Culture

LA JOLLA--Your immune system's "memory" T cells keep track of the viruses they have seen before. This immune cell memory gives the cells a headstart in recognizing and fighting off repeat invaders.

Now, a new study led by scientists at La Jolla Institute for Immunology (LJI) shows that memory helper T cells that recognize common cold coronaviruses also recognize matching sites on SARS-CoV-2, the virus that causes COVID-19.

The research, published Aug. 4, 2020 in Science, may explain why some people have milder COVID-19 cases than others--though the researchers emphasize that this is speculation and much more data is needed.

"We have now proven that, in some people, pre-existing T cell memory against common cold coronaviruses can cross-recognize SARS-CoV-2, down to the exact molecular structures," says LJI Research Assistant Professor Daniela Weiskopf, Ph.D., who co-led the new study with LJI Professor Alessandro Sette, Dr. Biol. Sci. "This could help explain why some people show milder symptoms of disease while others get severely sick."

"Immune reactivity may translate to different degrees of protection," adds Sette. "Having a strong T cell response, or a better T cell response may give you the opportunity to mount a much quicker and stronger response."

The new work builds on a recent Cell paper from the Sette Lab and the lab of LJI Professor Shane Crotty, Ph.D., which showed that 40 to 60 percent of people never exposed to SARS-CoV-2 had T cells that reacted to the virus. Their immune systems recognized fragments of the virus it had never seen before. This finding turned out to be a global phenomenon and was reported in people from the Netherlands, Germany, the United Kingdom and Singapore.

Scientists wondered if these T cells came from people who had previously been exposed to common cold coronaviruses--what Sette calls SARS-CoV-2's "less dangerous cousins." If so, was exposure to these cold viruses leading to immune memory against SARS-CoV-2?

For the new study, the researchers relied on a set of samples collected from study participants who had never been exposed to SARS-CoV-2. They defined the exact sites of the virus that are responsible for the cross-reactive T cell response. Their analysis showed that unexposed individuals can produce a range of memory T cells that are equally reactive against SARS-CoV-2 and four types of common cold coronaviruses.

This discovery suggests that fighting off a common cold coronavirus can indeed teach the T cell compartment to recognize some parts of SARS-CoV-2 and provides evidence for the hypothesis that common cold viruses can, in fact, induce cross-reactive T cell memory against SARS-CoV-2.

"We knew there was pre-existing reactivity, and this study provides very strong direct molecular evidence that memory T cells can 'see' sequences that are very similar between common cold coronaviruses and SARS-CoV-2," says Sette.

Looking closer, the researchers found that while some cross-reactive T cells targeted the SARS-CoV-2's spike protein, the region of the virus that recognizes and binds to human cells, pre-existing immune memory was also directed to other SARS-CoV-2 proteins. This finding is relevant, Sette explains, since most vaccine candidates target mostly the spike protein. These findings suggest the hypothesis that inclusion of additional SARS-CoV-2 targets might enhance the potential to take advantage of this cross reactivity and could further enhance vaccine potency.

Article #22: "Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans," by Jose Mateus et al. Please see paper PDF for full author and institution list.

Contact: Alessandro Sette at alex@lji.org (email). Daniela Weiskopf at daniela@lji.org (email).

DOI Information: Reporters wishing to link to this paper's abstract on sciencemag.org can use the following URL: https://science.sciencemag.org/lookup/doi/10.1126/science.abd3871

Note: This paper will be available for free when the embargo lifts at https://www.sciencemag.org.

News Release: A related news release is available from La Jolla Institute for Immunology in La Jolla, CA.

For Immediate Release: The paper, "Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans," by Jose Mateus and colleagues, has been added to the current Science Press Package, for immediate release (with no embargo).

Journal

Science

DOI

10.1126/science.abd3871

Researchers in China identified four key population categories useful in guiding COVID-19 public health policies aimed at minimizing the spread of the disease and reducing fatalities. The team, led by Dr. Baoguo Jiang of the Department of Orthopedics & Traumatology at Peking University People's Hospital, published their findings in the journal Precision Clinical Medicine on May 28.

"Our research develops a decision-making support model to describe SARS-COV-2 infection, and can be adjusted to reflect local transmission characteristics and public health capabilities," Dr. Jiang said. "This model will be instrumental for local authorities to determine the optimal disease suppression strategy in a data-driven and science-driven manner.

The study divided subjects into four main categories: "Isolated" (via quarantine or hospitalization), "not infected," "infected and not isolated," and "removed" (recovered or deceased). Within those broad categories, they analyzed the effectiveness of the three main things public health policy can control - whether face masks and other heightened hygiene measures are required in public, mandatory lockdowns, and mandatory social distancing.

Data collected were from Wuhan, China, where the COVID-19 outbreak began last year. In designing the study, the researchers calibrated the model based on 32,583 confirmed COVID-19 cases in Wuhan between December 2019 and March 2020. The "infected and not isolated" category presented an extra challenge, because not all infected persons displayed symptoms, yet had the potential to infect many others. To control for this, their model allows for a predetermined number of subjects presumed infected but not showing symptoms to progress to the "removed" (and recovered) category.

Public health officials in Wuhan estimated the probability of having close contact with someone infected with COVID-19 was reduced by about 75 percent amid stringent quarantine conditions. Implementing mandatory face masks and hygiene practices in public was estimated to reduce the likelihood of transmitting the infection by 50 percent.

"Our research demonstrates that implementation of case isolation and mass quarantine is the most effective measure to the complete suppression of COVID-19 outbreak," Dr. Jiang said.

The research team found that their study model could be applied in the U.S., U.K., and Italy, with only minor adjustments in likelihood of person-to-person transmission within each of the four main population categories. Population density accounted for most of those differences, explaining why cities like Wuhan and New York saw the disease spread more rapidly.

One of the study's key findings was that face masks and social distancing were not enough to reverse upward trend of the disease. Wuhan only saw reversal in COVID-19 infection rates after adding contact tracing and strict quarantines to their containment policy. Further, they found that if no quarantine was implemented and the disease was allowed to spread unchecked, over 10 million people in Wuhan alone - or about 91 percent of the population - would become infected before the population would achieve herd immunity. "Starting mass quarantine and case isolation earlier greatly improves the effectiveness of disease suppression and also demands fewer health care resources," Dr. Baoguo said.

Another important finding was that quarantine must be implemented at a rate of at least 50 percent, and a maximum of 10 weeks after the start of a COVID-19 outbreak to have a chance at reversing the infection rate. If less that 40 percent of the population remains quarantined or the quarantine begins more than 11 weeks after onset of the outbreak, it is too late, the study says.

Dr. Jiang said his team plans to further investigate how to optimally allocate prevention and control measures.

"On the one hand, through arduous efforts, our fight against COVID-19 has achieved major results with strategic significance," Dr. Jiang said. "The prevention and control measures have been normalized. On the other hand, an increasing number of asymptomatic COVID-19 carriers have been reported recently. More study on transmission characteristics of the disease among asymptomatic persons is necessary to better control the epidemic."

Researchers reported a novel technology enhancing the high transparency of refractive polymer film via a one-step vapor deposition process. The sulfur-containing polymer (SCP) film produced by Professor Sung Gap Im's research team at KAIST's Department of Chemical and Biomolecular Engineering has exhibited excellent environmental stability and chemical resistance, which is highly desirable for its application in long-term optical device applications. The high refractive index exceeding 1.9 while being fully transparent in the entire visible range will help expand the applications of optoelectronic devices.

The refractive index is a ratio of the speed of light in a vacuum to the phase velocity of light in a material, used as a measure of how much the path of light is bent when passing through a material. With the miniaturization of various optical parts used in mobile devices and imaging, demand has been rapidly growing for high refractive index transparent materials that induce more light refraction with a thin film.

As polymers have outstanding physical properties and can be easily processed in various forms, they are widely used in a variety of applications such as plastic eyeglass lenses. However, there have been very few polymers developed so far with a refractive index exceeding 1.75, and existing high refractive index polymers require costly materials and complicated manufacturing processes.

Above all, core technologies for producing such materials have been dominated by Japanese companies, causing long-standing challenges for Korean manufacturers. Securing a stable supply of high-performance, high refractive index materials is crucial for the production of optical devices that are lighter, more affordable, and can be freely manipulated.

The research team successfully manufactured a whole new polymer thin film material with a refractive index exceeding 1.9 and excellent transparency, using just a one-step chemical reaction. The SCP film showed outstanding optical transparency across the entire visible light region, presumably due to the uniformly dispersed, short-segment polysulfide chains, which is a distinct feature unachievable in polymerizations with molten sulfur.

The team focused on the fact that elemental sulfur is easily sublimated to produce a high refractive index polymer by polymerizing the vaporized sulfur with a variety of substances. This method suppresses the formation of overly long S-S chains while achieving outstanding thermal stability in high sulfur concentrations and generating transparent non-crystalline polymers across the entire visible spectrum.

Due to the characteristics of the vapor phase process, the high refractive index thin film can be coated not just on silicon wafers or glass substrates, but on a wide range of textured surfaces as well. We believe this thin film polymer is the first to have achieved an ultrahigh refractive index exceeding 1.9.

Professor Im said, "This high-performance polymer film can be created in a simple one-step manner, which is highly advantageous in the synthesis of SCPs with a high refractive index. This will serve as a platform material for future high-end optical device applications."

Hypermutation is an unusual occurence that can lead to many nearby mutations at once, severely damaging our genetic material and potentially causing cancer. The best known type of local hypermutation, called a mutation shower or thunderstorm, is quite uncommon and it leads to many mutations accumulated in a small area, e.g. a single gene.

Researchers from IRB Barcelona's Genome Data Science Lab, led by the ICREA researcher Fran Supek, have discovered a new type of hypermutation called mutation fog, which can generate hundreds of mutations in every cell. Such mutations are widely distributed, but accumulate in the most important regions of the genome, where genes reside (the so-called euchromatin). The fact that these mutations are spread around explains why they have remained undetected until now.

Surprisingly, the scientists have also identified that the newly discovered hypermutation type is related to a normal DNA repair process. When cells sense a mismatch in their DNA, they undergo a DNA repair reaction, in order to preserve genetic information. Remarkably, this reaction can become coupled to the APOBEC enzyme-typically used by human cells to defend against viruses and having an important role in fighting hepatitis and HIV. The work by the Genome Data Science Lab indicates that, in some cases, when both the APOBEC enzymes and the DNA repair process are active at the same time, APOBEC hijacks the DNA repair, generating the mutation fog.

"We think that this APOBEC-driven mutation fog has a mutagenic potential that matches or even exceeds that of well-known strong carcinogens, such as tobacco smoke or ultraviolet radiation," Fran Supek explains. Recent work by other research groups suggests that the process appears to be more active in late-stage metastatic cancers: it helps the cancer evolve, enabling it to resist drugs and radiation. "This finding makes APOBEC an attractive target for treating cancer, removing its ability to evolve and to become more aggressive," adds Supek.

The origin of a half of the mutations in some lung and breast cancers

A thorough analysis of more than 6,000 human cancer genomes, including lung tumours, breast tumours and melanomas, among others, led to the finding that the mutation fog is a common phenomenon. "More than half of all APOBEC mutations in some lung or breast cancers are generated by the hypermutation mechanism that we have found," says David Mas-Ponte, first author of the study and PhD student in the Genome Data Lab.

Some types of cancer, such as cervical or some head-and-neck cancers, are known to be due to viruses. However, this study has found mutations caused by this APOBEC system not only in these tumours but also in cancers that are not currently known to be virus-related. Further work should clarify what triggers the APOBEC system. "Understanding APOBEC better could have broad implications for cancer treatment," adds Mas-Ponte.

The HyperClust statistical method

Mas-Ponte and Supek designed a statistical method, called HyperClust, that can rapidly analyse large amounts of human genomic data to find unusual mutational processes that can lead to simultaneous mutations, such as these cases of mutation fog. This statistical method is described in the article, which has been published in Nature Genetics, and is also available as an open-source software in a Github repository.

This work has been funded by the ERC Starting Grant "HYPER-INSIGHT" awarded to Fran Supek; ICREA reaearcher and EMBO Young Investigator; and the Severo Ochoa grant awarded to IRB Barcelona. David Mas-Ponte was the recipient of an FPI-SO fellowship.

Scientists from Nanyang Technological University, Singapore (NTU Singapore) and the Agency for Science, Technology and Research (A*STAR) have showed that applying "temporal pressure" to the skin of mice can create a new way to deliver drugs.

In a paper published in Science Advances, the researchers showed that bringing together two magnets so that they pinch and apply pressure to a fold of skin, led to short term changes in the skin barrier and specifically the formation of "micropores" underneath its surface.

In tests, they showed that these micropores, of about 3 micrometres in area, allowed drugs applied on the surface of the skin to diffuse through it more easily. Six times greater quantity of drug diffused through the skin of mice with the micropores compared to the skin of mice which did not receive the temporal pressure treatment.

Lead author of the paper, Dr Daniel Lio, who did this research as part of his doctoral thesis at NTU's School of Chemical and Biomedical Engineering, Interdisciplinary Graduate Programme, said that while needles and microneedle injections damage the skin, micropores could pave the way towards painless transdermal delivery of drugs such as insulin.

"Our research project was first inspired by the traditional Chinese medicine 'tuina' therapy where physicians rub and apply pressure on skin and muscle tissue and apply a topical ointment," explained Dr Lio, who is now working at A*STAR's Enterprise Group.

Going a step further, the joint team which included Prof David Laurence Becker from NTU Lee Kong Chian School of Medicine and Skin Research Institute of Singapore; Assoc Prof Wang Xiaomeng from the NTU Lee Kong Chian School of Medicine, and Assistant Prof Xu Chenjie from the School of Chemical and Biomedical Engineering, tested the delivery of insulin through the skin of mice using the new method.

Reducing skin damage and pain from delivering drugs through skin

Experimental results showed that nanoparticles and insulin were effectively delivered through the skin of mice, at molecular masses up to 20,000 daltons.

This mass is 40 times the largest currently reported in the scientific literature for transdermal drug delivery (i.e. via patches), which is 500 daltons.

The amount of drug delivered via the temporal pressure method was also comparable to the amount delivered by a microneedle patch - dozens of needles smaller than the width of a human hair made from biocompatible compounds, commonly used to deliver small amounts of drugs through the skin over time.

Compared to conventional injection where the skin has to be penetrated and there is a risk of a hypoglycaemia effect - when the injected insulin acts too fast and the patient gets dizzy - the new method is able to slowly deliver drugs over time without breaking the skin, thus causing less pain.

In experiments, the team also found that with their method, cells in the skin layer (epidermis) were observed to have an increase in the number of "gap junctions" and a reduction in "tight junctions". These junctions control the amount of molecules being delivered between the cells: if there is an increased expression of gap junctions, more molecules can be delivered across the cell barrier, while tight junctions restrict the extracellular movement of molecules.

In the animal experiments, two magnets were used to apply pressure on the mouse dorsal skin for 1 or 5 minutes, depending on how fast the drug delivery is needed, before being removed and the drug is then topically applied like a cream.

The team hypothesised that for drugs that need to be delivered more slowly or in smaller doses - 1 minute would be sufficient, while for drugs to be delivered faster, more micropores would be needed, therefore 5 minutes would be required.

The drug was then left for 12 hours before the skin was imaged with fluorescent microscopy to see to what extent the drug had penetrated through the skin.

The team compared three types of skin: skin that received pressure treatment, skin which had not, and skin which had drugs delivered through microneedles.

Skin that received pressure treatment had similar amounts of drug delivered through the skin to that found with a microneedle patch, while skin that did not receive the pressure treatment had significantly less drug delivered.

Micropores were also observed to disappear a day after they were formed, which suggests that the skin cells have filled up the gaps.

Prof Becker, whose research expertise is in tissue repair and regeneration, said their paper highlighted the potential to use this method which could alleviate the need for diabetes patients to inject insulin multiple times daily using conventional needles and syringes.

"Patients who have to inject drugs daily, such as insulin, are constantly asking whether there is another way to deliver their medicines that doesn't involve hurting or penetrating the skin. Our new findings hold promise for them and we hope that we can refine this method so that one day it may be possible to deliver enough drugs through the skin via a patch and to rid them of their daily injections," Prof Becker added.

This multidisciplinary project, supported by the Skin Research Institute of Singapore (SRIS) - a collaboration between A*STAR, National Skin Center (NSC) and NTU, took two years and is continuing.

It is also supported by multiple grants from various agencies, which include A*STAR, SRIS, and the National Medical Research Council.

The team has since filed a patent for a pressure device, which looks like a vice-like clamp for the skin, through NTU's innovation and enterprise company, NTUtive, and is currently carrying out further experiments to refine the drug delivery mechanism.

Solar activity varies in 11-year cycles. As the activity cycle switches to a new one, the Sun is usually very calm for several years.

For a long time, researchers have believed that there is not much of interest going on in the Sun during the passive period, therefore not worth studying. Now this assumption is showed to be false by Juha Kallunki, Merja Tornikoski and Irene Björklund, researchers at Metsähovi Radio Observatory, in their peer-reviewed research article published in Solar Physics. This is the first time that astronomers are systematically studying the phenomena of the solar minimum.

Not all phenomena could be explained - yet

The researchers reached their conclusion by examining the solar radio maps detected by the Metsähovi Radio Observatory and comparing them with the data collected by a satellite observing the Sun in the ultraviolet range. The solar maps showed active areas, or radio brightenings, which can be observed on the maps as hotter areas than the rest of the solar surface. According to researchers, there are three explanations for radio brightenings.

First, some brightenings were observed in the polar areas on the solar maps that could be identified as coronal holes. Particle flows, or solar winds, ejected by coronal holes can cause auroras when they reach the Earth's atmosphere. The corona is the outer atmosphere of the Sun.

Second, the researchers observed brightenings from which, based on other observations, ejections of hot material from the surface of the sun could be detected.

Third, radio brightenings were found in areas where, based on satellite observations, strong magnetic fields were detected.

Researchers also found radio brightenings in some areas where no explanatory factor was found on the basis of satellite observations.

'The other sources used did not explain the cause of the brightening. We don't know what causes those phenomena. We must continue our research', Kallunki says.

Additional observations and research are also needed to predict whether the phenomena of the solar minimum indicate something about the next active period, about its onset and intensity, for example. Each one of the last four cycles has been weaker than the previous one. Researchers do not know why the activity curves do not rise as high as during the previous cycles.

'Solar activity cycles do not always last exactly 11 years, either', explains Docent Merja Tornikoski.

'A new activity period will not be identified until it is already ongoing. In any case, these observations of the quiet phase we are now analysing are clearly during a period when activity is at its lowest. Now we are waiting for a new rise in activity.'

Solar storms can cause danger

On the Earth, solar activity can be seen as auroras, for example. Solar activity can even cause major damage, as solar storms caused by solar flares can damage satellites, electricity networks and radio frequency communications. Research helps to prepare for such damage.

'In solar storms, it takes 2 to 3 days before the particles hit the Earth. They reach satellites higher up in orbit much faster, which would leave us even less time to prepare for damage', Kallunki points out.

Located in Kirkkonummi, Aalto University Metsähovi is the only astronomical radio observatory and continuously operational astronomical observation station in Finland. Metsähovi is internationally known for its unique, continuous datasets, including a solar monitoring programme spanning over 40 years that has collected data from scientifically very interesting high radio frequencies. This is possible thanks to the exceptionally precise mirror surface of the Metsähovi radio telescope.

Researchers have demonstrated the use of tinted, semi-transparent solar panels to generate electricity and produce nutritionally-superior crops simultaneously, bringing the prospect of higher incomes for farmers and maximising use of agricultural land.

By allowing farmers to diversify their portfolio, this novel system could offer financial protection from fluctuations in market prices or changes in demand, and mitigate risks associated with an unreliable climate. On a larger scale it could vastly increase capacity for solar-powered electricity generation without compromising agricultural production.

This is not the first time that crops and electricity have been produced simultaneously using semi-transparent solar panels - a technique called 'agrivoltaics'. But in a novel adaptation, the researchers used orange-tinted panels to make best use of the wavelengths - or colours - of light that could pass through them.

The tinted solar panels absorb blue and green wavelengths to generate electricity. Orange and red wavelengths pass through, allowing plants underneath to grow. While the crop receives less than half the total amount of light it would get if grown in a standard agricultural system, the colours passing through the panels are the ones most suitable for its growth.

"For high value crops like basil, the value of the electricity generated just compensates for the loss in biomass production caused by the tinted solar panels. But when the value of the crop was lower, like spinach, there was a significant financial advantage to this novel agrivoltaic technique," said Dr Paolo Bombelli, a researcher in the University of Cambridge's Department of Biochemistry, who led the study.

The combined value of the spinach and electricity produced using the tinted agrivoltaic system was 35% higher than growing spinach alone under normal growing conditions. By contrast, the gross financial gain for basil grown in this way was only 2.5%. The calculations used current market prices: basil sells for around five times more than spinach. The value of the electricity produced was calculated by assuming it would be sold to the Italian national grid, where the study was conducted.

"Our calculations are a fairly conservative estimate of the overall financial value of this system. In reality if a farmer were buying electricity from the national grid to run their premises then the benefit would be much greater," said Professor Christopher Howe in the University of Cambridge's Department of Biochemistry, who was also involved in the research.

The study found the saleable yield of basil grown under the tinted solar panels reduced by 15%, and spinach reduced by around 26%, compared to under normal growing conditions. However, the spinach roots grew far less than their stems and leaves: with less light available, the plants were putting their energy into growing their 'biological solar panels' to capture the light.

Laboratory analysis of the spinach and basil leaves grown under the panels revealed both had a higher concentration of protein. The researchers think the plants could be producing extra protein to boost their ability to photosynthesise under reduced light conditions. In an additional adaptation to the reduced light, longer stems produced by spinach could make harvesting easier by lifting the leaves further from the soil.

"From a farmer's perspective, it's beneficial if your leafy greens grow larger leaves - this is the edible part of the plant that can be sold. And as global demand for protein continues to grow, techniques that can increase the amount of protein from plant crops will also be very beneficial," said Bombelli.

"With so many crops currently grown under transparent covers of some sort, there is no loss of land to the extra energy production using tinted solar panels," said Dr Elinor Thompson at the University of Greenwich, and lead author of the study.

All green plants use the process of photosynthesis to convert light from the sun into chemical energy that fuels their growth. The experiments were carried out in Italy using two trial crops. Spinach (Spinacia oleracea) represented a winter season crop: it can grow with fewer daylight hours and can tolerate colder weather. Basil (Ocimum basilicum) represented a summer season crop, requiring lots of light and higher temperatures.

The researchers are currently discussing further trials of the system to understand how well it would work for other crops, and how growth under predominantly red and orange light affects the crops at the molecular level.

Computer systems that emulate key aspects of human problem solving are commonly referred to as artificial intelligence (AI). This field has seen massive progress over the last years. Most notably, deep learning enabled groundbreaking progress in areas such as self-driving cars, computers beating the best human players in strategy games (Go, chess), computer games, and in poker, and initial applications in diagnostic medicine. Deep learning is based on artificial neural networks - networks of mathematical functions that are iteratively reorganized until they accurately map the data describing a given problem to its solution.

In biology, deep learning has established itself as a powerful method to predict phenotypes (i.e., observable characteristics of cells or individuals) from genome data (for example gene expression profiles). Deep learning is usually a "black box" method: Neural networks are very powerful predictors when provided with enough training data. For example, they have been used to predict cell type from gene expression profiles, and protein structures from DNA sequence data. But standard neural networks cannot explain the learnt relationship of inputs to outputs in a human-understandable way. For this reason, deep learning has so far contributed little to advancing our mechanistic understanding of molecular functions within cells.

To address this lack of interpretability, CeMM Postdoctoral Fellow Nikolaus Fortelny and CeMM Principal Investigator Christoph Bock pursued the idea of performing deep learning directly on biological networks, instead of the generic, fully connected artificial neural networks used in conventional deep learning. They established "knowledge-primed neural networks" (KPNNs) that are based on signaling pathways and gene-regulatory networks. In KPNNs, each node corresponds to a protein or a gene, and each edge has a mechanistic biological interpretation (e.g., protein A regulates the expression of gene B).

The CeMM researchers show in their new study published in Genome Biology that deep learning on biological networks is technically feasible and practically useful. By forcing the deep learning algorithm to stay close to gene-regulatory processes that are encoded in the biological network, KPNNs create a bridge between the power of deep learning and our rapidly growing knowledge and understanding of complex biological systems. As a result, the approach provides concrete insights into the investigated biological systems, while maintaining high prediction performance. This powerful new methodology uses an optimized approach for deep learning, which stabilizes node weights in the presence of redundancy, enhances the quantitative interpretability of node weights, and controls for the uneven connectivity inherent to biological networks.

CeMM researchers demonstrated their new KPNN method on large single-cell datasets, including a compendium of 483,084 single-cell transcriptomes for immune cells established by the Human Cell Atlas consortium. In this dataset, the scientists discovered unexpected diversity in the cell-type-defining regulatory networks between immune cells from bone marrow and cord blood.

The KPNN method combines the predictive power of deep learning and its ability to infer activity levels across multiple hidden layers with the functional interpretability of biological networks. KPNNs are particularly useful for the single-cell RNA-seq data, which are generated at massive scale using single-cell sequencing assays. Moreover, KPNNs are broadly applicable to other areas of biology and biomedicine where relevant prior knowledge can be represented as networks.

The predictions and biological insights obtained by KPNNs will be useful for dissecting cell signaling and gene regulation in health and disease, for identifying novel drug targets, and for deriving testable biological hypotheses from single-cell sequencing data. More generally, the study illustrates the future impact that artificial intelligence and deep learning, will have on mechanistic biology as the scientific community learns how to make AI results biologically interpretable.

Plastic from used personal protective equipment (PPE) can, and should, be transformed into renewable liquid fuels - according to a new study, published in the peer-reviewed Taylor & Francis journal Biofuels.

Experts from The University of Petroleum and Energy Studies have suggested a strategy that could help to mitigate the problem of dumped PPE - currently being disposed of at unprecedented levels due to the current COVID-19 pandemic - becoming a significant threat to the environment.

Out today, the research show how billions of items of disposable PPE can be converted from its polypropylene (plastic) state into biofuels - which is known to be at par with standard fossil fuels.

Lead author Dr Sapna Jain explains that the transformation into biocrude, a type of synthetic fuel, "will not just prevent the severe after-effects to humankind and the environment but also produce a source of energy".

"Presently, the world is focusing to combat COVID-19, however, we can foresee the issues of economic crisis and ecological imbalance also," she explains.

"We have to prepare ourselves to meet the challenges which are forcefully imposed by the COVID-19 pandemic, so as to maintain sustainability.

"There is a high production and utilization of PPE to protect the community of health workers and other frontline workers of COVID-19. The disposal of PPE is a concern owing to its material i.e. non-woven polypropylene.

"The proposed strategy is a suggestive measure addressing the anticipated problem of disposal of PPE."

During the current COVID-19 pandemic specifically, PPE is being designed for single use followed by disposal. Once these plastic materials are discharged into the environment they end up in landfill or oceans, as their natural degradation is difficult at ambient temperature. They need decades to decompose. Recycling these polymers requires both physical methods and chemical methods. Reduction, reuse and recycling are the three pillars of sustainable development that can help to prevent the disposal of plastic to the environment.

The research team reviewed many related research articles as they looked to explore the current policies around PPE disposal, the polypropylene content in PPE, and the feasibility of converting PPE into biofuel.

In particular, they focused on the structure of polypropylene, its suitability for PPE, why it poses an environmental threat and methods of recycling this polymer.

Their conclusive findings call for the PPE waste to be converted into fuel using pyrolysis. This a chemical process for breaking down plastic at high temperature - between 300-400 degree centigrade for an hour - without oxygen.

Co-author Dr Bhawna Yadav Lamba says this process is among the most promising and sustainable methods of recycling compared with incineration and landfill.

"Pyrolysis is the most commonly used chemical method whose benefits include the ability to produce high quantities of bio-oil which is easily biodegradable," she states.

"There is always a need for alternative fuels or energy resources to meet our energy demands. The pyrolysis of plastics is one of the methods to mitigate our energy crisis."

She concludes: "The challenges of PPE waste management and increasing energy demand could be addressed simultaneously by the production of liquid fuel from PPE kits. The liquid fuel produced from plastics is clean and have fuel properties similar to fossil fuels."

Effective contact tracing and epidemic control measures are essential for safe opening of schools during COVID-19 pandemic, according to two studies published simultaneously in The Lancet Child & Adolescent Health journal.

Modelling the impact of UK schools reopening in September, one study suggests that a second COVID-19 wave could be avoided in the UK, if accompanied by a test-trace-isolate programme with sufficiently broad coverage. The second study, analysing data collected between January and April 2020 in New South Wales (Australia), finds low levels of transmissions in schools and nurseries when control measures are in place.

Children across the globe have been affected by school and nursery closures during the first wave of the COVID-19 pandemic as governments grapple with efforts to reduce transmission. However, school closures may have detrimental effects on children's physical and mental health and wellbeing and have the potential to increase inequality.

There is a lack of evidence on the role of schools in the transmission of coronavirus, with the majority of existing data based on modelling and very few studies using real-world data from schools to investigate outbreaks. Although much still remains unknown about transmission in educational settings, both studies published today point to the importance of the broader context under which schools are re-opened, as well as to the need for further research on the levels of transmission in children and teenagers.

Modelling reopening of UK schools

The modelling study, led by researchers at UCL and the London School of Hygiene and Tropical Medicine, provides the first estimates on the levels of test-trace-isolate coverage needed for schools and wider society to reopen while avoiding a second epidemic wave in the UK.

Using workplace, community, demographic and epidemiological data, the authors modelled six different scenarios of school reopening. These included full time and a part-time rota system with half of students attending school on alternate weeks, each within three testing scenarios reflecting various levels of contact tracing and testing. Alongside school reopening, the model included the relaxation of measures across society, which they assumed would accompany one another. For each scenario, they estimated the number of new infections and deaths, as well as the effective reproduction number (R).

The results of the modelling suggest a second wave in the UK might be avoided with increased levels of testing (between 59% and 87% of symptomatic people tested at some point during an active SARS-CoV-2 infection), and effective contact tracing and isolation.

For effective contact tracing and isolation, assuming 68% of contacts could be traced, 75% of individuals with symptomatic infection would need to be diagnosed and isolated if schools return full-time in September, or 65% if a part-time rota system were used. If only 40% of contacts could be traced, these figures would need to increase to 87% and 75%, respectively.

However, if levels of diagnoses and contact tracing fall below this across the UK population, reopening of schools together with gradual relaxing of the lockdown measures are likely to result in a secondary wave that would peak in December, 2020, if schools open full-time in September, and in February, 2021, if a part-time rota system were adopted in September.

In either of these scenarios of continual gradual relaxation control measures and insufficient test-trace-isolate, the authors caution that the second wave could result in the reproduction number (R) rising above 1 and a resulting secondary wave of infections 2 to 2.3 times the size of the original COVID-19 wave.

For the main study, the model assumed that children were as infectious as adults. However, since the evidence that the level of infectiousness in children compared to adults is non-conclusive, they also re-ran the model with the assumption that children and young people were 50% as infectious as adults, with the results remaining.

Dr Jasmina Panovska-Griffiths, UCL/Oxford, who lead the study, commented "Our modelling suggests that with a highly effective test and trace strategy in place across the UK, it is possible for schools to reopen safely in September. However, without sufficient coverage of a test-trace-isolate strategy the UK risks a serious second epidemic peak either in December or February. Therefore, we urge the government to ensure that test-trace-isolate capacity is scaled up to a sufficient level before schools reopen." [1]

She continues, "It's important to note that our model looked at the effects of school reopening alongside the loosening of the restrictions across society, as school reopening is likely to go hand in hand with more adults returning to work and other relaxed measures across society. Therefore, our results are reflective of a broader loosening of lockdown, rather than the effects of transmission within schools exclusively, suggesting an effective test-trace-isolate offers a feasible alternative to intermittent lockdown and school closures to control the spread of COVID-19." [1]

Professor Chris Bonell, LSHTM, one of the senior authors on the study, says, "Our study should not be used to keep schools shut because of a fear of a second wave but as a loud call to action to improve the infection control measures and test and trace system so we can get children back to school without interrupting their learning again for extended periods of time. This is even more important in the context of opening up other areas of society" [1]

The authors note some limitations of their study, highlighting that, as with any modelling study, their model rests on a series of assumptions. Although they model scenarios to resemble the UK, some of the assumptions are based on data from different settings.

Although rates of asymptomatic transmission are currently unclear this model assumes that asymptomatic infections account for 30% of onward-transmitted infections. They also note that their study does not account for the behaviour of young people who are not in school and have not assumed increased social mixing outside schools.

COVID-19 transmission in 25 schools and nurseries in New South Wales, Australia

A second, observational study, also published in The Lancet Child & Adolescent Health journal, looked at real world-data from January to April tracking COVID-19 spread within 25 schools and nurseries in New South Wales, Australia. The study finds that the risk of children and staff transmitting the virus in these educational settings was very low when contact tracing and epidemic management is in place.

Although 27 children or teachers went to school or nursery while infectious, only an additional 18 people later became infected (out of 1,448 contacts - a secondary attack rate of 1.2%).

The findings suggest that schools and nursery (known in Australia as early childhood education and care; ECEC) centres do not pose a high risk for onward transmission of coronavirus where effective contact testing strategies are in place.

Unlike many other countries, Australia, which had comparatively low COVID-19 incidence during the first wave of the epidemic, kept schools open during the first wave, with guidance in place for physical distancing and hygiene.

"Our findings are the most comprehensive data that we have yet on SARS-CoV-2 transmission in schools and early years education settings," says Professor Kristine Macartney, Director of the National Centre for Immunisation Research and Surveillance and with the University of Sydney, Australia. [1]

The study looked at laboratory-confirmed COVID-19 cases in the state of New South Wales and identified all staff, and children aged 18 and under who attended school or nurseries while infectious (including 24 hours before the onset of symptoms), using the state's centralised reporting system (the NSW Notifiable Conditions Information Management System).

All cases or their guardians were interviewed at diagnosis to track their attendance at school or nursery as well as any contact with other people during the time that they were infectious. All 3,103 schools and approximately 4,600 nurseries in New South Wales were eligible for analysis, which took place over a three-month period from the first COVID-19 case in 25 January to 10 April 2020 (end of school term).

Close contacts - defined as those with face to face interaction for a minimum of 15 minutes or 40 minutes in an indoor space with an infected person - were identified using timetables, interviews with parents and school officials. Once identified, they were monitored (with regular phone calls) and asked to quarantine for 14 days. If they began to show symptoms, they were asked to take a test, allowing the authors to calculate how many secondary transmissions were associated with each primary case identified.

Overall, 12 children and 15 adults were found to have attended schools or nurseries while infectious. These attendances took place across 15 schools and 10 nurseries.

Contact tracing identified 1,448 close contacts who were followed up with regular phone calls and instructed to be tested if they showed symptoms. 633 (43.7%) of these people were tested for COVID-19 after either showing symptoms or if they opted for a test (using either nucleic acid or antibody testing).

Of the 633 close contacts who were tested following symptoms, 18 were found to have COVID-19, meaning that 1.2% of all close contacts (1,448) were confirmed positive.

These 18 secondary transmissions happened in three schools and one nursery. The nursery outbreak was large, and involved transmission from one adult to six adults and seven children (35.1%; 13/37 contacts). Removing this one outbreak from the analysis resulted in a rate of one infection per 282 (0.4%) close contacts for education settings overall.

In a subset of seven schools and nurseries that underwent additional investigations including antibody testing, symptom surveys and extra nucleic acid testing for the virus, the child-to-child transmission rate was found to be 0.3%, and 1.0% for child-to-staff. The rate of staff-to-child transmission was 1.5% and staff-to-staff was 4.4%, suggesting that children are less likely than adults to spread the virus.

Of the total of 1.8 million children in New South Wales, the study identified only 98 children who were infected, accounting for 3.2% of total COVID-19 infections, confirming low rates of disease in this age group.

"The study adds valuable data but it is important to view these findings in the context of the NSW outbreak. It may be that higher rates of transmission occur in areas with higher levels of infection and where contact tracing and public health measures were not as rigorous as in Australia, where borders were closed and quarantine measures were strongly enforced. Schools were also closed temporarily for thorough cleaning if a pupil or staff member was found to be infected." says Professor Macartney. [1]

The one outbreak in a nursery setting was complex and occurred early in the outbreak, when criteria for testing was more narrow. The study suggests that the transmission stemmed from staff rather than children attending the centre, and a number of children were asymptomatic.

The authors caution that there are some limitations to the study, most notably that the majority of close contacts were tested after developing symptoms, suggesting that some asymptomatic or milder cases may have been missed. Furthermore, children were encouraged to stay home for distance learning from March 22 and although schools did remain open, there was a drop in school attendance from 90% to approximately 5% immediately before the school holidays in April.

In a linked commentary discussing both articles, Professor W John Edmunds, LSHTM, says, "Both studies give potential options for keeping schools open and show the clear importance of adequate contact tracing and testing. Macartney and colleagues suggest that educational settings can remain open provided measures, such as contact tracing, quarantine, and even school closures, are in place to limit spread when cases occur. Panovska-Griffiths and colleagues suggest that the safe reopening of schools in the UK could occur if the TTI programme is greatly improved. However, many questions remain, including whether there are age-related differences in susceptibility and the likelihood of transmission between children and adolescents. We urgently need large-scale research programmes to carefully monitor the impact of schools reopening, as Public Health England's sKID study aims to do. Only in this way can we take the most appropriate measures to mitigate the risks and allow us to reassure parents, pupils, and teachers alike that schools are safe to attend. There are no quick fixes to this terrible pandemic. However, it is becoming increasingly clear that governments around the world need to find solutions that allow children and young adults to return to full-time education as safely and as quickly as possible."

Shakespeare once wrote that the "eyes are the window to your soul." But scientists have found it challenging to peer into the brain to see how it derives meaning from a look into another's eyes.

Psychologists at Yale and Harvard have now found a new way to study this mystery by examining the universal and embarrassing tendency to avert one's gaze when caught looking at someone else.

In almost all cases, people instinctually follow the gaze of another. But the psychologists found an exception in the socially awkward situation in which a person caught staring averts their eyes: A third-party observer does not reflexively follow their gaze.

The researchers conclude that the brain tells the observer that there is no significance to the location where the embarrassed party has turned their attention.

"The brain is a lot smarter than we thought," said Yale's Brian Scholl, professor of psychology and senior author of the paper, published the week of Aug. 2 in the journal Proceedings of the National Academy of Sciences. "The brain is reading people's minds, not just where they are looking."

In a series of experiments, Scholl, Clara Colombatto of Yale, and Yi-Chia Chen of Harvard showed that the brain does not always turn the eyes to the focus of someone else's gaze, but only does so when it assesses that the gaze is "socially significant."

"Eye and head movements after you're 'caught' during gaze deflection do not automatically orient others' attention -- presumably because the brain can tell that such looks aren't directed toward anything in particular, but rather are just directed away from the person who was caught staring," Scholl said. "This shows how the brain is specialized not to perceive others' eyes, but rather to perceive the mind behind the eyes."

Understanding eye movement is particularly valuable during a pandemic, when they are all but the only facial feature visible above a mask, the authors said.

"This serves as a case study of both how social dynamics can shape visual attention in a sophisticated manner and how vision science can contribute to our understanding of common social phenomena," they write.

New Haven, Conn. -- Sarecycline, a drug approved for use in the United States in 2018, is the first new antibiotic approved to treat acne in more than 40 years. Now, researchers at Yale and the University of Illinois-Chicago have discovered how its unique chemical structure makes it effective.

Their new study is the most detailed biological analysis to date for sarecycline, one of a number of tetracycline antibiotics (such as doxycycline and minocycline) used to treat acne. The researchers report findings Aug. 3 in Proceedings of the National Academy of Sciences.

They found that unlike other tetracycline drugs, sarecycline binds to messenger RNA (mRNA) -- molecules within a cell that provide a code for making proteins -- in bacterial ribosomes. Ribosomes, found in all living cells, link amino acids together.

Sarecycline and other tetracyclines treat acne by inhibiting bacterial protein synthesis. They block ribosome function in Cutibacterium acnes, the pathogenic bacterium in acne.

"We show that the structure of sarecycline matters," said Dr. Christopher Bunick, associate professor of dermatology at Yale and co-corresponding author of the study. "This mode of action has never been seen before in this class of antibiotics, and suggests that sarecycline has unique properties among the tetracycline class."

Importantly, the researchers found an explanation for why sarecycline has such a low drug-resistance profile, boosting its effectiveness. Sarecycline thwarts TetM, a ribosome guardian protein that protects bacteria from outside interference.

Bunick and his team said the broader implication of the study is that structural knowledge of tetracycline compounds could be used to engineer better antibiotics.

"This could result in therapies with better or longer-lasting efficacy, fewer side effects, and lower drug resistance," Bunick said. "Future agents could be used not just in acne, but potentially in other skin disorders and infections as well."

For patients, especially those living with chronic conditions, nonadherence to prescription medicines due to cost is a common problem. By not filling prescriptions, skipping doses, delaying refills, or splitting pills, patients risk compromising the therapeutic benefit of their treatments. To understand the extent of this problem, Jamie Daw, assistant professor of Health Policy and Management at Columbia University Mailman School of Public Health and colleagues at the University of British Columbia, studied survey data from 11 high-income countries. They found that the largest disparities for non-adherence occurred among younger women in the U.S. The study results are published in the August issue of the journal Health Affairs.

The authors compared cost-related nonadherence among younger (ages 18-64) and older men and women (ages 65 or more) in eleven high-income countries including Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the United Kingdom, and the United States. They found that the largest disparities for non-adherence occurred among U.S. women compared with men -- 54 percent higher - compared to Canada at 33 percent and Australia at 17 percent higher.

Their analysis also showed that in the U.S., one in four younger women reported cost-related nonadherence compared with one in seven younger men, with no significant female-differences among older adults in any of the eleven countries.

"Prescription drug coverage systems --like those in the U.S. and Canada--that rely on employment-based insurance or require high patient contributions may disproportionally affect women, who are less likely to have full-time employment and more likely to be lower income. The disparities we found in access to medicines may produce health disparities between men and women that should be further explored," said Daw.

NASA's satellites were working overtime as they snapped pictures of the large Apple Fire in Banning Canyon near San Bernardino, California on Aug. 02, 2020. This fire began on July 31, 2020 and the cause of the fire is still under investigation. To date the fire has consumed 20,516 acres and is 5% contained.Much of the northern and eastern edge of the fire is located in very steep, rugged hillsides not easily accessible to firefighting vehicles. Low humidity, high temperatures, low moisture content in the surrounding vegetation and winds all contribute to the spread of fire once it breaks out. This fire is burning in an area that haso not had fire activity in recent years leaving it with plenty of fuel for growth. Hot, dry conditions are expected to continue in the area.