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Understanding the sequence of human DNA gives scientists information about diseases, including potentially how to diagnose or treat them. In a new paper published in Nature Biotechnology, scientists from the School of Life Sciences at the University have shown that it is now possible to selectively sequence fragments of DNA more quickly and cost effectively than previously, without searching through DNA strands that are not relevant to the biological question, reaching that answer quicker than before.

This could have major implications in how genetic diseases are understood are diagnosed.

Professor Matt Loose, of the DeepSeq Sequencing Facility in the School of Life Sciences at the University led this project. He said: "In simple terms, we can now sequence the bits of DNA that we want to and ignore bits we don't. The advances we present here mean we can search through and sequence regions from genomes even as large as the human genome."

The new study shows how the team can now rapidly scan human genomes and detect genetic abnormalities on the MinION, a portable DNA sequencer. They illustrate this by locating a change in the DNA responsible for a specific type of cancer in less than 15 hours. A human genome has 3 billion data points, and a typical whole genome analysis might take several days. Thus, the team have shown that this method can now be used to 'scan' genomes at high speeds to see if there are obvious problems without having to sequence entire genomes, or perform elaborate lab processes to select the genomic regions of interest.

The team have developed a new selective method, called ReadFish, which allows the DNA sequencer to select just those regions of the human genome (or any genome) of interest for a specific question and so only need to use a single sequencing run.

Prof Loose continues: "This breakthrough will enable us to look at a range of applications, such as rapidly searching fragments of the human genome to find evidence of genetic conditions or changes which may lead to illness such as cancer - which would have major implications for diagnosis.

"We are already seeing people using the method to identify the underlying causes for diseases in a host of different individuals for the first time*."

Alexander Payne, the study's lead author, says: "Having truly adaptive sequencing, that can respond as the experiment progresses, brings lots of exciting opportunities for customising and tuning your sequencing for the question at hand. I am really looking forward to seeing how ReadFish is used by the nanopore community."

Gordon Sanghera, CEO of Oxford Nanopore, makers of the real-time, portable sequencing technology on which this work was performed, said "Alexander Payne, Matt Loose and the team have taken advantage of real time sequencing technology to intelligently zoom in on specific areas of interest in the substantial human genome. The potential impact of this work could be profound in enabling more rapid answers, on devices that are small, low cost and easy to use. This research perfectly illustrates our goal of enabling the analysis of any living thing by anyone, anywhere"

The latest study follows on from the team's previously published research in 2016, where they initially demonstrated the novel technique for highly selective sequencing. This method used real-time nanopore sequencing and enabled, for the first time, people to analyse only DNA strands that contain pre-determined signatures of interest.

In 2018, this same team led an international consortium to sequence the entire human genome on the Oxford Nanopore Technologies hand held pocket sized MinION portable DNA sequencer. At the time this required more than 40 individual sequencing runs on the portable sequencer; the technology had advanced materially since then.

What The Study Did: Researchers linked administrative health care and demographic data from Medicare to the Federal Reserve Bank of New York/Equifax Consumer Credit Panel to characterize the financial presentation of Alzheimer disease and related dementias before and after diagnosis.

Authors: Lauren Hersch Nicholas, Ph.D., M.P.P., of the Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins University School of Medicine in Baltimore, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2020.6432)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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What The Study Did: Nationally representative data were used to examine if racial disparities in the occurrence of dementia in the United States changed from 2000 to 2016.

Authors: Melinda C. Power, Sc.D., of George Washington University in Washington, D.C., is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaneurol.2020.4471)

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What The Study Did: The distribution of race/ethnicity among cases of COVID-19]-associated multisystem inflammatory syndrome in children reported to the New York City Department of Health and Mental Hygiene is described in this observational study.

Authors: Ellen H. Lee, M.D., of the New York City Department of Health and Mental Hygiene in Long Island City, New York, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.30280)

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Media advisory: The full study is linked to this news release.

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About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

What The Study Did: This observational study assessed whether receiving unemployment insurance is associated with lower health-related social needs, better health care access and better mental health during the COVID-19 pandemic.

Authors: Seth A. Berkowitz, M.D., M.P.H., of the University of North Carolina at Chapel Hill, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2020.7048)

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A research team co-led by a scientist at the Hong Kong University of Science and Technology (HKUST) has developed a method to study how HIV mutates to escape the immune system in multiple patients, which could inform HIV vaccine design.

HIV, which can lead to AIDS, evolves rapidly and attacks the body's immune system. Genetic mutations in the virus enable it to evade immune responses mounted by T cells and antibodies, which makes it all the more difficult to design an effective solution. While there is no effective cure for the virus currently available, it can be controlled with medication.

Now, the international research team has devised a new method from conventional statistical physics to reveal patterns of selection in HIV evolution using 14 patient data sets, providing a means to efficiently distinguishing the mutations that help the virus escape the immune system from those that are only random variations.

"Our novel method enables us to sort out which genetic changes provide an evolutionary advantage from those that offer no advantage or have a deleterious effect," said Prof. Matthew MCKAY, a Professor from the Departments of Electronic and Computer Engineering and Chemical and Biological Engineering, who co-led the study with Prof. John BARTON, an Assistant Professor of Physics and Astronomy at University of California, Riverside.

"The method is quite general and could be used to study diverse evolutionary processes, such as the evolution of drug resistance of pathogens and the evolution of cancers. The accuracy and high efficiency of our approach enable the analysis of selection in complex evolutionary systems that were beyond the reach of existing methods," he added.

"Understanding the genetic drivers of disease is important in the biomedical sciences," said Prof. Barton. "Being able to identify genomic rearrangements is key to understanding how illnesses occur and how to treat them." Notable examples of genetic drivers of disease include mutations that allow viruses to escape from immune control, while others confer drug resistance to bacteria.

"It can be difficult, however, to differentiate between real, adaptive mutations and random genetic variation," he added. "The new method we developed allows us to identify such mutations in complex evolving populations."

"However, it is computationally difficult to extract this information from data," he said. "We used methods from statistical physics to overcome this computational challenge. Our method can be applied generally to evolving populations and is not limited to HIV."

Some well-known diseases that have known genetic causes are cystic fibrosis, sickle cell anemia, Duchenne muscular dystrophy, colorblindness, and Huntington's disease.

"Our approach isn't limited to HIV, but there are a few reasons why we focused on HIV as a test system," Prof. McKay said. "HIV has an extraordinary capability to mutate within humans to escape from the immune system. However, the details of these immune escape dynamics are not well understood. If we can gain a clearer picture of how HIV evolves within a person, this may help to develop better treatments against the virus."

November 30, 2020 - Insilico Medicine, a leading company in AI-powered drug discovery, today announced that the paper titled "Molecular Sets (MOSES): A Benchmarking Platform for Molecular Generation Models" was published in Frontiers in Pharmacology. In addition to the authors from Insilico Medicine and Neuromation, the author list includes Simon Johansson and Hongming Chen from AstraZeneca, Benjamin Sanchez Lengeling from Harvard University, and Alan Aspuru-Guzik from Vector Institute, Department of Computer Science, University of Toronto, and Canadian Institute for Advanced Research (CIFAR).

In 2018, Insilico Medicine presented Molecular Sets (MOSES) benchmarking platform that was employed by multiple research groups since then. MOSES contains a carefully curated dataset, a set of metrics, and a wide variety of baselines for comparing generative models for chemistry. Over the last two years, we extended the repository with new baselines, enhanced evaluation protocols, and implemented simple routines for using MOSES out of the box. Today, Insilico Medicine announces that the manuscript describing the platform has been accepted for publication in Frontiers in Pharmacology, "Artificial intelligence for Drug Discovery and Development" special issue. The paper will soon be available here: https://www.frontiersin.org/articles/10.3389/fphar.2020.565644. For more information on MOSES, please visit the GitHub repository https://github.com/molecularsets/moses.

"With the rapid development of new generative chemistry, it is crucial to compare machine learning models in a unified way; with MOSES, we can easily compare new models with existing approaches without reimplementing all the baselines. MOSES is a result of tight collaboration between multiple generative chemistry labs; together we polished the platform over the last two years and made it as simple and intuitive as possible. We are glad to help researchers obtain interpretable, reproducible results with our platform.", said Daniil Polikovskiy, senior author of the paper.

To cite the paper: https://www.frontiersin.org/articles/10.3389/fphar.2020.565644

Plastics in the ocean can release chemicals that cause deformities in sea urchin larvae, new research shows.

Scientists soaked various plastic samples in seawater then removed the plastic and raised sea urchin embryos in the water.

The study, led by the University of Exeter, found that urchins developed a variety of abnormalities, including deformed skeletons and nervous systems.

These abnormalities were caused by chemicals embedded in the plastics leaching out into the water, rather than the plastics themselves.

The plastic-to-water ratio in the study would only be seen in severely polluted places, but the findings raise questions about the wider impact of plastic contaminants on marine life.

"We are learning more and more about how ingesting plastic affects marine animals," said Flora Rendell-Bhatti, of the Centre for Ecology and Conservation on Exeter's Penryn Campus in Cornwall.

"However, little is known about the effects of exposure to chemicals that leach into the water from plastic particles.

"This study provides evidence that contamination of the marine environment with plastic could have direct implications for the development of larvae, with potential impacts on wider ecosystems.

"Our work contributes to the growing evidence that we all need to help reduce the amount of plastic contamination released into our natural environment, to ensure healthy and productive ecosystems for future generations."

Dr Eva Jimenez-Guri, also of the Centre for Ecology and Conservation, added: "Many plastics are treated with chemicals for a variety of purposes, such as making them mouldable or flame retardant.

"If such plastics find their way to the oceans, these chemicals can leach out into the water.

"Plastics can also pick up and transport chemicals and other environmental contaminants, potentially spreading them through the oceans."

The study used pre-production "nurdles" (pellets from which most plastics are made) from a UK supplier, and also tested nurdles and "floating filters" (used in water treatment) found on beaches in Cornwall, UK.

For the tests, each plastic type was soaked in seawater for 72 hours, then the plastic was removed.

Analysis of the water showed all samples contained chemicals known to be detrimental to development of animals, including polycyclic aromatic hydrocarbons and polychlorinated biphenyls.

Water from the different kinds of plastic affected urchin development in slightly different ways, though all sample types led to deformity of skeletons and nervous systems, and caused problems with gastrulation (when embryos begin to take shape).

The study also raised urchin embryos in water that had contained "virgin" polyethylene particles that had not been treated with additive chemicals or collected any environmental pollutants.

These urchins developed normally, suggesting that abnormalities observed in other samples were caused by industrial additives and/or environmentally adsorbed contaminants - rather than the base plastics themselves.

Nurdles and floating filters are not waste products, so they are not deliberately discarded, but the study highlights the importance of preventing their accidental release.

The researchers say most plastics may have similar effects as those in the study, so the findings emphasise the importance of finding alternatives to replace harmful additives, and reducing overall marine plastic pollution.

A major review of palliative care services around the world has highlighted huge inconsistencies in provision, with patients in some countries receiving a fraction of the support provided elsewhere.

More than 11 million cases have been reviewed at the University of Leeds' Academic Unit of Palliative Care, which found length of care for people with life limiting and terminal conditions varies acutely across different countries - and within the countries themselves.

The researchers found:

In the UK, cancer patients are referred to palliative care earlier than patients with other life limiting conditions, despite the need being the same among both groups

In the United States, patients receive on average 10 days' fewer palliative care than in non-US countries

The shortest average duration of care was six days in Australia, while the longest was 69 days in Canada

Palliative care is internationally defined as 'the active holistic care of individuals across all ages with serious health-related suffering due to severe illness and especially of those near the end of life. It aims to improve the quality of life of patients, their families and their caregivers'. Its function is to support patients and their families with needs that arise during a serious illness, months or potentially years before death.

It has been found to be most effective if introduced at least three to four months before a patient's death, when it can improve their quality of life and reduce financial costs.

But previous studies carried out into the duration of palliative care in countries around the world revealed a wide variation in length of care.

The multi-disciplinary research team led by Leeds conducted a systematic review and meta-analysis of 169 studies from 23 countries, involving 11,996,479 patients.

They found the global average length of care from initiation to the patient's death was 18.9 days. When US data was removed, the average length increased to 29 days.

Cancer patients received care for an average of 15 days, but non-cancer patients received only six days' care.

Duration of care also varied depending on the location, from 19 days in a specialist palliative care unit; 20 at home or in the community, and six days on a general hospital ward.

And countries with very high levels of development provided on average 18.91 days of care, compared with 43 days for countries at all other levels of development.

Dr Matthew Allsop, University Academic Fellow from the Leeds Institute of Health Sciences, who co-authored the paper, said: "This study highlights a major challenge to human health worldwide.

"Our work highlights a stark shortfall in the duration of palliative care being provided internationally, with clear variation reported across countries. There is no data from low- and middle-income countries to understand at what point patients are accessing care before death - it is in these countries that provision of palliative care is most lacking.

"Increased funding is essential to develop capacity, but so too is research - to determine when people are accessing palliative care and how existing services can be improved."

The work included researchers from Hull York Medical School, and the Department of Public Health and Primary Care, Ghent University, Belgium. It was supported by National Institute for Health Research infrastructure at Leeds.

Nine UK studies were included in the analysis, covering 50,021 patients. Care lasts on average 48 days in the UK, but this varies depending on the setting. Specialist palliative care lasts nine days, whereas in the community or at home the duration is 41 days.

Some 85% of studies covering 97% of participants were from the USA, with three studies featuring more than one million participants each. Sub analysis of this data was performed, comparing it with non-US countries. The researchers found the average length of care in the US was 18.9 days - but 10 days fewer than outside it.

The report suggests this could be explained by USA models of care that restrict hospice care to patients with prognoses of fewer than six months, and have financial implications for patients.

Meanwhile, in middle income countries, the duration of palliative care was often much longer. In Brazil, the average duration was 190 days; Egypt was 66 days and Thailand 33 days. The data came from smaller samples and further research is needed to understand these findings.

Dr Allsop said: "Death affects us all. The global burden of serious health-related suffering requiring palliative care is projected to almost double by 2060 - most people either receive no palliative care, or not the amount necessary to achieve maximum benefit.

"There is a clear and significant gap between current and ideal practice, which impacts on the benefit of palliative care for patients and health care services.

"Globally palliative care needs to be highlighted as an essential component of healthcare with efforts needed to increase capacity and access to support for patients and their families."

Esports players are up to 21 per cent healthier weight than the general population, hardly smoke and drink less too, finds a new QUT (Queensland University of Technology) study.

The findings, published in the International Journal of Environmental Research and Public Health, were based on 1400 survey participants from 65 countries.

First study to investigate the BMI (Body Mass Index) status of a global sample of esports players.

Esports players were between 9 and 21 per cent more likely to be a healthy weight than the general population.

Esports players drank and smoked less than the general population.

The top 10 per cent of esports players were significantly more physically active than lower level players, showing that physical activity could influence esports expertise.

QUT eSports researcher Michael Trotter said the results were surprising considering global obesity levels.

"The findings challenge the stereotype of the morbidly obese gamer," he said.

Mr Trotter said the animated satire South Park poked fun at the unfit gamer but the link between video gaming and obesity had not been strongly established.

"When you think of esports, there are often concerns raised regarding sedentary behaviour and poor health as a result, and the study revealed some interesting and mixed results," he said.

"As part of their training regime, elite esports athletes spend more than an hour per day engaging in physical exercise as a strategy to enhance gameplay and manage stress," he said.

The World Health Organisation guidelines for time that should be spent being physically active weekly is a minimum of 150 minutes.

"Only top-level players surveyed met physical activity guidelines, with the best players exercising on average four days a week," the PhD student said.

However, the study found 4.03 per cent of esports players were more likely to be morbidly obese compared to the global population.

Mr Trotter said strategies should be developed to support players classed at the higher end of BMI categories.

"Exercise and physical activity play a role in success in esports and should be a focus for players and organisations training esports players," Mr Trotter said.

"This will mean that in the future, young gamers will have more reason and motivation to be physically active.

"Grassroots esports pathways, such as growing university and high school esports are likely to be the best place for young esports players to develop good health habits for gamers."

The research also found esports players are 7.8 per cent more likely to abstain from drinking daily, and of those players that do drink, only 0.5 per cent reported drinking daily.

The survey showed only 3.7 per cent of esports players smoked daily, with player smoking frequency lower compared to global data at 18.7 per cent.

Future research will investigate how high-school and university esports programs can improve health outcomes and increase physical activity for gaming students.

Of course, there is no weather in our sense of the word in space - nevertheless, soil can also "weather" in the vacuum of space if it is constantly bombarded by high-energy particles, such as those emitted by the sun. The Martian moon Phobos is affected by a special situation: it is so close to Mars that not only the solar wind but also the irradiation by particles from Mars plays a decisive role there. A research team from TU Wien has now been able to measure this in laboratory experiments. In just a few years, a Japanese space mission will take soil samples from Phobos and bring them back to Earth.

Billions of years of particle irradiation

"There are different theories of how the Mars moon Phobos could have formed", says Paul Szabo, who is working on his PhD thesis in the research group of Prof. Friedrich Aumayr at the Institute of Applied Physics at TU Wien. "It is possible that Phobos was originally an asteroid that was then captured by Mars, but it could also have been created by a collision of Mars with another large object."

When investigating such celestial bodies, one must always bear in mind that their surfaces have been completely changed over billions of years by cosmic particle bombardment. The surface of the Earth remains unaffected by this, because our atmosphere shields the particles. However, the geology of celestial bodies without atmospheres, such as our Moon or Phobos, can only be understood if it is possible to correctly assess "space weathering".

Therefore, elaborate experiments were conducted at TU Wien: "We used a mineral like it is found on Phobos and bombarded it in vacuum chambers with different charged particles," explains Paul Szabo. "Using an extremely precise balance, we can measure how much material is removed in the process and how much each particle affects the surface.

The special properties of the moon Phobos must be taken into account: Its distance from the surface of Mars is less than 6000 km - not even two percent of the distance between our Moon and the Earth. Just like our Moon, it is in a tidally locked rotation around its planet: The same side always faces Mars.

"Because of the extremely small distance between Mars and Phobos, not only particles emitted from the Sun play a role on the surface of Phobos, but also particles from Mars," says Paul Szabo. The Martian atmosphere consists mainly of carbon dioxide. But in the outer regions of the atmosphere there are also larger amounts of oxygen. When particles from the solar wind penetrate there, oxygen ions can be created, which then hit Phobos at high speed and change the surface material.

Data for 2024 space mission

"With our measuring methods we were able to estimate the erosion of Phobos much more accurately than was previously possible," says Friedrich Aumayr. "Our results show that the effect of oxygen ions from the Martian atmosphere cannot be neglected. It is also important to distinguish between the two sides of Phobos: While the solar wind causes the weathering on the side facing away from Mars, the bombardment from the Martian atmosphere dominates on the other side, when the Sun is shielded from Mars.

These considerations could soon play an important role in the evaluation of real Phobos samples: As early as 2024, a spacecraft is meant to reach Phobos as part of the Japanese space mission MMX (Martian Moon eXploration) and bring soil samples back to Earth.

New research involving the University of East Anglia (UEA) shows how conservation polices can avoid having unintended consequences for local ecosystems and people.

The study investigates the closure of a marine area in the western Pacific Ocean to fishing and the possible impact on offshore fish supply chains and nearshore ecosystems. The landmark Palau National Marine Sanctuary (PNMS) came into force in January and protects 80 per cent of Palau's waters, making it one of the largest marine protected areas in the world.

The research, conducted by scientists at the Stanford Center for Ocean Solutions (COS) and University of Hawai'i at Mānoa, with partners in Palau and economists in Italy and the UK,
shows that the PNMS policies which restrict industrial offshore fishing could drive up offshore fish prices and, in turn, increase tourists' consumption of reef fish.

However, the results also highlight how food branding provides economic opportunities - if tourists are offered a local and sustainable offshore fish choice, this unintended environmental impact on nearshore reef ecosystems can be avoided.

Published in the journal Nature Food, the study is part of ongoing efforts to investigate how the PNMS can help Palauans conserve biodiversity and ensure future food security.

As other nations look to meet international protected area agreements and conservation
goals, studies that analyze socioeconomic trade-offs for food systems will become
increasingly important for designing effective and sustainable protected areas, as well as
sound conservation policies.

"Our study highlights why actions to protect nature need to consider impacts to local food supply and how food branding could curtail these impacts," explained lead author Dr Staci Lewis at COS. "The establishment of a sustainable brand of offshore fish could minimize the [PNMS's] unintended impacts to reef fish consumption as well as generate economic opportunities for local fishers."

The research team surveyed more than 400 tourists in Palau to understand how conservation policies might impact tourists' behaviour and food preferences. In particular, they explored how food systems respond to conservation policies, yet also create potential win-win solutions benefiting local economies and reef ecosystems.

Co-author Dr Silvia Ferrini, from UEA's School of Environmental Sciences, said: "This research brings under scrutiny the challenges of conservation policies. Local decision makers, scientists and economists worked together to broaden our understanding of conservation policies and design solutions to overcome unintended consequences.

"The moral is that the protection of natural resources commands a systematic analysis of the three pillars of sustainability: environment, economic and society. We anticipate that other conservation policies, for example the Fisheries Act 2020, might experience negative effects, and so timely and collaborating research is vital."

According to this study, tourists are willing to pay up to $15 more for a local, sustainable offshore fish meal. By offering tourists this choice, their demand for reef fish meals would not increase, avoiding environmental impacts to cultural and ecologically important Palauan reef systems.

One of the study's Palauan researchers, Lincy Marino from Palau International Coral Reef Center, said the research was important for Palau: "We Palauans rely on our natural resources, not just for food, but for our culture and traditions. This paper provides important information to our leaders so they can create policies that ensure the PNMS will benefit all of us."

Using post-mortem tissue samples, a team of researchers from Charité - Universitätsmedizin Berlin have studied the mechanisms by which the novel coronavirus can reach the brains of patients with COVID-19, and how the immune system responds to the virus once it does. The results, which show that SARS-CoV-2 enters the brain via nerve cells in the olfactory mucosa, have been published in Nature Neuroscience*. For the first time, researchers have been able to produce electron microscope images of intact coronavirus particles inside the olfactory mucosa.

It is now recognized that COVID-19 is not a purely respiratory disease. In addition to affecting the lungs, SARS-CoV-2 can impact the cardiovascular system, the gastrointestinal tract and the central nervous system. More than one in three people with COVID-19 report neurological symptoms such as loss of, or change in, their sense of smell or taste, headaches, fatigue, dizziness, and nausea. In some patients, the disease can even result in stroke or other serious conditions. Until now, researchers had suspected that these manifestations must be caused by the virus entering and infecting specific cells in the brain. But how does SARS-CoV-2 get there? Under the joint leadership of Dr. Helena Radbruch of Charité's Department of Neuropathology and the Department's Director, Prof. Dr. Frank Heppner, a multidisciplinary team of researchers has now traced how the virus enters the central nervous system and subsequently invades the brain.

As part of this research, experts from the fields of neuropathology, pathology, forensic medicine, virology and clinical care studied tissue samples from 33 patients (average age 72) who had died at either Charité or the University Medical Center Göttingen after contracting COVID-19. Using the latest technology, the researchers analyzed samples taken from the deceased patients' olfactory mucosa and from four different brain regions. Both the tissue samples and distinct cells were tested for SARS-CoV-2 genetic material and a 'spike protein' which is found on the surface of the virus. The team provided evidence of the virus in different neuroanatomical structures which connect the eyes, mouth and nose with the brain stem. The olfactory mucosa revealed the highest viral load. Using special tissue stains, the researchers were able to produce the first-ever electron microscopy images of intact coronavirus particles within the olfactory mucosa. These were found both inside nerve cells and in the processes extending from nearby supporting (epithelial) cells. All samples used in this type of image-based analysis must be of the highest possible quality. To guarantee this was the case, the researchers ensured that all clinical and pathological processes were closely aligned and supported by a sophisticated infrastructure.

"These data support the notion that SARS-CoV-2 is able to use the olfactory mucosa as a port of entry into the brain," says Prof. Heppner. This is also supported by the close anatomical proximity of mucosal cells, blood vessels and nerve cells in the area. "Once inside the olfactory mucosa, the virus appears to use neuroanatomical connections, such as the olfactory nerve, in order to reach the brain," adds the neuropathologist. "It is important to emphasize, however, that the COVID-19 patients involved in this study had what would be defined as severe disease, belonging to that small group of patients in whom the disease proves fatal. It is not necessarily possible, therefore, to transfer the results of our study to cases with mild or moderate disease."

The manner in which the virus moves on from the nerve cells remains to be fully elucidated. "Our data suggest that the virus moves from nerve cell to nerve cell in order to reach the brain," explains Dr. Radbruch. She adds: "It is likely, however, that the virus is also transported via the blood vessels, as evidence of the virus was also found in the walls of blood vessels in the brain." SARS-CoV-2 is far from the only virus capable of reaching the brain via certain routes. "Other examples include the herpes simplex virus and the rabies virus," explains Dr. Radbruch.

The researchers also studied the manner in which the immune system responds to infection with SARS-CoV-2. In addition to finding evidence of activated immune cells in the brain and in the olfactory mucosa, they detected the immune signatures of these cells in the cerebral fluid. In some of the cases studied, the researchers also found tissue damage caused by stroke as a result of thromboembolism (i.e. the obstruction of a blood vessel by a blood clot). "In our eyes, the presence of SARS-CoV-2 in nerve cells of the olfactory mucosa provides good explanation for the neurologic symptoms found in COVID-19 patients, such as a loss of the sense of smell or taste," explains Prof. Heppner. "We also found SARS-CoV-2 in areas of the brain which control vital functions, such as breathing. It cannot be ruled out that, in patients with severe COVID-19, presence of the virus in these areas of the brain will have an exacerbating impact on respiratory function, adding to breathing problems due to SARS-CoV-2 infection of the lungs. Similar problems might arise in relation to cardiovascular function."

Molecular cages, in which guest molecules cling to the cages' outer surfaces rather than enter an internal cavity, could cut the environmental impact of separating mixtures of industrial chemicals, research from KAUST suggests.

Molecular separations performed at scale by the chemical industry collectively account for as much as 15 percent of global energy consumption. One of the most energy-intensive separations involves benzene derivatives, called xylenes, which are produced as a mixture of three isomeric forms that must be separated for their various industrial uses. The most valuable isomer, para-xylene, is a key ingredient in polyester and polyethylene terephthalate (PET) polymer manufacture.

"Conventionally, these isomers are separated by energy-demanding methods, such as fractional crystallization," says Basem Moosa, a research scientist in Niveen Khashab's lab. "Alternative techniques that require less heat would lower the carbon footprint and overall pollution of xylene separation," he adds.

Khashab and her team have been investigating the possibility of separating xylene isomers using cage-like materials, which selectively absorb one xylene isomer in the mixture, as an energy-efficient alternative separation technique. Previous research has focused on porous inorganic materials called zeolites, but processing challenges and zeolites' limited selectivity have somewhat restricted their adoption by industry.

In their latest work, KAUST researchers turned to stable, easily made organic cage materials that incorporated nitrogen-based azo groups in their structure. The materials captured the para-xylene isomer with high selectively. "Compared with other organic materials, it showed one of the highest adsorbents for xylene separations," says Aliyah Fakim, a Ph.D. student in Khashab's team. Strikingly, however, the para-xylene adsorption did not involve the isomer entering the azo-cage. Instead, the isomer stuck to the outside of the cage, forming crystals in which each para-xylene molecule was surrounded by four cage molecules.

The team plans to refine the performance of the nonporous organic cages by lowering the activation temperature and reducing the time it takes to absorb and then release the para-xylene once extracted from the mixture.

However, the concept of separation using nonporous organic cages could be adopted for many industrial-scale chemical separations, lowering the energy demand of these major industrial processes, Khashab notes. "We believe that these structures will be a next-generation, disruptive technology for many energy-intensive chemical separations," she says. "The organic cages are cheap to scale up compared to other organic materials, and most interestingly, they can be easily tuned for selective separations, unlike their inorganic zeolite counterparts."

The climate in inner East Asia may already have reached a tipping point, where recent years' transition to abnormally hot and dry summers can be irreversible. This is the finding of a new international study by researchers at University of Gothenburg now published in Science.

Associated with the ongoing global warming, are changes that impact regional climate and ecosystems. In a worst- case scenario, these can reach what is known as a tipping point, at which point changes are fast and often times irreversible. Examples of tipping points are the sea ice in the Arctic disappearing in the summer or the melting of the Greenland ice-sheet.

Inner East Asia is a sensitive area

Inner East Asia, which includes Mongolia and nearby areas, is a sensitive region that has experienced a clear increase in the number of heat waves during the summer in recent decades. Together with stable high-pressure systems, which raise temperatures, reduced soil moisture can cause intense and long-lasting heat waves because of enhanced interaction between the land surface and the atmosphere.

"What this connection looks like in a longer preindustrial context is, however, unknown since long-term observations do not exist," says Deliang Chen, co-author to the study and leader of the Regional Climate Group (RCG) at the University of Gothenburg.

Annual growth rings from trees provide information on changes that effect their growth and this can be used to study changes in climate in the past.

"By choosing trees whose growth are sensitive to weather variations, the annual rings can be used to reconstruct different climate parameters with annual resolution hundreds of years back in time. Since trees have significant geographic coverage, this data can be used for detailed studies of climate changes over large areas," says Hans Linderholm, co-author of the study and head of the Gothenburg University Laboratory for Dendrochronology (GULD).

Study of tree rings showed a tipping point is close

Long-term observations of soil moisture are rare, but tree rings from trees, which are limited by access to water, can be used as indicators of this parameter. In the same way, trees that grow at high altitudes, where the growing season is short and cool, can be used to provide temperature-related information.

"In this study, we developed a new method for reconstructing both variations in soil moisture and changes in frequency of heat waves in inner East Asia, a region where the interaction between these parameters is very strong," says Peng Zhang, first author of the study and researcher in the Regional Climate Group at the University of Gothenburg.

These new reconstructions allow the scientists to study the recent warm and dry summers in a long-term perspective. The results show that the current high frequency of heat waves and low soil moisture have not been observed during the last 260 years.

"By combining observations, reconstructions and climate model data, we discovered that the link between land surface and atmosphere has become more pronounced in inner East Asia over the last 20 years, along with increased drying of soils. So we argue that reduced soil moisture enhances land-atmosphere coupling contributing to heating of the land surface, which causes more heat waves, which in turn reduces soil moisture and so on," says Peng.

The study's authors found that the recent pattern of increased warming and drought indicate that a tipping point in the climate is close, a change that could be irreversible and lead to a much dryer climate in the region.

"This would increase the stresses of ecosystems and societies in this already vulnerable region," says Peng.