlantic from west to east. Some ecologists see this this very productive ecosystem as a marine counterpart to rainforests on land. In these algal forests, large amounts of carbon dioxide are stored, making them an important part of the global carbon cycle.

Andreas Sichert from the Max Planck Institute for Marine Microbiology dedicated his PhD to the question how brown algae can be such a good sink of carbon: "Main constituents of algal biomass are their cell walls - a tight network of proteins and long-chained sugars. When the algae die, we actually have little clue about the fate of algal biomass in the ocean, for example which compounds are degraded fast or slowly".

Firm and flexible

The Atlantic coast is not a cozy habitat. Tides, wind and waves demand special adaptations from the inhabitants of this harsh environment. Brown algae developed a special cell wall structure, making them both firm and flexible, and enabling the plant to successfully withstand heavy currents and waves. A major component of the cell walls is the polysaccharide fucoidan, a long-chained sugar accounting for about a quarter of algal dry mass. Likely, fucoidan can regulate the water content of the cell wall which protects brown algae from drying out at low tide.

What role this sugar plays in the long degradation process of brown algae was analyzed by scientists from the research group Marine Glycobiology at the Max Planck Institute for Marine Microbiology and the MARUM, Center for Marine Environmental Sciences at the University of Bremen. For their study, they cooperated with colleagues from the Massachusetts Institute of Technology, from the University of Greifswald and from the University of Vienna. "It was already known that microbial communities hydrolyze fucoidan slower than other algal polysaccharides and thus fucoidan might act as carbon sink" says Andreas Sichert from the Max Planck Institute for Marine Microbiology, first author of the study, published in the scientific journal Nature Microbiology in May 2020. "Usually, polysaccharides are a favorite energy source for bacteria, but the reason why fucoidan should be barely digestible remained unclear".

Only specialists degrade this sugar

So far, the fucoidan degradation pathways were only partially known, but it was evident that they involve a substantial number of enzymes either distributed within a microbial community or housed within individual, highly specialized bacteria. The scientists from Bremen examined the latter theory and analyzed newly isolated bacteria of the genus Lentimonas, belonging to the phylum Verrucomicrobia. Even the isolation of these Lentimonas bacteria was challenging. "From initially more than thousand colonies, only one was able to degrade fucoidan in the end," remembers Christopher H. Corzett from the Massachusetts Institute of Technology, first author of the study next to Andreas Sichert.

"We could show that Lentimonas acquired a remarkably complex machinery for the degradation of fucoidan that uses about one hundred enzymes to liberate the sugar fucose - a part of fucoidan", says Jan-Hendrik Hehemann, leader of the research group Marine Glycobiology. „This is probably one of the most complicated biochemical degradation pathways for natural material that we know of." Fucose is then metabolized via a bacterial microcompartment, a proteinaceous shell that shields the cell from the toxic intermediate lactaldehyde. „The need for such a complex catabolic pathway underpins the recalcitrance of fucoidans for most marine bacteria and it shows that only highly specialized organisms in the ocean are able to break down this algal sugar," says Hehemann. „This can explain the slower turnover of the algal biomass in the environment and suggests that fucoidans sequester carbon in the ocean."

Potential for pharmacology

Scientists are also interested in enzymes for fucoidan degradation because it may be a pharmacologically active molecule that shows similar effects to heparin in blood clotting. "Enzymes that specifically fragment fucoidan and thus help to characterize its structure are of great scientific interest because they enable researchers to understand the effects of fucoidan and to open up these marine sugars for biotechnological applications," says Thomas Schweder, participating microbiologist from the University of Greifswald.

Credit: 
Max Planck Institute for Marine Microbiology

The wildlife trade encompasses all major branches of the biological tree of life

image: Blue land crab Cardisoma guanhumi Latreille, 1828, from Atlantic region, not listed in IUCN Red List but threatened by overexploitation.

Image: 
Marco Antonio de Freitas.

Besides being a major threat to biodiversity, the wildlife trade can be a cause of global public health issues and hundreds of billions of dollars of economic damage around the world from disease outbreaks, as might be the case for COVID-19. Despite its major ecological and socio-economic importance, no comprehensive analysis has been made of the global patterns of the wildlife trade.

"The illegal wildlife trade often has connections with organised crime. Criminal groups involved in drug trafficking, fraud and other illegal businesses are also active in the wildlife trade along routes used for other types of illicit products, and can combine this with different illegal activities, such as trafficking animals and drugs," points out Caroline Fukushima, researcher at the Finnish Museum of Natural History (Luomus), University of Helsinki. Based on such concerns, a group of researchers sought to describe the importance of all major groups of organisms in the global wildlife trade and called for more research on neglected groups.

"To us, it is evident that the phenomenon of the global wildlife trade is much more complex and widespread than previously acknowledged," says Stefano Mammola, researcher at the Italian National Research Council, as well as one of the authors. "Even though the wildlife trade permeates all branches of the tree of life - from fungi to plants, from small marine species to big terrestrial mammals - more attention is given to the trade of a small selection of charismatic species, preventing the development of comprehensive and effective conservation strategies."

Even the smallest, apparently insignificant organisms are traded

The research group found that trade is common among many different organisms, from mushrooms to large vertebrates. Sea cucumbers, anemones and corals in particular have extremely large proportions of threatened species being traded worldwide.

Additionally, when considering legal wildlife commerce on the global scale, the timber trade is the most relevant in monetary value, and plants emerged as the most traded group in sheer numbers of individuals.

Extensive data is needed on the trade and its consequences

Due to the obvious illegality of much of wildlife trafficking, it is difficult to obtain systematic and reliable data. For some groups such as invertebrates, the species listed in CITES or the IUCN Red List of Threatened Species are just the tip of the iceberg. The numbers of traded taxa in such databases are a gross underestimation of what is actually traded, as most species have never even been assessed for their relevance in the trade business.

"We are facing a biodiversity crisis. We need to be fast and effective in filling our gaps in knowledge, especially about non-vertebrate species. In this way, we can achieve a deep understanding of global trading patterns across the full canopy of the tree of life, and not just its most appealing twig," says Pedro Cardoso, at the Finnish Museum of Natural History.

The future challenge for conservation biologists is now to map global trade across all living beings, know what drives such trade and find ways to fight traffic that might put both wildlife species and human health in danger. A major consequence of the widespread trade are disease outbreaks, as might be the case for the possible origin of COVID-19 from wildlife markets. It is urgent to take these matters seriously, as their consequences reach far beyond wildlife species survival.

Credit: 
University of Helsinki

New method reveals where DNA is at risk in the cell

Researchers at Karolinska Institutet in Sweden have developed a new sequencing method that makes it possible to map how DNA is spatially organised in the cell nucleus - revealing which genomic regions are at higher risk of mutation and DNA damage. The technique is described in an article published in the scientific journal Nature Biotechnology.

Most cells in the human body contain approximately two metres of DNA. This long stretch of DNA is divided in 46 large pieces - the chromosomes - which occupy discrete regions of the cell nucleus known as chromosome territories.

How individual parts of the genome are spatially arranged in the nucleus strongly affects how they are being read by the cell's transcriptional apparatus. However, the spatial arrangement of individual genes in the three-dimensional (3D) space of the nucleus has remained largely unexplored.

Now, a team of researchers led by Dr. Magda Bienko at Science for Life Laboratory (SciLifeLab) and the Department of Medical Biochemistry and Biophysics at Karolinska Institutet has developed a new genomic method, named Genomic loci Positioning by Sequencing or GPSeq, which can be used to obtain high-resolution maps of how DNA is spatially organized in the cell nucleus.

The method works by gradually cutting the DNA from the nuclear periphery towards the centre, followed by reading the DNA sequence around each cut. Mathematical modelling can then be used to reconstruct the 3D genome structure and find where individual genes and regions between genes are located along the nuclear radius as well as in relation to each other.

"We found that the spatial distribution of different types of chromatin (composed of DNA, RNA and protein complexes) often differed from what we expected to find," says Dr. Bienko, one of the senior authors of the paper. "To our surprise, we found that the picture is not as simple as having all the inactive chromatin sitting at the nuclear periphery and the active chromatin amassed in the centre. Instead, there is a continuum, a gradient of increasing activity from the nuclear periphery towards the interior, even though the inactive chromatin can be found in the very centre of the nucleus too."

An important aspect of knowing where different genomic regions are located in the nucleus is that it is now possible to map where DNA damage and mutations are most likely to occur, explains Dr. Nicola Crosetto, a senior researcher at the same department at Karolinska Institutet and the other senior author of the paper.

"We discovered that DNA mutations that are often encountered in different cancer types are enriched in the inactive chromatin located at the nuclear periphery, which might have to do with the fact that many mutagens originate from outside the cell," he says. "On the other hand, DNA breaks and gene fusions are much more likely to be found in the nuclear centre, which might be due to the high levels of transcription that we find in the centre."

Credit: 
Karolinska Institutet

Researchers capture rarely heard narwhal vocalizations (video)

WASHINGTON--With the help of Inuit hunters, geophysicists recently recorded the various calls, buzzes, clicks and whistles of narwhals as they summered in a Greenland fjord. The recordings help scientists better understand the soundscape of Arctic glacial fjords and provide valuable insight into the behavior of these shy and mysterious creatures, according to the researchers.

Narwhals are difficult to study because they are notoriously shy and skittish and spend most of their time deep in the freezing Arctic Ocean. They tend to summer in glacial fjords around Greenland and Canada, but scientists often have trouble getting close enough to study them. Glacier fronts can be dangerous and hard to access, and the animals tend to swim off when approached by motorized boats.

But Inuit hunters familiar with the mysterious cetaceans can get closer to the animals without disturbing them. In July 2019, researchers accompanied several Inuit whale hunting expeditions in Northwest Greenland to study the narwhals that summer there in more detail.

Using underwater microphones attached to small boats, the researchers captured narwhal social calls and foraging sounds, getting as close as 25 meters (82 feet) to the elusive cetaceans. Listen to the vocalizations they captured here: https://www.youtube.com/watch?v=Nn5r7lcWhJQ&feature=youtu.be

The recordings help the researchers provide a baseline of the kinds of sounds that permeate the narwhals' pristine habitat. In combination with sightings, they also show narwhals get closer to glacier ice than previously thought for this area and the animals do forage for food in summer, contrary to some previous findings.

"Their world is the soundscape of this glacial fjord," said Evgeny Podolskiy, a geophysicist at Hokkaido University in Sapporo, Japan and lead author of a new study detailing the findings in AGU's Journal of Geophysical Research: Oceans. "There are many questions we can answer by listening to glacier fjords in general."

Getting close

Podolskiy and his colleagues had been working in Greenland fjords for several years, studying the sounds made by melting glaciers. Coincidentally, a population of narwhals summers in the fjords they were studying, and Podolskiy saw an opportunity to study the wily creatures.

"I realized working in the area and not paying attention to the elephant in the room -- the key endemic legendary Arctic unicorn just flowing around our glacier -- was a big mistake," he said.

The researchers tagged along on several Inuit hunting expeditions departing from the village of Qaanaaq, placing microphones underwater and recording the baseline sounds of the fjord.

They captured several types of sounds made by narwhals, including social calls, or whistles, and clicks used for echolocation, the biological sonar used by dolphins, bats, some whales and other animals to navigate and find food.

The closer narwhals get to their food, the faster they click, until the noise becomes a buzz not unlike that of a chainsaw. This terminal buzz helps the narwhals pinpoint the location of their prey.

"If you approach and target these fast fish, you better know precisely where they are; you need to gather this information more frequently," Podolskiy said.

Few studies have documented narwhals feeding in the summertime. Because the microphones picked up terminal buzz, a sound associated with finding food, the new study provides further evidence that narwhals do forage in summer.

Surprisingly, the researchers found narwhals come roughly within 1 kilometer (half a mile) of a glacier calving front, despite the fact that these areas are some of the noisiest places in the ocean and calving icebergs can be dangerous.

"There is so much cracking due to ice fracturing and bubbles melting out... it's like a fizzy drink underwater," Podolskiy said. "It seems we are dealing with animals living in one of the most noisy environments without having much trouble with that."

Credit: 
American Geophysical Union

NUI Galway research highlights the economic costs of workplace bullying

Findings from a new NUI Galway study on workplace bullying, led by Dr John Cullinan of the Discipline of Economics and Dr Margaret Hodgins from the Discipline of Health Promotion, has been published in the journal Occupational Medicine.

Workplace bullying is aggressive behaviour perpetrated by one or more persons, repeatedly and systematically over a prolonged time period, where the targeted person feels unable to defend themself. In a previous study, the NUI Galway research team highlighted the relationship between bullying and work-related stress in the Irish workplace. The current study builds on this to examine the economic costs of workplace bullying.

The research describes the range of impacts of workplace bullying on individuals and organisations. Using statistical methods, it estimates the number of workdays lost as a result of workplace bullying and calculates the economic value of the associated lost productivity. Overall, the research estimates a total of 1.7 million days lost due to bullying at a cost to the economy of €239 million per year. In addition, the study finds that although bullying is more prevalent in the public sector, it has a larger effect on absences in the private sector.

Commenting on the study, Dr John Cullinan said: "Workplace bullying is a pervasive problem with significant personal and wider costs. Our study highlights the considerable economic cost of workplace bullying in Ireland. In addition to lost productivity from workplace bullying, there are also likely to be costs associated with early retirement and presenteeism. Furthermore, bullying-related costs are unlikely to have gone away as a result of new COVID-19 work-from-home practices."

Dr Margaret Hodgins noted that: "To tackle the problem, organisations need an anti-bullying policy in order to signal to staff that bullying is unacceptable. However a policy is insufficient in itself and it is vital that it is implemented fairly and in a timely fashion. Ideally, organisations should be proactive, identifying how and when bullying occurs in the organisation, and be prepared to develop specific interventions that are appropriate to context."

Credit: 
University of Galway

Researchers call for new approach to some mental disorders

VANCOUVER, Wash. - Some of the most common mental disorders, including depression, anxiety and PTSD, might not be disorders at all, according to a recent paper by Washington State University biological anthropologists.

In the paper, published in the Yearbook of Physical Anthropology, the researchers propose a new approach to mental illness that would be informed by human evolution, noting that modern psychology, and in particular its use of drugs like antidepressants, has largely failed to reduce the prevalence of mental disorders. (This paper was made available online on Nov. 28, 2019 ahead of final publication in the issue on April 28, 2020). For example, the global prevalence of major depressive disorder and anxiety disorders remained steady at 4.4% and 4% respectively from 1990 to 2010.

The authors also theorize that depression, anxiety and post-traumatic stress disorder may be primarily responses to adversity; therefore, only treating the "psychic pain" of these issues with drugs will not solve the underlying problem. Kristen Syme, the first author on the paper and recent WSU Ph.D. graduate, compared it to medicating someone for a broken bone without setting the bone itself.

"The pain is not the disease; the pain is the function that is telling you there is a problem," said Syme. "Depression, anxiety and PTSD often involve a threat or exposure to violence, which are predictable sources for these things that we call mental diseases. Instead, they look more like sociocultural phenomena, so the solution is not necessarily fixing a dysfunction in the person's brain but fixing dysfunctions in the social world."

Syme and co-author Edward Hagen advocate for biological anthropologists to enter the study of the "diseases of the mind," to help find effective solutions, particularly for some problems that may be social instead of mental.

"Mental health research is still very much stuck in a view that comes out of the 19th century, and revived in 1980, of classifying everything by symptoms in the hopes of revealing underlying patterns that would lead to solutions, but it really has not," said Hagen, a WSU professor of evolutionary anthropology and corresponding author on the paper. "Even though we're using new measurements, like genetics, biomarkers and imaging, these still haven't added up to the insights needed to really improve people's lives."

Among the more problematic issues, the researchers point to the "chemical imbalance" theory of depression, which has helped create a boom in antidepressant drugs meant to modulate certain chemicals in the brain called neurotransmitters. A large meta-analysis of antidepressant trials in 2018 found that antidepressants had almost the same effect as a placebo, and their widespread use has not delivered measurable results. For example, in Australia alone, antidepressant use increased 352% from 1990 to 2002, yet there has been no observed reduction in the prevalence of mood, anxiety or substance use disorders in any country.

Instead of addressing mental issues by their symptoms, Hagen and Syme propose approaching mental illness by their probable causes. They acknowledge that some psychiatric disorders like schizophrenia are likely genetic and often inherited and others like Alzheimer's appear connected with aging.

However, the anthropologists argue that some conditions might be a mismatch between modern and ancestral environments such as attention-deficit/hyperactivity disorder, also known as ADHD. Hagen pointed out that there is little in our evolutionary history that accounts for children sitting at desks quietly while watching a teacher do math equations at a board.

Other disorders such as depression, anxiety and PTSD are not hereditary, occur at any age and are often tied to threatening experiences. Hagen and Syme propose they may be responses to adversity and serve as signals, much like physical pain does, to make people aware of the need for help.

These conditions also disproportionately affect people in developing countries. For instance, 1 in 5 people in conflict-affected countries suffer from depression versus 1 in 14 in worldwide.

"As anthropologists, we should be studying this a lot more because the mental health burden in the populations we often study is quite high," Hagen said. "In many cases, they're suffering from pervasive warfare, conflict and inadequate policing."

Credit: 
Washington State University

Increased usability and precision in vascular imaging

image: 3D imaging of the blood vessels of a mouse head using X-ray computer tomography and the newly developed contrast agent "XlinCA".

Image: 
Willy Kuo, University of Zurich

Various diseases in humans and animals - such as tumors, strokes or chronic kidney disease - damage the blood vessels. Capillaries, the smallest blood vessels in the body, are particularly affected. The large surface area of the capillary network enables oxygen to be exchanged between the blood and the surrounding tissue, such as the muscles when we exercise or the brain when we think.

Revealing the vascular structure

For the diagnosis and treatment of cardiovascular and other diseases, it is important to know the three-dimensional structure of blood vessels. This knowledge of the exact anatomy of the capillaries in humans and animals is also crucial for basic research. It enables researchers to investigate diseases that attack the blood vessels and evaluate new treatments. Researchers at the University of Zurich (UZH), the National Centre of Competence in Research Kidney.CH and the Biomaterials Science Center of the University of Basel have now developed a novel X-ray contrast agent called "XlinCA", with which capillaries can be made visible much more precisely using computer tomography.

Previous methods often faulty

Previously, contrast agents were added to polymerizing plastic resins before they were injected into the blood vessels of euthanized animals. However, it is very difficult to completely fill out the delicate capillaries in various organs with viscous resins. "Without years of experience using the right injection techniques, the capillaries are often only partially filled, or missing entirely. Up to a quarter of the resulting images are therefore unusable," says Willy Kuo, a postdoctoral researcher at the Institute of Physiology of UZH. By using "XlinCA" instead of other contrast agents, up to 25 percent fewer animals would be needed for experiments, states Kuo.

The basic problem with conventional methods is that plastic and water do not mix. This results in water inclusions where the contrast agent is absent, which causes disconnected vessel segments on the X-ray image. While the water-soluble X-ray contrast agents used in medicine may not have this problem, they cannot be solidified and leak through blood vessel walls into the surrounding tissue within minutes.

Optimum results thanks to custom contrast agent

Contrast agents for medical use in humans consist of small molecules and are relatively simple to produce. "A custom contrast agent for ex vivo use was significantly more difficult to synthesize, since it is made up of polymers - molecules bonded together in long chains," says Bernhard Spingler, professor at UZH's Department of Chemistry. "XlinCA" has several advantages over previously used X-ray contrast agents: It is easy to use and enables complete and uninterrupted vascular imaging. It also allows multiple organs or even whole animals such as mice to be examined at the same time.

Credit: 
University of Zurich

Miniature rock art expands horizons

image: The Yilbilinji rockshelter at Limmen National Park in the southwest Gulf of Carpentaria region of northern Australia.

Image: 
Flinders University

Australian archaeologists have discovered some of the most detailed examples of rare, small-scale rock art in the form of miniature stencils in a rockshelter traditionally owned by the Marra people.

The research, published in the journal Antiquity, examined the unusual art found in the Yilbilinji rockshelter at Limmen National Park in the southwest Gulf of Carpentaria region of northern Australia.

Traditionally owned by the Marra Aboriginal people, the site was documented by the research team in 2017 and instantly stood out as unique.

"It's the size of the rock art that makes this site unusual and highly distinctive," says Flinders University archaeologist ARC Future Fellow Dr Liam Brady.

"Typically, stencilled rock art around the globe features full or life-sized dimensions such as human and animal body parts, objects (e.g. boomerangs), and even plant matter," says Associate Professor Brady.

"However, many of the stencils at Yilbilinji are tiny or miniature-sized, and too small to have been made using real-life body parts and full-size objects."

Only two other examples of this miniature stencilled form of rock art, both human figures, are known from anywhere in the world: one at Nielson's Creek in New South Wales, and one at Kisar Island in Indonesia.

The research team - archaeologists, anthropologists, Marra rangers, and Limmen National Park rangers - recorded a total of 17 images of these miniature stencils during a 2017 field trip.

The images depict a wide range of motifs including, human figures, animals (crab, long-necked turtles), kangaroo paws, wavy lines, boomerangs, and geometric shapes.

The researchers set out to find out how these unusual images were made. One clue came from the fact most of the miniature stencils were made with rounded and curved edges meaning they were probably made using something that could be easily moulded and stuck to the rock surface.

Another clue came from anthropological research in the region. Co-author and anthropologist Dr John Bradley, from the Monash Indigenous Centre, has worked with Aboriginal people in the study area for more than 40 years.

He remembers seeing beeswax used by people for a range of purposes such as an adhesive for repairing spears and harpoons. He also saw children shaping beeswax into objects and animals such as cattle, horses and cowboys.

"Using these clues, the researchers decided to test if beeswax could have been used to make the miniature stencils," he says.

"Our experiments involving heating and shaping beeswax into human figures, animals, objects, and geometric shapes, and then stencilling onto a rock slab confirmed beeswax was an excellent material for making miniature stencils."

"Whoever made these miniature stencils - adults or children - is open for debate, as is their meaning," says Matthew Flinders Fellow Professor Amanda Kearney.

"However, what is important here is that this discovery adds another dimension to the Australian and global rock art record," she says.

In fact, since this discovery was made, three additional stencils have been discovered in the area - a human figure, an echidna and a freshwater turtle - which further highlights the archaeological potential at Limmen National Park.

Glenn Durie, Manager of Aboriginal Partnerships, Northern Territory Parks and Wildlife, says the research with Marra Traditional Owners, archaeologists, and park rangers means this discovery could be among the first of many more in the area.

Credit: 
Flinders University

Quantum simulators for gauge theories

To simulate in a laboratory what happens in particle accelerators has been an ambitious goal in the study of the fundamental forces of nature pursued by high-energy physicists for many years. Now, thanks to research conducted by the groups of statistical physics of SISSA - Scuola Internazionale Superiore di Studi Avanzati and the "Abdus Salam" International Centre for Theoretical Physics (ICTP), that goal is closer to reach.

"We have dealt with a gauge theory, more precisely the Schwinger model, which mathematically describes the interaction between microscopic charged particles, like electrons and positrons, and an electric field in a spatial dimension,"
said Federica Surace, PhD student at SISSA and lead author of the research, recently published on Physical Review X. "We have shown that this theory can be simulated in an experiment with ultracold atoms better than what calculators have done to date. This experiment was conducted in Prof. Lukin's laboratory at Harvard University."

Investigating the fundamental forces of nature

The study, to which PhD students Paolo P. Mazza, Giuliano Giudici, Alessio Lerose, and their supervisors Andrea Gambassi of SISSA and Marcello Dalmonte of ICTP also contributed, shows that the experiment carried out overseas can be interpreted as a "quantum simulator" of a gauge theory, an important connection because it confirms the potential of the latter to investigate the mysteries associated with the fundamental forces of nature.

"The theories which describe the fundamental interactions, known as gauge theories, are behind our current understanding of the physics of the universe, and to understand their dynamics is one of the most important unanswered questions in theoretical physics," adds Alessio Lerose, co-author of the publication. "To infer from this the behaviour of matter in extreme conditions, as in high energy collisions between heavy atomic nuclei, inside the stars and the primordial universe post Big-Bang, is a very complex challenge which has severely tested the theoretical and computational methods available to physicists."

The gauge theories allow, for example, to understand what happens in experiments like those conducted at CERN in Geneva. "These phenomena are very complex" Federica Surace adds. "Due to their quantum nature, it is very difficult to make reliable predictions, even with the most modern and powerful computers."

Quantum Simulators

One of the methods devised to carry out this type of investigation is precisely that of quantum simulators, made up of components, typically atoms cooled at temperatures close to absolute zero which are controlled by laser and magnetic fields, whose behaviour is governed by mathematical equations similar to those of the systems which scientists want to study, but which are much easier to create.

"These tools," continues Surace, "allow to investigate the gauge theories using experimental equipment as large as a room instead of an accelerator which is tens of kilometres long. The research in this field is just beginning and this goal is still a long way off and yet the first results are encouraging".

This is demonstrated by the work of the physicists of SISSA and of ICTP, and it has already provided important proof of the potential of quantum simulators already available in the laboratory to study the theories behind our understanding of the Universe.

"We have demonstrated that the model implemented by the quantum simulator created in Harvard is none other than one of the simplest gauge theories but which, in any case, foresees highly non-trivial phenomena, such as vacuum decay and the confinement of elementary particles," explains Alessio Lerose, underlining the importance of this result to create a simulator that can be used for all quantum systems. "At present, there is no "universal simulator", namely a quantum device which can be programmed to simulate any other quantum system, but creating one is a key objectives of the research in this area of physics. Quantum simulators now exist that possess an excellent level of control that allows for simulation of less complex systems. In reality, we now know that with some further effort it is also possible to simulate more complex quantum theories, such as the Schwinger model which has been the protagonist of our study".

Credit: 
Scuola Internazionale Superiore di Studi Avanzati

Bumblebees speed up flowering

image: If bumblebees find too little pollen, they pierce the leaves of non-?flowering plants in order to force them to produce flowers more quickly.

Image: 
Photograph: Hannier Pulido / ETH Zurich

Spring has sprung earlier than ever before this year, accompanied by temperatures more typical of early summertime. Many plants were already in full bloom by mid-?April, about three to four weeks earlier than normal. These types of seasonal anomalies are becoming increasingly frequent due to climate change, and the resulting uncertainty threatens to disrupt the timing of mutualistic relationships between plants and their insect pollinators.

A research team led by ETH Professors Consuelo De Moraes and Mark Mescher has now discovered that one peculiar bumblebee behaviour may help to overcome such challenges by facilitating coordination between the bees and the plants they pollinate. The group has found that bumblebee workers use their mouth parts to pinch into the leaves of plants that haven't flowered yet, and that the resulting damage stimulates the production of new flowers that bloom earlier than those on plants that haven't been given this "nudge".

Their study has just been published in the journal Science. "Previous work has shown that various kinds of stress can induce plants to flower, but the role of bee-?inflicted damage in accelerating flower production was unexpected," Mescher says.

Surprising behaviour from bumblebees

The researchers first noticed the behaviour during other experiments being undertaken by one of the authors, Foteini Pashalidou: pollinators were biting the leaves of test plants in the greenhouse. "On further investigation, we found that others had also observed such behaviours, but no one had explored what the bees were doing to the plants or reported an effect on flower production," Mescher explains.

Following up on their observations, the ETH researchers devised several new laboratory experiments, and also conducted outdoor studies using commercially available bumblebee colonies - typically sold for the pollination of agricultural crops - and a variety of plant species.

Based on their lab studies, the researchers were able to show that the bumblebees' propensity to damage leaves has a strong correlation with the amount of pollen they can obtain: Bees damage leaves much more frequently when there is little or no pollen available to them. They also found that damage inflicted on plant leaves had dramatic effects on flowering time in two different plant species. Tomato plants subjected to bumblebee biting flowered up to 30 days earlier than those that hadn't been targeted, while mustard plants flowered about 14 days earlier when damaged by the bees.

"The bee damage had a dramatic influence on the flowering of the plants - one that has never been described before," De Moraes says. She also suggests that the developmental stage of the plant when it is bitten by bumblebees may influence the degree to which flowering is accelerated, a factor the investigators plan to explore in future work.

The researchers tried to manually replicate the damage patterns caused by bees to see if they could reproduce the effect on flowering time. But, while this manipulation did lead to somewhat earlier flowering in both plant species, the effect was not nearly as strong as that caused by the bees themselves. This leads De Moraes to suggest that some chemical or other cue may also be involved. "Either that or our manual imitation of the damage wasn't accurate enough," she says. Her team is currently trying to identify the precise cues responsible for inducing flowering and characterising the molecular mechanisms involved in the plant response to bee damage.

Phenomenon also observed in the field

The ETH research team was also able to observe the bees' damaging behaviour under more natural conditions, with doctoral student Harriet Lambert leading follow-?up studies on the rooftops of two ETH buildings in central Zurich. In these experiments, the researchers again observed that hungry bumblebees with insufficient pollen supplies frequently damaged the leaves of non-?blooming plants. But the damaging behaviour was consistently reduced when the researchers made more flowers available to the bees.

Furthermore, it was not only captive-?bred bumblebees from the researchers' experimental colonies that damaged plant leaves. The investigators also observed wild bees from at least two additional bumblebee species biting the leaves of plants in their experimental plots. Other pollinating insects, such as honeybees, did not exhibit such behaviour, however: they seemed to ignore the non-?flowering plants entirely, despite being frequent visitors to nearby patches of flowering plants.

Delicate balance starting to tip

"Bumblebees may have found an effective method of mitigating local shortages of pollen," De Moraes says. "Our open fields are abuzz with other pollinators, too, which may also benefit from the bumblebees' efforts." But it remains to be seen whether this mechanism is sufficient to overcome the challenges of changing climate. Insects and flowering plants have evolved together, sharing a long history that strikes a delicate balance between efflorescence and pollinator development.

However, global warming and other anthropogenic environmental changes have the potential to disrupt the timing of these and other ecologically important interactions among species. Such rapid environmental change could result in insects and plants becoming increasingly out of sync in their development, for example. "And that's something from which both sides stand to lose," Mescher says.

Credit: 
ETH Zurich

Catch and release: collagen-mediated control of PEDF availability

image: Proposed mechanism of PEDF activation by type I collagen remodeling and maturation.

Image: 
Osaka University

Osaka, Japan - Cells are like tiny self-contained machines that are constantly fine-tuned in response to both internal and external signals. Some of these signals are induced by extracellular ligands, specialized proteins that bind to specific receptors on the cell surface, stimulating signaling pathways and altering gene expression.

One such ligand, called pigment epithelium-derived factor, or PEDF for short, is involved in multiple biological functions. Depending on which of its many cellular receptors it binds to, and even the timing of the binding, PEDF can either promote cell survival or trigger cell death. But until recently, researchers had no idea how PEDF itself was regulated.

In a study published in scientific journal PNAS, a research team led by Osaka University finally explain how cells make sure PEDF is in the right place at the right time.

"Previous studies had shown that collagen binding is very important for the function of PEDF," explains lead author of the study Kazuki Kawahara. "Therefore, we investigated the influence of collagen binding on the function of PEDF by examining the crystal structure of PEDF in complex with collagen."

Collagen is one of the most abundant proteins in the web-like structure called the extra-cellular matrix that surrounds human cells. This tangle of proteins and carbohydrates not only helps hold cells together, but also allows them to communicate with one another. As cells mature, the collagen matrix undergoes remodeling, characterized by tighter binding between collagen fibrils.

"The crystal structure revealed that PEDF binds to a cryptic site on the surface of type I collagen, where it is sequestered away from the cellular receptors," says Kawahara.

However, the researchers also found that a lysine residue in the binding site is involved in the crosslinking of collagen chains during collagen remodeling.

"We showed that PEDF binds to newly synthesized collagen but is gradually displaced as crosslinking increases," says senior author Yuji Kobayashi. "In this way, collagen controls the spatiotemporal accessibility of PEDF, regulating its interaction with target cell surface receptors."

PEDF has known anti-tumor and anti-angiogenic activities. Interestingly, the researchers found that PEDF selectively destroys developing vessels by binding to the newly synthesized collagen that is abundant on endothelial cells, which may then allow interaction with cellular receptors. This activity likely helps maintain homeostasis during tissue remodeling.

The researchers hope that this new information on the spatiotemporal control of PEDF will help in the development of novel therapies for cancer and vascular disease, as well as in the design of therapeutic biomaterials that target angiogenesis.

Credit: 
Osaka University

More effective human antibodies possible with chicken cells

Antibodies for potential use as medicines can be made rapidly in chicken cells grown in laboratories. Researchers refer to their technique as the human ADLib system, short for autonomously diversifying libraries. The technique automatically builds vast numbers, or libraries, of diverse antibodies using chicken immune system cells' natural method for shuffling their genes.

Often shaped like the letter Y, antibodies are produced by the immune system to fight infections and prevent re-infection. Small portions of that Y shape are highly variable. Antibodies use their unique shape to form a perfect molecular hug with specific antigens, molecules on the surface of the cause of an infection. To effectively eliminate an infection, antibodies must recognize, attach and stay attached to an antigen.

"Our ADLib system can generate human antibodies against various antigens faster than existing methods," said Hidetaka Seo, a project researcher at the University of Tokyo and first author of the recently published scientific paper.

In standard techniques, individual antibodies are first identified and then produced through a slow, multistep process involving bacteria, animal cells, or sometimes isolating antibodies from the blood of vaccinated or infected animals, and then modifying those animal antibodies for safe human use.

The first ADLib system was developed in 2005 by some members of the current research team, who at the time were working at the RIKEN research institute outside of Tokyo. The original ADLib system produced chicken antibodies using chicken immune system cells. In the years since, other researchers have generated human antibodies in whole live chickens.

"We had the idea for the human ADLib system at that time, but the technology was very difficult to develop," said Professor Kunihiro Ohta, a co-author of the recent research paper, who led the original ADLib research group at RIKEN and is currently dean of the Graduate School of Arts and Sciences at the University of Tokyo.

"This is the first case of human gene recombination sequences capable of providing practical antibody libraries being developed using avian cells grown in a laboratory," said Seo.

To develop the human ADLib system, researchers first inserted human genes to replace the chicken immune cells' antibody genes and the surrounding units of DNA known as pseudogenes. The cells then grow in a dish and multiply for several weeks, generating antibody genes of various new combinations. This random antibody-generator quality of the ADLib system leads to many useless antibodies, but it may generate more efficient antibodies than the "built-for-purpose" antibodies that a human or animal immune system naturally produces during an infection.

Separately, researchers coat tiny magnetic beads with antigens of interest. Finally, the chicken cells are burst open and the contents are washed over the magnetic beads. Any antibodies that stick to the antigen-coated magnetic beads are added to the antibody library. After isolating antibodies on the magnetic beads, the entire process of identifying them and checking their specificity can be completed within about 10 days. Researchers state this is much faster than conventional antibody generation methods, which can take a few months.

Many variations of antibodies might be able to bind an antigen, but staying attached is essential for proper immune function. The human ADLib system includes a second phase to strengthen antibodies' ability to attach and stay attached to their antigens, a process called binding affinity maturation.

Although binding affinity maturation is laborious in conventional methods, the human ADLib system provides a simple and effective method. Chicken cells with the desired antibodies are grown in the lab for another short period to further moderately diversify the antibody genes. Antibodies with stronger binding affinities to the antigen can be isolated from this second library.

Researchers have successfully achieved about a hundredfold improvement of the binding affinity.

Researchers have so far tested the human ADLib technique to find antibodies similar to those currently used to treat certain types of cancer.

"In the future, antibodies for therapeutics to overcome currently unmet medical needs could be generated by using the human ADLib system," said Yukoh Nakazaki, a co-author of the recent research paper and head of the research labs at Chiome Bioscience Inc. Chiome is improving this technology in partnership with the University of Tokyo.

The ADLib system is not limited to generating antibodies.

"If we replace the relevant chicken genes and pseudogenes with any other gene of interest, we could generate libraries of other proteins for agricultural, veterinary, or medical uses," said Seo.

Credit: 
University of Tokyo

Schizophrenia: When the thalamus misleads the ear

image: Diagram of the brain and thalamus. The green arrows represent the nerve connections between the two nuclei of the thalamus and the auditory cortex and Wernicke areas.

Image: 
UNIGE

There is an extremely high probability that individuals with 22q11.2 micro deletion syndrome - a rare genetic disorder - will develop schizophrenia together with one of its most common symptoms, auditory hallucinations. Scientists at the University of Geneva (UNIGE) and the Synapsy National Centre of Competence in Research (NCCR) have been studying this category of patients. They have succeeded in linking the onset of this hallucinatory phenomenon with the abnormal development of certain substructures of a region deep in the brain called the thalamus. These thalamic nuclei have been identified using a combination of functional and structural magnetic resonance imaging. They are involved in processing memory and hearing among other things. The authors suggest that there might be an explanation for these auditory hallucinations that is almost "mechanical": the immaturity of the axon connections that bind the thalamic nuclei to the cortex areas responsible for hearing. The results, published in the journal Biological Psychiatry: CNNI, pave the way for a new understanding of the pathophysiology and treatment of schizophrenia.

Several studies in recent years have demonstrated a link between schizophrenia and abnormalities in the development of the thalamus, a deep brain region that processes a number of cognitive functions, including working memory and hearing. More specifically, the volume of the thalamus is smaller on average in schizophrenic patients. Accordingly, it has been possible to link the onset of auditory hallucinations with an overly-intense neuronal connectivity between the thalamus and auditory cortex. An auditory hallucination is defined as the perception of sound in the absence of an external sound source. It is one of the most characteristic symptoms of schizophrenia, a psychotic disorder that affects approximately 1% of the population.

"We used a cohort of patients that is unique in the world in an attempt to analyse the mechanism behind this hallucinatory phenomenon in more detail," begins Stephan Eliez, a professor in the Department of Psychiatry in UNIGE's Faculty of Medicine. "For the last 19 years, a program backed by the University of Geneva has helped us enlist and monitor individuals suffering from a rare neurogenetic syndrome: 22q11.2 micro deletion syndrome, which is caused by the absence of a small piece of DNA in chromosome 22. These patients are often prone to auditory hallucinations among other things. More importantly, 30 to 35% of them develop schizophrenia during their lifetime. This is the category with the highest risk of falling victim to the psychotic disorder."

Monitoring from childhood to adulthood

This cohort, made up of over 200 patients living in Switzerland, France, Belgium, Luxembourg and England, represents a unique opportunity to follow individuals from childhood to adulthood and submitting them to a regular battery of tests (medical imaging, genetic analyses, etc. ). It offers the chance to understand the neuro-developmental processes involved in the onset of schizophrenia and possibly to determine potential treatments that could delay, slow down or even halt the progression of psychotic symptoms.

The study focused on 230 people aged 8 to 35 years: 120 from the cohort and 110 healthy individuals who served as controls. Participants underwent a brain scan every three years using functional and structural magnetic resonance imaging. They were not given any task to complete: the machine simply recorded the brain activity generated by floating thoughts activating the major neural networks by turns. The scientists focused in particular on the various sub-structures of the thalamus that each has its own functions.

Unparalleled precision

"We discovered that the thalamic nuclei involved in auditory and visual sensory processing and working memory are smaller in people with deletion syndrome than in others," explains Valentina Mancini, a researcher in UNIGE's Department of Psychiatry and the article's first author. "And among people with deletion syndrome, the volume of the medial geniculate nucleus (the MGN, one of the sub-parts of the thalamus involved in the auditory pathways) and that of the other nuclei used in memory are smaller in the group with auditory hallucinations relative to the group that doesn't experience any. The size of the MGN differs between the two groups from childhood with a divergent developmental trajectory".

The scientists made a further observation: in the patients suffering from auditory hallucinations, they noticed a hyper-connectivity between the thalamic nuclei and cortical areas devoted to the primary processing of hearing and Wernicke's area, which is highly significant for understanding language. This type of thalamo-cortical hyper-connection is normal during childhood, when the neural networks are being formed. The fact that it persists during adolescence and then into adulthood is the sign that the connections have never reached maturity.

"This characteristic could provide an almost mechanical explanation for the hallucinatory phenomenon in these patients," notes Stephan Eliez. "Our results also open up new perspectives for the more general understanding of the pathophysiology of schizophrenia. Identifying the markers that foreshadow the development of the disease in such detail gives us many new targets for action using specific neuroprotective drugs, for example, to prevent symptoms as much as possible."

Credit: 
Université de Genève

Patient notes could offer solution to the 'missing' Coronavirus diagnoses

GP's notes currently unavailable to medical researchers could provide clues to help manage major health crises - like COVID-19.

And according to a 'citizens' jury' study at Brighton and Sussex Medical School (BSMS), the main thing stopping the use of such information - concerns over patient privacy - could be overcome.

Lead author, Dr Elizabeth Ford, Senior Lecturer in Primary Care Research at BSMS
said: "In these times of a new and unknown disease like COVID-19, we really need all the health data we can get, in order to develop effective treatment quickly. For example, we've seen that the number of 'excess' deaths over the last few months doesn't tally with the number of actual deaths attributed to Coronavirus. Maybe information recorded by doctors during patient consultations could give us vital clues to understand these missing diagnoses?

"Patient notes, letters and reports held within medical records contain a range of valuable information that is currently unavailable to researchers. Understandably, there are concerns about private details being made available for research but if we can find a way past that, research could benefit public health hugely. That's why we ran this study, and found that although they were cautious about privacy, members of the public were largely supportive of the information being made available to university researchers."

Currently the structured parts of patients' medical notes are used in an anonymised way for health research, helping to develop major improvements in health care. Until now, however, the patient notes, where a doctor might write a summary regarding a patient's visit, and letters and reports following scans or visits to hospital, have not been available for health research - largely due to concerns about protecting privacy. Advances in computer science and text analytics mean that researchers are now able to extract specific clinical information from large quantities of patient documents and analyse many patient records at once.

During a three-day citizens' jury, 18 members of the public heard a range of expert presentations and arguments for and against sharing free text (from patient letters and notes from general practice and mental health care), and then questioned presenters and deliberated together.

Dr Ford said: "Jurors were largely supportive of using patient notes and letters for medical research, but felt people had the right to know what their medical data might be used for, so they could choose to opt out. They also wanted to see a clear commitment to improving technology to protect patient privacy.

"While this was obviously a small study on a complex subject, the results show a public interest in making free text data available to health researchers. Next steps would involve a larger study to gauge wider public interest in how we might be able to make such health information available while protecting patient privacy."

Credit: 
University of Sussex

Similar to humans, chimpanzees develop slowly

image: Similar to humans, chimpanzees require more than five years to reach key developmental milestones.

Image: 
Tatiana Bortolato, Taï Chimpanzee Project

Few species develop as slowly as humans, both in terms of developing adult skills and in terms of brain development. Human infants are born so underdeveloped that they cannot survive without adult care and feeding for some years after birth. Children still need to learn fundamental skills such as walking, eating, talking, using tools and much more. The timing of when these developmental milestones emerge is used by doctors to determine if your child and your child's brain are developing normally. However, we know little about the timing of when motor and social developmental milestones emerge in other long-lived, closely-related species, such as chimpanzees; nor what this means for their brain development. For example, when do chimpanzees start to walk, feed themselves, groom others and use tools? Fully charting development milestones in wild chimpanzees and other species can help us understand the evolutionary basis of such extended developmental periods.

Researchers at the Max Planck Institute for Evolutionary Anthropology in Leipzig have now systematically mapped a wide array of behavioural skills and determined at which point during development these skills emerge in wild chimpanzees. For this study, the researchers observed 19 chimpanzee infants (eight females and 11 males) from the Taï National Park, Côte d'Ivoire, from the first month after they were born until five years of age. The results showed that gross motor skills begin to emerge at around four months, communication traits at 12 months, social interaction skills at 14 months and fine motor skills at 15 months. "Not only the time frame, but also the order of emergence of the different skills is very similar to what we see in humans, reflecting a shared evolutionary history", says first author Aisha Bründl. "Our findings are in line with the delayed benefits hypothesis, which states that extended development is necessary for acquiring adult skills."

"Such developmental milestones may shed light on the maturation of the brain", says senior author Catherine Crockford, a co-leader of the Evolution of Brain Connectivity (EBC) project of the Max Planck Society. "Our findings suggest that some parts of the chimpanzee brain may develop slowly like in humans". This remains to be investigated as part of this new EBC-project, a collaboration between the Max Planck institutes for Evolutionary Anthropology and for Human Cognitive and Brain Sciences, in the context of which researchers collect, scan and analyse post mortem brains of great apes and relate these findings to ape behaviour.

In addition, the researchers found that more complex skills, like tool use and social interactions, emerge later, with larger differences between individual chimpanzees in when they emerge than less complex skills. "This variation may be caused by underlying differences in the social environment a chimpanzee is growing up in, but also other factors such as nutrition, and remains to be investigated further", explains co-author Patrick Tkaczynski.

"Such a developmental study requires long-term data, since chimpanzees have a similarly slow life history as humans", Roman Wittig, another senior author on the study and director of the Taï Chimpanzee Project points out. "We are lucky to have 40 years of observations on the same wild chimpanzees." Overall, this study is the most extensive description of developmental milestones in chimpanzees to date and brings us a step closer to shedding light on shared developmental pathways of great ape species.

Credit: 
Max Planck Institute for Evolutionary Anthropology