Culture

Eucalyptus trees can be genetically modified not to invade native ecosystems

image: Image of a modified set of eucalypt floral buds that do not develop further to make viable pollen or seeds (main image and lower right), compared to wild type flower buds (upper right) and open flower (middle right)

Image: 
OSU College of Forestry

CORVALLIS, Ore. - Eucalyptus, a pest-resistant evergreen valued for its hardy lumber and wellness-promoting oil, can be genetically modified not to reproduce sexually, a key step toward preventing the global tree plantation staple from invading native ecosystems.

Oregon State University's Steve Strauss led an international collaboration that showed the CRISPR Cas9 gene editing technique could be used with nearly 100% efficiency to knock out LEAFY, the master gene behind flower formation.

"The flowers never developed to the point where ovules, pollen or fertile seeds were observed," Strauss said. "And there was no detectable negative effect on tree growth or form. A field study should be the next step to take a more careful look at stability of the vegetative and floral sterility traits, but with physical gene mutation we expect high reliability over the life of the trees."

Findings were published in Plant Biotechnology Journal.

Strauss, Ph.D. student Estefania Elorriaga and research assistant Cathleen Ma teamed up with scientists at the University of Colorado, Beijing Forestry University and the University of Pretoria on the research. The greenhouse study involved a hybrid of two species, Eucalyptus grandis and E. urophylla, that is widely planted in the Southern Hemisphere; there are more than 700 species of eucalyptus, most of them native to Australia.

"Roughly 7% of the world's forests are plantations, and 25% of that plantation area contains nonnative species and hybrids," said Elorriaga, now a postdoctoral researcher at North Carolina State. "Eucalyptus is one of the most widely planted genera of forest trees, particularly the 5.7 million hectares of eucalyptus in Brazil, the 4.5 million hectares in China and 3.9 million hectares in India."

Those plantings, the scientists note, can lead to undesirable mingling with native ecosystems. Thus eliminating those trees' ability to sexually reproduce without affecting other characteristics would be an effective way to greatly reduce the potential for invasive spreading in areas where that is considered an important ecological or economic problem.

"This was the first successful application of CRISPR to solve a commercial problem in forest trees," Elorriaga said. "Research with CRISPR in forest trees to modify different traits is ongoing in many laboratories around the world. Global warming is having large impacts on forests of all kinds, and gene editing may be an important new breeding tool to supplement conventional methods."

Strauss points out that despite the promising findings, trees genetically modified as they were in this research could not legally be planted in Brazil, a nation with some of the largest economic value from eucalyptus tree farming.

"The trait could not be used there due to laws against modifying plant reproduction with recombinant DNA methods," he said. "It would also be disallowed for field research or commercial use under sustainable forest management certification in many parts of the world - something scientists have come together to severely criticize in recent years."

A little more than two years ago, Strauss was part of a coalition of forestry researchers to call for a review of what they see as overly restrictive policies regarding biotech research.

"Hopefully, studies like this one, that show how precise and safe the technology can be in modifying traits, and that help to promote ecological safety, will help to change regulations and certification rules," he said. "Happily, such discussions are well underway in many nations."

Credit: 
Oregon State University

Silver linings to New Zealand lockdown

image: Department of Psychological Medicine
University of Otago, Wellington

Image: 
University of Otago

Two thirds of New Zealanders believed there were 'silver linings' to the country's Alert Level 4 COVID-19 lockdown imposed in March last year, a University of Otago survey has found.

The researchers were able to question New Zealanders while they were at home, giving a unique insight into their lives during the nationwide lockdown between 25 March and 23 April, widely regarded as one of the strictest imposed anywhere in the world.

One year on from lockdown, the results of their study have been published in the international scientific journal, PLOS ONE.

Participants were asked 'Have you experienced any silver linings, or positive aspects during the COVID-19 Level 4 lockdown' and were able to answer 'yes, for me personally', and/or 'yes for wider society', or no. Of the 2,010 participants who completed the online survey, 64 per cent said they could see a silver lining to lockdown.

Lead researcher Dr Matthew Jenkins says New Zealanders talked about a wide range of positive experiences during lockdown, from pride in the country's response, to having more free time to exercise, take up hobbies, or build relationships with their neighbours.

"Lockdown represented a major flashpoint in people's lives and created an opportunity to stop, take stock and to reflect and connect with others.

"Many people reported that kindness and helping behaviours became more common over this period. They described an 'old fashioned sense of community and caring ... that was not apparent before lockdown'."

Increased flexibility in working from home and reduced time spent commuting was frequently mentioned as one of the silver linings of lockdown, enabling people to spend more time with their families.

"Because of the social distancing measures in place, technology became a major way for people to connect socially and for work via online services such as videoconferencing. One participant reported they 'got to speak with my Dad, who lives overseas, daily' while another joined a global online knitting group to maintain social interactions."

Others reported the pride they felt in the country's response to the pandemic, with one commenting, 'we may be a small country, but we are doing an amazing job'.

"There was an increased sense of national unity, expressed by one participant as '... it's brought New Zealanders together, united in our shared COVID experience'."

Participants also talked about the respite that lockdown offered for the environment, with one observing there was, 'less air pollution and nature (was) having a break from humans destroying it' and another enjoying 'hearing birds sing'.

Dr Jenkins says the research offers a valuable insight into what kinds of support could help people survive and thrive under adverse circumstances.

"Our findings show that in a time of turmoil, unrest and psychological distress, many people nonetheless found silver linings. We also speculate that, despite the impact of the lockdown, many people had their psychological needs for social connectedness and autonomy met, and these were likely to have influenced compliance with lockdown measures.

"Identifying these silver linings will help Governments and mental health practitioners identify the support required to help people survive and thrive during prolonged and stressful events, such as pandemics and lockdowns."

Credit: 
University of Otago

Nanoparticles reveal their location via mirror SELFI

image: Can a mirror turn an orange into a doughnut?

Image: 
Dr Fan Wang

Can a mirror turn an orange into a doughnut? The answer is definitely no in the real (macro) world. But at the nanoscale, a mirror can turn an "orange" shaped pattern into a "doughnut" shaped pattern by overlapping the "orange" with its reflected mirror image.

A team of researchers from the University of Technology Sydney (UTS) has shown for the first time that fluorescent nanoparticles placed near a mirror generate unique patterns that can be used to pinpoint their location.

The researchers attribute this effect to the light emitting nanoparticle's interference with its own mirror image. Using this method they can also detect the size of particles to a resolution of one nanometre - or around 1/80,000th of the diameter of a human hair.

This breakthrough in ultra-sensitive measuring technology, published in Nature Communications, could have many applications including tracking and analysing disease causing viruses and other pathogens.

"When we look in a mirror it doesn't change our physical shape, but that's not the case with emission patterns of nanoparticles," says leading co-author Dr Fan Wang from the UTS Institute for Biomedical Materials and Devices.

"If you put a nanoparticle in front of a mirror, it will change its image by itself, and the image shape reflects the spacing between the particle and the mirror. This is due to the phase difference between the emitter and its image," he says.

The researchers describe this encoding of position information from a particle emission's self-interference as the "SELFI effect". The resulting patterns include Gaussian, doughnut and archery target shapes.

"To the best of our knowledge, the spatial distribution of the spontaneous emission's SELFI from multiple emitters at the nanoscale has not been reported," says leading co-author Professor Dayong Jin.

"This SELFI leads to a fast, high-resolution and anti-drift sensing method to accurately resolve the position of a single nanoparticles."

The nanoparticles are doped with many rare-earth element ions to achieve the necessary luminescence to create an effective SELFI.

The authors note this new method is suitable for conventional widefield fluorescence microscopy setups without requiring system modification.

Credit: 
University of Technology Sydney

Misogynistic tweets correlate with violence against women

image: The UNSW study is the first to use big data to predict domestic violence from misogynistic tweets across a two-year period.

Image: 
Dave Akshar on Unsplash

Areas with a relatively greater amount of misogynistic tweets have higher incidences of domestic and family violence, a UNSW study has found.

The study, published in Psychological Science, not only found this connection with domestic and family violence carried over from one year to the next, but also occurred despite the 'usual suspects' of domestic violence, such as alcohol and inequality.

Examples of misogynistic tweets identified by the researchers included, "Women are all bitches," "Whore had it coming," and, "Make me a sandwich, slut."

"We found that misogynistic social media may not be harmless," Professor Tom Denson from UNSW's School of Psychology said.

"It contributes to norms of violence toward women and a hostile worldview that may slip into real-world violence.

"I imagine a lot of people are fairly flippant about what is posted on social media.

"This study suggests caution about posting misogynistic hate speech as even if the person who posts is not violent, such posts seem to create an atmosphere where violence toward women may be more likely."

The UNSW study is the first to use big data to predict domestic violence from misogynistic tweets across a two-year period.

"There is a growing interest in using big data to help address social problems such as criminality," Prof. Denson said.

The research team compiled all of the data reported by local law enforcement agencies in the US to the Federal Bureau of Investigation on arrests for domestic and family violence during a two-year period (2013 - 2014).

They also collected data on a number of population-level characteristics that are known to influence domestic and family violence, such as the availability of alcohol, income inequality, gender inequality, and population size.

"We then collected Twitter data from 2013-2014," Prof. Denson said.

"Twitter makes a randomly selected 1% of their tweets publicly available.

"We coded those tweets for misogynistic content using automated methods and used a geolocation algorithm to locate the origin of the tweets, which we were able to do with a pretty high degree of spatial specificity based on US Census Bureau defined areas."

The researchers ended up with tweets from 827 areas in 47 American states.

"We then combined the data sets and used the number of misogynistic tweets in each area to examine the relationship between misogynistic tweets and domestic and family violence arrests, while controlling for things like alcohol availability, population, and inequality."

The research is part of a growing number of studies examining the extent to which social media can be used to learn more about criminal offending, co-author and PhD candidate at UNSW School of Psychology, Siobhan O'Dean said.

"Other studies have used social media to predict theft, public disorder during right-wing events, and violence and arrests during the 2015 Black Lives Matter protests," Ms O'Dean said.

"Our research contributes to this imperative by finding out how social media can help determine where domestic and family violence is likely to occur.

"That information could be useful for not only law enforcement but also public health interventions which may intervene to counteract norms of misogynistic violence."

The researchers said future research using big data could examine the relationship between misogynistic social media directed toward proponents of the MeToo movement and Women's Marches with subsequent decreases or increases in violence against women.

Credit: 
University of New South Wales

Estimating costs of uterine transplantation

image: From left: Thomas Davidson and Lars Sandman, Linkoping University, and Mats Brannstrom, University of Gothenburg

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Photo: Emma Busk Winquist, Charlotte Perhammar and Cecilia Hedström

Sweden's acclaimed research on uterine transplants has taken a new step forward: into the field of health economics. Now, for the first time, there is a scientifically based estimate of how much implementing the treatment costs.

The current research is based on the nine uterine transplants from living donors carried out in 2013, under the leadership of Mats Brännström, Professor of Obstetrics and Gynecology at Sahlgrenska Academy, University of Gothenburg, and Chief Physician at Sahlgrenska University Hospital.

The transplants were performed within the scope of the world's first systematic, scientifically based study in the field. After the first birth in Gothenburg in 2014, there were a further seven births before a woman outside Sweden had a baby after a uterine transplant.

Now that the survey of costs is complete, the results have been reported with certain reservations. First, the number of cases studied is restricted to nine; second, the treatment has taken place as part of a research project, subject to the requirements this has entailed. Nonetheless, the study represents an initial indication of costs.

The researchers arrived at a total average sum per transplant, now reported in the journal Human Reproduction, of EUR 74,564 in current monetary value. This figure comprises costs relating to the recipient and donor alike.

The total includes, first, screening examinations and treatments, such as in vitro fertilization (IVF), in the year preceding the transplant; second, the actual operations on the donor and recipient; and third, costs in the two months after the transplant, including sick leave.

Sick leave (25.7%) was the single largest item in the cost calculation. The other categories were postoperative inpatient care (17.8%), surgery (17.1%), preoperative examinations (15.7%), anesthesia (9.7%), medication (7.8%), postoperative testing (4.0%), and readmission to hospital (2.2%).

The total is described as relatively high, due partly to the extensive scientific requirements. In a future clinical setting, the researchers say, aggregate transplant costs would likely be lower.

Thomas Davidson, Associate Professor in the area of Health Economics and Health Technology Assessment at Linköping University, and first author of the study, puts the matter in perspective.

"In terms of priorities, this study is important because it contributes key data for deciding whether to offer uterine transplants within publicly funded health care. A cost estimate is the starting point for upcoming assessment of whether the intervention is cost-effective."

Cost-effectiveness is usually measured in terms of cost per quality-adjusted life year (QALY) gained -- a yardstick that combines economic aspects with longevity and quality of life.

"In assessing cost-effectiveness, we have to relate both costs and effects, preferably measured in QALYs, to those of alternative treatments," Davidson says.

Lars Sandman -- Professor of Health Care Ethics, head of the Centre for Priority Setting in Health Care at Linköping University, and the study's co-author -- adds his comments.

"There are still essential issues we want to keep investigating. One is how we should regard the effects of a uterine transplant. Should the QALY gain generated include only the benefit to the mother of getting pregnant, giving birth and being the child's parent? Or should the benefit of a child being born and living on for a number of years, adding QALYs, be included as well? It makes a big difference in terms of the cost-effectiveness of the intervention, which is an important factor in the priority-setting context."

Professor Mats Brännström, corresponding author, sums up.

"All the costs of investigation, staff, and hospital care were funded through research grants. The grand total is close to what we'd calculated, and comparable to the current cost of kidney transplantation from a living donor. In all probability, future uterine transplantation will be more cost-effective thanks to the robot-assisted surgical technique we've developed, which means shorter hospital stays and patients returning to work sooner."

Credit: 
University of Gothenburg

Myositis-specific autoreactive T cells are pathogenic for dermatomyositis

Tsukuba, Japan - Dermatomyositis is an idiopathic inflammatory myopathy that has been regarded as an autoimmunity-based disorder, although its pathogenesis remains unclear. In this study, researchers from the University of Tsukuba used a mouse model to identify a mechanism by which dermatomyositis may develop in humans. The animal model and findings can be used to better understand the disease and develop disease-specific treatments.

Dermatomyositis belongs to a group of idiopathic inflammatory myopathies that are associated with the presence of specific autoantibodies in patient sera. Multiple myositis-specific autoantibodies, which target proteins ubiquitously expressed in the nucleus or cytoplasm, have been described. One of these autoantibodies is specific for transcriptional intermediary factor 1γ (TIF1γ).

"Autoimmune diseases constitute a difficult challenge for patients and doctors," says lead author of the study, Professor Naoko Okiyama. "Not only are the diagnosis and treatment of autoimmune diseases clinically difficult, but it is often unclear why and how the diseases developed. In this study, we investigated the role of a specific autoantibody present in the sera of patients with dermatomyositis, the anti-TIF1γ antibody, in the pathogenesis of the disease."

To achieve their goal, the researchers injected TIF1γ protein into normal mice, as well as several mouse models lacking proteins that play distinct roles in the body's immune response. The researchers' aim was to determine which part of the immune system contributes to the development of dermatomyositis. In normal mice, injection of TIF1γ resulted in the production of TIF1γ-specific T cells and anti-TIF1γ autoantibodies, thereby inducing myositis. In this myositis, CD8+ T cell infiltration into muscle cells resulted in muscle fiber wasting. Generally, CD8+ T cells are important for eliminating infected cells, cancer cells, and other damaged cells.

Importantly, the disease severity was significantly reduced when TIF1γ was injected into mice that lacked the ability to present antigens to CD8+ T cells. Adoptive transfer of CD8+ T cells, but not antibodies, collected from TIF1γ-treated mice led to myositis in recipient mice. This suggests that autoreactive CD8+ T cells against TIF1γ contribute to the pathogenesis of dermatomyositis, while autoantibodies against TIF1γ are simply non-pathogenic clinical diagnostic markers.

"In contrast to existing animal models of experimental myositis, which use muscle-specific antigens, our results show that autoreactive T cell-mediated autoimmunity to TIF1γ may play a causal role in dermatomyositis. This new experimental model may be a new tool to further investigate the disease and develop new therapeutics against dermatomyositis," says Professor Okiyama.

Credit: 
University of Tsukuba

Mosel vineyards are preparing for climate change by sharing their soil with aromatic

image: Pictures from te case study in Germany

Image: 
Diverfarming

The landscape of sloping vineyards on the banks of the River Mosel in Germany is a characteristic symbol of a region, which cannot be understood without its wine: the Mosel wine region. Tourists from all over the world, especially from the neighbouring countries of Belgium, Luxembourg, and The Netherlands visit the area in search of mountains and wine. However, the lack of new generations and the increase in temperatures and short heavy summer rainfall events caused by climate change endanger the production of wine.

In this sense, the European H2020 Diverfarming Project began in 2018 the diversification of a steep-slope, very stony (up to 70%) ecological vineyard. In the majority of the vineyards, the introduction of herbaceous species for plant cover has become widespread, with herbaceous plants in the alleys between the grapevines, but beneath them, it is combated with herbicides or mechanically. With the aim of reducing soil erosion, increasing soil fertility, and mitigating the effects of greenhouse-gas emissions, a team of researchers from the Trier University (Germany) coordinated by Professor Manuel Seeger and Professor Sören Thiele-Bruhn put into practice the introduction of aromatic plants (thyme and oregano) beneath the grapevines of the 'Weingut Dr. Frey' wine-making company.

After three years of diversification the team formed by the researchers Felix Dittrich, Thomas Iserloh, Roman Hüppi, Sophie Ogan, Sören Thiele-Bruhn, Manuel Seeger, and the winemaking entrepreneur Cord Treseler have published the first results of the diversification on the productivity of the grapevines and the quality of the wine. These results show the potential possibilities that these practices have since they have not generated negative effects in the wine production.

Although a certain amount of competition was observed between the aromatic cover and the grapevines for water and nutrients, these effects far from being negative, give rise to thinking that they may have a positive effect on the quality of the wine, as the researcher Manuel Seeger comments. This is related to the reduction of certain nutrients: while the availability of nitrate had no change in the crop diversification, the ammonium, phosphorus, and potassium levels did decrease in the uppermost area of the soil (the first 10 cm). However, it is known that there is a certain relationship between available potassium and wine quality. The results of this study point out that a change in the availability of the mineral acidity of the soil would seem to generate an increase in the quality of these wines. Moreover, the principle of yield compensation was observed: although the yield of the grapevine is slightly lower, this is compensated by an increase in quality.

The study highlights the extreme events at climate level that have taken place over the three years of the diversification. In 2018, storms produced one month's volume of rainfall in the zone in just one hour; whilst in 2019 and 2020 there were record high temperatures and drought. In this way, it is clear that the availability of water and the climate conditions are the most determining factor for the productivity of the vineyard. Despite that being the case, if we take the extreme conditions into account, the diversification has had no negative effects on the yield of the crop or on the quality of the wine. In standardised situations and with the long-term stabilisation of the diversification this opens the door to an increase in profits thanks to the diversification.

The conservation of the characteristic landscape of the zone, the reduction in contaminant emissions, and the increase in biodiversity both in the soil as well as in other organisms such as insects will contribute added value to this sector, which is currently open to changes that enable it to face this lack of a generational substitution and the scenarios which the effects of climate change are expected to bring. All of this is to save the future of the Mosel wine.

Credit: 
University of Córdoba

Using AI to diagnose neurological diseases based on motor impairment

The way we move says a lot about the state of our brain. While normal motor behaviour points to a healthy brain function, deviations can indicate impairments owing to neurological diseases. The observation and evaluation of movement patterns is therefore part of basic research, and is likewise one of the most important instruments for non-invasive diagnostics in clinical applications. Under the leadership of computer scientist Prof. Dr Björn Ommer and in collaboration with researchers from Switzerland, a new computer-based approach in this context has been developed at Heidelberg University. As studies inter alia with human test persons have shown, this approach enables the fully automatic recognition of motor impairments and, through their analysis, provides information about the type of the underlying diseases with the aid of artificial intelligence.

For the computer-supported movement analysis, subjects usually have to be tagged with reflective markings or virtual markers have to be applied to the video material produced in the framework of the assessment. Both procedures are comparatively complicated. Furthermore, conspicuous movement behaviour has to be known in advance so that it can be further examined. "A real diagnostic tool should not only confirm motor disorders but be able to recognise them in the first place and classify them correctly," explains Prof. Ommer, who heads the Computer Vision group at the Interdisciplinary Center for Scientific Computing at Heidelberg University.

Precisely that is made possible by the novel diagnostic method developed by his team, and known as "unsupervised behaviour analysis and magnification using deep learning" (uBAM). The underlying algorithm is based on machine learning using artificial neural networks and it recognises independently and fully automatically characteristic behaviour and pathological deviations, as the Heidelberg scientist explains. The algorithm determines what body part is affected and functions as a kind of magnifying glass for behavioural patterns by highlighting different types of deviation directly in the video and making them visible. As part of this, the relevant video material is compared with other healthy or likewise impaired subjects. Progress in treating motor disorders can also be documented and analysed in this way. According to Prof. Ommer, conclusions can also be drawn about the neuronal activity in the brain.

The basis for the uBAM interface is a so-called convolutional neural network, a type of neural network that is used for image recognition and image processing purposes especially. The scientists trained the network to identify similar movement behaviour in the case of different subjects, even in spite of great differences in their outward appearance. That is possible because the artificial intelligence can distinguish between posture and appearance. Besides the recognition and quantification of impairments, a detailed analysis of the symptoms is also important. "To study them in detail, we use a generative neural network," says Prof. Ommer. "That way we can help neuroscientists and clinicians focus on subtle deviations in motor behaviour that are likely to be overlooked with the naked eye, and make them easily visible by magnifying the deviation. Then we can exactly demarcate the type of disease in the individual case."

The research team has already been able to prove the effectiveness of this new approach with the aid of different animal models and studies with human patients. They tested, inter alia, the precision with which uBAM can differentiate between healthy and impaired motor activity. In their publication on the topic, the scientists report a very high retrieval rate both in mice and human patients. "In all, our study shows that, as compared to conventional methods, the approach based on artificial intelligence delivers more detailed results with significantly less effort," Björn Ommer emphasises.

With respect to the application, the scientists hope that uBAM will be used both in basic biomedical research and in clinical diagnostics and beyond. Prof. Ommer: "The interface can be applied where traditional methods prove too complicated, tedious, or not efficient enough. Potentially it could lead to a better understanding of neuronal processes in the brain and the development of new therapeutic options."

Besides the Heidelberg researchers working with Prof. Ommer, scientists from the University of Zurich and University Hospital Zurich, Balgrist University Hospital and the Neuroscience Center Zurich were also involved in developing the uBAM interface. Part of the funding for the study came from the German Research Foundation as well as the Branco Weiss Fellowship Society in Science and the Swiss National Foundation. The results were published in the journal "Nature Machine Intelligence".

Credit: 
Heidelberg University

The structure and function of cortical brain cells modulated by attention

image: Figure 1 of the study: Behavioural task and recording setup

Image: 
Demetrio Ferro, Jochem van Kempen, Michael Boyd, Stefano Panzeri and Alexander Thielee

To effectively perform any daily task, the human brain needs to process information from the outside world using various cognitive functions. This cognitive processing passes through a dense interconnected network of cells whose physiology is specialized. The interconnected cell network needs to perform this processing of information efficiently and interact cooperatively to provide us, in real time, with useful instructions for living.

Research published on 23 March in the journal Proceedings of the National Academy of Sciences of the United States of America challenges recent scientific advances seeking to find out how cognitive control and sensory information relate to the cortical machinery consisting of specialized overlapping layers of cells.

"We have had the opportunity to investigate for the first time how between different depths signals propagate between the two cortical areas V1 and V4, and how they are modulated by attention"

A study by Demetrio Ferro, first author of the article and a researcher at the Center for Brain and Cognition (CBC) of the UPF Department of Information and Communication Technologies (DTIC), which he has carried out together with researchers from the Centre for Neuroscience and Cognitive Systems, the Italian Institute of Technology (IIT), the University of Trento (Italy) and Newcastle University (UK).

Previously, it has been argued that this operation of the cell network is not implemented in a step-by-step flow process, that would the conventional algorithmic calculation we generally apply to the tools of our technology of everyday use. There might be a need for another important instrument of cognitive control to enable selecting which objects of the visual world are important for processing, i.e., focal attention.

Focal attention is an important tool of cognitive control in information processing

Anatomical arrangement of cortical brain cells

The most recent scientific evidence suggests that cognitive control over the variables in our environment may be implemented in a parallel processing flow associated with various rhythmic oscillations of neural signals used for integrating inbound details (colour, shape, spatial orientation) of the sensory visual domain.

"Moreover, it is interesting to ask ourselves whether we can inspect the architecture of neural processing units by their structure, that is, by how they are physically implemented in the anatomy of the cerebral cortex", Demetrio Ferro asserts.

And the researcher adds: "the circuits associated with these calculations show a layered structure made of laminar plates of overlapping specialized types of cell at cortical depth, each possibly specialized to perform certain functions".

For this study, the researchers worked with primates and analysed cortical electrophysiological signals at multiple depths recorded simultaneously in V1 and V4 brain areas. "Our analyses provided new knowledge about how information spreads along the dimension of depth within and between the two cortical areas V1 and V4", they assert in their study.

The authors reveal that "we have had the opportunity to investigate for the first time how this signal propagation circuit is modulated by attention, that is, to identify what depths interact with more or less force when we have more or less attention involvement".

"This study opens the way to associating deficits in fundamental cognitive functions such as attention at specific depths of neural tissue, and even the possibility of clinical-pharmacological intervention on their interaction"

First, "our contribution shows how the previous vision of canonical circuits within visual cortical areas is not immediately linked to the idea of parallel processing flows divided in frequency for cognitive control and sensory processing. Rather, the combination of the two is a more complex and interesting scene", Ferro explains.

Credit: 
Universitat Pompeu Fabra - Barcelona

First images of cells exposed to COVID-19 vaccine reveal native-like Coronavirus spikes

image: Artist image of protein spikes

Image: 
University of Southampton

New research has for the first time compared images of the protein spikes that develop on the surface of cells exposed to the Oxford-AstraZeneca vaccine to the protein spike of the SARS-CoV-19 coronavirus. The images show that the spikes are highly similar to those of the virus and support the modified adenovirus used in the vaccine as a leading platform to combat COVID-19.

The SARS-CoV-2 virus, which causes COVID-19, has a large number of spikes sticking out of its surface that it uses to attach to, and enter, cells in the human body. These spikes are coated in sugars, known as glycans, which disguise parts of the viral proteins to the human immune system.

The vaccine developed by the University of Oxford and AstraZeneca is an adenovirus-vectored vaccine, which involves taking a safe version of a virus and adding in the information from part of a pathogen, in this case the SAR-CoV-2 spike, in order to generate neutralising antibodies against that target.

In this new study, published in the journal ACS Central Science, scientists from the University of Oxford and the University of Southampton, worked together to characterise the SARS-CoV-2 spikes manufactured by the cells presented with the Oxford-AstraZeneca vaccine. The Oxford work was led by Professors Teresa Lambe, Peijun Zhang and Sarah Gilbert and Professor Max Crispin led the work in Southampton.

The Scientists exposed a range of cells in vitro to the Oxford-AstraZeneca vaccine. Using an imaging technique known as cryo-electron microscopy (cryoEM) they took thousands of images which they then combined to build up a clear picture of the resulting protein spikes on the cells. Professor Peijun Zhang, of the University of Oxford and the Electron Bio-Imaging Centre (eBIC) at Diamond Light Source, who led the imaging work said, "CryoEM is an immensely powerful technique which enabled us to visualise the dense array of spikes that had been manufactured and presented on the surface of the cells".

Further chemical analysis of the glycans that coat the newly developed protein spikes revealed that they bear a high resemblance to those surrounding the SARS-CoV-2 spikes. This is an essential feature of the vaccine as it means that it can deliver close mimics of the coronavirus that are important in triggering the immune response needed to protect against COVID-19.

Professor Crispin said, "In this study we set out to see how closely the vaccine induced spikes resembled those of the infectious virus. We were really pleased to see a large amount of native-like spikes."

"This study will hopefully provide further understanding for the public, helping them see how the Oxford-AstraZeneca vaccine works. Many people may not realise how their cells become little factories manufacturing viral spikes that then trigger the immune response needed to fight off the disease. This may also provide reassurance that the vaccine is doing its job and generating the material that we need to present to our immune systems."

Credit: 
University of Southampton

'Patchwork' tumors prevalent across multiple cancer types

Researchers at the Francis Crick Institute, as part of an international collaboration of scientists through the Pan-Cancer Analysis of Whole Genomes Consortium, have analysed the whole genomes of tumour samples from over 2,600 patients with different types of cancer. They identified a high prevalence of genetic diversity within individual tumours, which they further characterised. Their findings confirm that, even at late stages of development, tumour evolution is driven by changes that benefit the cancer.

When cancer cells divide, errors occur in the process of copying their DNA. These copying errors mean that different tumours can be made up of cells presenting a wide range of genetic diversity. This variation is a challenge for doctors as a treatment that works for one group of genetically related tumour cells, called a subclone, may not be effective against another. And certain subclones can initiate tumour spread or drug resistance.

Cancer researchers are working to understand what drives the evolution of these subclones, which arise at different points during the course of disease.

In their study, published in Cell today (7 April), researchers analysed the whole-genomes of 2,658 cancer samples, spanning 38 types of cancer. They found that 95% of samples contain at least one identifiable subclone.

They also showed that the levels of and types of genetic changes varied between cancer types. And even in the same tumour, the genetic makeup of different subclones varied widely.

Researchers think that these subclones arise due to particular evolutionary pressures present at different times during tumour development or affecting different areas of the tumour. For example, to resist a particular microenvironmental condition such as to evade the immune system.

In support of this theory, they found evidence that the evolution of subclones is affected by whether the genetic changes are helpful to the cancer subclones or not. Subclones with advantages are more likely to develop.

Peter Van Loo, author and group leader of the Cancer Genomics Laboratory at the Crick says: "Cancers are constantly changing over time, so it's important to recognise that a sample taken from a tumour reflects a single point in time and the cancer will continue to evolve after this. They can grow into a patchwork with sections driven by different mutations and evolutionary pressures.

"Understanding more about the evolution of subclones, why they develop in one direction over another, as well as how common they are, could help doctors better predict the levels of and types of variation likely to be present in a specific cancer type."

Research in this area has already shown that understanding this genetic diversity can be harnessed to predict survival or relapse, which could help doctors and patients make important treatment decisions.*

The researchers have created an open-access resource that documents the genetic variation they found in the subclones. Their computational methods are also available for others to analyse cancer genomes.

Maxime Tarabichi, author and postdoc in the Cancer Genomics Laboratory at the Crick says: "We combined a number of high-quality computational methods to analyse these complex genetic data. Reassuringly, when we put the methods together in different ways and put them through independent simulations, the results always gave findings that fit the same story."

Credit: 
The Francis Crick Institute

The opportunities and risks of digitalization for sustainable development

Digitalisation can support transitions towards a more sustainable society if technologies and processes are designed in line with suitable criteria. This requires a systemic focus on the risks and benefits of digital technologies across the three dimensions of sustainable development: the environment, society, and the economy. This is the conclusion of a study prepared by a team of researchers at the Institute for Advanced Sustainability Studies (IASS) in Potsdam. Applying this precautionary approach to digitalisation requires the active involvement of developers, users, and regulators.

Digitalisation is a complex and dynamic process often regarded as the fourth major innovation cycle in human history. The use of a systemic risk-benefit perspective could shed light on the links and interdependencies between digital technologies and the environmental, economic, and social dimensions of sustainability, emphasise the team of researchers at the IASS.

The flexibility of digital services creates important opportunities for efforts to achieve sustainability goals. However, this can also lead to path dependencies that are difficult to reverse or otherwise correct unless they are discovered at an early stage. These closely intertwined opportunities and risks call for informed and judicious decision-making in order to foster sustainable development.

Digital innovations will not deliver the 17 UN Sustainable Development Goals (SDGs) as a matter of course; instead, the development of digital innovations must be guided by:

a systemic perspective that acknowledges the connections and interdependencies between their environmental, economic and socio-cultural impacts,

a professional technology assessment informed by interdisciplinary insights, and

an inclusive decision-making style that facilitates broad participation in the development of digital services.

Digital products help reduce demand for energy and raw materials

What else will it take to foster more sustainable outcomes? Co-author and research group leader at the IASS, Pia-Johanna Schweizer, explains: "Ensuring that all sectors of society have access to digital media and possess the digital literacy needed to use them is vital to delivering an inclusive digital transformation. We also need fast and reliable Internet access nationwide - including in rural areas." Similarly, targeted support is needed for small and medium-sized enterprises as they modernize their processes.

The development of digital products and production processes that reduce energy and material demand are also important building blocks for a sustainable digital future, says co-author Grischa Beier. As Pia-Johanna Schweizer explains "Above all, it is crucial to establish clear rules for data security and data sovereignty. If these challenges are not adequately addressed, acceptance of digital innovations is likely to erode and efforts towards a sustainable digitalisation process may be jeopardized."

Finally, new societal initiatives are needed to help shape an enabling environment for the development of sustainable digital technologies and services. The three authors recommend a participatory process in which stakeholders co-design the objectives, rules and regulations for a governance structure that engages with the Sustainable Development Goals of the United Nations.

Credit: 
Research Institute for Sustainability (RIFS) – Helmholtz Centre Potsdam

Manual workers face twice the risk of developing ALS

image: Construction workers in Malta

Image: 
Source: Mark Zammit Cordina, Times of Malta

ALS is a progressive neurological disease that attacks the nerves that interact with the body's muscles. The disease typically leads to complete paralysis of the body, robbing patients of their ability to walk, speak, eat and breathe.

Researchers studied ALS patients and healthy elderly volunteers living in Malta who took part in an ongoing study aiming at identifying genetic and environmental risk factors. Malta is a sovereign microstate in the middle of the Mediterranean Sea, and is home to a geographically and culturally isolated population. Recently, Maltese ALS patients were found to have a unique genetic makeup compared to their European counterparts.

In this study, based on demographic data collected over a four-year period, the researchers found that manual workers were twice as likely to develop ALS. Indeed, close to two thirds of ALS patients reported a blue-collar job as their main occupation during their entire career.

"We have long known that Italian football players, American National Football League players and military serviceman have an increased risk of ALS compared to the general population. A common thread running through these professions is sustained or strenuous physical exertion. Our study supports this notion," said the study's lead researcher Dr Ruben J. Cauchi, PhD, a senior lecturer at the University of Malta's School of Medicine and lead investigator at the University of Malta's Centre for Molecular Medicine and Biobanking.

Despite the fact that Malta does not have professional football players nor an elite military service, the study found that sweat-inducing jobs including those in construction and carpentry were associated with a higher ALS risk. Patients in these occupations were more prone to develop bulbar-onset ALS, a form of the disease in which speech or swallowing problems appear before muscle weakness in the limbs. Patients with bulbar-onset ALS fare worse than those with limb-onset.

The setting up of a national ALS Registry and Biobank at the University of Malta in 2017, with the aim of identifying and tracking ALS patients and healthy volunteers, was key for this discovery. Right now, the research team is studying the interplay between genetics and environmental exposures in causing ALS in patients.

Credit: 
University of Malta

Foetus in bishop's coffin was probably his grandson

image: The bundle found at the feet of Peder Winstrup

Image: 
Gunnar Menander

Bishop Peder Winstrup died in 1679, and is one of the most well-preserved human bodies from the 1600s. Researchers at Lund University in Sweden may now have solved the mystery of why a foetus was hidden in his coffin in Lund Cathedral. DNA from the bishop and the foetus, along with kinship analyses, has shown that the child was probably the bishop's own grandson.

Something is protruding between Bishop Peder Winstrup's two calves. The X-ray reveals small bones. Could it be an animal? When the image is studied more closely, the osteologists from Lund University can see faint signs of what is to become the collarbones - it is a human foetus.

Inside the coffin they find the bundle, wrapped in a piece of linen cloth. Judging by the length of the femur, it was 5-6 months old and stillborn. The discovery raised a number of questions - one of them was why it was in the bishop's coffin.

"It was not uncommon for small children to be placed in coffins with adults. The foetus may have been placed in the coffin after the funeral, when it was in a vaulted tomb in Lund Cathedral and therefore accessible", says Torbjörn Ahlström, professor of historical osteology at Lund University, and one of the leading researchers behind the study.

The burial book from Lund Cathedral confirms that coffins of children were placed here, without them being related to the family.

"Placing a coffin in a vault is one thing, but placing the foetus in the bishop's coffin is quite another. It made us wonder if there was any relationship between the child and the bishop", says Torbjörn Ahlström.

Therefore, researchers at Stockholm University analyzed samples from Peder Winstrup and the foetus. The results show that it was a boy, and that they had a second-degree kinship, that is, they shared roughly 25% of the same genes. Since they had different mitochondrial lineages, but there was a Y-chromosome match, the relationship was determined to be on the father's side.

"Archaeogenetics can contribute to the understanding of kinship relations between buried individuals, and in this case more specifically between Winstrup and the foetus", says Maja Krzewinska at the Center for Paleogenetics at Stockholm University, who was involved in the analysis.

As is the case for second-degree relationships, the following constellations involving Winstrup and the foetus are possible: uncles, nephews, grandparents, grandchildren, half-siblings and double cousins. What is the most probable relationship in this scenario can be deduced from the knowledge that exists about the Winstrup family.

By studying this, the researchers were able to rule out a number of possible relationships, however, one remained a distinct possibility.

"It is possible that the stillborn baby boy was Peder Pedersen Winstrup's son, and therefore the bishop was his grandfather", says Maja Krzewinska.

Perhaps it is a family drama we see the contours of here. Peder Pedersen Winstrup did not follow in his father's and grandfather's footsteps and study theology, instead he became interested in the art of fortification. He lost his father's property in the Great Reduction in 1680, and probably lived on alms from relatives during the latter part of his life. With Peder Pedersen Winstrup's death, the male lineage came to an end for the noble family Winstrup. Placing the deceased foetus in the bishop's coffin must have been a heavily symbolic act: he had given birth to a son, albeit stillborn.

Credit: 
Lund University

New method advances single-cell transcriptomic technologies

Single-cell transcriptomic methods allow scientists to study thousands of individual cells from living organisms, one-by-one, and sequence each cell's genetic material. Genes are activated differently in each cell type, giving rise to cell types such as neurons, skin cells and muscle cells.

Single-cell transcriptomics allows scientists to identify the genes that are active in each individual cell type, and discover how these genetic differences change cellular identity and function. Careful study of this data can allow new cell types to be discovered, including previously unobserved stem cells, and help scientists trace complex developmental processes.

"Single-cell transcriptomics have revolutionised biology but are still an area in active development," explains Helena Garcia Castro, a PhD student in the Department of Biological and Medical Science at Oxford Brookes University and co-author of the paper.

"Current methods use cell dissociation protocols with 'live' tissues, which put cells under stress, causing them to change, and limiting accurate investigations."

To solve this problem, the research team used historical research and revived a process from the 19th and 20th centuries to create the ACME (ACetic acid MEthanol dissociation) method.

Scientists realised that with this method, cells did not suffer from the dissociation as it stops their biological activity and 'fixes' them from the very beginning of the investigation.

The ACME method then allows cells to be cryopreserved, one or several times throughout the process, either immediately after the dissociation process, in the field or when doing multi-step protocols.

Dr Jordi Solana, Research Fellow at Oxford Brookes University adds: "This means scientists can now exchange samples between labs, preserve the cell material and large sample sets can be frozen in order to be analysed simultaneously, without destroying the integrity of the genetic material in the cell.

"We took the method from the old papers and repurposed it to make it work with current single-cell transcriptomic techniques. With our new method, we will now set out to characterise cell types in many animals."

Scientists are now able to collaborate with other laboratories and research a wider variety of animal cells, thanks to the ACME method. This would not have been possible without the technology to dissociate and freeze live cell tissues.

Credit: 
Oxford Brookes University