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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses a uridine-specific endoribonuclease, called nonstructural protein 15 (Nsp15), to evade the immune system. It works by cleaving viral RNA and preventing the activation of double-stranded RNA sensors. Although how Nsp15 recognizes its RNA target for cleavage remains unclear.
Research conducted by scientists at the National Institutes of Health in the USA shows that Nsp15 targets uridines (U). Following detection of U, Nsp15 can then further cleave a broad spectrum of RNA substrates.
Overall, this work establishes SARS-CoV-2 Nsp15 as a largely non-specific endoribonuclease with recognition for a minimal consensus motif (N)(U)^(R>U>>C) (where N is any base and R is a purine). Our data show that Nsp15 acts in a distributive fashion to catalyze cleavage following uridines.”
The study “Characterization of SARS2 Nsp15 Nuclease Activity Reveals it’s Mad About U” is available as a preprint on the bioRxiv * server.
The researchers used a combination of techniques including cryo-EM, molecular dynamic simulations, and in vitro RNA cleavage assays to evaluate Nsp15’s substrate preferences beyond U. They performed a cryo-EM reconstruction of Nsp15 that’s RNA bound through information collected in its pre- and post-cleavage states.
Nsp15 did not have any other base binding sites for RNA binding and recognition, indicating detection of U is critical for proper RNA cleavage.
Several N-terminal domain residues from a nearby protomer interacted with the B 2 adenine in the cryo-EM model. Considering they are essential for oligomerization and nuclease activity, the results suggest the N-terminal domain could help with engaging the RNA in the active site.
Thus, our structure-based point mutations suggest Nsp15 could be inhibited by disrupting the EndoU/NTD interface at the edge of the active site, which should destabilize the hexamer and lead to inactive monomeric enzyme,” wrote the researchers.
N278 was the key residue found for maintaining Nsp15’s uridine preference. The residue is identical in Nsp15’s found in SARS-CoV-2 and MERS, but it differed across other coronaviruses. N278 interacts with S294 to move hydrogen bonding to favor uridines. This was further confirmed with a variation of N278 showing reduced activity on cleaving uridine-containing substrates.
Teen Mom Jade Cline bares major cleavage in new photos after getting a Brazilian butt lift &
The MTV star took to Instagram on Monday to share two black and white photos of her flaunting her cleavage as she posed in her car.
Jade wore a tight white lace top, while she appeared to sport a full face of makeup as her hair cascaded in loose curls past her shoulders.
In addition to her plastic surgeries being documented on the MTV show, Jade has been open with her social media followers about her decision to alter her body by going under the knife.
She regularly flaunts her new body while rocking tight fitting outfits , though she's also spoken candidly about the tough healing process.
One viewer asked her if her doctor "really did a chin removal" and if she could share before and after pictures.
The mom of one replied that she did not have a chin removal done, adding: "I didn't have anything done to my face.
The Brazilian butt lift done is a procedure that requires transferring fat from other parts of the body and into the buttocks to create an hourglass figure.
When a fan asked how tolerable the pain was after the procedure on a scale of one to 10, the Young and Pregnant alum replied "20."
Jade also confirmed that she paid for the surgery herself answering the question by simply writing "Yes."
The COVID lab-leak hypothesis: what scientists do and don't know
The Wuhan Institute of Virology has carried out research on coronaviruses for years because these pathogens are endemic to the region where it's located. Credit: Kyodo News via Getty
Most scientists say SARS-CoV-2 probably has a natural origin, and was transmitted from an animal to humans. However, a lab leak has not been ruled out, and many are calling for a deeper investigation into the hypothesis that the virus emerged from the Wuhan Institute of Virology (WIV), located in the Chinese city where the first COVID-19 cases were reported. On 26 May, US President Joe Biden tasked the US Intelligence Community to join efforts to find SARS-CoV-2's origins, whatever they might be, and report back in 90 days.
Nature looks at the key arguments that support a lab leak, and the extent to which research has answers.
Scientists found SARS-CoV-2's closest known relative, RATG13, in a horseshoe bat. Credit: Shutterstock
In theory, COVID-19 could have come from a lab in a few ways. Researchers might have collected SARS-CoV-2 from an animal and maintained it in their lab to study, or they might have created it by engineering coronavirus genomes. In these scenarios, a person in the lab might have then been accidentally or deliberately infected by the virus, and then spread it to others — sparking the pandemic. There is currently no clear evidence to back these scenarios, but they aren't impossible.
One holds that it's suspicious that, almost a year and a half into the pandemic, SARS-CoV-2's closest relative still hasn't been found in an animal. Another suggests it is no coincidence that COVID-19 was first detected in Wuhan, where a top lab studying coronaviruses, the WIV, is located.
Some lab-leak proponents contend that the virus contains unusual features and genetic sequences signalling that it was engineered by humans. And some say that SARS-CoV-2 spreads among people so readily that it must have been created with that intention. Another argument suggests that SARS-CoV-2 might have derived from coronaviruses found in an unused mine where WIV researchers collected samples from bats between 2012 and 2015.
As for finding an intermediate host animal, researchers in China have tested more than 80,000 wild and domesticated animals; none have been positive for SARS-CoV-2. But this number is a tiny fraction of the animals in the country. To narrow the search down, researchers say, more strategic testing is needed to isolate animals that are most susceptible to infection and those that come in close contact with people. They also suggest using antibody tests to identify animals that have previously been infected with the virus.
Nobel laureate backs away from 'smoking gun' lab-leak claim - Los Angeles Times
For those concerned with the origins of the virus causing the COVID-19 pandemic, a few words from Nobel laureate David Baltimore seemed to settle the debate, decisively in favor of the theory that the virus was man-made before it escaped from a Chinese laboratory.
A feature of the virus' genome known as the furin cleavage site "was the smoking gun for the origin of the virus," Baltimore said.
Using virologists' shorthand for the virus, SARS2, he continued: "These features make a powerful challenge to the idea of a natural origin for SARS2."
I believe that the question of whether the sequence was put in naturally or by molecular manipulation is very hard to determine but I wouldn't rule out either origin.
Proponents of the lab-leak hypothesis — that is, that the virus escaped from a lab rather than reaching humans as a natural spillover from a wild animal host — could scarcely have hoped for a more substantial endorsement of their views.
Baltimore is one of the nation's most eminent scientists, a former president of Rockefeller University and Caltech, where he still serves as president emeritus and remains on the faculty as distinguished professor of biology.
Here's the problem: Baltimore regrets using the phrase "smoking gun" to describe his conclusion, and doesn't agree that it validates the lab-leak theory.
Per Racaniello, Baltimore "said he should not have used the phrase 'smoking gun.' What he meant to say was that it was a striking suggestion of a possible origin of the virus."
All this might seem inside baseball to casual followers of the COVID origin debate, but it's more important than that. As I reported in my earlier column, the question of the origin of the virus boils down to two categorical possibilities.
With Open Legs and Cleavage, Ana Bárbara Dazzles Everyone – SparkChronicles
Altagracia Ugalde Mota, better known as Ana Bárbara , once again surprised the users of the Instagram platform after uploading an attractive photo on her profile, with which she consisted of her admirers since she wasted her beauty with an open pose that took more than one breath away.
According to the latest updates in her stories, the interpreter of "Bandido", "Que poco" and "No es brujería" took a short break and traveled to the municipality of San Miguel de Allende, where she had the opportunity to greet several of his admirers on the streets of this city in Guanajuato.
With her most recent publication through her personal account on the camera’s social network, the successful production company dazzled everyone present with a colorful image, in which she appears posing with her legs spread while sitting at the entrance of a house mustard color that made it stand out much more thanks to its intense set.
In this snapshot, Ana Bárbara entertained her followers by modeling a revealing outfit in red and printed with white lines that made her show a little more than normal, which consisted of baggy pants and a light shirt that she wore unbuttoned until the end. abdomen that revealed part of her charms.
To accompany her clothing, the Mexican regional music singer wore a black hat with silver details and dark glasses that helped protect her from the strong rays of the sun.
So far, the publication has managed to add more than 21 thousand reactions of likes and hundreds of messages from its followers, where they filled it with a large number of words of support and affection.
Amanda Holden and Davina McCall flaunt cleavage as they 'take plunge' in racy outfits - Daily Star
She wrote: '@davinamccall and I are taking the PLUNGE together, exciting project on the way. (oh and if @tessdaly & @claudiawinkle need a night off...)'.
Amanda's caption jokes that the pair of them could fill the roles of Claudia Winkleman and Tess Daly on Strictly Come Dancing.
Davina wore a bright pink blazer with matching trousers and large silver hooped earrings while Amanda wore a sleeveless silver dress with a deep neckline.
'I plunged on show two and I had the cleavage to match. Now it's a "plunge-off" between me and Amanda.'
She also said that she wanted to "work harder" as she hadn't angered fans of the show enough to gain complaints, referring to a dress Amanda once wore that saw over 200 complaints come in about how low cut it was.
The star continued: 'If I get one I'll be a bit pleased, if I'm honest. There was always that red latex dress I wore on last night's show.'
Amanda was previously seen showing off her figure in beachwear while visiting Portugal but after the country got put onto the amber list, she rushed to return home before quarantine rules changed.
The change is causing chaos in Portugal airports as British travellers try to get back before the deadline of 4am on Tuesday morning.
While out on vacation Amanda proudly showed off her daughters in a beach photo captioned with the hashtag "#sisters"
Pretty in pink: Kunzite - Jeweller Magazine: Jewellery News and Trends
Although other varieties of spodumene have been known since the 1800s, kunzite was first discovered just over a century ago, making it a relatively new addition to the world of gemstones.
It received its name in honour of Tiffany & Co.’s then-head gemmologist, George Frederick Kunz.
Mostly occurring in various shades of pale pink, kunzite may also be violet to vivid purple in colour. A stand-out feature of this gemstone is its trichroic nature, where different colours may be seen from different crystallographic directions.
This is of particular importance in the cutting process. Because the most intense colour is seen in the direction of the c-axis (the length of the crystal), the stone should be cut with its table facet perpendicular to the c-axis to achieve the best colour.
Kunzite is generally a fairly clean, inclusion- free stone, and is cut deep for maximum colour. However, kunzite has two directions of cleavage – where the stone can split perfectly with the right amount of pressure – making it difficult to cut.
It is also known to be brittle and unpredictable. As a result, many skilful and experienced cutters enjoy the challenge of kunzite, producing beautiful fantasy-cut stones of all kinds.
One notable example is the 3,051-carat specimen named ‘Fragility of the Eternal’ – a fantasy-cut by Victor Tuzlukov, which is believed to be the world’s largest cut kunzite.
Given the fragile nature of this gemstone, it is important to know its best uses in jewellery and suitable cleaning methods.
With a hardness of only 6.5–7 on Mohs’ scale, and its cleavage affecting its durability, kunzite is best suited to jewellery that is less exposed in everyday wear, such as pendants and earrings.
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