Culture

Probiotics may help manage childhood obesity

Probiotics may help children and adolescents with obesity lose weight when taken alongside a calorie-controlled diet, according to a study being presented at e-ECE 2020. The study found that obese children who were put on a calorie-restricted diet and given probiotics Bifidobacterium breve BR03 and Bifidobacterium breve B632, lost more weight and had improved insulin sensitivity compared with children on a diet only. These findings suggest that probiotic supplements and a calorie-controlled diet may help manage obesity in the younger population and reduce future health risks, such as heart disease and diabetes.

Obesity is a global health concern and can lead to a number of life-threatening conditions, such as diabetes and heart disease. Treatment and prevention is a serious public health challenge, especially in children and adolescents. Bifidobacteria are a group of probiotic bacteria that are part of the natural gut microbiome and help with preventing infection from other bacteria, such as E.coli, and digestion of carbohydrates and dietary fibre. During digestion, they release chemicals called short-chain fatty acids, which play an important role in gut health and controlling hunger. Low numbers of Bifodobacteria may impair digestion, affect food intake and energy expenditure, leading to body weight gain and obesity.

Previous studies suggested that probiotic supplementation with Bifidobacteria could help restore the composition of the gut microbiome, which may aid weight loss and could be a potential approach for obesity management. However, current research uses mixtures of different strains of probiotics and does not examine the effects of administering Bifidobacteria alone.

Dr Flavia Prodam and her team at the University of Piemonte Orientale, aimed to assess the impact of Bifidobacteria probiotic treatment in children and adolescents with obesity on a controlled diet, on weight loss and gut microbiota composition. 100 obese children and adolescents (6-18 years) were put on a calorie-controlled diet and randomly given either probiotics Bifidobacterium breve BR03 and Bifidobacterium breve B632, or a placebo for 8 weeks. Clinical, biochemical and stool sample analyses were carried out to determine the effect of probiotic supplementation on weight gain, gut microbiota and metabolism.

The results suggested that children who had taken probiotics had a reduction in waist circumference, BMI, insulin resistance and E.coli in their gut. These beneficial effects demonstrate the potential of probiotics in helping to treat obesity in children and adolescents, when undergoing dietary restrictions.

"Probiotic supplements are frequently given to people without proper evidence data. These findings start to give evidence of the efficacy and safety of two probiotic strains in treating obesity in a younger population," Dr Prodam comments.

The study suggests that supplementation with probiotics could modify the gut microbiome environment and beneficially affect metabolism, helping obese children or adolescents who are also undergoing a restricted diet to lose weight. However, larger studies over a longer period of time are needed to investigate this.

Dr Prodam explains, "The next step for our research is to identify patients that could benefit from this probiotic treatment, with a view to creating a more personalised weight-loss strategy. We also want to decipher more clearly the role of diet and probiotics on microbiome composition. This could help us to understand how the microbiota is different in young people with obesity."

Credit: 
European Society of Endocrinology

Warning: Epidemics are often followed by unrest

image: Massimo Morelli, Bocconi University

Image: 
Paolo Tonato

If you have not been hearing much of the French Gilets Jaunes or of the Italian Sardines in the last few months, it's because "the social and psychological unrest arising from the epidemic tends to crowd-out the conflicts of the pre-epidemic period, but, at the same time it constitutes the fertile ground on which global protest may return more aggressively once the epidemic is over," writes Massimo Morelli, Professor of Political Science at Bocconi, in a paper recently published in Peace Economics, Peace Science and Public Policy.

Professor Morelli and Roberto Censolo (University of Ferrara) argue that we can get an informed opinion about the possible effects of COVID-19 on protest and future social unrest by looking at the great plagues of the past, so they analyze 57 epidemic episodes between the Black Death (1346-1353) and the Spanish Flu (1919-1920). They state that while the epidemic lasts the status quo and incumbent governments tend to consolidate, but warn that a sharp increase in social instability in the aftermath of the epidemic should be expected.

Revolts not evidently connected with the disease are infrequent within an epidemic period, but epidemics can sow other seeds of conflict. Government conspiracy, "the filth of the poor", foreigners and immigrants have often been singled out as the cause of an epidemic. "Overall, the historical evidence shows that the epidemics display a potential disarranging effect on civil society along three dimensions," the authors write. "First, the policy measures tend to conflict with the interest of people, generating a dangerous friction between society and institutions. Second, to the extent that an epidemic impacts differently on society in terms of mortality and economic welfare, it may exacerbate inequality. Third, the psychological shock can induce irrational narratives on the causes and the spread of the disease, which may result in social or racial discrimination and even xenophobia." Focusing on five cholera epidemics, Morelli and Censolo count 39 rebellions in the 10 years preceding an epidemic and 71 rebellions in the 10 years following it.

On the other hand, the authors note that, in the short-term, the necessary restrictions of freedom during an epidemic may be strategically exploited by governments to reinforce power.

Credit: 
Bocconi University

Rare immune cells drive gut repair

image: Organoids made from the small intestine express the receptor CD44 (magenta) in the stem cell crypt buds (left), but when ILC1 are added to the culture, these CD44-positive crypt buds grow, which could cause abnormal tumor growths in a chronically inflamed environment

Image: 
Geraldine Jowett

Scientists from King's College London have discovered an unexpected tissue reparative role for a rare immune cell type in the gut that could tip toward fibrosis or cancer if dysregulated. The breakthrough will have important implications for treating patients who suffer from inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis.

In a paper published today in Nature Materials, the team of researchers from King's College London found that type-1 innate lymphoid cells (ILC1) can promote tissue repair, but when they accumulate in inflamed tissues, can also contribute to IBD co-morbidities such as cancer and fibrosis. It was previously assumed that these cells drove inflammation, so these findings could inspire completely new therapeutic approaches for those suffering from IBD.

To understand the impact of ILC1 on the gut, the academics combined ILC1 with intestinal organoids, miniature versions of the normal intestine that are grown in a dish. Whilst they intended to harness this system to study ILC1-driven inflammation in organoids, they instead found that ILC1 secreted additional proteins that promoted both growth of the intestinal barrier and remodelling of the supporting structure beneath it; a response closely resembling wound healing. However, ILC1's healing response was only half the story; the team also found that accumulation of ILC1 could trigger fibrotic lesions or exacerbate tumour growth, two common complications of IBD that severely impact a patient's quality of life.

Lead author King's College London PhD student Geraldine Jowett admits this finding came as somewhat of a surprise. "Even though the signals we identified were established biomarkers that had previously been associated with IBD, it was exciting, unexpected, and important to discover that these signals were actually coming from ILC1." she said.

Jowett explains: "It's a matter of balance: On the one hand ILC1s' ability to secrete this protein could suggest that we have been thinking about them the wrong way, and that encouraging this healing response could provide hope for the two thirds of patients who currently don't respond to anti-inflammatory treatments.

"On the other hand, ILC1 may only be beneficial in small doses, and could actually make things worse for IBD patients if they become dysregulated, leading to tumour growth or fibrotic scar tissue formation, outcomes we would want to avoid at all costs."

This discovery has the potential to inspire new strategies for therapeutic intervention, such as allowing physicians to identify patients that are at high risk for developing IBD co-morbidities that require invasive surgery.

The team's findings may also have implications for COVD-19 patients, as ILC1 are more typically known as the key first responders to viral infections in the lung and the gut. Even young, asymptomatic patients infected with SARS-CoV2 have presented with early signs of lung fibrosis. Since ILC1 are enriched during chronic viral infections, it is possible that ILC1 also accumulate and play a role in driving fibrosis in the lungs of COVID-19 patients, providing a potential therapeutic target for the urgent research efforts currently underway.

The team's findings required the authors to develop a complex culture system, as ILC1 are so rare in the gut that they can be hard to study. To accomplish this, they cultured ILC1 alongside human stem cell-derived intestinal organoids in a dish. They then encapsulated the tissues in a synthetic soft material called a hydrogel, allowing them to mimic the 3D environment of normal intestinal tissue.

Pinning down how the ILC1 could drive fibrosis was particularly challenging and required the team's expertise in materials science. "Culturing cells in a dish can be so artificial that the results become irrelevant for disease pathology, so it was critical that we performed our key experiments within an environment that could appropriately respond to the biological cues that drive fibrosis," explains Dr Eileen Gentleman, co-senior author on the study.

The new hydrogels the team developed for this study were designed using complex computational models, which were key to creating materials that were soft enough to support the organoids, and uniform enough to allow for reproducible measurements of the changes in stiffness created by ILC1.

King's College London Mucosal Immunologist and co-senior author Dr Joana Neves remarks: "Many environmental and genetic factors can contribute to IBD, so by combining ILC1 from patients with IBD with this synthetic culture system we were able to provide that extra layer of certainty that it was the ILC1 themselves that were driving the wound healing response, without interference from patients' diets, mutations, or treatment regimens."

Thus, the reductionist system developed by this team provides a powerful template for studying the impact of rare cell types on complex processes of development and teasing apart components of multifactorial diseases.

The study was a collaboration of different departments at King's College London, as well as other UK and international partners. Dr Chris Lorenz, Interim Head of Physics at King's explains their involvement: "Our coarse-grain molecular dynamics simulations provided a detailed description of how changes in the chemistry of the underlying polymeric building blocks affected the structural properties of the resulting hydrogels. As a result, we were able to inform the design of the hydrogels made by Eileen's group such that in the end the softness and uniformity of the hydrogels were optimised."

Credit: 
King's College London

Card-based system, designed to monitor asymptomatic persons, helps limit COVID-19 spread

The COVID-19 pandemic has had an adverse impact on the global economy. Researchers around the globe have been working hard to find ways to stop the spread of the disease either in the form of drugs or SOP changes that revolve around guidelines given by the WHO for maintaining hygiene and social distancing norms. The challenge of stopping the spread is especially challenging as many individuals who are exposed to the novel SARS coronavirus do not show the symptoms of COVID-19 and risk exposing non-infected individuals.

Researchers are now using GIS and IT systems to find ways to monitor populations and the movement of infected individuals to track the spread of the disease and efficiently tackle problems arising due to exposure to the novel coronavirus.

A team of researchers based in Hong Kong have devised a system to track asymptomatic individuals through the use of anonymous transit smart cards and terminals. The proposed system is connected to a central database of infected individuals maintained by the medical authorities. The location and movement of individuals is tracked by this system and it issues an alert in case they check in at a location where others are visiting. Non-infected individuals are flagged as asymptomatic carriers if they have been detected at a location where infected individuals have also been present. Through a combination of metrics such as gathering size and infection rates, the system calculates an index (called the alert level) by comparing the changes in the number of persons listed as infected individuals and asymptomatic individuals over the previous days. The alert level is designed to give an idea of the severity of the spread of the infection. The alerts issued by the system can be used to issue warnings to non-infected persons about a possible risk of COVID-19 infection in a specific location and also to block the entry of suspected carriers at a terminal.

The system has received recognition as a top solution for tourism destinations from the UN World Tourism Organization (UNWTO) in the recent Healing for Destinations tourism solutions contest. The system is in use in elderly homes, wet markets, public schools and restaurants in Hong Kong.

"The spread of COVID-19 is a mathematical problem." Explains Keith Lau, who is one of the principal researchers on the project. "By monitoring asymptomatic individuals and limiting the participation of individuals in large gatherings, we can see a reduction in exponential growth of cases, and this is reflected in our data. Our system makes it easy for local authorities to identify problems during pandemics such as the COVID-19 pandemic and invest their resources appropriately to minimize impacts on economic trade."

Credit: 
Bentham Science Publishers

Mini-organs could offer treatment hope for children with intestinal failure

Pioneering scientists at the Francis Crick Institute, Great Ormond Street Hospital (GOSH) and UCL Great Ormond Street Institute of Child Health (ICH) have grown human intestinal grafts using stem cells from patient tissue that could one day lead to personalised transplants for children with intestinal failure, according to a study published in Nature Medicine today (Monday 7th September).

Children with intestinal failure cannot absorb the nutrients that are essential for their overall health and development. This may be due to a disease or injury to their small intestine.

In these cases, children can be fed intravenously via a process called parenteral nutrition, however this is associated with severe complications such as line infections and liver failure. If complications arise or in severe cases these children may need a transplant. However, there is a shortage of suitable donor organs and problems can arise after surgery, such as the body rejecting the transplant.

In their proof-of-concept study, the research team showed how intestinal stem cells and small intestinal or colonic tissue taken from patients can be used to grow the important inner layer of small intestine in the laboratory with the capacity to digest and absorb peptides and digest sucrose in food.

This is the first step in efforts to engineer all the layers of the intestine for transplantation. The researchers hope that one day, laboratory grown organs could offer a safe and longer-lasting alternative to traditional donor transplants.

"It's urgent that we find new ways to care for children without a working intestine because, as they grow older, complications from parental nutrition can arise," says Dr Vivian Li, senior author and group leader of the Stem Cell and Cancer Biology Laboratory at the Crick.

"We've set out a process to grow one layer of intestine in the laboratory, moving us a step closer to being able to offer these patients a form of regenerative medicine, which uses materials created from their own tissue. This would reduce some of the risks that transplant patients face, such as their immune system attacking the transplant."

The researchers took small biopsies of intestine from 12 children who either had intestinal failure or were at risk of developing the condition. In the lab, they then stimulated the biopsy cells to grow into "mini-guts", also known as intestinal organoids, generating over 10 million intestinal stem cells from each patient over the course of 4 weeks.

The researchers also collected small intestine and colon tissue, that would otherwise have been discarded, from other children undergoing essential surgery to remove parts of their gut. Using laboratory techniques, cells were removed from these tissues leaving behind a skeleton structure which formed scaffolds.

The researchers placed the "mini-guts" onto these scaffolds, where they grew on this structure to form a living graft. Due to specific culture conditions, the stem cells changed into many of the different types of cells that exist in the small intestine. The grafts were able to digest and absorb peptides, the building blocks of proteins, as well as digest sucrose into glucose sugars.

"Although this research is in the lab right now, we're concentrating on making this a realistic and safe treatment option," explains senior author NIHR Professor Paolo De Coppi, Consultant Paediatric Surgeon at GOSH and Head of Surgery, Stem Cells & Regenerative Medicine Section at the UCL Great Ormond Street Institute of Child Health (ICH).

"What's significant here is we've shown that scaffolds can be created using tissue from the colon, not only tissue from the small intestine. In practice, it is often easier to obtain tissue from the colon, so this could make the approach much more feasible. It's an important step forward in regenerative medicine and we're optimistic about what this means for patients, but more research lies ahead before we can safely and effectively translate this approach to treatment."

As well as proving that biopsies taken from children could be used to grow functioning intestinal grafts, the researchers also demonstrated that the grafts survive and mature when transplanted into mice.

"By applying our basic science knowledge of intestinal stem cell biology, we have developed a time efficient and clinically relevant method for rebuilding human small intestine grafts for transplantation," says Laween Meran, lead author, Gastroenterology Registrar and Clinical Research Training Fellow at the Stem Cell and Cancer Biology Laboratory at the Crick and the ICH.

"Now that we've shown the grafts are successful on a small scale, the next crucial steps will be to start growing the other layers of the intestine such as muscle and blood vessels, whilst also scaling up our methods to create viable grafts relevant to individual patient needs".

Credit: 
The Francis Crick Institute

Why rats would win Australian survivor

image: Australia's smallest rodent, the molinipi (Pseudomys delicatulus), considers one of Australia's largest rodents, the otter-like rakali (Hydromys chrysogaster). They share an skull shape gradient that goes back further than either species' arrival to their shared continent.

Image: 
llustration by Alison K. Carlisle (aka Papadore Illustrations).

Australian rodents skulls all correspond to one simple, size-dependent shape that is more than ten million years old but it turns out this lack of change is the secret behind their survivor reputation.

A new study, co-led by scientists from Flinders University and The University of Queensland, has revealed that the skulls of rodents resemble each other in any given size, meaning little adaptation seems to be necessary for a rodent to survive in a variety of habitats.

Flinders University Associate Professor Vera Weisbecker, who supervised the study says everyone knows rodents all look similar, but researchers expected far more variety in the details of their skull shape when compared to what was found.

"It seems intuitive that a group of animals that displays a wide variety of shapes should be more successful in evolution. However, Australian rodents demonstrate that shape diversity doesn't always mean evolutionary success. So it really does show if the skull ain't broke, don't fix it."

Dr Ariel Marcy, from The University of Queensland, says rodents first entered Australia around four million years ago, and quickly adapted to the diversity of habitats available on our continent.

"Because well-adapted skulls are key to the survival of mammals, we expected to find a lot of locally adapted skull shapes."

"What we found was the opposite of what we expected: there was low variation in the skull shape of rodents, and body size explained most of it."

"Native rodents just scale from being a small 'mouse' shape to being a bigger 'rat' shape!" Dr Marcy said.

"And this relationship between skull shape and size is at least ten million years old, because invasive rodents - like the house mouse and Norway rat - share this pattern, too."

To understand the patterns of adaptation they expected to see, the team scanned hundreds of rodent skulls of 38 species from museums using 3D surface scanners, and analysed their shape using a statistical procedure called geometric morphometrics.

The researchers think this astonishing conservatism of shape may have to do with the very successful specialization of rodent jaws, allowing their skulls to be a true multi-purpose tool.

"Rodent skulls and jaws have a complicated yet highly versatile arrangement that seems to work well in a multitude of conditions. We think that this discourages evolutionary change. We saw unusual skull shapes only in extreme cases of ecological adaptation, for example in the water mouse or rakali which is a very unusual meat-eating predatory rodent."

Dr Weisbecker notes that the results make an important point in one of the biggest questions in evolutionary biology - why some groups of animals are more diverse than others.

Credit: 
Flinders University

Vortex top-hats emerge in superfluids

image: Expansion within a vortex fluid. A non-uniform vortex fluid expands to form a Rankine vortex. (Darker colours represent high density.)

Image: 
FLEET

An Australian-led study has provided new insight into the behaviour of rotating superfluids.

A defining feature of superfluids is that they exhibit quantised vortices – they can only rotate with one, or two, or another integer amount of rotation.

Despite this key difference from classical fluids, where vortices can spin with any strength, many features of the collective dynamics of vortices in both classical and quantum fluids are similar.

However, in this study the FLEET team at the University of Queensland demonstrate one stark difference in the behaviour between classical and quantum fluids. The authors consider the expansion of vortex clusters to show that for any initial arrangement of quantised vortices, a ‘Rankine’ super-vortex will form.

“The behaviour of many vortices in a superfluid is often chaotic and difficult to describe theoretically,” explains lead author Oliver Stockdale. “Our study overcomes this challenge by providing an exact solution to the vortex dynamics.”

The solution shows that a cluster of chiral vortices (vortices which all spin in the same direction) expands to form a constant density distribution that has a shape similar to a top hat. Such a distribution of vortices, known as a Rankine vortex, is forbidden in classical fluids due to their viscosity.

Why all superfluids ultimately become Rankine distributions

“Superfluids have zero viscosity and can support a Rankine vortex”, explains Oliver. “The striking result of this finding is that all initial distributions of vortices, regardless of how they are arranged, expands to form a Rankine vortex. This long-time equivalent behaviour is known as the universal dynamics and demonstrates the mechanism for how a superfluid dissipates its energy via quantised vortices.”

The authors employ a recently developed theory that describes the vortices themselves as a fluid.

“Just as hydrodynamics describes the behaviour of many fluid particles, it can be used to describe the motion of many vortices, which form a ‘vortex fluid’ within the ordinary fluid,” says co-author Matt Reeves.

“However, the vortex fluid exhibits additional ‘anomalous’ stresses; these extra forces arise due to the nature of the vortices that restrict their rotation to be quantised.

The anomalous terms give unusual fluid behaviours, including a viscosity which is negative. Essentially, the negative viscosity causes the exact opposite behaviour to a normal, classical fluid – it steepens the vortex density gradients, until the distribution becomes a Rankine vortex.”  nbsp;An example expansion within vortex fluid theory can be seen in Fig. 1, where an initially non-uniform vortex fluid expands to form a Rankine vortex.

To support their theoretical findings, the authors simulate the dynamics of thousands of vortices computationally. As opposed to describing the vortices as a fluid, these simulations consider each vortex as an individual entity. As with the vortex fluid theory, the authors find that any initial vortex distribution expands to form a Rankine vortex. An example of the numerical result can be seen in Fig. 2, where a Gaussian initial distribution expands to form a Rankine vortex.

Finally, the authors analysed data from an experiment that observed the expansion of a vortex cluster in a real superfluid, which was created using ultracold rubidium atoms.

“Whilst the vortex fluid theory assumes there are many vortices present, the experiment could only create approximately eleven vortices. Despite the low vortex number, there was evidence that the Rankine vortex emerged after the cluster expanded,” explains project leader Prof Matthew Davis. The experimental vortices can be seen in Fig. 3, as highlighted by the white circles.

Not only did this study demonstrate the first solution to the complicated vortex fluid theory, it provided the theory’s first experimental test. The experiment quantitatively predicted key features of the theory and demonstrated a platform to further test properties of the Rankine vortex, such as predictions that it supports an analogue fraction quantum Hall effect.

Vortices are a ubiquitous phenomenon in superfluid systems. To work towards FLEET’s goal of producing an ultra-efficient superfluid transistor, a more complete understanding of how vortices behave in flowing superfluids is needed. This study by the FLEET team is a step towards such a transistor.

The study

The paper Universal dynamics in the expansion of vortex clusters in a dissipative two-dimensional superfluid was published in Physical Review Research in July 2020 (DOI 10.1103/PhysRevResearch.2.033138).

This study was carried out in collaboration with the ARC Centre of Excellence for Engineered Quantum Systems (EQUS), the Graduate School of China Academy of Engineering Physics, and the Dodd-Walls Centre for Photonic and Quantum Technologies (NZ).

Journal

Physical Review Research

DOI

10.1103/PhysRevResearch.2.033138

Credit: 
ARC Centre of Excellence in Future Low-Energy Electronics Technologies

Inheritance in plants can now be controlled specifically

image: An inversion (left) in thale cress (background) can be undone with CRISPR/Cas (center) to reactivate the exchange of genes (right) in the said section.

Image: 
(Figure: Michelle Rönspies/KIT)

A new application of the CRISPR/Cas molecular scissors promises major progress in crop cultivation. At Karlsruhe Institute of Technology (KIT), researchers from the team of molecular biologist Holger Puchta have succeeded in modifying the sequence of genes on a chromosome using CRISPR/Cas. For the first time worldwide, they took a known chromosome modification in the thale cress model plant and demonstrated how inversions of the gene sequence can be undone and inheritance can thus be controlled specifically. The results are published in Nature Communications (DOI: 10.1038/s41467-020-18277-z).

About 5,000 years ago, genetic information of thale cress was modified. To date, it has spread widely and is of major interest to science. On the chromosome 4 of the plant, a so-called inversion occurred: The chromosome broke at two points and was reassembled again. The broken out section was reinserted, but rotated by 180°. As a result, the sequence of genes on this chromosome section was inverted. This chromosome mutation known as "Knob hk4S" in research is an example of the fact that evolution cannot only modify the genetic material of organisms, but determine it for a long term. "In inverted sections, genes cannot be exchanged between homologous chromosomes during inheritance," molecular biologist Holger Puchta, KIT, explains.

Researchers Remove Obstacle to Crop Cultivation

Inversions do not only affect thale cress (Arabidopsis thaliana), a wild plant used as a model organism in genetics due to its completely decoded genome and its small chromosome number. Inversions can also be found in crop plants. They are an obstacle to cultivation that uses modifications of the genetic material to produce maximum yields and a good taste of the plant and to make the plant resistant to diseases, pests, and extreme climatic conditions.

For the first time, researchers from the Chair for Molecular Biology and Biochemistry held by Puchta at KIT's Botanical Institute have now succeeded in undoing natural inversions. "We considerably extended the applications of the CRISPR/Cas molecular scissors," Puchta says. "We no longer use the scissors for exchanging arms between chromosomes, but also for recombining genes on a single chromosome. For the first time, we have now demonstrated that it is possible to directly control inheritance processes. We can achieve genetic exchange in an area, in which this has been impossible before. With this, we have established chromosome engineering as a new type of crop cultivation."

Molecular Scissors Precisely Cut the DNA

Together with researchers from the team of Professor Andreas Houben, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) in Gatersleben, and Professor Paul Fransz from the University of Amsterdam, KIT scientists took the most prominent natural inversion hk4S on chromosome 4 of thale cress and demonstrated how this inversion can be undone and how genetic exchange can be achieved in cultivation. Their findings are reported in Nature Communications. The researchers also think that it is possible to use CRISPR/Cas to produce new inversions, which would be another step towards combining desired traits and eliminating undesired properties in crop cultivation.

Holger Puchta is considered a pioneer of genome editing with molecular scissors using the natural principle of mutation to precisely modify the genetic information in plants without introducing foreign DNA. His current project "Multidimensional CRISPR/Cas mediated engineering of plant breeding," CRISBREED for short, now focuses on the recombination of plant chromosomes by means of CRISPR/Cas technology. For this project, Puchta was granted the renowned Advanced Grant by the European Research Council (ERC) for the second time in a row. CRISPR (stands for Clustered Regularly Interspaced Short Palindromic Repeats) represents a certain section on the DNA that carries the genetic information. Cas is an enzyme that recognizes this section and cuts the DNA precisely at that point in order to remove, insert, or exchange genes, recombine chromosomes, and for the first time modify the gene sequence on them.

Credit: 
Karlsruher Institut für Technologie (KIT)

A difficult year for forests, fields and meadows

image: Near Davos, the researchers are observing how the coniferous forest responds to different climatic conditions.

Image: 
ETH Zurich

It was - once again - an unusually hot year: in 2018, large parts of Europe were beset by an extremely hot and dry summer. In Switzerland, too, the hot weather got people sweating - right on the heels of a string of unusually warm months. It was - at the time - the third hottest summer and the fourth warmest spring since measurements began in 1864.

A solid base of measurements

Obviously, such unusual weather conditions also had an impact on ecosystems. Scientists from the group led by Nina Buchmann, Professor of Grassland Sciences, have now used extensive measurement data to show exactly how forests, fields and meadows reacted to the exceptional conditions in 2018. The researchers evaluated measurements from five sites, all of which are part of the Swiss FluxNet initiative, explains Mana Gharun, a postdoc in Buchmann's group and the study's lead author: "The five sites cover all altitude levels from 400 to 2,000 metres above sea level. This means we've taken very different ecosystems into account."

At each of these sites, Buchmann's group has been taking measurements for years at very high temporal resolution of how much CO2, water vapour and other greenhouse gases are exchanged between plants, the atmosphere and the soil, right across the entire ecosystem. This allows the researchers to determine how the sites react to different climatic conditions.

Sharp drop in productivity

Their evaluation, which the researchers have just published in a special issue of the journal Phil Trans B, shows that the heat and drought of 2018 had a particularly severe impact on ecosystems at lower altitudes. In the mixed forest on the Lägeren mountain near Zurich and in the meadows close to Chamau, productivity fell by an average of 20 percent compared with the two previous years. The situation is different for ecosystems at higher altitudes: the coniferous forest near Davos, the meadow near Früebüel and the Weissenstein alpine pasture on the Albula Pass all benefited from warmer temperatures and a longer growing season. The more favourable growth conditions there led to higher productivity in these ecosystems.

However, respiration rates for plants and soil organisms also increased at almost all the sites. This means that while these systems absorbed more CO2 from the atmosphere, they also released more CO2 back into it. "Overall, this results in a lower net carbon uptake for the two forests and the Chamau meadow," Gharun notes. "This finding is unfortunate, since the general expectation is that under warmer conditions these ecosystems would act as carbon sinks to help mitigate climate change," she adds.

Buchmann points out that it is still too early for a final assessment: "We definitely need long-?term data series before we can put these findings in their proper context." She and her group have been collecting measurement data at the abovementioned sites for many years, so she has a good foundation for such long-?term studies.

A lot of snow after the winter

What made 2018 exceptional was not just the warm temperatures in spring and summer, but also the heavy precipitation during the preceding winter: when spring came, the mountains were covered by snow, which then melted very quickly due to the warm conditions. This benefited the higher-?altitude ecosystems in particular. In contrast, the situation at lower altitudes was more difficult, as the ecosystems there were unable to use the excess water from winter to build up a soil moisture reservoir for the summer. Accordingly, they suffered more from the summer drought and heat.

"Water availability is a decisive factor in how ecosystems survive periods of heat," Buchmann says. "Thus, it is important to look beyond the actual dry period when studying a drought." Another unsettling consideration is that the new CH2018 climate change scenarios predict more rain and less snow in winter. The higher levels of precipitation expected in the winter months is therefore of limited benefit to ecosystems when the water runs off quickly, rather than being stored as snow.

Stressed trees

Forests are now in a critical situation. There are several indications of this, one of which is that not only spruce trees but also old beech trees are now showing stress symptoms in many places across the Swiss Plateau. This is probably also due to the fact that the following year, 2019, was also warmer and drier than average. "What we are seeing in the forests is a memory effect," Buchmann explains, "so it's possible that the impacts of such periods may not show up until long after the actual extreme event."

How well the trees survive periods of drought and heat also depends on the depth at which they absorb water. Beech roots, for example, penetrate the soil to a depth of 50 or 60 centimetres and are therefore more likely to reach deeper moist layers. Spruce roots, on the other hand, reach a depth of only about 20 centimetres, making them more likely to be affected by droughts. "Things are going to get uncomfortable for lowland spruce in the medium term," Buchmann notes. "That's not a good forecast for forestry."

Gloomy outlook for farmers

What about the meadows? The two researchers have not yet found a memory effect there because meadows recover more quickly after a dry period. Nevertheless, meadows at lower altitudes produce significantly less forage in a year like 2018 - bad news for farmers. Grassland farming is the central pillar of Swiss agriculture. If less grass grows on meadows in the future because of increasing summer droughts, this will have direct consequences for milk and meat production.

Credit: 
ETH Zurich

How to have a blast like a black hole

image: Magnetic reconnection is generated by the irradiation of the LFEX laser into the micro-coil. The particle outflow accelerated by the magnetic reconnection is evaluated using several detectors. As an example of the results, proton outflows with symmetric distributions were observed.

Image: 
Osaka University

Laser Engineering at Osaka University have successfully used short, but extremely powerful laser blasts to generate magnetic field reconnection inside a plasma. This work may lead to a more complete theory of X-ray emission from astronomical objects like black holes.

In addition to being subjected to extreme gravitational forces, matter being devoured by a black hole can be also be pummeled by intense heat and magnetic fields. Plasmas, a fourth state of matter hotter than solids, liquids, or gasses, are made of electrically charged protons and electrons that have too much energy to form neutral atoms. Instead, they bounce frantically in response to magnetic fields. Within a plasma, magnetic reconnection is a process in which twisted magnetic field lines suddenly "snap" and cancel each other, resulting in the rapid conversion of magnetic energy into particle kinetic energy. In stars, including our sun, reconnection is responsible for much of the coronal activity, such as solar flares. Owing to the strong acceleration, the charged particles in the black hole's accretion disk emit their own light, usually in the X-ray region of the spectrum.

To better understand the process that gives rise to the observed X-rays coming from black holes, scientists at Osaka University used intense laser pulses to create similarly extreme conditions on the lab. "We were able to study the high-energy acceleration of electrons and protons as the result of relativistic magnetic reconnection," Senior author Shinsuke Fujioka says. "For example, the origin of emission from the famous black hole Cygnus X-1, can be better understood."

This level of light intensity is not easily obtained, however. For a brief instant, the laser required two petawatts of power, equivalent to one thousand times the electric consumption of the entire globe. With the LFEX laser, the team was able to achieve peak magnetic fields with a mind-boggling 2,000 telsas. For comparison, the magnetic fields generated by an MRI machine to produce diagnostic images are typically around 3 teslas, and Earth's magnetic field is a paltry 0.00005 teslas. The particles of the plasma become accelerated to such an extreme degree that relativistic effects needed to be considered.

"Previously, relativistic magnetic reconnection could only be studied via numerical simulation on a supercomputer. Now, it is an experimental reality in a laboratory with powerful lasers," first author King Fai Farley Law says. The researchers believe that this project will help elucidate the astrophysical processes that can happen at places in the Universe that contain extreme magnetic fields.

Credit: 
Osaka University

New insight into mammalian stem cell evolution

image: The researchers compared 134 gene sets belonging to the pluripotency gene regulatory networks of 48 mammalian species, and found that this network is highly conserved across species.

Image: 
Mindy Takamiya/Kyoto University iCeMS

The genes regulating pluripotent stem cells in mammals are surprisingly similar across 48 species, Kyoto University researchers report in the journal Genome Biology and Evolution. The study also shows that differences among these 'gene regulating networks' might explain how certain features of mammalian pluripotent stem cells have evolved.

Pluripotent stem cells can self-renew and give rise to all other types of cells in the body. Their characteristics are controlled by a network of regulatory genes and molecules, but little is known about how this network has evolved across mammals.

To this end, Ken-ichiro Kamei of Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS), with Miho Murayama and Yoshinori Endo of the Wildlife Research Center, compared 134 gene sets belonging to the pluripotency gene regulatory networks of 48 mammalian species.

They found that this network has been highly conserved across species, meaning genetic sequences have remained relatively unchanged over the course of evolution. This high degree of conservation explains why human genetic sequences can reprogram other mammalian tissue cells to turn into pluripotent stem cells. However, since it is also evident that the regulating networks differ across mammals, there might be more efficient combinations of reprogramming factors for each species. Improving techniques for deriving induced pluripotent stem (iPS) cells from mammalian cells, including those from endangered species, could provide a big boost to research and conservation.

"We have been trying to generate induced pluripotent stem cells from various mammalian species, such as the endangered Grévy's zebra and the bottlenose dolphin," says Kamei.

Interestingly, the team found relatively high evolutionary changes in genes just downstream of one of the core gene regulatory networks. "This could indicate that mammalian pluripotent stem cells have diversified more than we thought," says Inoue-Murayama.

The differences between gene regulatory networks in mammalian pluripotent stem cells might also be associated with unique adaptions.

For example, the naked mole rat has been positively selected for a pluripotency regulatory gene that could be involved in giving it its extraordinary longevity and cancer resistance. The gene might also be involved in the development of the extremely sensitive hairs that help them navigate underground.

The researchers also found evidence of positive selection for certain pluripotency gene regulatory network genes involved in the adaptation of large animals, such as the minke whale, the African elephant and the flying fox, to their environments. Surprisingly, these same genes are associated with cancer in other mammals. Since these large animals are known for being relatively resistant to cancer, the researchers suggest that the adaptive alterations these genes underwent in these animals somehow also changed some of their functions, thus giving this group a degree of cancer resistance.

The researchers say the study is among the first to compare the pluripotency gene regulatory networks across major taxa, and could be applicable to evolutional biology studies and for facilitating and improving the generation of induced pluripotent stem cells from new species.

Credit: 
Kyoto University

Rare hyperinflammatory syndrome in children with COVID-19 described

image: Petter Brodin, researcher at SciLifeLab and the Department of Women's and Children's Health, Karolinska Institutet, Sweden. Photo: Ulf Sirborn

Image: 
Ulf Sirborn

Researchers at Karolinska Institutet and Science for Life Laboratory in Sweden and Tor Vergata University of Rome in Italy have mapped the immune response in children affected by a rare but life-threatening inflammatory syndrome associated with COVID-19. The study, which is published in the scientific journal Cell, reveals that the inflammatory response differs from that in Kawasaki disease and severe acute COVID-19.

In the current SARS-CoV-2 pandemic, with very few exceptions, children have presented with mild symptoms. However, paediatricians have discovered a new, life-threatening hyperinflammatory syndrome resembling Kawasaki disease and named Multisystem Inflammatory Syndrome in Children associated with COVID-19, MIS-C (see box).

In a new collaborative study, researchers have worked out the immunological aspects of this rare condition. They compared blood samples from 13 MIS-C-patients treated at Karolinska University Hospital in Stockholm, Sweden and Bambino Gesù Children's Hospital in Rome, Italy, with samples from 28 Kawasaki disease patients collected from 2017 to 2018, prior to COVID-19. The analyses also included samples from children with mild COVID-19.

"Our results show that MIS-C is truly a distinct inflammatory condition from Kawasaki disease, despite having some shared features," says Petter Brodin, paediatrician and researcher at the Department of Women's and Children's Health, Karolinska Institutet, and one lead author of the study. "The hyperinflammation and cytokine storm detected in children with MIS-C is also different from that seen in adult patients with severe, acute COVID-19, which we recently described in another publication."

When comparing MIS-C to these other inflammatory states, the study observed differential frequency of specific immune cell populations, inflammatory cytokines and chemokines in the blood. Unlike children with Kawasaki disease and children with mild COVID-19, children who developed MIS-C were lacking IgG-antibodies to common cold coronaviruses. The researchers also found several autoantibodies that target the body's own proteins and that may contribute to the pathogenesis of MIS-C. They are now also looking into genetic risk factors for developing MIS-C after SARS-CoV-2 infection.

"There is an urgent need to better understand why a small minority of children infected with SARS-CoV-2 develop MIS-C, and we are adding a piece to the puzzle," says Dr Brodin. "Better knowledge of the pathogenesis is important for development of optimal treatments that can dampen the cytokine storm and hopefully save lives, as well as for vaccine development to avoid MIS-C caused by vaccination."

Credit: 
Karolinska Institutet

Gen Z not ready to eat lab-grown meat

Gen Z are the new kids on the block. As a cohort of 5 million people born between 1995-2015 encompassing 20 percent of the Australian population and 2 billion people globally -- they're consumers to be reckoned with.

New research by the University of Sydney and Curtin University to published on 8 September in Frontiers in Nutrition, found that, despite having a great concern for the environment and animal welfare, 72 percent of Generation Z were not ready to accept cultured meat - defined in the survey as a lab-grown meat alternative produced by in-vitro cell cultures of animal cells, instead of from slaughtered animals.

However, despite their lack of enthusiasm for the new meat alternative, 41 percent believed it could be a viable nutritional source because of the need to transition to more sustainable food options and improve animal welfare.

"Our research has found that Generation Z - those aged between 18 and 25 - are concerned about the environment and animal welfare, yet most are not ready to accept cultured meat and view it with disgust," said the study's lead researcher, Dr Diana Bogueva from the University of Sydney's School of Chemical and Biomolecular Engineering.

59 percent of participants were concerned about the environmental impact of traditional livestock farming specifically, however many were not clear on what those impacts were nor did they understand the associated resource depletion.

"In-vitro meat and other alternatives are important as they can help to reduce greenhouse emissions and lead to better animal welfare conditions. However, if cultured meat is to replace livestock-based proteins, it will have to emotionally and intellectually appeal to the Gen Z consumers. It may be through its physical appearance, but what seems to be more important is transparency around its environmental and other benefits," said Dr Bogueva.

Gen Z's concerns about cultured meat

The participants had several concerns relating to cultured meat, including an anticipated taste or disgust, health and safety, and whether it is a more sustainable option.

Societal concerns were also prevalent throughout the study, with a large number of respondents worried that eating cultured meat would be in conflict with perceptions of gender and national identity.

"Gen Z value Australia's reputation as a supplier of quality livestock and meat, and many view traditional meat eating as being closely tied to concepts of masculinity and Australian cultural identity," said Dr Bogueva.

Others were concerned about animal welfare, whereas some viewed cultured meat as a conspiracy orchestrated by the rich and powerful and were determined not to be convinced to consume it. Several participants were also unsure whether cultured meat was an environmentally sustainable option.

"Generation Z are also unsure whether cultured meat is actually more environmentally sustainable, described by several respondents as potentially "resource consuming" and not being "environmentally friendly"," said Dr Bogueva.

"The respondents were effectively divided into two groups: the "against" described cultured meat as "another thing our generation has to worry about" and questioned the motivations of those developing it, while supporters described it as "money invested for a good cause" and "a smart move" by people who are "advanced thinkers."

"This Generation has vast information at its fingertips but is still concerned that they will be left with the legacy of exploitative capitalism that benefits only a few at the expense of many. They have witnessed such behaviour resulting in climate change and are now afraid that a similar scenario may develop in relation to food, particularly as investors are pursuing broader adoption of cultured meat," Dr Bogueva said.

Gen Z's five main attitudes towards cultured meat

17 percent of respondents rejected all alternatives, including cultured meat, seeing it as chemically produced and heavily processed.

11 percent rejected all alternatives in favour of increased consumption of fruit and vegetables, saying they will stick with a vegetarian diet.

35 percent rejected cultured meat and edible insects but accepted plant-based alternatives because they "sounded more natural" and are "normal".

28 percent believed cultured meat was acceptable or possibly acceptable if the technology could be mastered.

A fifth group (9 percent) accepted edible insects but rejected cultured meat as it was too artificial and not natural like insects

How the research was conducted

The researchers collected Generation Z's opinions of cultured meat via an online survey. 227 randomly selected, Australian-based respondents were asked questions about their demographics, dietary preferences (such as how often they liked to eat meat), how they felt about cultured meat and whether they thought it was necessary to accept and consume, as well as their preference for different meat alternatives (such as insects, plant based and cultured meat).

Credit: 
University of Sydney

Rubbing skin activates itch-relief neural pathway

image: Schematic diagram of mechanisms underlying itch relief by stroking skin. Rubbing or stroking of the skin activates vesicular glutamate transporter 3+-low threshold mechanoreceptors (VGLUT3+-LTMRs; red), followed by excitation of itch inhibitory interneurons (blue) in the superficial dorsal horn. The inhibitory interneurons use dynorphin as a neurotransmitter to inhibit pruritogen-responsive neurons (green).

Image: 
Sakai et al., JNeurosci 2020

Stop scratching: rubbing skin activates an anti-itch pathway in the spinal cord, according to research in mice recently published in JNeurosci.

It can be hard to resist the relief of scratching an itch, even though scratching damages skin, especially in sensitive areas like the eyes. But stroking can relieve an itch, too. Sakai et al. investigated the neural pathway behind this less-damaging form of itch relief.

The research team triggered the urge to scratch in mice by administering an itch-inducing chemical underneath their skin. The team then recorded the electrical response from dorsal horn neurons in the spinal cord while they stroked the animals' paws. The neurons fired more often as the mice were stroked and less often after the stroking ended. These neurons respond to both touch and itch, so the increase corresponds to the added touch, not increased itchiness, while the decrease corresponds to itch relief. The same decrease could be seen when the team directly stimulated touch-sensing neurons under the skin. However, inhibiting both sensory neurons and a subtype of anti-itch interneurons in the spinal cord failed to decrease the response from dorsal horn neurons, while activating sensory neurons stopped the mice from scratching. The results show that stroking sets off a cascade, activating sensory neurons under the skin that then activate anti-itch interneurons in the spinal cord, resulting in reduced dorsal horn neural activity and itch relief.

Credit: 
Society for Neuroscience

How do stone forests get their spikes? New research offers pointed answer

video: This video shows an experiment in which a dissolving block of candy develops into an array of sharp spikes. The block starts out with internal pores and is entirely immersed under water, where it dissolves and becomes a "candy forest" before collapsing.

Image: 
NYU's Applied Mathematics Lab

Stone forests--pointed rock formations resembling trees that populate regions of China, Madagascar, and many other locations worldwide--are as majestic as they are mysterious, created by uncertain forces that give them their shape.

A team of scientists has now shed new light on how these natural structures are created. Its research, reported in the latest issue of the journal Proceedings of the National Academy of Sciences (PNAS), also offers promise for the manufacturing of sharp-tipped structures, such as the micro-needles and probes needed for scientific research and medical procedures.

"This work reveals a mechanism that explains how these sharply pointed rock spires, a source of wonder for centuries, come to be," says Leif Ristroph, an associate professor at New York University's Courant Institute of Mathematical Sciences and one of the paper's co-authors. "Through a series of simulations and experiments, we show how flowing water carves ultra-sharp spikes in landforms."

The researchers, who included Michael Shelley, a professor at the Courant Institute, note that the study also illuminates a mechanism that explains the prevalence of sharply pointed rock spires in karst--a topography formed by the dissolution of rocks, such as limestone.

In their study, the scientists simulated the formation of these pinnacles over time through a mathematical model and computer simulations that took into account how dissolving produces flows and how these flows also affect dissolving and thus reshaping of a formation.

To confirm the validity of their simulations, the researchers conducted a series of experiments in NYU's Applied Mathematics Lab. Here, the scientists replicated the formation of these natural structures by creating sugar-based pinnacles, mimicking soluble rocks that compose karst and similar topographies, and submerging them in tanks of water. Interestingly, no flows had to be imposed, since the dissolving process itself created the flow patterns needed to carve spikes.

The experimental results reflected those of the simulations, thereby supporting the accuracy of the researchers' model (see "Video2ExperimentSimulation" in the below drive). The authors speculate that these same events happen--albeit far more slowly--when minerals are submerged under water, which later recedes to reveal stone pinnacles and stone forests.

Credit: 
New York University