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In a new research paper currently available on the bioRxiv * preprint server, a research group from the United Kingdom (UK) provides experimental evidence that B.1.617 lineage of the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) – also known as the Indian variant of concern – shows enhanced cleavage of spike glycoprotein by furin, which can enhance its transmissibility and pathogenic traits.
Naturally, this opened the door for the potential evolution of SARS-CoV-2 variants with increased transmission due to a more optimized cleavage site. One of initial examples was a UK variant (B.1.1.7) which harbors a P681H mutation that boosts post-translational S1/S2 cleavage during viral budding.
Initially, these researchers isolated several B.1.617 SARS-CoV-2 variants and compared their S1/S2 cleavage patterns to that of a previously circulating viral strain that belonged to the lineage B.1.238, known to contain only D614G mutation.
Finally, they have performed specific assays to appraise whether the optimized cleavage site characteristic for B.1.617 spike glycoprotein enables improved cleavage directly by furin. More specifically, they have measured the propensity of recombinant furin to cleave fluorescently labeled peptides corresponding to the S1/S2 cleavage site of SARS-CoV-2.
And while spike glycoprotein of a wild-type virus exhibited both full length and cleaved protein, B.1.617.1 showed significantly enhanced cleavage (i.e., up to 95%), coupled with almost a total lack of a full-length protein. This implies P681R alone is responsible for the enhanced cleavage of spike glycoprotein observed in the B.1.617 lineage.
More specifically, P681R substantially enhanced the ability of furin to cleave the peptide, reinforcing the notion that the arginine substitution can be considered responsible for the enhanced cleavage of the B.1.617 spike glycoprotein.
In conclusion, this study has shown that enhanced S1/S2 cleavage observed in B.1.617 and B.1.1.7 SARS-CoV-2 variants (which both contain P681H mutation) may be contributing considerably to their increased transmissibility and even pathogenicity.
“As well as B.1.1.7 and B.1.617, several other emerging lineages contain mutations in the furin cleavage site”, say the authors in this bioRxiv paper. “We would advise that these lineages be kept under close monitoring for any early evidence of more rapid transmission or higher pathogenesis,” they add.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Nicole Scherzinger poses up a storm as she flashes cleavage dressed in a plunging tangerine suit
And Nicole Scherzinger took to Instagram once more on Saturday to show off her slim physique in a vibrant ensemble.
The former Pussycat Dolls singer, 42, looked sensational as she posed against a wall wearing an orange two-piece suit.
Stunning: Nicole Scherzinger posed up a storm as she flashed cleavage dressed in an orange suit in a series of photos uploaded to her Instagram on Saturday
The sultry snap offered fans a glimpse of her ample assets as she wore no shirt beneath her jacket.
Two gold necklaces could also be seen hanging at different lengths around her neck, while a selection of rings were also visible on her fingers.
In two of her latest pictures, Nicole's raven locks were tucked back behind her left ear, but allowed to flow over her right shoulder.
Sales of suits are on the rise, but they're no longer reserved for the 9-5; it's all about taking your suit from desk to drinks by opting for more glammed up styles.
Nicole Scherzinger nailed the look this week as she was spotted out for dinner looking sleek in a satin suit by Veronica Beard.
Respiratory syncytial virus induces β2-adrenergic receptor dysfunction in human airway smooth
Pharmacologic agonism of the β 2 -adrenergic receptor (β 2 AR) induces bronchodilation by activating the enzyme adenylyl cyclase to generate cyclic adenosine monophosphate (cAMP). β 2 AR agonists are generally the most effective strategy to relieve acute airway obstruction in asthmatic patients, but they are much less effective when airway obstruction in young patients is triggered by infection with respiratory syncytial virus (RSV). Here, we investigated the effects of RSV infection on the abundance and function of β 2 AR in primary human airway smooth muscle cells (HASMCs) derived from pediatric lung tissue. We showed that RSV infection of HASMCs resulted in proteolytic cleavage of β 2 AR mediated by the proteasome. RSV infection also resulted in β 2 AR ligand–independent activation of adenylyl cyclase, leading to reduced cAMP synthesis compared to that in uninfected control cells. Last, RSV infection caused stronger airway smooth muscle cell contraction in vitro due to increased cytosolic Ca 2+ concentrations. Thus, our results suggest that RSV infection simultaneously induces loss of functional β 2 ARs and activation of multiple pathways favoring airway obstruction in young patients, with the net effect of counteracting β 2 AR agonist–induced bronchodilation. These findings not only provide a potential mechanism for the reported lack of clinical efficacy of β 2 AR agonists for treating virus-induced wheezing but also open the path to developing more precise therapeutic strategies.
By Terri J. Harford , Fariba Rezaee , Manveen K. Gupta , Vladimir Bokun , Sathyamangla V. Naga Prasad , Giovanni Piedimonte
RSV infection may reduce the efficacy of bronchodilators by dysregulating β 2 -adrenergic receptor location, abundance, and function.
Amanda Holden flashes cleavage in bustier as fans are distracted from stunning outfit - Daily Star
Though her main focus was supposed to be on the horse racing event and her fashionable head gear, fans couldn't get enough of Amada's beauty that oozed effortlessly through the pic.
Amanda, 50, kept her make up light in the pic and allowed only a few of her blonde locks to flow down her cheeks.
She also added a blush of pink lipstick to her plump lips as she gazed seductively away from the camera.
The elaborate hat on her head certainly drew some attention, but Amanda's fans seem to have had their eyes firmly set on other things, as the photo gave the impression that she was completely topless.
Captioning the post and promoting her hat, the BGT presenter wrote: "I've loved being a regular visitor to Royal Ascot over the years.
"In celebration of the doors re-opening next month, I slipped on this beautiful @philiptreacy creation I hope the weather will be just as glorious as today on June 15th - 19th #RoyalAscotMillineryCollective2021."
"You look alluring and marvellous in this beautiful creation but the best creation of all is you," another said.
Mother of two Amanda has often spoken openly about her fashion choices and the clothes she chooses to wear.
In 2019, Amanda told The Daily Mail: "Clothing is everything. It's my armour. I dress for myself, nobody else.
Pregant Georgia Fowler joins Jessica Gomes at the Michael Lo Sordo show at Australian Fashion
Some of Australia's most stunning models attended the Michael Lo Sordo show at Afterpay Australian Fashion Week 2021 on Tuesday.
Leading the fashion pack was Georgia Fowler, 28, who opted for an unusual pyjama-style leisure suit.
The pregnant beauty looked chic in the satin two-piece, which featured a deep v-neck that showed off a hint of cleavage, and was double-buttoned under the midriff.
The stunner, who is expecting her first child with boyfriend Nathan Dalah later this year, paired the top with matching, wide-legged pants in the same pearl fabric.
Georgia added a pair of black stilettos with a thick strap across the toes, and accessorised with a long, rope chain, dainty earrings and a number of rings.
For makeup, she opted for defined brows, a matte nude lip, warm blush, and had her brunette hair pulled off her face.
Jessica Gomes, 35, also opted for a matching clothing set, consisting of an olive-toned midriff top with long sleeves, which showed off a hint of cleavage.
Abbie Chatfield oozes sophistication at Australian Fashion Week | Daily Mail Online
And now Abbie Chatfield is acting as a roving reporter at Afterpay Australian Fashion Week in Sydney this week.
For Monday's assignment, the 25-year-old slipped into a sophisticated structured shirt dress, slightly unbuttoned to expose some of her signature cleavage.
Glamazon: Former Bachelor star Abbie Chatfield showed off some cleavage in a white shirt dress as she acted as a roving reporter at Afterpay Australian Fashion Week in Sydney on Monday
Abbie struck a number of poses in the thigh-grazing dress, which featured pockets on either side of the garment.
She finished the look with a pair of nude-hued strappy heels and a pair of gold, drop-down earrings.
The beauty wore a matte style makeup palette as well as rouge lipstick and had her blonde tresses down.
It comes after the former Bachelor star spoke to Yahoo this month about eating disorders and how it was normal for girls to avoid eating when she was at school.
'That was kind of just the "normal" culture of going to an all-girls Catholic school, where everyone would have these water bottles and we would put a dash of lemon water in it, with gum and an apple, and that was what we'd eat in a day,' she said.
Blue Sapphire Stone Available with Star Lanka in Brilliant Hues and Saturation Fashioned by
Australia's softball team became the first athletes to land in Japan for the Olympics on Tuesday, in a major milestone for the pandemic-postponed Games.
Alizeh Shah receives flak for wardrobe choices
Alizeh Shah has landed into hot waters again as her wardrobe choice came under scrutiny once again. Subjected to severe criticism and backlash, this time the Ehd-e-Wafa star triggered the masses as she donned a baggy shirt.
Despite wearing a baggy top that ticked all boxes of modest clothing, the neckline left many people disturbed owing to the fact that her cleavage was showing.
Earlier, Anoushay Abbasi was at the receiving end of moral policing where she posted a picture of herself all dressed in a Barbie style mini frock.
Alizeh Shah rose to prominence within a very short span of time. With her flawless acting skills and bubbly persona, ...
Dolly Parton Says She Doesn't Wear Sweatpants | PEOPLE.com
While Dolly Parton doesn't "wear sweat clothes," she tells WSJ. Magazine , "I do like to be comfortable like everybody else"
In an interview with WSJ. Magazine published Monday, the country legend revealed she "[doesn't] wear sweat clothes" at home — but insisted that doesn't mean she sacrifices relaxation for fashion.
To that end, she has her "own little house clothes, like a little dress-type teddy, a long teddy, then I have a little jacket or shirt to match if I get cold."
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Parton's beauty routine might also seem unconventional to some. As the "Jolene" songstress explained, she does "all my beauty work and cleaning my face in the morning because I usually try to keep my makeup on at night."
The reasoning? "I never know if there's going to be an earthquake or a tornado or a storm and I'm going to have to go out in the middle of the night !" she said, joking in addition, "I don't like to go home and just tear down completely, because my poor husband has to look at me."
"And in the morning when I get up I start all over again, put on my makeup and then touch it up through the day," Parton shared.
If she's going out in the evening, she'll start with her base look from the morning and "just add a little more shadow, a little more glitter, redder or brighter lipstick ," she said. "I'm so used to doing my own makeup and hair I can do it really fast."
RELATED VIDEO: Dolly Parton Addresses Those Tattoo Rumors, Reveals the Moving Reason Behind Her "Tasteful" Ink
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