The former Bank of England governor says countries should invest in a cleaner economic recovery.

A chronology of key events

Key facts, figures and dates

Even two filmmaking legends can cast the wrong villains amid massive industry change.

Here's how the new Turner Classic Movies "Essentials" guest — the man behind "The Incredibles" and "Ratatouille" — has been influenced by Hitchcock, '50s sci-fi and James Bond.

• Dating apps like Tinder, Bumble, and Hinge have reported increased use amid the coronavirus pandemic, while touting virtual dating alternatives for users instead of meeting up in person.
• Swaths of users are still encouraging matches to break quarantine to have sex and go on dates, despite social distancing guidelines and fines to comply with them.
• An illustrator on Instagram has been collecting screenshots of these situations, and told Business Insider that users will brand themselves as "badasses," dispute the effectiveness of isolating, and lash out in anger and hurl abusive language when they're rejected.
• Spokespeople for Grindr, Tinder and Bumble told Business Insider they've informed users to adhere to social-distancing guidelines, but did not respond to inquiries about actions they're taking against users in places where violating lockdown orders can be against the law.
• Visit Business Insider's homepage for more stories.

As millions remain confined to their homes to prevent the spread of coronavirus, the desire for human contact and connection has risen dramatically and led some to search for ways to break those social distancing rules.

Popular dating apps — including Tinder, Bumble, and Hinge — have reported significant increases during the outbreak of swiping activity, matches between users, and messages exchanged. It's also led to the introduction of a breed of users who are interested in shirking lockdown orders, and are encouraging their matches to join them in doing the same.

Dating app users have shared stories across social media, and recently with Mashable, about messages they've received from matches who ask them to come over or want to hook up. Artist Samantha Rothenberg, who uses the handle @violetclair on Instagram, has been collecting these screenshots from followers, and told Business Insider she's received close to a thousand of such stories.

"Because of how common it is, I can honestly say that anyone who is on a dating app right now has dealt with this," Rothenberg told Business Insider. "People are horny, and a lot of people are putting that ahead of the risk and the danger."

For dating platforms whose end goal is inherently to bring its millions of users together in real life, the coronavirus outbreak has put them in a curious predicament. Dating apps are forced to balance a desire to keep people on their platform for the sake of business, with a moral responsibility to discourage users to engage in behavior with potential life-or-death implications.

Since the start of the outbreak, apps have rolled out in-app virtual dating options and touted ways users can go on virtual dates. However, the prevalence of users who are trying to meet up in person, as documented by Rothenberg and screenshots across social media, raise questions about whether these dating platforms are doing enough to stymie such behavior in the time of coronavirus.

Rothenberg has long collected screenshots of users' horror stories from dating app interactions, which she often will depict in illustrations she posts to her Instagram account. But ever since the pandemic led states to instill lockdown orders starting in March, nearly all of the screenshots she's received have had to do with coronavirus.

These lockdown-violating users fall into a few general categories, according to Rothenberg. There's the users who try to paint themselves as "badasses" for breaking the rules, though Rothenberg says they're more like "a--holes." There are the matches who propose meeting up and, after getting rejected, reverse course to say they're were joking or "testing" you, she says. You'll also encounter the anti-quarantine user, whose reasoning is based on claims about herd immunity and the ineffectiveness of social distancing measures.

The last group is made up of users who react to "no" with anger and verbal abuse, Rothenberg told Business Insider. Women told Mashable recently about encounters with men on dating apps who badgered and harassed them after they turned down in-person meetings, going to the point of gaslighting.

These types of users are what led Rothenberg to launch a petition on Change.org to hold dating apps responsible for enforcing social distancing guidelines during the pandemic. She's also been active about calling out dating apps in her Instagram Stories she posts with screenshots she receives.

"People are angry, they tell me, 'can you believe this, this is disgusting, this is wrong,'" Rothenberg said. "Because I have this platform, I feel I have a bit of a responsibility to put these [stories] out in the open and share, and bring some light into what's going on out there to people who may not know."

In late March, platforms sent out various messages and alerts to their users that Rothenberg documented on Instagram. A message to Bumble users from CEO Whitney Wolfe Herd said: "Please don't meet your Bumble matches IRL for now." Hinge users were told to "stay safe and keep connected."

Tinder, arguably the most well-know dating app, also discouraged users to meet up in a platform-wide message sent March 26.

"We know there's a lot to stay to each other as we all do our best to stay healthy and prevent the spread of the coronavirus," the message from Tinder said. "We hope to be a place for connecting during this challenging time, but it's important to stress that now is not the time to meet IRL with your match."

Dating apps' responsibilities to pivot from IRL to TXT

As companies across industries adjust business to stay afloat, dating apps have transitioned to emphasize alternatives to in-person meetups. Although online dating success has long been measured by the amount of conversations that turn to real-life connections, platforms are forced to rethink their strategy as users continue turning to them en masse. A poll conducted by Hinge found that 70% of its users said they were open to going on dates on Zoom, FaceTime, and other video platforms.

Some dating brands have introduced new features amid the pandemic. Hinge launched "Date from Home" in April, where users can indicate to a match they're ready to move their conversation off-app. Plenty of Fish started rolling out a livestreaming feature in March to users in the U.S. to allow matches to go on short virtual dates. Tinder, relatively late to the game, announced this week it was launching a video chat feature by the end of June.

A spokesperson for Match Group — the parent company on Tinder, Hinge, Plenty of Fish, and other dating platforms — told Business Insider that it made updates to its products "to help users better navigate stay-from-home policies and date digitally via phone or video."

Other apps that already enabled video chat and voice call, like The League and Bumble, are pushing these features to their users more than ever. 

But while users on these dating apps are swiping and messaging at new highs, the transition to virtual-only hasn't been as seamless for those on Grindr, the most popular dating app for gay men. Steve, a 26-year-old living in Washington, D.C., told Business Insider that activity on Grindr is "completely dead." He said he doesn't check the app nearly as often any more, but messages he does get on the app are largely from people who say they want to meet up despite the quarantine.

Grindr, like other apps, has attempted to pivot to virtual dating: The platform recently introduced Circles, where groups of up to 20 users can join chats centered around certain topics and interests. However, Steve said he's seen these groups largely dissolve into "all d--k pics."

"I dont think Grindr has the ability to rebrand itself honestly at this point for something other than hookups," Steve said. "They tried to take the opportunity to rebrand itself as something else, and it just right away became sexual."

A Grindr spokesperson told Business Insider it had sent in-app notifications to all users asking them to "refrain from in-person meetings right now."Nonetheless, an app-wide message sent to users — and shared by users on Twitter — made no mention of asking users to social distance. 

For users across these dating apps who encourage the violating of social distancing guidelines, it's unclear how much responsibility platforms have to keep their users' indoors. In some states under lockdown, authorities have doled out fines and even arrested residents found failing to follow at-home guidelines.

Grindr, Bumble and Match Group — the parent company of Tinder, Hinge, Plenty of Fish and others — told Business Insider in statements they have encouraged users to adhere to coronavirus guidelines from the World Health Organization and the Center for Disease Control.

None of the companies responded to Business Insider's requests for comment about whether asking to violate social-distancing guidelines on the platforms is a breach of policy or would garner any ban or suspension on a user.

SEE ALSO: What you need to know about Grimes, the Canadian musician who just had a baby with tech billionaire Elon Musk

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NOW WATCH: Why electric planes haven't taken off yet

• I tested a roughly $33,000 Polaris Slingshot R, a three-wheeled "autocycle."
• The three-wheeler category includes vehicles from Can-Am and Harley-Davidson, offering a motorcycle experience in a less demanding package.
• My Slingshot R had a new, Polaris-developed, 203-horsepower engine and an automatic transmission.
• In all but three US states, no motorcycle license is required to operate the Slingshot (New York, Massachusetts, and Alaska continue to require the motorcycle certification).
• The Slingshot is insanely fun, with a modest learning curve — it's a great alternative to a two-wheeler, although the price is definitely steep for the Slingshot R.
• Visit Business Insider's homepage for more stories.

Motorcycles are cool, but they aren't for everybody. Fortunately, there are some alternatives out there that offer an equally compelling, open-air experience.

One of the most popular is the the Polaris Slingshot, manufactured by the Minnesota-based powersports company. Until recently, Slingshots were available only with manual transmissions and GM-sourced engines, but for 2020, Polaris has updated the autocycle with an in-house motor and an automatic.

The automatic transmission in particular really broadens the Slingshot's potential. So I was excited to sample the machine, which I first saw about five years ago.

Polaris was kind enough to loan me a tester for a few weeks. Here's how it went:

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The Polaris Slingshot is a three-wheeled autocycle/motorcycle that Polaris industries has produced since 2014. My 2020 Slingshot R tester cost about $33,000 and was outfitted in a menacing red-and-black paint job.

The cheapest Slingshot is about $20,000.

This wasn't my first crack at a Slingshot. Polaris brought the vehicle to Insider's New York offices when the vehicle first launched.

And I generally have a gander at the Slingshot when I visit the annual New York motorcycle show.

The Slingshot is classified as either a motorcycle or an autocycle, depending on which state it's being operated in.

Yep, it looks like the Batmobile. Or Batcycle. Hard to avoid feeling like a superhero when you're behind the wheel. In all but three US states, no motorcycle license is required to drive the Slingshot. In New Jersey, you are required to wear a helmet.

Up front, you have 18-inch forged aluminum wheels, with an 20-incher at the back. The brakes have two-piece composite rotors.

Permanent open-air motoring isn't for everybody. Polaris does sell and older model, the Grand Touring, which has a cockpit canopy. The Polaris R has a waterproof interior and drain holes in the floorboards, should you get caught in bad weather.

My tester was the top-level "R" trim, complete with dual roll bars for drier and passenger.

Let's talk fender fairings! The Slingshot's are dramatic and large — I was reminded of Chevy Corvettes while driving this thing. Like a motorcycle, there's no rear-view mirror, so you have to adjust slightly to using the sideviews.

There's a new engine under the hood. Previously, Polaris used a 2.4-liter, four-cylinder GM-sourced Ecotech motor, making up to 175 horsepower. But my R had a ProStar four, also at 2.4-liters, cranking out 203 horsepower with a five-speed automatic transmission (a manual remains available). It's an in-house engine that was impressive in action.

The top speed is limited at 125 mph, and the 0-60mph run, according to Polaris and confirmed by yours truly, is about five seconds.

The four-banger redlines at 8,500 rpm and even with the automatic transmission does a pretty fair imitation of proper motorcycle acceleration. The auto is a tad crunchy, but in this context, that's a plus. It keeps you aware of what the engine is doing.

The rear wheel — fat and wide — is yoked to the motor and transmission with a belt drive. The suspension is surprisingly compliant, but you do have to be mindful of bumps, potholes, and manhole covers if you want to preserve you lower spine.

Polaris says the interior has been upgraded for 2020. No one would call it premium, but for a vehicle like this, it's rather comfortable.

The steering wheel is leather-wrapped, multifunctioned, and flat-bottomed to make getting into and out of the driver's seat easier.

The instrument cluster is a basic analog affair with a central digital display. The red button to on the right steering-wheel spoke allows you to switch between Comfort and Slingshot modes (the latter being the high-performance option).

The bucket seats are waterproof and extremely well-bolstered, with three-point seat belts.

The Slingshot's tubular frame is apparent in the doorless frame.

Not really much cargo capacity here, although I did use the Slingshot for a grocery-store run and quick jaunt to Target to buy a basketball.

There is a place to stow a smartphone, located just above the push-button gear selector.

The Slingshot also has push-button start-stop.

The glove compartment is the only other storage available ...

... And it's actually pretty roomy. One could stash a rain jacket in there, for example.

The RideCommand infotainment system is basic — but good! On a vehicle such as this, I wasn't expecting much, but the audio setup sounded decent, the screen was responsive, and Bluetooth and USB connectivity was on-par with what you'd find in any modern automobile.

There's even GPS navigation, which can display a map and provide turn-by-turn guidance.

The ride-mode selector is doubled in the infotainment system.

So what's the verdict?

I love three-wheelers. They aren't as cool as two-wheeled motorbikes, but they provide easy access to open-air motoring, and the driving/riding experience is much more engaging than what you find in convertible automobiles.

For anybody who dislikes the impracticality of motorcycles but wants to partake of the open-road lifestyle, machines like the Slingshot (the Can-Am Spyder and the Harley-Davidson Freewheeler, to name two) are ideal.

Not for nothing, they also offer aging riders a chance to yank their helmets and biker jackets out of storage to pursue moderately safer riding. With the Slingshot, gearing-up isn't necessary.

The trade-off, of course, is price. The Slingshot R that I tested costs more than an entry-level car or SUV. So, an expensive plaything. But there's nothing wrong with that. Everybody needs a hobby.

No doubt about it, the Slingshot captures attention. I lost count of how many little kids a stopped in their tracks as I tooled around the Jersey suburbs. The last vehicle that provoked such astonishment was the Lamborghini Huracán Performante. If you become a Slingshotter, prepare to be pointed at and asked for photo-ops.

Driving-wise, the Slingshot scratches an itch: on the road, the experience is unexpurgated — you don't have to be constantly vigilant, as you would on a bike, but you do need to remain aware. Highway trips are demanding. And noisy. And exhilarating. The Slingshot R is also fast and torque-y and the power goes to the single back wheel, so the while the two-wheeled front is stable, the back end can get pretty wiggly, especially in Slingshot mode, if you stomp the throttle.

I had iffy springtime Northeast weather to contend with, so I took the Slingshot out only on warm and sunny days; the rest of the time, I parked it in my garage. But the vehicle can handle being rained on, and one could also buy a cover to protect it from the elements. To be honest, however, I think it's a better choice in warm, dry climates. 

The performance is aggressively go-kart-y. This thing will make you a better drive, thanks to its point-and-shoot steering, crisp suspension, and easy access to power. It's insanely fun on curves and into corners. But it's also worthy of short road trips. In fact, the relative comfort was a shocker: I took the Slingshot out for a few hours one day and suffered no ill-effects to my lower back.

Drawback? The design is thoroughly sporty, so if you don't go in for that, the Slingshot might not be your bag. It isn't a throwback, nor is it at all steam-punky. 

It also isn't a motorcycle, in that there aren't any handlebars, you don't throw a leg, and the single wheel takes up the rear. 

But the Slingshot is a absolute blast, and if you're a weekend warrior who wants to carve up a canyon or a country road without having the grapple with a motorcycle's demands — and you don't mind dropping some dollars — the Slingshot is perfect.

The acclaimed actress and her husband, Julius Tennon, will also serve as executive producers.

It’s rather unfortunate that the best some of us can do in a time of a global pandemic is to stay at home in order to help. Quarantines for that matter, are tough challenges for the regular person. However, they don’t have to feel like an unproductive slog, why not treat yourself to some self-improvement […]

The post 12 Free Web Development Courses to Take While in Self-Isolation appeared first on SpyreStudios.

The world lost an incredible talent with the death of Tomie dePaola. 

The world lost an incredible talent with the death of Tomie dePaola. 

oscon: There's still time left to apply for #OSCON scholarships from @github + @newrelic. Deadline is 6/15 http://t.co/xQwx30jnaN

oscon: RT @andreabledsoe: So proud our #womenintech resource center is live, w/ great articles +enter to win a #OSCON scholarship...

strataconf: A roundup from the data journalism beat http://t.co/y8RVUwHO4G Global open data, scholarships, mapping a civil war & more #strataconf

strataconf: Innovative ways journalists are using data to tell stories http://t.co/y8RVUwHO4G Global open data, scholarships, mapping a civil war & more

strataconf: A roundup of healthcare tools used in the field from #hdpalooza http://t.co/0d2x3OlaeC including @MedCPU @SVBiosystems @CHRankings & more

Elana Medo has dedicated many decades of her life to making mother’s milk available to premature babies. Now a questionable trade secret lawsuit threatens to destroy her life’s work and leave preterm infants without access to life-saving milk. The cost of a Corporation Stealing from an Individual has been the loss of human lives — […]

The post Trade Secrets Claimed by Prolacta to Steal Founders’ Company – Again appeared first on ReadWrite.

Here are the latest developments in the coronavirus crisis.

An investigation over several months has revealed how Coca-Cola ignored the water-saving regulations and how the City of Cape Town failed to take any action.

The Amateur Traveler talks to Raul from Atlanta about his recent trip to Krakow Poland. Learn about this former capital of Poland which is a treasure trove of history. Raul will take us to the cloth hall in the old town, Kazimierz and the Wawel Castle. We will also talk about his trips to the unusual Wieliczka salt mine with its rock salt carvings. A very poignant side trip to Auschwitz and Birkenau makes us confront the unspeakable evil done in those two places. Raul also traveled to Wadowice, the boyhood home of the man who would later be Pope John Paul II, and Black Madonna, the home of the Black Madonna. In between we talk about Polish food (lard for your bread sir?), museums, transportation and history.

Hear about travel to Gdansk Poland as the Amateur Traveler talks to Roma and Russell from RoamingRequired.com about travel to this historic and beautiful city on the Baltic coast of Poland.

Hear about travel to Poland as the Amateur Traveler talks again to Chris Bogdon about his recent trip to Poland. Chris brought his kids and his parents to experience the country where his family came from. Chris did an overview of the country on a bus tour.

Outfit a spacecraft with a huge but incredibly lightweight mirror, and it can travel indefinitely, without fuel, at speeds that eventually exceed those of conventional rocket-powered craft.

TL;DR: Have a hot meal wherever you go with the Go portable solar oven for $119, a 14% savings as of May 9.

As we look toward upcoming summer festivities, our calendars are looking pretty bleak. Nearly every event has been postponed. Festival season was straight-up canceled. And gatherings in public places are basically extinct. With fewer options on the table, you're probably going to be spending a lot of time enjoying the great outdoors in small groups or on your own as the weather warms up. By then, you'll be sick of staying home, so it's a good thing nature isn't canceled.

As you head outside for your camping, hiking, biking, and beach excursions, you'll probably need a way to cook your own food, especially if restaurants are still closed or operating on abbreviated hours. We've got just thing, and it's on sale: the Go Portable Solar Oven. All you need is a little bit of sun and this lightweight grill can cook just about anything. Read more...

Dr Paola Subacchi, director of Chatham House’s International Economics Department, has been awarded the prestigious Order of the Star of Italy.

12 March 2015 , Volume 91, Number 2

Charles Collot, Frank Merle and Pierre Raphaël
J. Amer. Math. Soc. 33 (2020), 527-607.
Abstract, references and article information

Protease-activated receptor 2 (PAR-2) is activated by secreted proteases from immune cells or fungi. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells. We hypothesized that epithelial remodeling during diseases characterized by cilial loss and squamous metaplasia may alter PAR-2 polarization. Here, using a fluorescent arrestin assay, we confirmed that the common fungal airway pathogen Aspergillus fumigatus activates heterologously-expressed PAR-2. Endogenous PAR-2 activation in submerged airway RPMI 2650 or NCI–H520 squamous cells increased intracellular calcium levels and granulocyte macrophage–colony-stimulating factor, tumor necrosis factor α, and interleukin (IL)-6 secretion. RPMI 2650 cells cultured at an air–liquid interface (ALI) responded to apically or basolaterally applied PAR-2 agonists. However, well-differentiated primary nasal epithelial ALIs responded only to basolateral PAR-2 stimulation, indicated by calcium elevation, increased cilia beat frequency, and increased fluid and cytokine secretion. We exposed primary cells to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency, at concentrations and times that altered epithelial morphology without causing breakdown of the epithelial barrier to model early disease states. These altered primary cultures responded to both apical and basolateral PAR-2 stimulation. Imaging nasal polyps and control middle turbinate explants, we found that nasal polyps, but not turbinates, exhibit apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyps and turbinates maintained basolateral PAR-2 polarization, suggesting that the calcium responses originated from nonciliated cells. Altered PAR-2 polarization in disease-remodeled epithelia may enhance apical responses and increase sensitivity to inhaled proteases.

Research Event

Event participants

Dr Sławomir Dębski, Director, Polish Institute of International Affairs
Dr Stanley Bill, Senior Lecturer in Polish Studies, University of Cambridge

15 October 2019

In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena.

The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.

Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes.

6 February 2014 , Volume 70, Number 1

Creative righting of wrongs

5 June 2014 , Volume 70, Number 3

The Golan Heights is home to thousands of Druze who cling on tenaciously while looking over their shoulder at the chaos in their homeland

M. Burstein
Nov 1, 1970; 11:583-595
Articles

Invitation Only Research Event

Event participants

7 May 2020 , Volume 96, Number 3

The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex vivo pediatric human airway epithelial (HAE) model of hRSV infection (data are available via ProteomeXchange and can be accessed at https://www.ebi.ac.uk/pride/ with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells. hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium.

Expert

27 February 2020