The presence of receptors for SARS-CoV-2 on a wide variety of human cells supports the idea that COVID-19 is not just a respiratory disease but an illness across multiple organs.


Human cell types within corresponding organs that express the genes for both ACE2 and CTSL (green dot) or both ACE2 and TMPRSS2 (orange dot).

by Chris Baraniuk

When the SARS-CoV-2 virus enters the human body, it breaks into cells with the help of two proteins that it finds there, ACE2 and TMPRSS2. While there has been much discussion of viral infection in gut and lung cells, researchers have dug into massive gene expression datasets to show that other potential target cells also producing ACE2 and TMPRSS2 are scattered throughout the body—including in the heart, bladder, pancreas, kidney, and nose. There are even some in the eye and brain.

The results, published in a preprint on bioRxiv April 21, show that such cells are strikingly abundant. Many are epithelial cells, which line the outer surface of organs. The new findings add to an emerging picture of SARS-CoV-2 as a virus that can target cells in many places in the human body, rather than being focused on a particular organ or part of the respiratory tract.

Cardiologist Frank Ruschitzka at the University Hospital of Zürich and colleagues separately published a letter in The Lancet April 17 in which they described how virus particles had been found in the vascular endothelium, a thin layer of cells lining blood vessels in various organs of the body, for instance.

“This is not just a virus pneumonia,” Ruschitzka, who was not involved in the latest study, tells The Scientist, referring to COVID-19. “This is a disease like we have never seen before—it is not an influenza, it hits the vessels all over, it hits the heart as well.”

To uncover the locations of cells bearing ACE2 and TMPRSS2, the preprint researchers turned to the Human Cell Atlas, a project that has allowed scientists to pool together data on human cells since 2016.

By scouring single-cell sequencing records of around 1.2 million individual cells from human tissue samples, the team was able to find out which of those cells produce both ACE2 and TMPRSS2, and note their locations in the body. The analysis used 16 unpublished datasets of lung and airway cells and 91 published datasets spanning a range of human organs.

Coauthor Christoph Muus, a graduate student at Harvard University and the Broad Institute, explains that while the data show cells in many locations in the body produce SARS-CoV-2 receptors, it’s not certain that the virus can infect all of those tissues.

“Expressing the receptor is a necessary condition but not necessarily a sufficient condition,” he says. For example, potential target cells were found in the testes, but scientists still don’t know if SARS-CoV-2 infects and replicates in that part of the body.

Jeremy Kamil, a virologist at Louisiana State University Health Shreveport, says the preprint provides important details about the human body that may help scientists understand how SARS-CoV-2 infects hosts. By finding viral protein fragments in tissue samples from patients who died because of COVID-19, scientists might be able to firm up which organs are genuine sites of infection, he adds.

“I’d say this paper gives people a roadmap at where you might want to look in the body to understand where this virus is going,” he says.

One limitation of the work is that relatively little metadata about the people who donated tissue samples were available for the various datasets, though information about age and gender were included in many. The researchers don’t know, for example, whether there was an ethnicity bias in the data, whether patients had pre-existing conditions, or whether they were taking any medications. All of these things could affect gene expression in particular cells.

Smoking status was available for a subset of the data, and the team used this to show that smoking is correlated with a greater expression of the ACE2 gene in the upper airway, but lower expression in certain lung cells. Further research is needed to understand whether this affects smokers’ susceptibility to COVID-19. Data from China suggest that smokers are 14 times more likely to develop a severe form of the disease.

Some researchers from the same group using similar data have also recently published papers in Cell and Nature. In those cases, the researchers focused on certain groups of cells. The study reported in Nature examined cells potentially involved in viral transmission and found that nasal epithelial cells, in particular, were associated with expression of ACE2 and TMPRSS2. The authors report that the virus might exploit cells that secrete fluids in the nasal passage, which might help it spread from one person to another in droplets released, say, when someone sneezes.

The Cell study, meanwhile, also found ACE2 and TMPRSS2 transcripts in nasal, gut, and lung cells but the researchers also found that the protein interferon activated ACE2 expression in vitro. The human body uses interferon to fight infections, so it is not clear whether the protein is of overall benefit or detriment to COVID-19 patients.

The use of so many different data sources backs up the validity of the preprint authors’ findings, says Marta Gaglia, a molecular biologist at Tufts University. She agrees with the researchers that discovering ACE2- and TMPRSS2-producing cells in various places around the body does not prove the virus can always infect such cells.

“I think the reality is that most of the problems come from the lung,” she adds. Plus, while doctors treating COVID-19 patients may detect problems in multiple organs, those issues might not necessarily be caused directly by SARS-CoV-2 infection, says Gaglia. A problematic immune system response, for instance, could damage certain tissues in the body as an indirect consequence of viral infection.

https://www.the-scientist.com/news-opinion/receptors-for-sars-cov-2-present-in-wide-variety-of-human-cells-67496?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_source=hs_email&utm_medium=email&utm_content=87213170&_hsenc=p2ANqtz-_vGzY0JSZbqON-CbrWnU2wp22vNPAa-zcPDPoSZR69MA0qXhi3ukYIXekJJKZ_A_GfMi8lV1cuO5y2DnnkhV-rdYFrPQ&_hsmi=87213170

Artificial Intelligence Invents New Styles of Art That People Like

By Chris Baraniuk

Now and then, a painter like Claude Monet or Pablo Picasso comes along and turns the art world on its head. They invent new aesthetic styles, forging movements such as impressionism or abstract expressionism. But could the next big shake-up be the work of a machine?

An artificial intelligence has been developed that produces images in unconventional styles – and much of its output has already been given the thumbs up by members of the public.

The idea is to make art that is “novel, but not too novel”, says Marian Mazzone, an art historian at the College of Charleston in South Carolina who worked on the system.

The team – which also included researchers at Rutgers University in New Jersey and Facebook’s AI lab in California – modified a type of algorithm known as a generative adversarial network (GAN), in which two neural nets play off against each other to get better and better results. One creates a solution, the other judges it – and the algorithm loops back and forth until the desired result is reached.

In the art AI, one of these roles is played by a generator network, which creates images. The other is played by a discriminator network, which was trained on 81,500 paintings to tell the difference between images we would class as artworks and those we wouldn’t – such as a photo or diagram, say.

The discriminator was also trained to distinguish different styles of art, such as rococo or cubism.

Art with a twist

The clever twist is that the generator is primed to produce an image that the discriminator recognises as art, but which does not fall into any of the existing styles.

“You want to have something really creative and striking – but at the same time not go too far and make something that isn’t aesthetically pleasing,” says team member Ahmed Elgammal at Rutgers University.

Once the AI had produced a series of images, members of the public were asked to judge them alongside paintings by people in an online survey, without knowing which were the AI’s work. Participants answered questions about how complex or novel they felt each image was, and whether it inspired them or elevated their mood. To the researchers’ surprise, images produced by their AI scored slightly higher in many cases than those by humans.

AIs that can tweak photos to mimic the style of famous painters such as Monet are already widely available. There are even apps that do this, such as DeepArt. But the new system is designed to produce original works from scratch.

Outside the comfort zone

“I like the idea that people are starting to push GANs out of their comfort zone – this is the first paper I’ve seen that does that,” says Mark Riedl at the Georgia Institute of Technology in Atlanta.

The results of the survey are interesting, says Kevin Walker at the Royal College of Art in London. “The top-ranked images contain an aesthetic combination of colours and patterns in composition, whereas the lowest-ranked ones are maybe more uniform,” he says (see image above).

Walker also notes that creative machines are already producing work for galleries. For example, two of his students are experimenting with AI that can learn from their drawing style to produce its own images. One, Anna Ridler, has used this technique to develop frames for a 12-minute animated film.

Art such as Ridler’s still relies heavily on human guidance, however. So will we ever value paintings generated spontaneously by a computer?

Riedl points out that the human story behind an artwork is often an important part of what endears us to it.

But Walker thinks the lines will soon get blurry. “Imagine having people over for a dinner party and they ask, ‘Who is that by?’ And you say, ‘Well, it’s a machine actually’. That would be an interesting conversation starter.”

Reference: arxiv.org/abs/1706.07068

https://www.newscientist.com/article/2139184-artificially-intelligent-painters-invent-new-styles-of-art/

Name that break computer systems

By Chris Baraniuk

Jennifer Null’s husband had warned her before they got married that taking his name could lead to occasional frustrations in everyday life. She knew the sort of thing to expect – his family joked about it now and again, after all. And sure enough, right after the wedding, problems began.

“We moved almost immediately after we got married so it came up practically as soon as I changed my name, buying plane tickets,” she says. When Jennifer Null tries to buy a plane ticket, she gets an error message on most websites. The site will say she has left the surname field blank and ask her to try again.

Instead, she has to call the airline company by phone to book a ticket – but that’s not the end of the process.

“I’ve been asked why I’m calling and when I try to explain the situation, I’ve been told, ‘there’s no way that’s true’,” she says.

But to any programmer, it’s painfully easy to see why “Null” could cause problems for software interacting with a database. This is because the word ‘null’ can be produced by a system to indicate an empty name field. Now and again, system administrators have to try and fix the problem for people who are actually named “Null” – but the issue is rare and sometimes surprisingly difficult to solve.

For Null, a full-time mum who lives in southern Virginia in the US, frustrations don’t end with booking plane tickets. She’s also had trouble entering her details into a government tax website, for instance. And when she and her husband tried to get settled in a new city, there were difficulties getting a utility bill set up, too.

Generally, the more important the website or service, the stricter controls will be on what name she enters – but that means that problems chiefly occur on systems where it really matters.

Before the birth of her child, Null was working as an on-call substitute teacher. In that role she could be notified of work through an online service or via phone. But the website would never work for Null – she always had to arrange a shift by phone.

“I feel like I still have to do things the old-fashioned way,” she says.

“On one hand it’s frustrating for the times that we need it, but for the most part it’s like a fun anecdote to tell people,” she adds. “We joke about it a lot. It’s good for stories.”

“Null” isn’t the only example of a name that is troublesome for computers to process. There are many others. In a world that relies increasingly on databases to function, the issues for people with problematic names only get more severe.

Some individuals only have a single name, not a forename and surname. Others have surnames that are just one letter. Problems with such names have been reported before. Consider also the experiences of Janice Keihanaikukauakahihulihe’ekahaunaele, a Hawaiian woman who complained that state ID cards should allow citizens to display surnames even as long as hers – which is 36 characters in total. In the end, government computer systems were updated to have greater flexibility in this area.

Incidents like this are known, in computing terminology, as “edge cases” – that is, unexpected and problematic cases for which the system was not designed.

“Every couple of years computer systems are upgraded or changed and they’re tested with a variety of data – names that are well represented in society,” explains programmer Patrick McKenzie.
“They don’t necessarily test for the edge cases.”

McKenzie has developed a pet interest in the failings of many modern computer systems to process less common names. He has compiled a list of the pitfalls that programmers often fail to foresee when designing databases intended to store personal names.

But McKenzie is living proof of the fact that name headaches are a relativistic problem. To many English-speaking westerners, the name “Patrick McKenzie” might not seem primed to cause errors, but where McKenzie lives – Japan – it has created all kinds of issues for him.

“Four characters in a Japanese name is very rare. McKenzie is eight, so for printed forms it’ll often be the case that there’s literally not enough space to put my name,” he says.

“Computer systems are often designed with these forms in mind. Every year when I go to file my taxes, I file them as ‘McKenzie P’ because that’s the amount of space they have.”

McKenzie had tried his best to fit in. He even converted his name into katakana – a Japanese alphabet which allows for the phonetic spelling of foreign words. But when his bank’s computer systems were updated, support for the katakana alphabet was removed. This wouldn’t have presented an issue for Japanese customers, but for McKenzie, it meant he was temporarily unable to use the bank’s website.

“Eventually they had to send a paper request from my bank branch to the corporate IT department to have someone basically edit the database manually,” he says, “before I could use any of their applications.”

McKenzie points out that as computer systems have gone global, there have been serious discussions among programmers to improve support for “edge case” names and names written in foreign languages or with unusual characters. Indeed, he explains that the World Wide Web Consortium, an internet standards body, has dedicated some discussion to the issue specifically.

“I think the situation is getting better, partly as a result of increased awareness within the community,” he comments.

For people like Null, though, it’s likely that they will encounter headaches for a long time to come. Some might argue that those with troublesome names might think about changing them to save time and frustration.

But Null won’t be among them. For one thing, she already changed her name – when she got married.
“It’s very frustrating when it does come up,” she admits, but adds, “I’ve just kind of accepted it. I’m used to it now.”

http://www.bbc.com/future/story/20160325-the-names-that-break-computer-systems