Sunday, April 11, 2021

Human airway cells prevent SARS-CoV-2 multibasic cleavage site cell culture adaptation - Docwire

Virus propagation methods generally use transformed cell lines to grow viruses from clinical specimens, which may force viruses to rapidly adapt to cell culture conditions, a process facilitated by high viral mutation rates. Upon propagation in VeroE6 cells, SARS-CoV-2 may mutate or delete the multibasic cleavage site (MBCS) in the spike protein. Previously, we showed that the MBCS facilitates serine protease-mediated entry into human airway cells (Mykytyn et al., 2021). Here, we report that propagating SARS-CoV-2 on the human airway cell line Calu-3 – that expresses serine proteases – prevents cell culture adaptations in the MBCS and directly adjacent to the MBCS (S686G). Similar results were obtained using a human airway organoid-based culture system for SARS-CoV-2 propagation. Thus, in-depth knowledge on the biology of a virus can be used to establish methods to prevent cell culture adaptation.

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From Publisher: Docwire News



Scott Disick, and Amelia Hamlin, who flashes cleavage in black cardigan, shop for jewelry in

For a romance reported to be a casual thing, Scott Disick and Amelia Hamlin are sure spending a lot of time together lately.

And on Wednesday, the reality star, 37, and the celebrity offspring 19, were spotted checking out some bling at a jewelry store in Miami.

Amelia seemed delighted, smiling happily as she and Kourtney Kardashian's ex perused the cases at a showroom in the Miami Design District.

Bling or ring? Amelia Hamlin smiled happily as she and Scott Disick checked out jewelry at a showroom in the Miami Design District on Wednesday during their South Florida getaway

Amelia, the daughter of RHOBH's Lisa Rinna and veteran LA Law star Harry Hamlin, was dressed in a black cardigan fastened with a single button.

She appeared not to be wearing anything underneath the knit top and flashed cleavage and her tummy button in the outfit.

Flashed skin: Amelia, 19, wore a black cardigan fastened with a single button and appeared not to be wearing anything underneath the knit top on the outing with the 37-year-old reality star

Celebrity offspring: The teen flashed cleavage and her tummy button in the outfit and she paired the cardigan with black knit shorts and brown slides

Swipe through any social media feed or shopping page, and you'll soon discover knitted co-ords are still a coveted look.

From Publisher: Mail Online



Bella Hadid shows off her cleavage in a fitted T-shirt as she plays around with trippy filters |

And Bella Hadid ensured her her fans would take a second glance as she messed around with a trippy Instagram filter on Tuesday.

Another effect saw multiple versions of Bella swirl around the background as she posed for the camera.

Bella looked phenomenal in the snaps as she showcased her incredible figure in a scarlet stripey top with a low-cut neckline.

Drawing further attention to her ample cleavage, the Vogue covergirl donned a chunky necklace that matched her stack of gold bangles and eye-catching earrings.

She teamed the T-shirt with a pair of vibrant jeans with a giant gold Von Dutch logo across the leg.

Bella's mind-bending snaps were no doubt inspired by her recent turn on the virtual runway for Mugler's Spring Summer 2021 show.

The result was an artful and trippy video, which made generous use of reverse film and moody lighting.

From Publisher: Mail Online



Homefront: Oh, Those Eggs! - Portland Press Herald

“We stirred to the smell of toast. We waited patiently at the Formica kitchen table. Her mother brewed tea in an English pot and served us in delicate cups with saucers embellished with scrolling flowers. When we were ready she slipped eggs into the waiting boiling water. My first experience with soft-cooked eggs was in that kitchen. The tiny spoon glided along the inside of the thin shell. So silky and rich. Yellow yolk mopped up with toast served from a toast stand.

“At my house, when Susan and I woke, our welcome was a bit different. We hid in my room and tried to sneak out for the day before anyone saw us.

“The memories conjured — the closeness of a teenage best friend, the music, the wild times at concerts, the moist warmth of Sue's mother's kitchen, its white starched curtains. But oh, those eggs.” — JUDE MALONEY, Brunswick

Mainers, what are you cooking this spring while you continue to wait out this virus? A favorite family recipe for comfort and consolation? Have you joined the sourdough brigade? Or has pandemic fatigue set in so you're making the fastest, simplest meal you can devise?

Place an egg from the fridge in a pot of boiling water for 4 minutes. (If the egg is at room temperature, allow just 3 minutes.

Scoop the egg out of the pot with a slotted ladle, and place it in an egg cup. Cut the top off, sprinkle with freshly ground pepper and flaky sea salt to taste. Serve alongside hearty toasted bread.

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From Publisher: Press Herald



Kourtney Kardashian flaunts cleavage in string silk bikini for sultry Poosh display - Daily Star

Wanting to get in on the sizzling action, she took to her Instagram feed with a seriously hot display.

Holding up her phone, she captured the selfie image herself while setting her cleavage free in a skimpy leather-look bikini top that demanded attention.

Keeping her attire coordinated, she rocked matching brown casual trousers that were pulled up high onto her hips.

The scorching reveal formed part of promotion to drum up sales via her tried and tested Poosh products.

She wrote: "Our April @poosh shop drip: Find out which 13 Poosh-approved products made my list of favorites."

Earlier this week, Kourtney's sister Khloe almost caused the internet to come to crashing halt when a picture appeared online showing the bombshell completely unfiltered.

Her skin was un-varnished, curves were less defined and her hair was pulled back into a low and casual ponytail.

Khloe looked like any other person posing in a bikini with her natural underlying beauty shinning through.

However, the reality star was alleged to be "horrified" that the image had made it's way into the public domain and assigned her teams to have the picture removed.

From Publisher: Dailystar.co.uk



The interaction between blood clotting and SARS-CoV-2 infection

Coagulopathy - a condition in which the blood's ability to clot is impaired, is recognized as a significant aspect of morbidity in COVID-19 patients. In a recent study, Prof Lewis Cantley and a team of researchers explored the role of coagulation factors in the SARS-CoV-2 infection. Their recent study is posted on the bioRxiv * server.

"Coagulation-induced cleavage enhances spike activation and increases viral entry into target cells."

They found that the proteases involved in clotting can also directly cleave the SARS-CoV-2 glycoprotein spike, enhancing the viral entry. They also found that protease inhibitors promiscuously inhibited the spike cleavage by both transmembrane serine proteases as well as coagulation factors. Spike cleavage by proteases is crucial to the viral entry; it facilitates membrane fusion and hijacks of the host cell by the viral genome.

Even as anti-SARS-CoV-2 vaccines are currently administered across the world, the continuing existence of a large reservoir of active cases over a long period will cause viral variants to emerge.

Because the coagulation cascade is orchestrated by a chain reaction of serine protease zymogens that are each activated by proteolytic processing, the researchers investigated if the proteases involved in the clotting also play a role in the SARS-CoV-2 spike cleavage.

They found that the coagulation factors, serine proteases factor Xa and thrombin, directly cleave SARS-CoV-2 spike, with more significant proteolytic activity against the SARS-CoV-2 peptide substrates than TMPRSS2. They also found that the S1/S2 boundary appears to be an even more optimal factor Xa substrate than peptide substrates derived from known physiological targets of factor Xa in coagulation.

They reported that the serine protease inhibitors suppress SARS-CoV-2 entry via inhibition of TMPRSS2. They observed that the TMPRSS2 is likely the primary cellular target of camostat and nafamostat.

Further, they found that the nafamostat is a versatile inhibitor of spike activation by various transmembrane serine proteases (TTSPs) and coagulation factors.

"We have mitigated the risk of artifact by using multiple orthogonal platforms, including VSV-based pseudovirus, HIV-based pseudovirus, and syncytia formation."

From Publisher: News-Medical.net



3C-Like-Proteinase Inhibitors Pipeline Insight Report 2021: A Cysteine Protease that is Excised

3C-like-proteinase is a cysteine protease that is excised from polyproteins by its own proteolytic activity and forms a homodimer with one active site per subunit.

Various studies are going on to study this protein in order to identify therapeutics against the SARS-CoV in particular and other pathogenic coronaviruses. A number of patented inhibitors with promising clinical potential have been developed through different methods.

The companies and academics are working to assess challenges and seek opportunities that could influence 3C-like-proteinase inhibitors R&D. The therapies under development are focused on novel approaches for 3C-like-proteinase inhibitors.




Why Star Trek: TNG's Deanna Troi Doesn't Wear a Uniform | CBR

During Star Trek: The Next Generation 's run, Deanna Troi went through a number of outfits and only donned an official Federation uniform for a small part of it. The remainder of the time, she wore civilian garb, which often meant she revealed a great deal of cleavage. Marina Sirtis ultimately rose above it to find a compelling character, but TNG still left her with a bewildering wardrobe problem. The reasons largely came down to behind the scenes decisions and a large helping of sexism. But in-canon, the reasons for Troi's lack of uniform are far more empowering.

Sirtis has proven quite good-natured about her outfits on the show, though she also described the relief she felt when finally putting on the standard Federation blue. However, how TNG explained that transition sheds quiet insight into the way Jean-Luc Picard ran his ship . Behind the scenes, it's a testament to how the Tori became more than eye candy and transitioned over the course of the show.

Even as the character developed in more substantive directions, it wasn't reflected in her attire. After her brief appearance in the infamous "skants" (the skirt-uniforms patterned off of the women's uniforms in TOS ) in the very first episode, she appeared in a series of jumpsuits, flowing dresses and even a spandex aerobics outfit before finally gaining a Starfleet uniform in Season 6, Episode 10, "Chain of Command: Part 1." She wore the uniform for the remainder of the series and the four movies that followed, though she did change back into civilian wear during less formal occasions.

Troi holds the rank of lieutenant commander when she first joins the Enterprise-D; the pips can clearly be seen on her collar in Season 1, Episode 1, "Encounter at Farpoint." However, she doesn't wear them on her civilian clothes after that, which infers she prefers a more informal relationship with her fellow officers. This aligns with her position on the ship. As a counselor, she needs those around her to feel at ease. That dynamic changes very late in the series -- Season 7, Episode 16, "Thine Own Self" -- when she passes the test for promotion and playfully notes she now outranks Data at the end of the episode. However, even then, she often approaches others as a peer first and a superior officer second.

That ultimately says a great deal about how Picard runs the Enterprise-D, and more importantly why Deanna is on the bridge in the first place. TNG always endured a little snickering about the "counselor" position, and critical fans speculated what role a therapist could possibly have on the bridge. However, despite her title, Troi actually fulfills a significant diplomatic and protocol role: advising Picard on how to address potential enemies and allies and generally serving as his consigliere alongside Riker. While a counselor might not normally belong on the bridge, Deanna Troi does.

Picard clearly values her insight and acumen, and might very well relax military protocol in her case if it helps her do her job. Captain Jericho's insistence that she dress "appropriately" in "Chain of Command" reinforces this notion, as do her efforts to take on more command responsibilities by seeking promotion. Roddenberry may have envisioned her as eye candy, but the character defied and ultimately transcended the costume choices which she was originally saddled with.

From Publisher: CBR



Boron insertion into alkyl ether bonds via zinc/nickel tandem catalysis | Science

The carbon–oxygen bonds that hold alkyl ethers together are relatively inert. Lyu et al. report that zinc and nickel can team up to insert boron between the carbon and oxygen using an unusual mechanism. First, a dibromoborane pries open the bond with help from a zinc ion. Next, the nickel stitches together the carbon and boron, and the oxidation of metallic zinc starts the cycle over again. Versatile reactivity at the inserted boron center can then add carbons to the original ether or swap out oxygen for nitrogen.

Mild methods to cleave the carbon-oxygen (C−O) bond in alkyl ethers could simplify chemical syntheses through the elaboration of these robust, readily available precursors. Here we report that dibromoboranes react with alkyl ethers in the presence of a nickel catalyst and zinc reductant to insert boron into the C−O bond. Subsequent reactivity can effect oxygen-to-nitrogen substitution or one-carbon homologation of cyclic ethers and more broadly streamline preparation of bioactive compounds. Mechanistic studies reveal a cleavage-then-rebound pathway via zinc/nickel tandem catalysis.

From Publisher: Science



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