Tech

New discovery by SMART allows early detection of shade avoidance syndrome in plants

image: Raman spectroscopy and the carotenoid Raman peak allows for early detection of Shade Avoidance Syndrome (SAS) in the (a) model plant Arabidopsis thaliana and (b) leafy vegetables Kai Lan and Choy Sum.
Diagrams adapted from Sng et al., 2020. Plant Methods 16: 144.

Image: 
Singapore-MIT Alliance for Research and Technology

Negative effects of shade avoidance syndrome (SAS), where plants reach for more light to overcome shaded conditions, are irreversible and early detection is crucial for sustainable agricultural practices

Study found Raman spectroscopy can detect SAS in plants within a few hours, while conventional methods rely on morphological changes that can take one to three days

New method can be widely applied across various plant species and crops

Singapore, 25 November 2020 - Researchers from the Disruptive & Sustainable Technologies for Agricultural Precision (DiSTAP) Interdisciplinary Research Group (IRG) of Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore and Temasek Life Sciences Laboratory (TLL) have discovered a way to use Raman spectroscopy for early detection of shade avoidance syndrome (SAS) in plants. The discovery can help farmers with timely intervention against SAS, leading to better plant health and crop yield.

SAS is an adaptive response and an irreversible phenomenon, where plants reach for more light to overcome shaded conditions. It is commonly seen in plants experiencing vegetative shade which is detrimental to plant health, as it leads to a number of issues including hindrance of leaf development, early flowering and weakening of the plant's structure and immune system.

Thus, early detection of SAS is key for sustainable agriculture and improved crop yield. However, existing methods for detection of SAS in plants are restricted to observing structural changes, making it difficult to detect SAS early.

In a paper titled "Rapid metabolite response in leaf blade and petiole as a marker for shade avoidance syndrome" published in the prestigious journal Plant Methods, SMART DiSTAP and TLL scientists explain their new way of detecting SAS early on, allowing farmers to intervene in time to prevent the irreversible effects of SAS. The team built a tabletop Raman spectroscopy instrument that allows measurement of carotenoid levels in plants, which can indicate whether a plant has SAS.

"Our experiments with Raman spectroscopy detected a decrease in the carotenoid contents of plants that have SAS," said Dr Gajendra Pratap Singh, co-first author of the paper and Scientific Director and Principal Investigator at DiSTAP. "While plants with longer exposure to shade developed more severe SAS, these morphological changes were only seen after one to three days. However, changes in the carotenoid peak intensities were detected much earlier, from just four hours of shade treatment."

Using Raman spectroscopy, the scientists are able to non-destructively measure carotenoid content in the plant leaves, and have discovered its correlation to the severity of SAS and as a peak biomarker for early diagnosis. This cuts down the time taken to detect SAS from days to a matter of hours. The method can also be used to detect SAS in plants due to high-density planting and can be particularly useful to improve urban farming practices.

"We conducted our experiments on a number of edible plants, including frequently consumed Asian vegetables like Kai Lan and Choy Sum," said Mr Benny Jian Rong Sng, the paper's co-first author and PhD student from Dr In-Cheol Jang's group at TLL and Department of Biological Sciences, National University of Singapore. "Our results showed that Raman spectroscopy can be used to detect SAS, induced by shade as well as high-density planting. Regardless of the food crop, this technology can be applied to improve agriculture and to meet the nutritional demands of today's growing populations."

Dr In-Cheol Jang, Principal Investigator at TLL and DiSTAP, who led the project said the novel discovery can go a long way in assisting farmers to improve urban farming practices. "We look forward to helping urban farmers achieve higher crop yields by detecting SAS within shorter time periods. By adopting scalable, precision agri-technologies like Raman spectroscopy-enabled sensors, we can better position cities like Singapore to grow more produce with less resources, while achieving desirable nutritional profiles for global food security."

Credit: 
Singapore-MIT Alliance for Research and Technology (SMART)

Grabbing viruses out of thin air

image: A proposed future society.

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Tohoku University

The future could hold portable and wearable sensors for detecting viruses and bacteria in the surrounding environment. But we're not there yet. Scientists at Tohoku University have been studying materials that can change mechanical into electrical or magnetic energy, and vice versa, for decades. Together with colleagues, they published a review in the journal Advanced Materials about the most recent endeavours into using these materials to fabricate functional biosensors.

"Research on improving the performance of virus sensors has not progressed much in recent years," says Tohoku University materials engineer Fumio Narita. "Our review aims to help young researchers and graduate students understand the latest progress to guide their future work for improving virus sensor sensitivity."

Piezoelectric materials convert mechanical into electrical energy. Antibodies that interact with a specific virus can be placed on an electrode incorporated onto a piezoelectric material. When the target virus interacts with the antibodies, it causes an increase in mass that decreases the frequency of the electric current moving through the material, signalling its presence. This type of sensor is being investigated for detecting several viruses, including the cervical-cancer-causing human papilloma virus, HIV, influenza A, Ebola and hepatitis B.

Magnetostrictive materials convert mechanical into magnetic energy and vice versa. These have been investigated for sensing bacterial infections, such as typhoid and swine fever, and for detecting anthrax spores. Probing antibodies are fixed onto a biosensor chip placed on the magnetostrictive material and then a magnetic field is applied. If the targeted antigen interacts with the antibodies, it adds mass to the material, leading to a magnetic flux change that can be detected using a sensing 'pick-up coil'.

Narita says that developments in artificial intelligence and simulation studies can help find even more sensitive piezoelectric and magnetostrictive materials for detecting viruses and other pathogens. Future materials could be coilless, wireless, and soft, making it possible to incorporate them into fabrics and buildings.

Scientists are even investigating how to use these and similar materials to detect SARS-CoV-2, the virus that causes COVID-19, in the air. This sort of sensor could be incorporated into underground transportation ventilation systems, for example, in order to monitor virus spread in real time. Wearable sensors could also direct people away from a virus-containing environment.

"Scientists still need to develop more effective and reliable sensors for virus detection, with higher sensitivity and accuracy, smaller size and weight, and better affordability, before they can be used in home applications or smart clothing," says Narita. "This sort of virus sensor will become a reality with further developments in materials science and technological progress in artificial intelligence, machine learning, and data analytics."

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Tohoku University

Signaling switch in pancreatic β-cells determines anti-diabetic drug effectiveness

image: cAMP (cyclic AMP):
An intracellular signaling molecule that regulates a variety of cellular functions such as insulin secretion.
PKC (Protein Kinase C):
An enzyme that adds phosphoric acid to proteins (phosphorylation), thereby regulating various intracellular signals such as insulin secretion.

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Adapted version of the Graphical Abstract in the JCI paper (DOI: 10.1172/JCI140046)

An international research group has clarified the action mechanism of incretin-based drugs (*1) in the treatment of diabetes. The research group headed by Professor SEINO Susumu included Researcher Okechi Oduori et al. (Division of Molecular and Metabolic Medicine, Kobe University Graduate School of Medicine), Professor SHIMOMURA Kenju (Fukushima Medical University), Professor Patrik Rorsman (University of Oxford, UK/University of Gothenburg, Sweden), and their teams.

Incretin-based drugs are used worldwide in the treatment of diabetes and in Japan they are currently prescribed to 70% of diabetic patients. However, the mechanism by which incretin-based drugs improve blood glucose levels has been poorly understood.

The findings of the study were published online in the American Scientific Journal Journal of Clinical Investigation on November 16, 2020. A commentary on this paper by Professor Colin G. Nichols and his colleagues at Washington University, St Louis, has also been published.

Main Point

This study revealed for the first time that Gs, a major G-protein signal in normal pancreatic β-cells (*2), is switched to another G-protein signal Gq in the diabetic β-cells to promote insulin secretion, and that incretin-based drugs act on this Gq to promote insulin secretion, thereby improving blood glucose levels.

Research Findings

Incretins are the gut hormones that are secreted by enteroendocrine cells after meal ingestion. The most important function of incretins is to promote insulin secretion from pancreatic β cells. GLP-1 and GIP are known as incretins.

While both GLP-1 and GIP are required to maintain normal blood glucose levels in healthy subjects, incretins in patients with type-2 diabetes (T2D) don't function properly. To improve incretin action, incretin-based drugs are used for the treatment of T2D. However, the reason why these drugs are effective has remained unknown.

This research investigated the mechanism of insulin secretion by G-protein signaling in normal β cells and diabetic β cells. Until now, it has been well accepted that the G protein Gs functions as a major signal that promotes insulin secretion in normal β cells. The research group revealed that in diabetes, there is a switch from Gs to Gq signaling in the pancreatic β cells due to continuous β cell excitation (*4). Furthermore, the group discovered that incretin-based drugs act on Gq to amplify insulin secretion, thus improving blood glucose levels.

The Significance of this Research

The results of this research are important not only for illuminating the mechanism behind diabetes, but for diabetes therapies. They might also provide a basis for the development of new treatments.

Credit: 
Kobe University

Sheep show the contamination by microplastics in the agricultural soils of Murcia

image: Sheeps during the study

Image: 
Nicolas Beriot (Diverfarming project)

In recent times, the increase in plastic residues has been reasserted as being a major environmental problem. This material, which is present in packaging and day-to-day objects, plays a decisive role in intensive agriculture zones.

In the Region of Murcia, known as "Europe's market garden", mulch film (plastic covering over the crop lines) increases production in vegetable fields, but involves using large amounts of plastic. This low-density plastic is difficult to completely remove from the fields and, with time, decomposes into smaller particles which are absorbed by the soil, transported by water or wind, and are also ingested by other animals.

In order to know the status of contamination by microplastics in this zone, researchers from the universities of Wageningen and Cartagena analysed the presence of these plastics in agricultural soil, and also in sheep faeces, to determine the possible ingestion of plastics by the livestock that feed on post-harvest agricultural residues.

They found that 100% of the soil samples analysed contained microplastics, as did 92% of the samples of sheep faeces studied. This, in turn, translates into concentrations of 2,000 particles of microplastics per kilogram of soil, and 1,000 particles per kilogram of dry faeces.

This analysis reveals a relevant concentration of plastics and warns about the ingestion of this material by sheep; future studies should analyse how ingesting the plastic affects the organism of these animals.

Despite the negative effects of the plastic and its accumulation in intensive agriculture zones, it is very difficult to do away with that material since techniques such as the use of mulch film enable savings in water and pesticides; these prove to be determining factors in semi-arid zones with scant rainfall, as is the case of the Murcia zone.

Reverting this trend will therefore require a change in paradigm in current agricultural production so as to relegate intensive cropping to a secondary role. The Diverfarming project, financed by the H2020 call of the European Commission seeks, in this sense, to bring about a change in European agriculture towards an agriculture that is more sustainable and respectful to the environment. By means of the combination of crop diversification and sustainable farming practices they seek to look after the planet whilst ensuring the farmers' economic benefits.

Diverfarming is a project financed by the Horizon 2020 Programme of the European Commission, within the challenge of "Food Security, Sustainable Agriculture and Forestry, Marine, Maritime and Inland Water Research and the Bioeconomy", under agreement 728003. It counts on the participation of the Universities of Cartagena and Córdoba (Spain), Tuscia (Italy), Exeter and Portsmouth (United Kingdom), Wageningen (Netherlands), Trier (Germany), Pecs (Hungary) and ETH Zurich (Switzerland), the research centres Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria (Italy), the Consejo Superior de Investigaciones Científicas (Spain) and the Natural Resources Institute LUKE (Finland), the agrarian organisation ASAJA, and the companies Casalasco and Barilla (Italy), Arento, LogísticaDFM and Industrias David (Spain), Nieuw Bromo Van Tilburg and Ekoboerdeij de Lingehof (Netherlands), Weingut Dr. Frey (Germany), Nedel-Market KFT and Gere (Hungary) and Paavolan Kotijuustola and Polven Juustola (Finland).

Credit: 
University of Córdoba

Using a soft crystal to visualize how absorbed carbon dioxide behaves in liquid

image: The CO2-absorbing soft crystal developed for this study (Photo: Shin-ichiro Noro).

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Shin-ichiro Noro

A team of scientists has succeeded in visualizing how carbon dioxide (CO2) behaves in an ionic liquid that selectively absorbs CO2. The finding is expected to help develop more efficient methods to capture CO2 in the atmosphere, one of the major factors causing global warming.

Carbon dioxide (CO2) levels in the atmosphere -- a major factor in global warming -- continue to rise every year, creating grave concerns about the future of Earth. To halt global warming, our industrial society needs to emit much less CO2. One way of achieving this is to separate and collect CO2 before it is released into the atmosphere. While some such efforts are already underway, they have not been very efficient. There is thus an urgent need to develop technology that can separate and collect CO2 more efficiently, both to protect the environment but also to promote recycling of CO2 as a resource.

The use of ion liquids to effectively absorb CO2 has been the subject of intensive research. Yet more investigation of how CO2 absorbed in ionic liquids behaves is needed to improve the materials used in the CO2 separation and collection process. As ionic liquids are a fluid with no regular structure, it has been difficult to directly observe the state of CO2 absorbed in them.

In the present study, a team of scientists that included Professors Shin-ichiro Noro and Takayoshi Nakamura, both of Hokkaido University's Graduate School of Environmental Science, focused on a soft crystal, a substance that possesses both the softness of a liquid and the regularity of a crystal. They synthesized a soft crystal containing components of an ionic liquid that absorbed CO2. As anticipated, the soft crystal maintained its regularity even after it absorbed CO2, making it possible to conduct X-ray diffraction analysis.

The analysis showed the absorbed CO2 interacts with both fluorine and oxygen atoms of the bis(trifluoromethylsulfonyl)imide anion, a component of the ionic liquid. Furthermore, the scientists' theoretical analysis showed that dispersion and electrostatic interactions exist between CO2 and the framework, creating the force that binds CO2 to the anion.

The team's findings are expected to be helpful in designing and developing ionic liquids capable of efficiently separating and collecting CO2, and will likely accelerate practical applications of such liquids, a pivotal step to alleviating the negative effects of global warming.

Shin-ichiro Noro focuses on the development of porous materials to contribute to environmental restoration and conservation, while Takayoshi Nakamura's work is focused on the development of molecular devices for a wide variety of applications.

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Hokkaido University

Minimal waste production is a fundamental law for animal locomotion

Is there a unifying principle underpinning animal locomotion in its rich diversity? A thermodynamic analysis performed by a Skoltech professor and his French collaborators at Université Paris Diderot, Université Paris Saclay, and the Muséum national d'Histoire Naturelle, shows why and how waste minimization prevails on efficiency or power maximization when it comes to free locomotion irrespective of the available mode and gaits. The research is published in the Physical Review Letters.

"Locomotion is a hallmark of animal life", says Skoltech professor Henni Ouerdane, "and that is why it has fascinated thinkers since at least Aristotle's time". Prof. Ouerdane adds that "in the late 19th century Eadweard Muybridge's invention, the zoopraxiscope, a precursor of the motion picture, mesmerized crowds witnessing the beautiful complexity of biomechanics; and that detailed comparisons between living and man-made machines naturally followed, but with very limited success to explain life."

For the man-made machines, maximization of energy conversion efficiency is a must to save resources, but does this apply to animals when they freely move about? Answering this question poses a formidable challenge considering the multiform character of animal life and habitats. Power maximization is the obvious target under stressful contexts, prey chasing or flight; but no clear principle, if any, seemed to apply to free locomotion. In fact, the detailed interplay between energy management and locomotion, and in particular the optimization of energy expenditure across gaits, had always remained elusive.

Prof. Ouerdane and his main collaborator, Prof. Christophe Goupil, had previously extensively studied the nonequilibrium thermodynamics of energy converters, but the leap to the physics of life was a daunting prospect. Indeed, the formulation of a generic compact model of locomotion of highly complex systems such as living organisms seemed out of reach. "Of course, the literature on the topic is rich and abundant, but many models rely on large sets of fitting parameters to reproduce part of the observed energetics of muscle action, which somehow hinders a clear vision of the thermodynamic processes at work. Further, the basic muscle model derives from original works using dead, dissected muscles, while one wants to understand the chemical-to-mechanical energy conversion in living organisms", says Prof. Goupil.

The first step to a thermodynamic model of locomotion was a proper model of metabolic energy conversion in actual, living muscles. This work, published in the New Journal of Physics in 2019, by Prof. Ouerdane and his collaborators, emphasized the necessity to consider rigorously the particular boundary conditions to which a living muscle under load is subjected, and their feedback effects related to the metabolic intensity. Their work thus bridged an outstanding gap between inert muscle models and live muscle put to work by an actual animal.

"In our latest work, introducing the energy cost of efforts, we unraveled a fundamental extremal principle of the nonequilibrium thermodynamics of animal locomotion: free locomotion entails minimization of metabolic waste production. We used published experimental data for walk, trot, and gallop, each gait representing different biomechanical working conditions. We recovered the trends with our model, and provided new insights into animal locomotion, hence reaching beyond our case study", says Prof. Ouerdane.

This research contributes to significant progress in the understanding of locomotion in any environment (terrestrial, aerial, aquatic) independently of the phylogeny. Interestingly, it also sheds light on a natural principle that can drive the innovative design of future man-made waste-efficient machines, and it may also feed bioinspired robotics for problems related to, e.g., proprioception and variable mechanical impedance of actuators, which in turn could advance the development of physics-based theories of life.

Credit: 
Skolkovo Institute of Science and Technology (Skoltech)

New modified wheat could help tackle global food shortage

Researchers at the University of York have created a new modified wheat variety that increases grain production by up to 12%.

Wheat is one of the most important food crops in the world, providing 20% of human calories; with ever increasing global food demand, increasing crop yield is critically important.

Wheat breeders work hard to increase yield to meet global demand, but since the 'green revolution' of the 1960s, the rate of yield increase has been slowing and is currently less than 1% per year.

Most improvements have been made by breeding varieties that produce higher numbers of grain, but it should also be possible to increase yield by producing plants with bigger grains. When this has been achieved, however, it is accompanied by a decrease in grain numbers.

Researchers at the University of York have now resolved this issue by directly modifying the growth of the young developing grain by increasing the amount of a protein that controls growth rates in plants.

This resulted in plants that produced grain that are up to 12% bigger than in the conventional variety. In field experiments conducted by their collaborators in Chile, they found that there was no decrease in grain number, resulting in an increase in yield.

Professor Simon McQueen-Mason, from the University of York's Centre for Novel Agricultural Products (CNAP) at the Department of Biology, said: "Experts predict that we need to increase global food production by 50% by 2030 in order to meet demand from population growth. The negative impacts of climate change on crop yields are making this even more challenging. While researchers are working hard to meet this challenge, there remains a lot to do."

"Attempts to increase the yield of wheat have been thwarted by the apparent trade-off between grain size and grain number. We decided to side-step this complex control system by giving a boost to the natural growth system that controls the size of plant tissues.

"We did this by increasing the levels of a protein called expansin, which is a major determinant of growth in plants. We targeted this modification so that it was confined to developing wheat grain, and are delighted by the results."

Research partners at the Universidad Austral de Chile conducted field experiments that demonstrated the effectiveness of the plants under agricultural conditions.

The team are now looking at ways to make this research accessible to farmers and the wider industry to help inform their decisions on crop production.

Credit: 
University of York

RUDN University mathematicians applied 19th century ideas to modern computerized algebra systems

image: A team of mathematicians from RUDN University added new symbolic integration functionality to the Sage computerized algebra system. The team implemented ideas and methods suggested by the German mathematician Karl Weierstrass in the 1870s.

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RUDN University

A team of mathematicians from RUDN University added new symbolic integration functionality to the Sage computerized algebra system. The team implemented ideas and methods suggested by the German mathematician Karl Weierstrass in the 1870s. The results were published in the Journal of Symbolic Computation.

The first computer program capable of calculating integrals of elementary functions was developed in the late 1950s. By creating it, the developers confirmed that a computer could not only perform simple calculations but was also able to deal with tasks that required a certain degree of 'thinking'. Symbolic integration, i.e. integration that involves letters and abstract symbols instead of numbers, is an example of such a task. At the same time, scientists realized that neither humans nor computers were able to determine whether a given integral can be taken in elementary functions (provided such a human or computer used the methods studied in a university course of analysis and took a finite number of steps). Therefore, in the 1960s mathematicians working on symbolic integrators started to refer to methods that had been suggested by Liouville in the 1830s. From that time on, computer scientists have been tapping into the classic scientific heritage.

The calculation of primitives of algebraic functions is one of the bottlenecks in the process of integrator development. Before World War I, the integration of algebraic functions or Abelian integrals had been considered one of the most important issues in mathematics, but later on, it was forgotten. "Current computer algebra systems are able to fulfill even the most exotic requests of mathematical analysis students, but at the same time, many of these systems fail to recognize integrals in elementary functions. Only several packages allow for the integration of algebraic functions or with Abelian integrals, but their development stopped 15 years ago, and their functionality leaves much to be desired," says Mikhail Malykh, a Doctor of Science in Physics and Mathematics, and an assistant professor at the Department of Applied Informatics and Probability Theory, RUDN University.

One of the theories developed by the German mathematician Karl Weierstrass in the 1870s reduces the calculation of an integral of an algebraic function to finding a given set of known integrals of all three types. The initial integral is represented as a sum of standard integrals (this construction is knowns as the normal representation of an Abelian integral). The team from RUDN University confirmed that this representation is indicative of whether a given integral can be calculated in elementary functions. To confirm their theory, the mathematicians tested them on simple elliptical integrals using a software package that had been created by the team in 2017. The package helps calculate coefficients of the normal form of an integral. In the future, the team plans to conduct similar studies for a wider range of integrals.

"This work is just one step on our way to an ambitious goal: we want to express Weierstrass's theory of Abelian integrals and functions using the language of computer algebra and to implement it in the Sage system, giving researchers from all over the world free access to it," added Mikhail Malykh from RUDN University

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RUDN University

New immunotherapy shows promise against rare childhood cancer

A novel CAR T-cell therapy developed by researchers at UCL and designed to target cancerous tumours, has shown promising early results in children with neuroblastoma, a rare form of childhood cancer.

For this proof-of-principle study, researchers at the UCL Great Ormond Street Institute for Child Health (GOS ICH) and the UCL Cancer Institute modified the patient's own T-cells (a type of immune cell), equipping them to recognise and kill neuroblastoma tumour cells.

Twelve children with relapsed or refractory (where the disease does not respond to treatment) neuroblastoma were treated as part of the Cancer Research UK-funded phase I clinical trial.

The research, published in Science Translational Medicine, is one of the first studies to demonstrate CAR T-cells achieving rapid regression against a solid cancer (non-blood cancer). Although the beneficial effects only lasted a short while, the study provides important evidence that this specific CAR T-cell treatment could be used as a future treatment for children with solid cancers.

Neuroblastoma is a rare type of cancer that mostly affects babies and young children and develops from specialised nerve cells (neuroblasts) left behind from a baby's development in the womb.

Up to 100 children in the UK are diagnosed with neuroblastoma each year. Current treatment for children with an aggressive type of neuroblastoma includes surgical removal, chemotherapy with stem-cell transplant, radiotherapy and antibody therapy. Despite this intensive treatment long-term survival is between 50-60 per cent.

In CAR T-cell therapy, a type of immunotherapy, T-cells are engineered to contain a molecule called a chimeric antigen receptor (CAR) on their surface which can specifically recognise cancerous cells.

For this study the patients' own T-cells were modified with a CAR to target the GD2 surface protein, which is highly abundant on almost all neuroblastoma cells, but found at very low levels in healthy cells.

Researchers found that when using a sufficient dose* of the modified CAR T-cells, this treatment induced rapid reduction in tumour size in some of the patients treated. These effects were transient. Importantly, in all patients the CAR T-cells did not cause any harmful side effects in healthy tissues that express the GD2 molecule.

Lead author, Dr Karin Straathof, Research group leader at UCL GOS ICH and Consultant Paediatric Oncologist at Great Ormond Street Hospital NHS Trust said: "It's encouraging to see the anti-tumour activity induced by these modified T-cells in some of the patients on this study.

"While the anti-tumour activity seen was only transient, it provides an important proof-of-principle that CAR T-cells directed at the GD2 molecule could be used against solid cancers in children.

"New treatments are needed for high-risk neuroblastoma and with more research we hope to develop this further into a treatment that results in lasting responses and increases the number of patients that can be cured."

Senior author, Dr Martin Pule (UCL Cancer Institute) said: "Targeting of solid cancers by CAR T-cells is dependent on their infiltration and expansion within the tumour microenvironment, and thus far fewer clinical responses have been reported.

"The rapid regression in neuroblastoma cells is promising, particularly as this activity was observed in the absence of neurotoxicity which occurs with antibody-based approaches that target GD2."

Dr Pule added: "Targeting neuroblastoma with GD2 CAR T-cells appears to be a valid and safe strategy but requires further modification to promote CAR T-cell longevity."

Dr Sue Brook, medical advisor at Cancer Research UK, said: "Children who have hard to treat cancers like neuroblastoma have limited treatment options open to them, especially when the cancer returns.

"The early results for the GD2 CAR-T treatment look promising, especially due to the initial safety data. However more work is needed on making the response last longer, and we are looking forward to seeing the next steps in its development."

The research team are preparing for their next clinical study in collaboration with Autolus, a clinical-stage biopharmaceutical company developing next-generation, programmed T-cell therapies for the treatment of cancer. This study will evaluate AUTO6NG, which builds on this approach utilising the same GD2 CAR alongside additional programming modules designed to enhance efficacy and persistence.

Credit: 
University College London

The invasive species that Europe needs to erradicate most urgently are identified

image: Research team

Image: 
University of Cordoba

Species such as the golden apple snail are putting the agricultural sector in the Ebro river basin in quite a predicament. Meanwhile, in the southern part of the Iberian Peninsula, water hyacinths are threatening to destroy the natural ecosystem of the Guadiana River. Invasive species change not only the habitat of many other species but they also directly impact the region's economy. Some of these species are already wreaking havoc on certain areas but others could do so in the future and have a huge impact, both environmentally and financially.

In order to help management centers and administrations make decisions, an international team of European researchers, led by the University of Newcastle and the Belgian Nature and Forests Agency with which the University of Córdoba collaborated, assessed the priority of erradicating different invasive species in Europe. One of the new aspects they also included is a study of possible scenarios regarding invasive species that are not currently present in the region or that are in an emerging stage, for which there are still opportunities to curb their spread.

"It would be ideal to erradicate all the invasive species but financial and labor resources are limited, even more so now, when we are dealing with other priorities", explains researcher Pablo González Moreno, an expert on invasive species and a member of the ERSAF (Assessment and Restoration of Farming and Forest Systems) group at the University of Córdoba, who collaborated on the study, researching the feasibility of erradicating different invasive plant species.

One of the species identified as a very high priority is the common myna from the starling family that has been able to establish small colonies in Spain and Portugal and that, due to its aggressive territorial nature and ability to adapt, could spread to more areas and displace other native species. Other very high priority species for Europe are the Berber toad, the ring-tailed coati (a carnivorous mammal) and the red-vented bulbul, another bird species.

Among the species that have yet to arrive in Europe but that could in the future, the highest priority is for the rusty crayfish (Faxonius rusticus), a freshwater crayfish that is causing serious problems in the northern US and Canada. Also a priority are the northern snakehead (Channa argus), an Asian fish that came to the US via collectors who had purchased them, and Cryptostegia grandiflora, a kind of vine native to Madagascar.

In order to draw up this list, the international team first analyzed the risk of establishment, spreading and the impact of different invasive species. This research was previously published and financed by the European Union. This risk ranking was compared to an assessment of erradication strategies for these species in terms of effectiveness, cost, level of acceptance by different social sectors, estimated time needed to act and possibility of the species coming back after being erradicated.

Having analyzed feasibility, the team met up to pool their assessments and together drew up a list of invasive species already established in Europe, as well as those who could do so in the future, according to their priority, supplying data on the regions where they are found or could be found, the erradication method, their effectiveness and their minimum and maximum cost, among other things. This is an open access list and any person or entity can consult it.

In this aspect, this study is important, not only in helping to manage the invasive species currently found in Europe, but also in having a future management scenario in case these species are able to get to Europe.

At a European level, this research has been able to create a network of researchers partnering up with managers in several European countries. "This is a way for the collective to get in touch with each other and to reach consensuses on the degree of management, something that was proving difficult to do in Europe. Having European regulations is an important step. Invasive species don't understand what borders are", concludes researcher Pablo González.

Credit: 
University of Córdoba

A new strategy for the greener use of calcium carbide

image: Born-Oppenheimer molecular dynamics of an acetylide molecule HO-Ca-CCH solvated in DMSO

Image: 
Mikhail Polynski, assistant teaching fellow at the Institute of Chemistry of St Petersburg University

Calcium acetylide was discovered more than 150 years ago. It is a yellowish-white, beige, or grey solid, a compound of calcium and carbon. Calcium acetylide is currently used to produce gaseous acetylene. In industry, it is widely used in the production of acetic acid and ethyl alcohol, as well as it can be used in the production of plastics, rubber, and rocket engines.

The carbon needed for the synthesis of calcium acetylide is mined in an unsustainable way. As a result, the fossil resource is depleted (the unsustainable approach) and, furthermore, the amount of carbon increases above the earth's surface. 'We are working on a strategy for the carbon-neutral cycle of production. In particular, to obtain calcium acetylide, you can use carbon that is obtained via thermal decomposition (pyrolysis) of waste, and the resulting substance can be used in industry to create new compounds,' said Konstantin Rodygin, a research associate at the Laboratory of Cluster Catalysis, St Petersburg University.

'Nowadays, a key challenge for humanity is to create a new generation of industrial processes that make it possible to obtain the most important organic compounds and materials within the carbon-neutral approach. Of utmost importance is the replacement of fossil resources with renewable ones, thus solving environmental problems. As shown in our works, organic synthesis based on calcium acetylide opens up fresh opportunities for implementing carbon-neutral technologies. Moreover, understanding the chemical processes of the transformation of carbide species in chemical processes in solution is of key importance,' said Valentin Ananikov, a member of the Russian Academy of Sciences and the Head of the Laboratories of Cluster Catalysis and Metal-Complex and Nanoscale Catalysts at the Zelinsky Institute.

The chemists were able to propose a new strategy for using the substance by simulating the processes that occur at the level of atoms and molecules during the interaction of calcium acetylide, water, and a dimethyl sulfoxide solvent. Calcium acetylide is a salt containing negatively charged acidic residues of acetylene (the so-called acetylide anions with a charge of '?2') and positively charged calcium ions. The researchers investigated the acidity of acetylide anions, water, and some other substances in a dimethyl sulfoxide solvent. In that solvent, an unusual phenomenon can be observed; the interaction of acetylide anions with water, hydrolysis, proceeds incompletely. The so-formed anions, having a charge of '-1', can undergo a wide range of key organic chemical reactions.

'After performing the analysis, we realized that instead of water, one can use other protonating substances to transfer acetylide into solution. Also, one can potentially use a less toxic and more 'green' solvent instead of dimethyl sulfoxide to perform reactions involving calcium acetylide, if the solvent meets some newly-discovered criteria. Thus, chemical synthesis of new substances with calcium acetylide can be 'greener' due to the potential of calcium acetylide to react in less toxic solvents, as well as due to more sustainable approaches to the synthesis of the carbide itself' said Mikhail Polynski, a co-author of the article, assistant teaching fellow at the Institute of Chemistry of St Petersburg University.

Noteworthy, one of the co-authors of the new article is Mariia Sapova, a graduate of St Petersburg University, who started work on the project during her master's studies. 'The challenging project attracted me from the start, as the idea of combining various computational methods opens up ample opportunities for the simulation of complex processes, such as, in our case, the dissolution process. This work gave me a broadened understanding of science in general and, moreover, encouraged me to go out of my comfort zone, modelling crystals, and to challenge the limits of applicability of various methods in computational chemistry. I think that methodologically complex modeling approaches like the proposed in the article should be developed further, so we can perform truly realistic modelling of chemical processes,' noted Mariia Sapova.

As Mikhail Polynski specified, the newly presented research is purely theoretical; it is a computer simulation of the process of obtaining acetylides from calcium acetylide. 'We used the so-called quantum chemical methods, Born-Oppenheimer molecular dynamics. As a result of such a simulation, it is possible to make a short molecular movie showing how the motion of atoms and molecules looks like at very short, picosecond, time scales,' concluded Mikhail Polynski.

Credit: 
St. Petersburg State University

Pitt researchers create nanoscale slalom course for electrons

image: Illustration of sketched serpentine nanowires created from lanthanum aluminate and strontium titanate. The side-to-side motion of the electrons as they travel gives them additional properties that can be used to make quantum devices

Image: 
Jeremy Levy

PITTSBURGH--A research team led by professors from the Department of Physics and Astronomy have created a serpentine path for electrons, imbuing them with new properties that could be useful in future quantum devices.

Jeremy Levy, a distinguished professor of condensed matter physics, and Patrick Irvin, research professor, are coauthors of the paper "Engineered spin-orbit interactions in LaAlO3/SrTiO3-based 1D serpentine electron waveguides," published in Science Advances on November 25.

"We already know how to shoot electrons ballistically through one-dimensional nanowires made from these oxide materials," explains Levy. "What is different here is that we have changed the environment for the electrons, forcing them to weave left and right as they travel. This motion changes the properties of the electrons, giving rise to new behavior."

The work is led by a recent PhD recipient, Dr. Megan Briggeman, whose thesis was devoted to the development of a platform for "quantum simulation" in one dimension. Briggeman is also the lead author on a related work published earlier this year in Science, where a new family of electronic phases was discovered in which electrons travel in packets of 2, 3, and more at a time.

Electrons behave very differently when forced to exist along a straight line (i.e., in one dimension). It is known, for example, that the spin and charge components of electrons can split apart and travel at different speeds through a 1D wire. These bizarre effects are fascinating and also important for the development of advanced quantum technologies such as quantum computers. Motion along a straight line is just one of a multitude of possibilities that can be created using this quantum simulation approach. This publication explores the consequences of making electrons weave side to side while they are racing down and otherwise linear path.

One recent proposal for topologically-protected quantum computation takes advantage of so-called "Majorana fermions", particles which can exist in 1D quantum wires when certain ingredients are present. The LaAlO3/SrTiO3 system, it turns out, has most but not all of the required interactions. Missing is a sufficiently strong "spin-orbit interaction" that can produce the conditions for Majorana fermions. One of the main findings of this latest work from Levy is that spin-orbit interactions can in fact be engineered through the serpentine motion that electrons are forced to undertake.

In addition to identifying new engineered spin-orbit couplings, the periodic repetition of the serpentine path creates new ways for electrons to interact with one another. The experimental result of this is the existence of fractional conductances that deviate from those expected for single electrons.

These slalom paths are created using a nanoscale sketching technique analogous to an Etch A Sketch toy, but with a point size that is a trillion times smaller in area. These paths can be sketched and erased over and over, each time creating a new type of path for electrons to traverse. This approach can be thought of as a way of creating quantum materials with re-programmable properties. Materials scientists synthesize materials in a similar fashion, drawing atoms from the periodic table and forcing them to arrange in periodic arrays. Here the lattice is artificial--one zig-zag of the motion takes place in a ten nanometer of space rather than a sub-nanometer atomic distance.

Levy, who is also director of the Pittsburgh Quantum Institute, stated that this work contributes to one of the main goals of the Second Quantum Revolution, which is to explore, understand, and exploit the full nature of quantum matter. An improved understanding, and the ability to simulate the behavior of a wide range of quantum materials, will have wide-ranging consequences. "This research falls within a larger effort here in Pittsburgh to develop new science and technologies related to the second quantum revolution," he said.

Credit: 
University of Pittsburgh

Researchers uncover the unique way stem cells protect their chromosome ends

Telomeres are specialised structures at the end of chromosomes which protect our DNA and ensure healthy division of cells. According to a new study from researchers at the Francis Crick Institute published in Nature, the mechanisms of telomere protection are surprisingly unique in stem cells.

For the last 20 years, researchers have been working to understand how telomeres protect chromosome ends from being incorrectly repaired and joined together because this has important implications for our understanding of cancer and aging.

In healthy cells, this protection is very efficient, but as we age our telomeres get progressively shorter, eventually becoming so short that they lose some of these protective functions. In healthy cells, this contributes to the progressive decline in our health and fitness as we age. Conversely, telomere shortening poses a protective barrier to tumour development, which cancer cells must solve in order to divide indefinitely.

In somatic cells, which are all the cells in the adult body except stem cells and gametes, we know that a protein called TRF2 helps to protect the telomere. It does this by binding to and stabilising a loop structure, called a t-loop, which masks the end of the chromosome. When the TRF2 protein is removed, these loops do not form and the chromosome ends fuse together, leading to "spaghetti chromosomes" and killing the cell.

However, in this latest study, Crick researchers have found that when the TRF2 protein is removed from mouse embryonic stem cells, t-loops continue to form, chromosome ends remain protected and the cells are largely unaffected.

As embryonic stem cells differentiate into somatic cells, this unique mechanism of end protection is lost and both t-loops and chromosome end protection become reliant on TRF2. This suggests that somatic and stem cells protect their chromosome ends in fundamentally different ways.

"Now we know that TRF2 isn't needed for t-loop formation in stem cells, we infer there must be some other factor that does the same job or a different mechanism to stabilise t-loops in these cells, and we want to know what it is," says Philip Ruis, first author of the paper and PhD student in the DNA Double Strand Breaks Repair Metabolism Laboratory at the Crick.

"For some reason, stem cells have evolved this distinct mechanism of protecting their chromosomes ends, that differs from somatic cells. Why they have, we have no idea, but it's intriguing. It opens up many questions that will keep us busy for many years to come."

The team have also helped to clarify years of uncertainty about whether the t-loops themselves play a part in protecting the chromosome ends. They found that telomeres in stem cells with t-loops but without TRF2 are still protected, suggesting the t-loop structure itself has a protective role.

"Rather than totally contradicting years of telomere research, our study refines it in a very unique way. Basically, we've shown that stem cells protect their chromosome ends differently to what we previously thought, but this still requires a t-loop," says Simon Boulton, paper author and group leader in the DNA Double Strand Breaks Repair Metabolism Laboratory at the Crick.

"A better understanding of how telomeres work, and how they protect the ends of chromosomes could offer crucial insights into the underlying processes that lead to premature aging and cancer."

The team worked in collaboration with Tony Cesare in Sydney and other researchers across the Crick, including Kathy Niakan, of the Human Embryo and Stem Cell Laboratory, and James Briscoe, of the Developmental Dynamics Laboratory at the Crick. "This is a prime example of what the Crick was set up to promote. We've been able to really benefit from our collaborator's expertise and the access that was made possible by the Crick's unique facilities," says Simon.

The researchers will continue this work, aiming to understand in detail the mechanisms of telomere protection in somatic and embryonic cells.

Credit: 
The Francis Crick Institute

What makes a happy couple, a happy family?

"Happy families are all alike; every unhappy family is unhappy in its own way," Leo Tolstoy wrote famously in 1878 in the opening lines of Anna Karenina. Turns out the Russian author was onto something.

Cohesive families, indeed, seem to share a few critical traits--psychologists agree. Being emotionally flexible may be one of the most important factors when it comes to longevity and overall health of your romantic and familial relationships.

That's the finding of a new University of Rochester meta-analysis, published in the Journal of Contextual Behavioral Science, which statistically combined the results of 174 separate studies that had looked at acceptance and commitment therapy, mindfulness, and emotion regulation.

The researchers' aim was to clarify how mindful flexibility--on one hand--and inattentive, mindless, and rigid inflexibility on the other--were linked to the dynamics within families and romantic relationships.

"Put simply," says coauthor Ronald Rogge, an associate professor of psychology at the University of Rochester, "this meta-analysis underscores that being mindful and emotionally flexible in tough and challenging situations not only improves the lives of individuals, it might also strengthen and enrich their close relationships."

Psychological flexibility versus inflexibility

Psychological flexibility is defined as a set of skills that people use when they're presented with difficult or challenging thoughts, feelings, emotions, or experiences. Such skills encompass:

Being open to experiences--both good and bad--and accepting them no matter how challenging or difficult they might be

Having a mindful attentive awareness of the present moment throughout day-to-day life

Experiencing thoughts and feelings without obsessively clinging to them

Maintaining a broader perspective even in the midst of difficult thoughts and feelings

Learning to actively maintain contact with our deeper values, no matter how stressful or chaotic each day is

Continuing to take steps toward a goal, even in the face of difficult experiences and setbacks

The opposite--psychological inflexibility--describes six specific behaviors, including:

Actively avoiding difficult thoughts, feelings, and experiences

Going through daily life in a distracted and inattentive manner

Getting stuck in difficult thoughts and feelings

Seeing difficult thoughts and feelings as a personal reflection and feeling judged or shameful for having them

Losing track of deeper priorities within the stress and chaos of day-to-day life

Getting derailed easily by setbacks or difficult experiences, resulting in being unable to take steps toward deeper goals.

Psychologists consider the rigid and inflexible responses to difficult or challenging experiences dysfunctional, ultimately contributing to and exacerbating a person's psychopathology.

How flexibility shapes interactions

Through their analysis, coauthor Jennifer Daks, a PhD candidate in the Rochester Department of Psychology, and Rogge discovered that within families, higher levels of various forms of parental psychological flexibility were linked to:

Greater use of adaptive parenting strategies

Fewer incidents of lax, harsh, and negative parenting strategies

Lower perceived parenting stress or burden

Greater family cohesion
Lower child distress

Within romantic relationships, higher levels of various forms of psychological inflexibility were linked to:

Lower relationship satisfaction for themselves and their partners

Lower sexual satisfaction

Lower emotional supportiveness

Greater negative conflict, physical aggression, attachment anxiety, and attachment avoidance

The results suggest that psychological flexibility and inflexibility may play key roles in both couples and families in shaping how individuals interact with the people closest to them, the researchers write.

The meta-analysis, also commonly referred to as a "study of studies," cements and adds to the findings of Rogge's earlier work in which he and a team tested the effects of couples' watching movies together and talking about the films afterward. In that work, Rogge and his colleagues demonstrated that couples could bring mindful awareness, compassion, and flexibility back into their relationships by using movies to spark meaningful relationship discussions, leading to both immediate and long-term benefits.

That study, conducted in 2013, found that an inexpensive, fun, and relatively simple watch-and-talk approach can be just as effective as other more intensive therapist-led methods--more than halving the divorce or separation rate from 24 to 11 percent after the first three years of marriage.

"The results suggest that husbands and wives have a pretty good sense of what they might be doing right and wrong in their relationships," Rogge said about the earlier study. "You might not need to teach them a whole lot of skills to cut the divorce rate. You might just need to get them to think about how they are currently behaving. And for five movies to give us a benefit over three years--that is awesome."

Watching and discussing movies with your partner that feature onscreen couples can have a positive effect on your relationship, Rogge recently told People magazine. It's an easy exercise that "could be a lifesaver during quarantine," he says.

Which movies work? As Good as It Gets, Funny Girl, Gone with the Wind, Love Story, Indecent Proposal, The Devil Wears Prada, and Father of the Bride are a few of the films Rogge and his fellow researchers used in their 2013 study of couples.

Looking for some LGBTQ recommendations? Rogge suggests The Kids Are Alright, The Wedding Banquet, The Birdcage, and episodes of Grace and Frankie.

Credit: 
University of Rochester

Solar CNO neutrinos observed for the first time

Scientists who are members of the Borexino Collaboration have provided the first experimental proof of the occurrence of the so-called CNO cycle in the Sun: They have managed to directly detect the distinctive neutrinos generated during this fusion process. This is an important milestone on the route to better understanding the fusion processes that occur in the Sun. At the same time, although the CNO cycle plays a minor role in our Sun, it is most likely the predominant way of producing energy in other more massive and hotter stars. The Borexino Collaboration's findings have been published in the latest issue of the journal Nature.

How does the Sun generate energy? As a gigantic fusion reactor, it continuously converts hydrogen into helium - a process also referred to as 'hydrogen burning'. Essentially, this involves two types of processes. On the one hand, there is the proton-proton reaction (pp reaction). This begins with the direct fusion of two hydrogen nuclei to create the intermediate hydrogen isotope deuterium from which helium is subsequently formed. On the other hand, the heavier elements carbon (C), nitrogen (N) and oxygen (O) are involved in the second type of reaction chain, known as the CNO cycle or Bethe-Weizsäcker cycle. While the pp reaction is predominant in smaller stars such as our Sun, the CNO cycle is the main process for generating energy in more massive and hotter stars.

As is the case with all fusion processes that occur within the Sun, countless neutrinos are produced in addition to helium and the enormous amounts of energy which cause the Sun and its sister stars to shine. The neutrinos reach the Earth in their billions and normally pass through it unhindered. "However, we are able to detect these neutrinos using the Borexino experiment's huge detector located 1400 meters underground," points out Prof. Michael Wurm, a neutrino physicist at the PRISMA+ Cluster of Excellence at Johannes Gutenberg University Mainz (JGU) and a member of the Borexino Collaboration. "They provide us with clear insights into the processes in the Sun's core."

While the Borexino Collaboration has been able to detect neutrinos originating from several reactions along the pp chain in recent years, their current achievement has been to explicitly identify neutrinos released in the CNO cycle, which are significantly less abundant in comparison. "Although on the basis of model calculations we expected the CNO cycle also to occur in the Sun, direct evidence of this has never been obtained before. Only a characteristic neutrino signal can provide conclusive proof that this actually happens - now we have that conclusive proof without a shadow of a doubt."

In addition, the research team was also able to estimate the total flow of CNO neutrinos reaching the Earth. About 700 million of them fly through a square centimeter of our planet each second, but this accounts for only one hundredth of the total number of solar neutrinos. "This is consistent with the theoretical expectations that the CNO cycle in the Sun is responsible for about one percent of the energy it produces," adds Dr. Daniele Guffanti, a postdoc in Michael Wurm's team and also a member of the Borexino Collaboration.

The two neutrino physicists from Mainz consider the new results to be an important milestone along the route to obtaining a complete understanding of the fusion processes which not only drive our Sun but also massive stars, and make these latter light up our night sky. It also paves the way for a better insight into the elements that compose the solar core, particularly with regard to how frequently heavier elements such as carbon, nitrogen and oxygen can be found in the solar plasma in addition to hydrogen and helium - researchers call this metallicity. Neutrinos might once again be our only guides to help us discover this.

Credit: 
Johannes Gutenberg Universitaet Mainz