Ferrets (Mustela putorius furo) are mustelids of special relevance to laboratory studies of respiratory viruses and have been shown to be susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and onward transmission.
There was no evidence of SARS-CoV-2 transmission from humans to ferrets based on viral and antibody assays. To better understand this discrepancy in experimental and natural infection in ferrets, we compared SARS-CoV-2 sequences from natural and experimental mustelid infections and identified two surface glycoprotein Spike (S) mutations associated with mustelids. While we found evidence that angiotensin-converting enzyme II provides a weak host barrier, one mutation only seen in ferrets is located in the novel S1/S2 cleavage site and is computationally predicted to decrease furin cleavage efficiency.
These data support the idea that host factors interacting with the novel S1/S2 cleavage site may be a barrier in ferret SARS-CoV-2 susceptibility and that domestic ferrets are at low risk of natural infection from currently circulating SARS-CoV-2. We propose two mechanistically grounded hypotheses for mustelid host adaptation of SARS-CoV-2, with possible effects that require additional investigation.
It is not yet known whether natural infection of animals plays a role in public health epidemiology or has the potential to establish endemic reservoirs and threaten wildlife. SARS-CoV-2 has been observed to be capable of natural human-to-animal reverse zoonoses, transmitting from infected individuals into mink, dogs and felines.
The study observed household data support the idea that there may be important barriers to natural infection in ferrets; however, ferrets have been shown to be susceptible to infection and onward transmission in experimental laboratory infections.
To further investigate this, the available genomic sequences of SARS-CoV-2 viruses of naturally infected American minks and experimentally infected ferrets (32 sequences representing 24 animals, accessed 1 August 2020) were analysed. There are viral sequences available from two natural reverse zoonotic events in mink farms in Europe, which allowed us to infer founder-effect mutations versus acquired mutations of relevance to spillover.
The results suggest that virus and host genetic barriers significantly limit natural infection in ferrets, and these are only likely to be overcome by a concentrated and/or diverse inoculum of human-derived virus.
The data presented here remind us that synthesis of data from surveillance work, natural experiments, and controlled, laboratory-led studies can lead us to novel hypotheses and investigations and allow us to better respond to this pandemic and prepare for the next. This household provides evidence that human-to-ferret SARS-CoV-2 transmission in domestic settings may be lower risk than would be expected from laboratory experiments. (ANI)
Study shows Ferret resistance to SARS-CoV-2 infection Study shows Ferret resistance to SARS-CoV-2 infection ANI
16th April 2021, 10:37 GMT+10
Everlane Swimwear: Shop An All-New Line Of Bikinis, One-Pieces & More | StyleCaster
Out of all the brands that claim to have a "cult following," no one's grip on shoppers is stronger than that of Everlane. Their commitment to radical transparency via ethical practices, high-quality garments and a curated-but-cool minimalist aesthetic has made them the kind of brand that fans line up to buy from. No, really—I've walked by their store on Prince Street in New York City and seen lines wrapping around the block. Knowing this, I had a feeling Everlane's swimwear debut would be a hit even before I saw the collection. Then, I saw them, and I was even more sure.
Whether they're pedaling denim, sneakers or the perfect white tee, Everlane always guarantees great quality, fit and style—so of course, the same is true of their long-awaited swimwear line. The seven pieces in the collection are all made from Italian Econyl fabric created using 13,768 pounds of recycled plastic, so you can feel good about your purchase. And you'll look good in it, too: The pieces were fit-tested on 112 women.
Pricing ranges from $30 for bikini bottoms to $70 for a square-neck one-piece, and everything comes in multiple colorways and sizes XXS-XXL (A solid range for stretchy swimwear, but @Everlane, more please!).
The drop feature two one-piece options with different necklines, two bikini bottom silhouettes and three mix-and-match top styles. Everything comes in an Everlane-chic array of eight colors, ranging from sunny Marigold to earthy Herb, so you can mix and match to your heart's content.
Fair warning: You won't find any strappy string bikinis, dramatically high-cut sides or other trendy details in this range, but you will find an array of suits guaranteed to fit well and designed to last. Skip the trendy suits this year and invest in a few you'll love for years to come, won't you?
When in doubt, always go for a tie-back triangle top and low-rise bikini bottom . Perfect tan lines guaranteed with every single wear.
The square-neck one-piece is the priciest suit in Everlane's debut range, but it seems well worth the $70. This classic silhouette will certainly stand the test of time in any of its four colorways.
I love, love, love a tie-front top in lieu of a traditional string bikini. It's just a touch more special, but still super minimalist. Oh, and catch me wearing these high-rise bottoms with absolutely everything.
Looking to show off some cleavage? Look no further than this one-piece , with just enough plunge to spice things up, but still an ample amount of support for the girls.
Carfilzomib, Bortezomib Combo Shows Potential for Reducing Tumor Growth in Melanoma Cells
The in vitro study of melanoma cells analyzed the molecular mechanisms of the pair of proteasome inhibitors, finding that they reduced B16-F1 tumor growth.
The in vitro study of melanoma cells analyzed the molecular mechanisms of the pair of proteasome inhibitors, finding that they reduced B16-F1 tumor growth. The treatment combination also showed promise in a C67BL/6 xenograft mouse model, with researchers observing significant reductions in tumor size in the mice.
In the in vitro model, the combination inhibited tumor growth through apoptosis via endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) accumulation, and mitochondrial membrane potential (MMP) loss in the melanoma cells.
"BZ- and CFZ-induced apoptosis were confirmed by the presence of cleaved caspase 3, 8, 9, and 12. Western blotting revealed that the overall effect of BZ on caspase activation was stronger than that of CFZ at the same concentration," researchers wrote.
"In addition, the high level (10% compared to 2%) of fetal bovine serum (FBS) in the Dulbecco's modified Eagle's media (DMEM) reduced the caspase activation signals in BZ- and CFZ-treated cells. Time-dependent Western blot analyses with cells cultured in 2% FBS also showed that the activation of caspase 3 was evident at 24 h after treatment with 100 nM BZ and CFZ," they said.
While bortezomib began to activate caspase 8, 9, and 12 after 16 hours and enhanced their activation at 24 hours, carfilzomib slightly activated caspase 9 and 12 at 16 hours but caspase 8 at 24 hours.
These findings, say the researchers, indicate that both treatments can induce apoptosis by activating canonical caspases that are implicated in the intrinsic and extrinsic pathways. However, they note that each treatment had different contributions.
"To determine ER stress induction, B16-F1 cells were treated with various concentrations of BZ and CFZ for 24 hours, and the expression of ER stress-associated proteins, such as GRP94, GRP78, soluble XBP1, and CHOP, and the cleavage of ATF6α was examined by Western blot analysis," authors explained.
They continued, "the concentration-dependent Western blotting data clearly showed that the levels of some of the ER stress markers, such as GRP78, ATF6α, and XBP1, were greater in the BZ-treated cells than in the CFZ-treated cells at the same concentration."
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Eli Lilly axes 163 Dermira staffers, shutters Menlo Park site as it closes in around Dupixent
Eli Lilly made it clear when it shelled out $1.1 billion for Dermira that lebrikizumab is really what it wanted to buy. One year in, the pharma giant is completing its cleavage of the rest.
Days after unveiling the sale of Qbexza — Dermira’s only approved product, a piece of cloth to block excessive sweating — Lilly revealed plans to close down the biotech’s Menlo Park facility, putting 163 jobs on the chopping block. The San Francisco Business Times first reported on the WARN notice filed in early April.
Specifically, they are grooming lebrikizumab to take on Regeneron and Sanofi’s blockbuster atopic dermatitis treatment Dupixent, with monthly dosing and competitive effects in clearing eczema.
Among the jobs being cut are the CEO role — occupied this past year by Lilly vet and former Immunocore CCO Andrew Hotchkiss — 5 vice president posts, 11 senior manager positions and 75 sales jobs, BioSpace reported . Some field employees may cross over to Journey Medical, which bought Qbrexza, although the details are unclear.
Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.
In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?
Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.
Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.
Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.
Olive Garden's Pay Policies Get Targeted For Encouraging Racial Discrimination And Sexual
IMAGE DISTRIBUTED FOR DARDEN- A group of veterans celebrate Veterans Day with a free meal at the ... [+] Olive Garden restaurant in Kissimmee, Fla. on Sunday, Nov. 11, 2012. (Scott A. Miller/AP Images for Darden)
The sub-minimum wage for tipped American workers came under fresh attack Thursday in what may be its biggest and most direct challenge yet. The One Fair Wage (OFW) nonprofit organization has sued the Darden Restaurant group on Constitutional grounds, claiming the pay practices of the company that owns chains like Olive Garden and The Capital Grille increases racial discrimination and sexual harassment in ways that violate the 14th Amendment and the Civil Rights Act of 1964.
"Oftentimes managers will not just tolerate harassment but go out and encourage it," said Jayaraman, whose colleagues on the call spoke of the common industry-wide order to show more cleavage, flirt with the customers or submit to patrons who tell them to take off their masks to see what they look like before calculating their tip. "She's told (this) by her boss who can fire her. That makes her vulnerable to customers and managers and subject to harassment all day from everybody."
Darden server Ptorsha Cozart explained, "You have to deal with being harassed if you want to pay your rent." She also noted that she and her scarce Black co-workers often get assigned to wait on Black patrons, who usually get seated at the back of her restaurant.
According to law, establishments that pay a subminimum wage must make up the difference between an employee's earnings — wage plus tips — and the state's regular minimum wage. But many restaurant owners get caught failing to pay employees properly.
Darden isn't breaking any laws by paying its servers what plaintiffs say is the lowest legal wage in every state where it operates — as little as $2.13 an hour in 15 of them. But they're singling out the company primarily because it's the largest member of the National Restaurant Association (NRA) and its officers frequently hold leadership positions. The NRA actively opposes the abolition of the subminimum wage as well as the nationwide effort to raise the regular minimum wage to $15 per hour.
The statement goes on to say that Darden's tipped employees earn more than $20 per hour on average, though a press release put out March 25 quotes the chairman and CEO saying they earn an average $17 an hour. Either way, as of last month, every hourly restaurant employee is guaranteed to make at least $10 an hour, including tips, with that amount to rise by $1 per hour for each of the next two years.
Darden manages 1,800 chain restaurants, including Olive Garden, LongHorn Steakhouse, Cheddar's Scratch Kitchen, Yard House, Capital Grille, Seasons 52, Bahama Breeze, and Eddie V's.
The Equal Employment Opportunity Commission authorized the lawsuit, which was filed in the United States District Court for the Northern District of California - Oakland Division.
Alessandra Ambrosio oozes chic sporty as she showcases statuesque figure in sports bra and
Alessandra Ambrosio ushered in her milestone 40th birthday with family and friends, beginning on Sunday, April 11.
Over the course of the proceeding four days, the former supermodel has been able to fit in some form of her daily workout to help maintain her statuesque figure.
And on Thursday she decided to meet up with one of her gal pals and head on over to a nearby gym in the Brentwood neighborhood of Los Angeles .
Working it: Alessandra Ambrosio took advantage of some down time and went to her gym in the Brentwood neighborhood of Los Angeles, four days after ushering in her 40th birthday
The Brazilian-born beauty came dress for success when it comes to sporty in white leggings and a white cropped sweatshirt. In homage to her native country, it read: 'Rio de Janeiro -- Basil' across the front of the sweatshirt.
She also donned stylish sunglasses on another gloriously sunny Southern California day, and pulled her long brown tresses back into a loose ponytail.
In keeping with the fashion color theme, she also wore white slip-on shoes, and a black and white animal print face mask, amid the still dangerous COVID-19 pandemic.
Sporty: The former supermodel showed off her figure in white leggings and a matching sweatshirt when she met up with a gal pal ahead of her workout at a gym
Shedding skin: Ambrosio took off the sweatshirt before leaving the gym and heading home, revealing a white sports bra
Opinion: Jason Kenney, once considered invincible, is facing an uprising - The Globe and Mail
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Say what you will about Alberta Premier Jason Kenney's handling of the COVID-19 crisis, but at least his thinking on the subject isn't quite as misinformed as it once was.
Mr. Kenney has attempted to downplay it, saying this is what happens in a democracy and that some internal opposition to government measures isn't a bad thing. Unless, of course, you're a premier burdened with dreadful polling numbers and Albertans angry with him for being either too lax or too strict when it comes to dealing with the pandemic. (Seventy-five per cent of those recently polled by Angus Reid believe he's doing a bad job handling the crisis.)
There is a theory that the caucus revolt is being managed – that it's a piece of performative theatre approved by the Premier as a way of satiating a restriction-angry rural electorate. I think that would be too clever by half. No, this is a genuine uprising about which Mr. Kenney should be worried.
These MLAs are challenging a leader who has been chastened over the past year. The aura of invincibility that once enveloped Mr. Kenney after his impressive takeover of the Progressive Conservative Party and later merger with the Wildrose Party to form the UCP evaporated long ago. The Premier has not produced a whole lot of remedies for all that ails his province economically. His well-worn schtick of criticizing Prime Minister Justin Trudeau for everything now comes across as tired and misplaced.
Mr. Kenney should be concerned about another splintering of the centre-right in Alberta. The last major cleavage led to the Wildrose Party in the 2000s, which, it can be argued, ultimately led to the New Democratic Party's rise to power in 2015. The Premier maintains, correctly, that any fracturing of the centre-right creates a pathway for the NDP to form government – especially with a leader as popular as Rachel Notley.
Complicating matters is the existence of the Wildrose Independence Party and the separatist Maverick Party, the latter led by former Conservative MP Jay Hill. While their polling numbers don't pose much of a threat today, it would only take a few UCP MLAs willing to sit in the legislature under a new banner to cause greater problems for the Premier.
It's difficult to say if we're anywhere near that point. I suspect we're still a long way from seeing any UCP floor-crossers. But the dissidents in Mr. Kenney's caucus have been emboldened. They know the Premier can't kick them all out and that they have him over the proverbial barrel.
Alberta's rural MLAs are a tough, often ornery bunch. They have an independent streak that makes managing them often difficult. The Premier is likely hoping that, post-pandemic, fences can be mended, differences cast aside. That all will come to their senses and realize the NDP is the real enemy.
There is also a good chance there will be a federal election in the coming months, which will galvanize the centre-right in Alberta against Mr. Trudeau's Liberals. Mr. Kenney and his dissident MLAs will unite in their contempt for the Prime Minister.
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