Tech

The embryo of an animal first looks like a hollow sphere. Invaginations then appear at different stages of development, which will give rise to the body's structures (the brain, digestive tract, etc.). According to a hypothesis that dates back more than a century, buckling could be the dominant mechanism that triggers invagination - buckling being a term that describes the lateral deformation of a material under compression. Although this explanation has long won the support of biologists, it has never been subjected to formal proof, mainly because of the difficulty - if not the impossibility - of measuring the tiny forces involved. This gap has finally been filled thanks to a study carried out by a multidisciplinary team of scientists from the University of Geneva (UNIGE). This tour de force, published in the journal Developmental Cell, owes its success to a long collaboration between specialists in biological experimentation, analytical theoretical physics and computer simulation.

"The basic question underpinning our work is to find out how to shape cellular tissue," begins Aurélien Roux, a professor in the Department of Biochemistry in UNIGE's Faculty of Science. Observing embryo development has made it possible to describe several mechanisms that are at work. One of these is apical constriction: a local curvature of the surface of the embryo under the effect of a coordinated deformation of the cells themselves (their "apex" tightens and their "base" relaxes). But, as Professor Roux continues: "This mechanism is by no means powerful enough to explain the appearance of major invaginations during the development of the blastocyst (one of the early stages of the embryo)."

A century ago, biologists suggested that buckling is the physical mechanism that generates these deep folds. The same phenomenon is observed when you flatten a sheet of paper and bring the two opposite edges together: the middle of the sheet rises. In the case of embryos, the lateral force comes from cells which, when they proliferate, exert increasing pressure on the surface. Moreover, this surface is confined in a vitelline envelope, which - although it is elastic - prevents any spatial expansion.

Since the description of the phenomenon is quite eloquent and the analogies in nature are legion, the explanation easily won consensus in the biologist community. It has long been unthinkable to measure the forces present on the surface of embryos in order to verify that it really is a question of buckling (which obeys the well-known laws of material physics) and not another mechanism.

Analytical, IT and biological approaches

Nevertheless, the Geneva scientists - keen to provide quantitative proof of the phenomenon - conducted a long-term study. Anastasiya Trushko, a researcher the Department of Biochemistry, and Professor Roux managed to manufacture small envelopes with all the physical properties of the natural vitelline. They also succeeded in growing a monolayer formed of a hundred cells on the inner surface. These small models, less than half a millimetre in diameter, were perfectly controlled under laboratory conditions, and were used to recreate the phenomenon of invagination in vitro and to study it under microscope. The forces involved were determined in particular thanks to small variations in the thickness of the envelope of the artificial embryos.

Meanwhile Carles Blanch-Mercader and Karsten Kruse, respectively a researcher and professor in UNIGE's Departments of Biochemistry and Theoretical Physics, used the measurements to show that the relationship between the strength and shape of the artificial embryos was as expected for buckling. With the help of material physics equations, they were able to extract the macroscopic mechanical parameters from the cellular tissues, such as their stiffness.

Finally, in order to link these macroscopic characteristics to biological processes at cellular level, Aziza Merzouki and Bastien Chopard - respectively a researcher and professor in the Computer Science Department at UNIGE - simulated the development of the embryo by computer, viewing it as a set of independent cells. "The IT approach gives the unique possibility of observing certain aspects of the phenomenon that are normally inaccessible," explains Bastien. "We can then follow in detail the temporal evolution of the buckling and, above all, understand how the biological processes (proliferation, contractility) at cell level modify the mechanical parameters of the tissue."

Repeated round trips

There were endless round trips between the three researchers and their teams to determine the correct values for the numerous parameters that come into play and so that the three approaches arrived at the same result, i.e. as close as possible to reality. It took six years of painstaking work to get there.

"By quantifying buckling as precisely as possible, we were able to demonstrate that it is a potential mechanism for explaining the formation of invagination in embryos," concludes Professor Roux, before adding: "It is likely that other mechanisms, such as apical constriction, initiate the folding and that the buckling accentuates it before finally obtaining the expected result."

Many diseases are caused by defects in signaling pathways of body cells. In the future, bioactive nanocapsules could become a valuable tool for medicine to control these pathways. Researchers from the University of Basel have taken an important step in this direction: They succeed in having several different nanocapsules work in tandem to amplify a natural signaling cascade and influence cell behavior.

Cells constantly communicate with each other and have ways to pick up signals and process them - similar to humans who need ears to hear sounds and knowledge of language to process their meaning. Controlling the cell's own signaling pathways is of great interest for medicine in order to treat various diseases.

A research team of the Department of Chemistry at the University of Basel and the NCCR Molecular Systems Engineering develops bioactive materials that could be suitable for this purpose. To achieve this, the researchers led by Professor Cornelia Palivan combine nanomaterials with natural molecules and cells.

In the journal ACS Nano, they now report how enzyme loaded nano-capsules can enter cells and be integrated into their native signaling processes. By functionally coupling several nano-capsules, they are able to amplify a natural signaling pathway.

Protecting the cargo

In order to protect the enzymes from degradation in a cellular environment the research team loaded them into polymeric small capsules. Molecules can enter the compartment through biological pores specifically inserted in its synthetic wall and react with the enzymes inside.

The researchers conducted experiments with nano-capsules harboring different enzymes that worked in tandem: the product of the first enzymatic reaction entered a second capsule and started the second reaction inside. These nano-capsuled could stay operative for days and actively participated in natural reactions in mammalian cells.

Tiny loudspeakers and ears

One of the many signals that cells receive and process is nitric oxide (NO). It is a well-studied cellular mechanism since defects in the NO signaling pathway are involved in the emergence of cardiovascular diseases, but also in muscular and retinal dystrophies. The pathway encompasses the production of NO by an enzyme family called nitric oxide synthases (NOS). The NO can then diffuse to other cells where it is sensed by another enzyme named soluble guanylate cyclase (sGC). The activation of sGC starts a cascade reaction, regulating a plethora of different processes such as smooth muscle relaxation and the processing of light by sensory cells, among others.

The researchers lead by Palivan produced capsules harboring NOS and sGC, which are naturally present in cells, but at much lower concentrations: the NOS-capsules, producing NO, act similarly to loudspeakers, "shouting" their signal loud and clear; the sGC-capsules, act as "ears", sensing and processing the signal to amplify the response.

Using the intracellular concentration of calcium, which depends on the action of sGC, as an indicator, the scientists showed that the combination of both NOS and sGC loaded capsules makes the cells much more reactive, with an 8-fold increase in the intracellular calcium level.

A new strategy for enzyme replacement therapy

"It's a new strategy to stimulate such changes in cellular physiology by combining nanoscience with biomolecules", comments Dr. Andrea Belluati, the first author of the study. "We just had to incubate our enzyme-loaded capsules with the cells, and they were ready to act at a moment's notice".

"This proof of concept is an important step in the field of enzyme replacement therapy for diseases where biochemical pathways malfunction, such as cardiovascular diseases or several dystrophies", adds Cornelia Palivan.

Researchers have used biosolids to produce hydrogen from wastewater, in new technology that supports the comprehensive recycling of one of humanity's unlimited resources - sewage.

The innovation focuses on the advanced upcycling of biosolids and biogas, by-products of the wastewater treatment process.

Developed by researchers at RMIT University in Melbourne, Australia, the patented technology uses a special material derived from biosolids to spark chemical reactions for producing hydrogen from biogas.

The approach means all the materials needed for hydrogen production could be sourced on-site at a wastewater treatment plant, without the need for expensive catalysts.

The method also traps the carbon found in biosolids and biogas, which could in future enable a near zero-emission wastewater sector.

Lead researcher Associate Professor Kalpit Shah said existing commercial methods for producing hydrogen were emission and capital-intensive, and relied heavily on natural gas.

"Our alternative technology offers a sustainable, cost-effective, renewable and efficient approach to hydrogen production," said Shah, Deputy Director (Academic) of the ARC Training Centre for Transformation of Australia's Biosolids Resource at RMIT.

"To enable the transition to a circular economy, we need technology that enables us to squeeze the full value from resources that would ordinarily go to waste.

"Our new technology for making hydrogen relies on waste materials that are essentially in unlimited supply.

"By harnessing the power of biosolids to produce a fully clean fuel from biogas - while simultaneously preventing greenhouse gas emissions - we can deliver a true environmental and economic win."

Biosolids are commonly used as fertiliser and soil amendment in agriculture, but around 30% of the world's biosolids resource is stockpiled or sent to landfill, creating an environmental challenge.

Dr Aravind Surapaneni, Senior Research and Planning Scientist at South East Water and Deputy Director (Industry) of the ARC Training Centre for Transformation of Australia's Biosolids Resource, said research into new and valuable uses for biosolids was vital.

"The wastewater sector is constantly looking to develop new ways to transform biosolids into high-value products, in environmentally sustainable and responsible ways," Surapaneni said.

How the tech works

In the new method, published in the International Journal of Hydrogen Energy, biosolids are first converted to biochar - a carbon-rich form of charcoal used to improve soil health.

The biosolids-derived biochar contains some heavy metals, which makes it an ideal catalyst for producing hydrogen out of biogas.

As part of the experimental bench-scale study, researchers tested the process with a methane-rich gas that resembles biogas.

They showed the biochar made from biosolids is highly effective for decomposing the gas into its component elements - hydrogen and carbon.

The decomposition process can also be conducted in a specially designed and hyper-efficient reactor developed and patented by RMIT, which can produce both hydrogen and a high-value biochar that is coated with carbon nanomaterials.

By converting the carbon found in biogas and biosolids into advanced carbon nanomaterials, their method can also capture and sequester the greenhouse gas to prevent its release into the atmosphere.

The carbon nanomaterial-coated biochar produced through the novel technique has a range of potential applications including environmental remediation, boosting agricultural soils and energy storage.

Patented reactor technology

Shah said the unique reactor developed by the RMIT School of Engineering team was at the heart of this innovative recycling approach.

"We've radically optimised heat and mass transfer in our reactor, while shrinking the technology to make it highly mobile," he said.

"There are no reactors available that can achieve such phenomenal heat and mass integration, in such a small and cost-effective package.

"And while it's already energy efficient, with further integration, this reactor could turn biosolids and biogas conversion into a process that actually produces energy instead of consuming it."

As well as being used in wastewater treatment, the novel reactor has potential applications in the biomass, plastics and coating industries.

The research was supported by South East Water, which will be trialling the biosolids and biogas conversion technology in a pilot plant currently under fabrication.

Dr David Bergmann, Research and Development Manager at South East Water, said the technology had potential for adoption by the industry.

"Supporting these kinds of innovative emerging technologies is an important part of our commitment towards reduced emissions and a circular economy approach involving wastewater," Bergmann said.

The Lower Saxony Ministry of Food, Agriculture and Consumer Protection has written a report on PFAS concentrations in sheep and beef liver based on samples from the 2019 National Residue Control Plan. The BfR has compared these data with PFAS concentrations in sheep and beef liver samples sourced from the food control programmes of various German federal states, which were taken in the period 2007 to 2020. The BfR concludes that the concentrations of PFAS in sheep and beef liver detected in Lower Saxony do not differ signifi-cantly from the concentrations known from the investigations undertaken by the other federal states. In order to assess the health risks posed by the PFAS concentrations in sheep and beef liver, the BfR used the more comprehensive data from the federal states.

Overall, the BfR concludes that sheep or beef liver with the identified concentrations can contribute considerably to the total intake of PFAS in individuals who consume these foods. PFAS are also ingested through many other kinds of foods. At least in the case of high intakes of sheep or bovine liver, this source of exposure can lead to a comparatively high exhaustion (up to the limit) of the tolerable weekly intake (TWI) for a single food, especially for perfluorooctane sulfonic acid (PFOS). The exhaustion of the TWI for perfluorooctanoic acid (PFOA, EFSA 2018) by consumption of sheep or bovine liver is considerably lower compared to the exhaustion of the TWI for PFOS.

Electricity and magnetism are closely related: Power lines generate a magnetic field, rotating magnets in a generator produce electricity. However, the phenomenon is much more complicated: electrical and magnetic properties of certain materials are also coupled with each other. Electrical properties of some crystals can be influenced by magnetic fields - and vice versa. In this case one speaks of a "magnetoelectric effect". It plays an important technological role, for example in certain types of sensors or in the search for new concepts of data storage.

A special material was investigated for which, at first glance, no magnetoelectric effect would be expected at all. But careful experiments have now shown that the effect can be observed in this material, it only works completely differently than usual. It can be controlled in a highly sensitive way: Even small changes in the direction of the magnetic field can switch the electrical properties of the material to a completely different state.

Symmetry controls the coupling

"Whether the electrical and magnetic properties of a crystal are coupled or not depends on the crystal's internal symmetry," says Prof. Andrei Pimenov from the Institute of Solid State Physics at TU Wien. "If the crystal has a high degree of symmetry, for example, if one side of the crystal is exactly the mirror image of the other side, then for theoretical reasons there can be no magnetoelectric effect".

This applies to the crystal, which has now been examined in detail - a so-called langasite made of lanthanum, gallium, silicon and oxygen, doped with holmium atoms. "The crystal structure is so symmetrical that it should actually not allow any magnetoelectric effect. And in the case of weak magnetic fields there is indeed no coupling whatsoever with the electrical properties of the crystal," says Andrei Pimenov. "But if we increase the strength of the magnetic field, something remarkable happens: The holmium atoms change their quantum state and gain a magnetic moment. This breaks the internal symmetry of the crystal".

From a purely geometrical point of view, the crystal is still symmetrical, but the magnetism of the atoms has to be taken into account as well, and this is what breaks the symmetry. Therefore the electrical polarization of the crystal can be changed with a magnetic field. "Polarization is when the positive and negative charges in the crystal are displaced a little bit, with respect to each other", explains Pimenov. "This would be easy to achieve with an electric field - but due to the magnetoelectric effect, this is also possible using a magnetic field".

It's not the strength, it's the direction

The stronger the magnetic field, the stronger its effect on electrical polarization. "The relationship between polarization and magnetic field strength is approximately linear, which is nothing unusual," says Andrei Pimenov. "What is remarkable, however, is that the relationship between polarization and the direction of the magnetic field is strongly non-linear. If you change the direction of the magnetic field a little bit, the polarization can completely tip over. This is a new form of the magnetoelectric effect, which was not known before." So a small rotation may decide whether the magnetic field can change the electrical polarization of the crystal or not.

Possibility for new storage technologies

"The magnetoelectric effect will play an increasingly important role for various technological applications," says Andrei Pimenov. "In a next step, we will try to change magnetic properties with an electric field instead of changing electrical properties with a magnetic field. In principle, this should be possible in exactly the same way".

If this succeeds, it would be a promising new way to store data in solids. "In magnetic memories such as computer hard disks, magnetic fields are needed today," Pimenov explains. "They are generated with magnetic coils, which requires a relatively large amount of energy and time. If there were a direct way to switch the magnetic properties of a solid-state memory with an electric field, this would be a breakthrough".

Doctors have developed a new data mining method to detect many young people with emerging psychosis. The new methods, based on advanced data mining to pick up early risk sign from schools, hospitals, and general doctors, will be presented at the ECNP virtual congress, and is in press with a peer-reviewed journal (* see notes, below).

Psychosis is a condition which causes you to lose touch with reality, causing you to suffer from hallucinations or delusions. There are a variety of possible causes, including migration and social stress, trauma, substance abuse, etc. It represents a significant care burden, affecting about 20 million people and costing Europe around €94 billion European every year (2011 estimate).

Clinical experience has shown that the best way to manage it is to stop it developing. Over the last 25 years doctors have developed ways of detecting young people at risk of developing psychosis and predicting which young people might go on to develop the disorder, and so have been able to take steps to lower risk. However the way clinicians were detecting young people was not systematic and may have missed many at-risk people. Now doctors in the UK have developed new data mining methods which can potentially detect most people who are at risk of developing psychosis. This, in turn would allow to offer them preventive psychological interventions that can halve their risk of developing full-blown psychosis.

Research leader Professor Paolo Fusar-Poli, of the institute of Psychiatry at King's College, London, said "Prevention is the most promising way of improving mental health of young people. This generation's mental health is particularly under stress, especially facing the ongoing COVID-19 worry, and we need to intervene urgently. The future for those at risk of psychosis is to intervene before the disorders strike".

"We have developed a data mining method (using Natural Language Processing), to search medical records for those at risk of progressing to psychosis. Many medical records are fairly unstructured, with information of mental health being hidden in sections which do not allow systematic research. Our data-mining system does a more complete search of the records people who have been referred to hospital (secondary care), looking for keywords such as weight loss, insomnia, cocaine, guilt, etc. We can look for 14 different terms which we then evaluate for the risk of psychosis. At that point patients might be invited for a one-to-one interview. We have found that prevention can halve the risk of psychosis developing".

The systems have evaluated 92,151 patients over a long follow up period. They were able to confirm that their method worked well to detect young people at risk, although Professor Fusar-Poli cautioned that "these results need further replication in other countries before they can enter clinical routine but they look very promising. Replication will be facilitated by international research consortia such as the ECNP-funded Prevention of Mental Disorders and Mental Health Promotion Network" (see https://www.ecnp.eu/research-innovation/ECNP-networks/List-ECNP-Networks/Prevention-mental-disorders-and-mental-health-promotion).

Prof. Fusar-Poli suggested that detection of these young people is the first step towards prevention. Preventive interventions in these people can translate in several benefits:

"This translates into real benefits. Although the initial cost for establishing specialised services detecting young people at risk of psychosis is greater, intervening before the onset of psychosis is associated with fewer treatments, fewer days in hospital, in addition to the tangible and social health benefits, meaning that the NHS saved around £1000 per patient diagnosed. Our detection systems can extend these benefits to many other young people who might be at risk of psychosis"

Professor Fusar-Poli will present the work while chairing a session on the prevention of mental disorders (see below) at the ECNP congress.

He continued "We have been working with the ECNP special group on Prevention of Mental Disorders and Mental Health Promotion, and with the EU-Funded European Brain Research Area (EBRA, see https://www.ebra.eu/psmd/) to set up a Europe-wide system of advance warning for young people at risk of psychosis. It is essential that we bring the best expertise to bear on this problem, and we can all learn from the experience of others"

Commenting, Professor Andreas Meyer-Lindenberg (Mannheim), member of the ECNP executive board said: "This work is an excellent example of the transformative role of artificial intelligence and big data processing in psychiatry. While much attention in this field has been focused on biological data and biomarkers, this result shows the gains that can be made if the wealth of written information that clinicians produce in their daily work is mined using innovative approaches."

Professor Meyer-Lindenberg was not involved in this work, this is an independent comment.

Note: All the early-warning systems meet accepted requirement for data protection

*This press release includes material from the following article, in press with the peer-reviewed journal Schizophrenia Bulletin (with permission): USING NATURAL LANGUAGE PROCESSING ON ELECTRONIC HEALTH RECORDS TO ENHANCE DETECTION AND PREDICTION OF PSYCHOSIS RISK, Jessica Irving, MSc; Rashmi Patel, MD, PhD; Dominic Oliver, MSc; Craig Colling, MSc; Megan Pritchard, MSc; Matthew Broadbent, MA; Helen Baldwin, MSc; Daniel Stahl, PhD; Robert Stewart, MD, PHD; Paolo Fusar-Poli MD, PhD

A recent study suggested that we have probably approached the limit of predictability for tropical cyclone (TC) track prediction. If that's true, there's little we can do to improve TC forecasts as an incorrect position affects the utility of all other guidance, including wind, precipitation, and storm surge guidance. This would be bad news for disaster prevention and mitigation.

"The reason some scientists ask whether the limit of predictability is near or has already been reached is that there's a diminishing trend in the reduction of positional error in National Hurricane Center (NHC) tropical cyclone forecasts. From this, there seems to be little room for improvement," explained Dr. Feifan Zhou, a scientist with the Institute of Atmospheric Physics at the Chinese Academy of Sciences, referring to a question asked by Landsea and Cangialosi (LC18) in a paper published in 2018 .

Not willing to give up potential opportunities for improved TC forecasts, Zhou used the same dataset as in LC18 (except excluding tropical depressions) and an approach called Statistical Analysis and Forecast Error estimation, proposed by Zoltan Toth and his collaborators at the National Oceanic and Atmospheric Administration of USA. In a study co-authored by Zhou and Toth and recently published in the Bulletin of the American Meteorological Society (BAMS), they explore what the past trend is in the reduction of TC forecast track error, and how such errors may be further reduced in future decades.

In accordance with theoretical expectations, they found that the true forecast track error (i.e., forecast minus real TC position) increases exponentially with lead time. The 24-hour forecast error growth rate appears to be rather stable over the years, with only relatively small year-to-year fluctuations, possibly influenced by seasonal circulations such as ENSO or MJO. As Zhou explains, "the exponential growth of true forecast track error implies that the dynamics of TC motions could be viewed as linear, and that there is no model induced error in TC position forecasts. In other words, the transposition of TCs is dominated by the large-scale environmental circulation, which is well simulated in modern numerical weather prediction (NWP) models."

Interestingly, Zhou and Toth also found that the true analysis error also changes exponentially over long periods of time. "The near-exponential reduction of analysis error that we found over the years means that initial errors in the NHC official forecasts are reduced by approximately the same fraction each year. This suggests that the efficiency of international NWP research and development affecting the official forecasts, by and large, is constant over the years", added Zhou.

Based on these features, the team set up an error model using just four parameters. Assuming that the level of investments, and the pace of improvements to the observing, modeling, and data assimilation systems continue unabated, their 4-parameter error model indicates that the time limit of predictability at the 181 nm error level that was reached at day 5 in 2017, may be extended beyond 6 / 8 days in 10 / 30 years' time.

"That is to say in 10 years' time, the forecast skill at day 6 would be the same as it was at day 5 in 2017. Considering also some results from Zhang et al. (2019 , we can add that this one day per decade extrapolated error reduction, given the assumption above, may hold for at least 25 years into the future. That's a long time, with lots of potential for TC track error reductions along the way", explained Dr. Toth.

The more optimistic assessment of TC track predictability by Zhou and Toth (2020) is apparently due to their recognition that true forecast error behaves exponentially (i.e., grows over forecast days, and is reduced by NWP development over the years). This is in contrast to LC18, who tentatively assume that perceived errors (i.e., forecast minus analysis position) may be reduced linearly.

QUT researchers are working to design faster, cheaper, and better ways to store food.

Published in journal PLOS ONE, researchers used QUT's supercomputing facilities to examine the micromechanical behaviour of plant tissues and how biological cells behave while dehydrated or dried.

Lead investigator Dr Charith Rathnayaka is a computational scientist from QUT's Faculty of Science and Engineering investigating the physics, mathematics, and biology of agricultural cell structures to improve food production.

"By developing the computational model, it is possible to estimate how the cells are being damaged when they are being processed for preservation, storage or packaging," Dr Rathnayaka said.

"This innovation has the potential to influence the future of food drying processes globally in terms of reducing cost, optimising food processing, energy conservation and increasing dried food shelf life."

Key findings: -

Study looks at how plant cells behave under different types of mechanical forces

Research involved two-step simulation and experimental stages

The computational model developed conclusively demonstrated it can simulate the micromechanical behaviour of dried plant cells

Provide insight on improving design of industrial machinery for food drying processes

Implications to move beyond plant cells to biomedical and human cosmetic applications.

Dr Rathnayaka said the findings of this study could lead to better designs for industrial drying of fruits, vegetables, or any other plant biological material.

As an example, he described the process by using fresh fruit such as apples which were simultaneously dried and imaged and then compared against the predictions from the simulations.

The experimental data revealed microscopic tissues of the apple and the differences between fresh conditions and extremely dried conditions, with imagery featured in journal Soft Matter. (pics)

"One specific reason for using apple as representative plant-food material was due to the abundant availability of experimental findings," he said.

"It showed that by controlling the processing conditions such as temperature, pressure, humidity and processing speed, it is possible to control the damage on apple cells to extract the best nutritional value."

He said the results also showed that at extreme dryness levels, the cells naturally get damaged even without processing.

"Due to the high pressure in the cells at fresh conditions, they are highly vulnerable to higher forces that take place during processing such as cutting, packing, or extruding," he said.

"This provides valuable insights for not only processing apples but many other comparable fruits and vegetables."

Dr Rathnayaka said the study's findings have implications for further research into food processing under drought conditions.

He said there is a need to find innovative ways to investigate harvesting and processing produce under extreme climatic conditions.

"Currently there is a research gap in accurately evaluating and predicting drought and heat resistance of plant-food tissues," he said.

"The COVID-19 pandemic has placed even more of an emphasis on the ever-growing importance of plant-food security and more efficient ways to quantify and predict the performance of agricultural produce during droughts."

One of the largest ever studies of patients with untreatable bipolar disorder has shown that ECT (Electroconvulsive Therapy) was able to reduce suicide risk by 84% in high-risk patients, as well as giving effective treatment to around 72% of sufferers.

Bipolar disorder, where patients exhibit emotional instability and may experience very severe mood swings, is amongst the most common mental health disorders. It affects around 1% of Europeans, meaning that approximately 5 million Europeans suffer. Bipolar disorder can cause mixed states of mania and depression; this mix can lead to an increased risk of suicide, since sufferers may simultaneously experience both the symptoms of depression (such as the sense of guilt and worthlessness) and symptoms of mania (such as increased activity and tendency to act without thinking twice). Most patients can control the condition via prescription drugs, but almost a third of patients are resistant to treatment.

Now the largest-ever study to follow bipolar patients and treatment from a single centre has confirmed that ECT can reduce suicide risk, and allow a majority of patients affected by treatment-resistant bipolar disease to return to a more normal life. This work is presented at the ECNP conference, after part-publication in the peer-reviewed journal The World Journal of Biological Psychiatry*.

Between January 2006 and July 2019, 670 patients were referred to the University of Pisa psychiatry clinic for ECT treatment for bipolar disorder. Dr Giulio Emilio Brancati, of the Department of Clinical and Experimental Medicine at the University of Pisa, said "ECT was invented in Italy, but despite this there are very few clinics in Italy which offer the treatment nowadays. A lot of patients who have failed with other treatments are referred to the Pisa clinic, which is why we were able to gather so much data from a single clinic".

The treatment showed great success in treating bipolar sufferers, with remission rates of over 60% for symptoms characteristic of bipolar "mixed states", such as emotional overreactivity, motor hyperactivity, aggressiveness and persecutory delusions, uncooperativeness, catatonia and associated movement disturbances.

"Most importantly, 77 of our patients were classified as being at severe risk of suicide. After treatment only 2 remained at severe risk, while 65 showed no risk at all. This is an 84% drop in suicidality after ECT treatment. We have not found this level of acute improvement with any other treatment", said Giulio Brancati. He continued:

"This is a real-life study, not a clinical trial. A formal trial would have been difficult and probably unethical in these patients, many of who were severely ill. They were generally referred to us only after multiple treatment failures, so most of these patients were running out of treatment options. When we sampled the patients who came to us we found that around 93% had tried and failed with pharmacological treatment, 88% had failed on 2 different drugs. In fact, on average each patient who came to us had tried 5 different drugs, without success".

The public tends to have a negative view of ECT, largely based on media representation of the very different psychiatric world of the 1950s, but patients and psychiatrists are generally positive about the effects of ECT on otherwise untreatable or difficult to treat mental health conditions. Modern ECT is given under general anaesthetic, and can lead to rapid recovery from Major Depression (the main side effect is a possible transitory loss of recent memory). It's normally given 2 to 3 times per week, with between 6 and 16 treatments needed to show a positive effect. The use of ECT in general has recently dropped by around a third in the USA. This is despite the success of the treatment and the willingness of famous sufferers, such as Carrie Fisher, to come forward and talk about their treatment. Despite ECT being invented in Italy, the use of the technique is extremely restricted, leading to Italy having fewer centres specialising in ECT than most other countries of comparable size.

"ECT is used for major depression, but much less so for the other phases of Bipolar Disorder, especially for so-called mixed states, which have a lower visibility. We find that many patients with treatment resistant bipolar catatonic and mixed states are misdiagnosed as having schizophrenia. These patients need to be given a chance via receiving the right treatment", said Giulio Brancati.

Commenting, Dr Henricus Ruhe, psychiatrist at Radboudumc Netherlands, and Chair of the ECNP Abstract and Poster Committee, said:

"This study again shows that ECT can be a life-saving treatment and should not be withheld to patients suffering from difficult to treat mood disorders such as bipolar disorder. Although we should acknowledge adverse effects like (mostly temporary) memory impairments, these results show how well, and often how fast the response to ECT can be.

This effectiveness generally outweighs the adverse effects in these severely ill patients, who otherwise might suffer for much longer or not have effective treatment at all. Unfortunately, despite the long-term evidence, ECT is still viewed as a controversial treatment by the general public and the media, but also by many patients and relatives. This is also the case in Italy where very few centres can offer ECT nowadays.This prejudice against modern ECT unjustly stigmatizes both patients and psychiatry, and denies treatment to seriously-ill patients".

This is an independent comment, Dr Ruhe was not involved in this work.

Grafting is a horticultural technique that joins plants together by means of tissue regeneration, combining desirable characteristics of both plants. Generally, grafts have been thought to be compatible only between the same or closely related species. However, scientists at Nagoya University and colleagues in Japan recently found that the tobacco plant Nicotiana benthamiana promotes adhesion of tissue and can maintain grafts between a broad range of species.

Their findings, published recently in the journal Science, have also shown that using tobacco as an intermediary, the upper part (scion) of a tomato plant grafted onto the lower part (rootstock) of a Chrysanthemum morifolium (widely known as Florist's daisy) successfully bore fruit.

Grafting has been conducted for thousands of years for the propagation of fruits and vegetables, in which a productive scion is attached onto a rootstock that is resistant to diseases and environmental stresses. However, exactly how grafts are established has been unclear, and grafting is considered difficult between different family species.

A team of scientists from Nagoya University, Teikyo University, RIKEN, Chubu University, and GRA&GREEN Inc. (a start-up venture company from Nagoya University) recently conducted a study on grafting between different family species.

The team focused on Nicotiana in the Solanaceae family, because a previous study had shown that its scion can be grafted onto the rootstock of Arabidopsis thaliana in the mustard family. The team conducted grafting experiments using plants of seven Nicotiana species and their partners from 84 species in 42 families. The results showed that Nicotiana, used as either scion or rootstock, succeeded in maintaining grafts for more than a month with 73 species in 38 families.

Next, the scientists examined the cellular mechanisms that enable Nicotiana to form grafts with plants from a wide range of families. They analyzed transcriptomes at graft junctions between Nicotiana and Arabidopsis and hypothesized that the expression of β-1,4 glucanases secreted into the extracellular region is involved in cell wall digestion. In further experiments, when β-1,4 glucanases were overexpressed in Arabidopsis, the adhesion property of the grafts was enhanced. Thus, they concluded that the expression of β-1,4 glucanases is a key in facilitating tissue adhesion of the grafts.

In addition, they conducted experiments to see whether Nicotiana can act as an intermediary in the grafting of different family species, by using a tomato scion and the rootstock of Florist's daisy, a garden plant resistant to environmental stress. About three months later, the tomato plant successfully produced a small fruit.

"Using Nicotiana as an intermediate, we also achieved other grafts in which the scion, interscion, and rootstock all belonged to different plant families," says Nagoya University bioscientist Michitaka Notaguchi, the corresponding author of this study.

"Our latest results regarding the key molecules involved, not just interfamily grafting itself, could help improve plant grafting techniques so that the variety of root systems available to aid crop production can be increased with minimal destruction of ecosystems."

The ongoing COVID-19 pandemic has shown how important it is to have tools that can rapidly diagnose viral infectious diseases. Aside from the SARS-CoV-2 virus, which has currently taken the spotlight, the zika, dengue, and chikungunya viruses have also become major threats to human health in many parts of the world, particularly in tropical countries. All three viruses are transmitted by mosquitoes and cause diseases that have similar symptoms, making early diagnosis particularly difficult without complex molecular diagnostic equipment.

In a recent effort to make the diagnosis of these mosquito-borne diseases faster and easier, a team of scientists, led by Professor Min-Gon Kim from the Gwangju Institute of Science and Technology in Korea, have developed a compact, fully automatic, and inexpensive tool that can identify the presence of these viruses from a blood serum sample. The device, named LAMDA (stands for lab-on-paper for all-in-one molecular diagnostics) by the scientists, is essentially a mini laboratory on a paper strip--vaguely reminiscent of over-the-counter pregnancy tests.

LAMDA performs all the steps of a standard nucleic acid test (a molecular diagnostic test), namely sampling, extraction, amplification, and detection of the target viral RNA, without external intervention at any intermediate step. To use LAMDA, one has to simply place a drop of blood serum and some drops of distilled water on two pads. The liquids naturally flow through the paper strip horizontally and reach the base of a small vertical stack of layers that extracts all the RNA from the sample and multiplies any existing viral RNA of the three diseases.

The top layer of the vertical stack comprises individual "reaction" patches, each designed to detect one of the three diseases. After the RNA is extracted, it flows up to the top layer, where "LAMP (Loop-mediated isothermal amplification)" reactions cause the fluorescent indicators on a patch to become dim if its target viral RNA is present in the sample.

In this way, LAMDA can correctly diagnose any of the three mosquito-borne diseases in less than an hour. Excited about the results, which are published in Elsevier's Biosensors and Bioelectronics, Prof Kim remarks: "We believe that with minor modifications, such as a portable system to maintain reaction temperature at 65°C and a means to detect the fluorescence change with a smartphone, the proposed all-in-one paper chip can become a portable, low-cost, user-friendly, sensitive, and specific nucleic acid test platform with great potential in point-of-care diagnostics."

LAMDA could be an excellent option for resource-limited clinics and hospitals, which are unfortunately common among countries most affected by mosquito-borne diseases. It could also bolster future research in the field of diagnostics for other infectious diseases. "We certainly hope that our approach and achievements with LAMDA will be helpful to advance research and development of on-site medical diagnostic tools," Prof Kim concludes.

Perhaps, a generation of accurate and high-utility pocket diagnostic tools is on the horizon!

The ongoing COVID-19 pandemic has shown that the world needs technology that can quickly and accurately identify invisible dangers, including harmful substances or airborne environmental pollutants. Colorimetric sensors--devices that intuitively reveal information about their environment through color changes--are an attractive option in this regard. But, for more people to benefit from these sensors, they must be easy to produce at a large scale. This is a major limitation with currently available colorimetric sensors, which require complex structures with intricate fabrication procedures. Other problems with existing devices include slow response times and unsaturated colors.

Now in a new study published in Advanced Science, scientists at Gwangju Institute of Science and Technology, Korea, have attempted to tackle these limitations by developing a new type of colorimetric sensor made up of a thin layer of viruses called M13 bacteriophages. They used this type of virus because it can change its structure--and thus its optical properties--in response to changes in the surrounding environment, such as the presence of harmful compounds. Prof Young Min Song, who led the study, explains, "In our study, we introduced the M13 bacteriophage, which is a nanometer-sized filamentous virus, as a sensing layer owing to its volumetrically expanding properties."

The scientists genetically engineered the M13 bacteriophages by combining them with a "highly lossy ultra-thin resonance promoter layer" (HLRP) as the substrate. Then, they maximized the resonance of the coating layer of the viruses by optimizing the substrate such that the bacteriophage became extremely sensitive toward specific airborne substances. This made it possible for the "viruses" to detect chemicals at very low concentrations--as low as tens of parts per billion. Prof Song explains the technique, "Specifically, through optimization of the virus layer deposition, the virus layer was coated with ultra-thin dimension, which enhanced the detection rate. The HLRP with resonance enhancement was applied to obtain a distinct color even with a nanometer-scale thickness change in the M13 bacteriophage virus layer. Consequently, the color change was maximized by optimized resonance conditions."

The scientists tested the new sensor with environmental variables, like changes in humidity, and with compounds like volatile organic chemicals and endocrine disrupting chemicals. In both cases, changes in these stimuli could be successfully observed through distinct color changes in the sensor, thus showing its practical applicability.

This new design for highly effective and mass-producible colorimetric sensor holds much promise for a variety of real-life applications, such as detecting harmful industrial chemicals or assessing air quality. To top it all, these sensors could become invaluable tools in clinical settings, as Prof Song remarks, "In the future, advances in genetic engineering will enhance the sensitivity of the sensors and extend their applicability to the medical industry, where they could be used as diagnostic kits for detecting specific viruses and pathogens."

With further research, this technology will hopefully work as a powerful means to show the true colors of invisible airborne threats.

CABI scientists have led the first assessment of naturalised, invasive and potentially invasive plant species present in Laikipia County, Kenya, which hosts the highest populations of endangered large mammals in the country.

The research led by Dr Arne Witt suggests that a range of invasive alien plants pose a series risk to the County - home to the second-highest number of endangered wildlife in East Africa including elephant, rhino, Grevy's zebra, reticulated giraffe and wild dogs.

Together with CABI colleagues Winnie Nunda and Tim Beale along with help from Dr Darren Kriticos of the University of Queensland, Australia, Dr Witt argues that without efforts to eradicate, contain, or control invasive plant species in Laikipia County many rare and iconic wildlife species may be lost.

As outlined in the journal Koedoe: African Protected Area Conservation and Science, the researchers strongly advocate the use of biological controls as cost effective, safe and environmentally sustainable ways to manage some of the invasive plants as part of an integrated management plan.

Broadscale roadside surveys were carried out in Laikipia County, to record all naturalised and invasive species. This data was supplemented by CLIMEX eco-climatic niche models of nine species that the scientists consider to pose the biggest threat to conservation initiatives in the East African region.

Widespread species in the County included Opuntia stricta, O. ficus-indica, Austrocylindropuntia subulata and other succulents. Of the 145 alien plant species recorded, 67 and 37 (including four species of uncertain origin) were considered to be already naturalised or invasive, respectively, and a further 41 species had been recorded as being naturalised or invasive outside of Laikipia. Most (141) of these species were introduced as ornamentals only or had uses in addition to being ornamentals, with the majority (77) having their origins in tropical America.

Based on the current eco-climatic conditions, most of Laikipia is unsuitable for Chromolaena odorata, marginally suitable for Mimosa pigra and Lantana camara, and a better climatic match, ranked from least to most favourable, for Tithonia diversifolia, Cryptostegia grandiflora, Parthenium hysterophorus, Prosopis juliflora, O. stricta, and Parkinsonia aculeata.

Dr Witt said, "The County is home to the second-highest abundance of wildlife in East Africa, after the Mara-Serengeti ecosystem, and hosts the highest populations of endangered large mammals in Kenya.

"Alien plant invasions pose significant threats to conservation and livelihoods in Laikipia. As such, it would be prudent to develop and implement management strategies to reduce the threats of all invasive and potentially invasive plant species.

"It is imperative that all naturalised, invasive and potentially invasive plant species be removed from the grounds of all tourist facilities and possibly also villages that fall within areas where the main land-use practice is livestock production and conservation.

"Those plants which have already escaped cultivation should be eradicated, if possible, or their further spread contained. Finally, biological control solutions for widespread and abundant species should be implemented wherever possible, as has been done for O. stricta and initiated for O. engelmannii."

Dr Witt added that there are many benefits to the use of biological controls including the fact that many agents establish self-perpetuating populations, often across the whole range of the target species, and most projects only require a one-off investment.

"There are a number of widespread and abundant invasive plant species in Laikipia that could be targeted for biological control," he said. "The cochineal Dactylopius opuntiae (Cockerell) 'stricta' biotype (Dactylopiidae), recently introduced for the control of O. stricta, is already established in Laikipia. Species such as O. ficus-indica and O. monacantha have also been brought under good control through the introduction of cochineal in the last century."

Permission is currently being sought from the regulatory authorities to introduce another biotype of D. opuntiae for the control of O. engelmannii. Cereus jamacaru has also been brought under good biological control in South Africa, an option should this species become invasive, although populations are currently such that it can still be eradicated in Laikipia.

Additional information

Main image: The reticulated giraffe is among a range of endangered species whose habitat is at risk from invasive plants in Laikipia County, Kenya (Credit: Arne Witt).

Full paper reference

Arne B.R. Witt, Winnie Nunda, Tim Beale, Kriticos, D.J., 'A preliminary assessment of the presence and distribution of invasive and potentially invasive alien plant species in Laikipia County, Kenya, a biodiversity hotspot', 9 Sept 2020, Koedoe: African Protected Area Conservation and Science, DOI: 10.4102/koedoe.v62i1.1605

This paper, including the full lists of species surveyed, is available to view open access here: https://koedoe.co.za/index.php/koedoe/article/view/1605/2566

Dipanjan Pan, professor of chemical, biochemical, and environmental engineering at UMBC, and collaborators published a seminal study in Nature Communications that demonstrates for the first time a method of biosynthesizing plasmonic gold nanoparticles within cancer cells, without the need for conventional bench-top lab methods. It has the potential to notably expand biomedical applications.

Conventional laboratory-based synthesis of gold nanoparticles require ionic precursors and reducing agents subjected to varying reaction conditions such as temperature, pH, and time. This leads to variation in nanoparticle size, morphology and functionalities that are directly correlated to their internalization in cells, their residence time in vivo, and clearance. In order to avoid these uncertainties, this work demonstrates that biosynthesis of gold nanoparticles can be achieved efficiently and directly inside cancer cells without requiring conventional laboratory methods.

The researchers examined how various cancer cells responded to the introduction of chloroauric acid to their cellular microenvironment by forming gold nanoparticles. These nanoparticles generated within the cell can potentially be used for various biomedical applications, including in x-ray imaging and in therapy by destroying abnormal tissue or cells.

In the paper, Pan and his team describe their new method of producing these plasmonic gold nanoparticles within cells in minutes, within a cell's nucleus, using polyethylene glycol as a delivery vector for ionic gold. "We have developed a unique system where gold nanoparticles are reduced by cellular biomolecules and those are able to retain their functionality, including the capacity to guide the remaining cluster to the nucleus," says Pan.

They also worked to further demonstrate the biomedical potential of this approach by inducing in-situ biosynthesis of gold nanoparticles within a mouse tumor, followed by photothermal remediation of the tumor. Pan explains that the mouse study exemplified how "the intracellular formation and nuclear migration of these gold nanoparticles presents a highly promising approach for drug delivery application."

"Gold is the quintessential noble element that has been used in biomedical applications since its first colloidal synthesis more than three centuries ago," Pan notes. "To appreciate its potential for clinical application, however, the most challenging research ahead of us will be to find new methods of producing these particles with uncompromised reproducibility with functionalities that can promote efficient cellular binding, clearance, and biocompatibility and to assess their long-term term effects on human health. This new study is a small but important step toward that overarching goal."

ITHACA, N.Y. - High-grade serious ovarian carcinoma (HGSOC) is the fifth-leading cause of cancer-related deaths in women in the United States, yet little is known about the origins of this disease.

Now, scientists at the College of Veterinary Medicine have collaborated on a study that pinpoints which specific genes drive - or delay - this deadly cancer.

"We've taken the enormous collection of genomic mutation data that's been mined on cancer genetics and tried to make functional sense of it," said John Schimenti, professor of genetics in the Department of Biomedical Sciences and senior author of the study, which published Sept. 1 in Cell Reports.

Schimenti teamed with biomedical sciences colleague Alexander Nikitin, professor of pathology and director of the Cornell Stem Cell Program, and members of their respective labs to gain a better understanding of HGSOC.

Cancer researchers have known for a while that the disease is almost always caused by multiple genetic "hits." One mutation alone does not turn a cell cancerous; generally at least two or three are required, and often different combinations of genes can cause the same cancer.

Adding complexity, Schimenti said, is the fact that once one key genome-destabilizing mutation arises, others will follow. Sequenced tumors yield a plethora of mutations -- some are the originators of the cancer itself, while many others are spinoffs.

"It's a longstanding issue in cancer research," he said. "What are the genetic drivers, and what are the passengers in the process?"

To address these complexities, the researchers wanted to test combinations of possible genetic suspects, and then parse out which of the many associated mutations were sparking the cancer.

To do so, they turned to the Cancer Genome Atlas, an international collaborative database that compiles the genetic information from patient tumor samples and the mutated genes associated with them. They took a list of 20 genes known to mutate in HGSOC and, using CRISPR gene-editing technology, created random combinations of these mutations in cultured cells from the ovary surface, including regular epithelial cells and epithelial stem cells, to see which cell type was more susceptible to the mutations.

The researchers then noted which combination of mutations turned which group of cells cancerous - pinpointing both the genes driving the process and which cell type the cancer originated in.

The study revealed what the team had originally suspected - that ovarian surface stem cells were more apt to become cancerous when hit with mutations. They also unexpectedly discovered genes that had the opposite effect.

"We found there were various genes that would help the process along, but interestingly, there were other genes that, when mutated, actually inhibited the cancer initiation process," Schimenti said.

Knowing which are the cells of origin and which genes are necessary in initiating this highly aggressive form of ovarian cancer can be powerful information, both for ovarian and other types of cancers. "The cancer driver screening methodology we used should be applicable to answering the same kinds of questions for cells and cancers in other organs and tissues," Nikitin said.

Schimenti said the findings could be particularly useful for ovarian cancer patients who have their tumors biopsied and sequenced for genetic data.

"In the past, you would know which genes were mutated but you wouldn't know what role they played," he said. "Now you know which ones are important. And eventually, you could develop drugs to target the mutated genes that you know are causing the problem."