Deleterious mutations occurring at the CS have been frequently documented in Vero cells, a popular laboratory cell line for testing replication of SARS-CoV-2. These mutations have been observed to reduce the polybasic nature of the site, potentially affecting the virus’ ability to gain cell entry.
Researchers based at Imperial College London, UK, have recently highlighted the effects of these deleterious CS mutations through a ferret animal model, demonstrating that furin cleavage sites are a necessary component in the virus’ ability to replicate. The paper is available to read at Nature Microbiology .
The research team synthesized a number of pseudoviruses based on SARS-CoV-2 containing the wild-type and mutant (Δ) cleavage sites, that either had or lacked the ability to be cleaved by furin. Ferrets are a common and practical animal model to test the transmission of respiratory viruses. However, prior to testing in this model, the efficiency of viral transmission was first observed in Vero and human cell lines.
Through competition assays, they demonstrated that ΔCS was able to quickly become the dominant virus in Vero cells, over the wild-type counterpart. However, in human cell lines (intestinal cells, airway epithelial cells, and lung cells) the wild-type was able to rapidly proliferate far greater than ΔCS, and completely replace it within 72 hours.
Pseudoviruses containing either the wild-type or ΔCS mutant spikes were then tested in human cell lines: 293T cells expressing human ACE2, Caco-2 cells, and Calu-3 cells. Spike mutants lacking furin cleavage were able to enter the 293T cells 3-fold more efficiently than the wild-type virus. However, they were significantly less efficient at entering Caco-2 and Calu-3 cells.
It turns out that entry of SARS-CoV-2 into 293T cells relies on a different process than entry to Caco-2, Calu-3, and human airway epithelial cells; the former is dependent on cathepsins, and the latter on the serine protease TMPRSS2.
The researchers then compared cell entry of SAR-CoV-2 in cell variants that expressed ACE2 with or without TMPRSS2. They observed that TMPRSS2 expression promoted cell entry for all coronavirus pseudoviruses, but crucially this protease expression also supported wild-type SARS-CoV-2 entry above mutant lacking furin CS. Furthermore, they found that SARS-CoV-2 containing furin CS have escape mechanisms from IFITM proteins that would otherwise disable virus-cell entry.
Finally, the team tested the CS variant strains in a ferret model. The research team found, consistent with findings from human cell line tests, wild-type SARS-CoV-2 virus-containing furin CS was far more successful in replicating and transmitting than mutant CS variants, indeed completely outcompeting such variants.
Ferrets and mink represent reliable models for observation and testing of respiratory viruses, such as influenza, avian flu, and now the novel SARS-CoV-2.
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New study analyzes the influence of the extreme weather and geological conditions on the forced
In August of 2009, typhoon Morakot passed over Taiwan, triggering over 22,000 landslides and adding another chapter to the forced migration of indigenous settlements in the mountainous areas. A new study recently published in the journal Tectonophysics has analyzed how extreme weather such as that caused by Morakot, when coupled with local geological conditions, can trigger landslides that have caused two forced settlement relocations of one Paiwan group in southern Taiwan in the last 350 years.
In this study, researchers from National Central and National Tsing Hua universities in Taiwan and Geosciences Barcelona (GEO3BCN-CSIC) in Spain combined information from the oral tradition of the Paiwan people with geological data to assess the effects of natural disasters on the communities that inhabit the Central Range of southern Taiwan.
Part of these interviews focused on the indigenous peoples stories of past natural disasters that had had an important impact on the community. The villagers recounted major events in their migration history, among which was the story of a “collapse of the rock in the mountain across the river” that was followed by a “great wáter that appeared suddenly”. The interviewees indicated that this rise in the water was a cause of their ancestors having abandoned the vilage of Tjuvung about 350 years ago when they moved to Paridrayan.
The authors then carried out site investigations in the area of Tjuvung and Paridrayan to determine the local geological and geomorphological conditions and their possible relation to the events that caused the abandonment of Tjuvung and forced the settlement migration as recorded in the Paiwan group oral traditions.
“The oral traditions told a story. What we did was to investigate whether or not there was a geological reason that could fit with these stories. We found that there was a plausible geological explanation”, said Dennis Brown , researcher from Geosciences Barcelona.
Geological measurements collected in the field were combined with Lidar data, satelliite data, and climate data. With all this information, the researchers were able to verify the occurrence of a landslide triggered by rainfall during a time of known enhanced typhoon activity in Taiwan. The data analysis also corroborated the oral tradition which says that the river was blocked resulting in a barrier lake that was deep enough to flood the lower parts of Tjuvung village.
“This is an area of high mountains, sharp relief, and dense jungle cover where typhoons and earthquakes are common. The locations of landslides are conditioned by the regional geology in that they occur on dip-slopes where the regional cleavage is parallel to the slope”, said Dennis Brown.
“Rainfall and the vibrations caused by earthquakes are two of the most common causes of landslides in the region. “Landslides typically occur along a planar element in the rocks, be it fractures, bedding, or cleavage. In our case, this part of southern Taiwan has a well-developed cleavage along which slip occurs. This fabric is the defining element in the geomorphology of the área”, said Giletycz.
“Landslides are difficult, if not impossible, to prevent, but the risks can be reduced if enough is known about the regional geology to more accurately determine the placement of man-made infrastructure”, concludes Dennis Brown.
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Agricultural trade slides by 7% in 2020 - BusinessWorld
THE VALUE of agricultural trade dropped by 7.1% year on year to $18.78 billion in 2020 as both exports and imports declined, the Philippine Statistics Authority (PSA) reported on Friday.
The PSA said agricultural exports declined by 7.1% to $6.20 billion in 2020. These products made up 9.5% of the country’s total outbound shipments last year.
Edible fruits and nuts and peel of citrus fruit melons, which accounted for the largest share or 37.5% of the total exports, were valued at $2.32 billion.
Meanwhile, exports of animal or vegetable fats and oils and their cleavage products were worth $32 million; preparations of meat, of fish or of crustaceans, molluscs, and other aquatic invertebrates were valued at $231.49 million; and preparations of vegetables, fruit, nuts or other parts of plants were at $142.40 million.
Cereals were the top imported goods at $2.55 billion. Miscellaneous edible preparations came second at $1.56 billion, and residues and waste from food industries or prepared animal fodder ranked third at $1.43 billion.
Among ASEAN countries, Malaysia was the top destination of the country’s exports, accounting for 33.8% or $226.77 million of the total, while Vietnam was the major source of imports at 27.4% or $1.19 billion.
The PSA said the top agricultural products exported to other ASEAN countries were tobacco and manufactured tobacco substitutes valued at $230.82 million; animal or vegetable fats and oils and their cleavage products, and prepared edible fats, and animal or vegetable waxes at $126.52 million; and preparations of cereals, flour, starch or milk; pastry cooks' products worth $62.59 million.
Boron insertion into alkyl ether bonds via zinc/nickel tandem catalysis
The boron moiety in the insertion products could also be conveniently converted into various other functional groups. For instance, the team could treat the crude product (3a) 2H-benzoxaborin, with hydrogen peroxide to obtain 1,2-tyrosol (6a) in excellent yield. The Suzuki-Miyaura coupling of the 3a molecule with bromo-benzene efficiently formed o-phenethylphenol (labeled as 7a). The method also allowed efficient one-carbon ring expansion reactions and provided boron-retentive ring expansion. During the experiments, the nature of the alkyl group in the coupling reaction and the role of the nickel catalyst were key to understand the subsequent steps of carbon-boron bond formation.
In this way, Hairong Lyu and colleagues demonstrated a method for boron insertion into alkyl ether bonds under the catalysis of nickel and zinc. Since ethers are readily available and robust substates, the boron-insertion method can also streamline the synthesis of complex target molecules by minimizing the functional group manipulations or by protecting group usages. The distinct reaction mode revealed by the mechanistic studies can have implications on Lewis acid / transition metal tandem catalysis reactions that are beyond this work. Explore further
Jingjing Wu et al. Synergy of synthesis, computation and NMR reveals correct baulamycin structures, Nature (2017). DOI: 10.1038/nature23265
Angelica Ross, Indya Moore and Janet Mock lead the stars at Pose premiere | Daily Mail Online
Angelica Ross, Indya Moore and Janet Mock turned up the glamour factor at the Pose season three premiere in New York this week.
The stars of the FX program posed up a storm at Jazz At Lincoln Center on Wednesday evening in aid of the its final season.
Janet, 38, showed off her cleavage in a skintight gold gown that emphasized her statuesque figure as she strutted her stuff for the cameras.
Meanwhile Indya, 26, flaunted their endless legs in a high-waisted pair of black shorts and slipped into a matching blazer.
Indya was modeling a gleaming gold bra-lette that perfectly complemented the buttons on their fitted jacket.
Sharpening their features with makeup they added an extra splash of glitz to the outfit with a pair of drop earrings.
The TV star also modeled Faberge rings and balanced expertly on a pair of ankle-strap stilettos for their latest red carpet moment.
Jaden Smith and Chloe Bailey Caught Getting Flirty on Instagram
AceShowbiz - Jaden Smith and Chloe Bailey are apparently into each other lately and they have no intention to keep their feelings to one another a secret. The two young stars have caught fans' attention as they're getting flirty on Instagram.
One of the evidence was found on Chloe's Thursday, April 29 post. The one-half of Chloe x Halle showed no remorse despite criticism over her sultry contents, posting new sexy snaps of her rocking a black leather mini dress that bared her cleavage and toned tummy.
Striking various seductive poses against the wall, the 22-year-old singer wrote in the caption, "she's dangerous." Jaden, noticing Chloe's post, couldn't deny her charm as he acknowledged in his comment, "She really is."
And apparently the feeling is mutual. One week prior, Chloe also shot her shot with Jaden when the 22-year-old star posted a picture of him staring blankly to the camera while sitting and leaning against the wall in a white long-sleeve T-shirt and jeans.
"I'm Tryna Deluxe Myself," the son of celebrity couple Will Smith and Jada Pinkett Smith captioned it. Chloe then made her presence be known by simply leaving a fire emoji in the comment section.
Some others, however, doubt that Jaden and Chloe are really each other's type. "It's a running joke pretty much every where that he only dates," one skeptical user commented, adding, "White girls, calm down it's not that serious." Another warned Chloe, "Nope. Chloe stay away from jaden weird a**," as another shaded Jaden and his exes, "Chloe would be a step up from cokehead thieves."
Detect and destroy: CRISPR-based technologies for the response against viruses - Docwire News
Cell Host Microbe. 2021 Apr 22:S1931-3128(21)00151-7. doi: 10.1016/j.chom.2021.04.003. Online ahead of print.
New COVID variant strain B.1.1.7 found in Lewis County – The Lewis County Herald
Lewis County Public Health Director Anita Bertram says that a COVID-19 positive test sample from a local resident earlier this month contains the B.1.1.7 strain.
This strain is also known as the United Kingdom (UK) variant. The UK variant is a mutation of the SARS CoV-2 virus, which causes COVID-19.
This is the first confirmed case of this strain detected in Lewis County. The first confirmed case in Kentucky was reported in January.
Bertram said random sequence testing of specimens completed by LabCorp identified the B.1.1.7 variant in the Lewis County case. She said the specimen collection date was early this month.
"Sequencing takes a long time to complete and we were only just notified," Bertram said. "It is confirmation that this variant is here in Lewis County."
She said there is evidence that B.1.1.7 has increased transmissibility, so it has a greater ability to spread quickly in people.
"Now, more than ever, we must all be vigilant in taking the steps we know are effective – wearing face masks, social distancing, avoiding gatherings, handwashing and not going to work, school or events if you have any of the symptoms," Bertram said.
The health department is planning two vaccination clinics in May in the Clarksburg and Tollesboro communities. Vaccines are also being administered at the health department by appointment.
Lewis County ranks high in the state for unvaccinated individuals and has had the highest rate of COVID-19 incidence of all Kentucky counties over the past week.
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