Saturday, April 3, 2021

Cindy Crawford flashes cleavage in bathrobe in behind-the-scenes video from photo-shoot | Daily

Cindy Crawford bared her cleavage in a bathrobe in a sizzling new clip she posted to her Instagram page on Friday.

The 55-year-old - who shot to fame as one of the great 1990s Supermodels - was sharing a behind-the-scenes glimpse of a new photo-shoot.

Her shoot was for the skincare line Meaningful Beauty which she launched in 2005 with the French plastic surgeon Jean-Louis Sebagh.

In the behind-the-scenes video Cindy's robe fell slightly open at the top to offer just a hint of the black garment she had on underneath.

Her cosmetics had been expertly applied by Hung Vanngo and her hair was in a sumptuous do by Dimitris Giannetos.

Cindy also took the show to her Insta Stories where she shared footage of herself on the set having the hair and makeup done.

At that point she was wearing a true blue tank top that was partly tucked in as she sat in her hair at the a makeup table.

From Publisher: Mail Online



Did you hear about this:

SpringWorks (SWTX) Announces Dosing of First Patient in Phase 1b Combination Study Evaluating

Gamma secretase inhibition prevents the cleavage and shedding of BCMA from the surface of myeloma cells. In preclinical models, nirogacestat has been shown to increase the cell surface density of BCMA and reduce levels of soluble BCMA, which may enhance the activity of BCMA-targeted therapies.

In addition to its ongoing clinical collaborations with BCMA-directed therapies, SpringWorks is conducting a global Phase 3, double-blind, randomized, placebo-controlled clinical trial (the DeFi Trial) to evaluate nirogacestat as a monotherapy in adults with progressing desmoid tumors.

Receive full access to all new and archived articles, unlimited portfolio tracking, e-mail alerts, custom newswires and RSS feeds - and more!

From Publisher: StreetInsider.com



Grammy Awards 2021: From Skeleton Dress To Cleavage Baring Outfits, Here's Grammys RED CARPET

The Grammys has produced some of the most iconic looks in fashion history and it's the one ceremony where we can expect to see daring, wild and the weirdest looks on the red carpet and this year too some celebs stepped on the red carpet in the most unusual manner, take a look!

Miley Cyrus's younger sister Noah turn heads when she hit the red carpet wearing an ivory Schiaparelli Couture dress complete with a massive bodice.

Nominated for Best New Artist, the singer stepped out in a voluminous white Schiaparelli Couture gown, that became a hot topic of trend on social media

Phoebe Bridgers opted for a sparkling skeleton-print dress for the Grammy Awards on Sunday that obviously became the talk of the town!

She walked the red carpet in a black dress with a jewel-encrusted skeleton pattern from top to bottom.

Singer Doja Cat made jaws drop as she hit the red carpet in a feathered, plunging Roberto Cavalli x Fausto Puglisi gown that zipped all the way down past her belly button.

Singer Ingrid Andress opted for a chic ivory Armani suit, she completed the sleek look with a crystallized body chain.

From Publisher: _____



Miley Cyrus Flashes Her Cleavage In Snaps Taken By A Famous Friend - The Inquisitr

Miley Cyrus gave Instagram followers a show this weekend, sharing a series of racy snaps that were taken by one of her famous friends.

The pictures, shared on Sunday, showed Miley flashing some cleavage and showing off some rock star attitude. They captured some viral attention, garnering praise from followers and some of Miley's other famous friends. It's the latest racy image that Miley has shared on social media, following up some other even more revealing images that she has posted in recent weeks.

The series of pictures, which can be seen below, showed Miley wearing an all-black outfit, including a top that showed off plenty of skin. In one of the images, she held both sides of her shirt, pulling it slightly open to show off her cleavage as she struck a pose. 

The image showed her sitting on the ground surrounded by tables and chairs, and was taken in black-and-white, giving it an artistic effect. Other pictures taken in the same setting showed Miley flashing a middle finger and putting a mean look on her face.

"Harry, that's easy," she replied. "Justin Bieber I've known way too long, and it's like a family. Harry Styles!"

The revealing snaps of Miley earned some big attention from her followers, racking up more than 1.1 million likes in just a matter of hours. Many of her followers took to the comments section to share some praise for the snaps.

"You are top!!!!" wrote another, ending the comment with a long series of fire emoji. Many others used emoji, using hearts and fire to show their appreciation.

This is not the first time that Miley has shown some skin on social media. She has posted some even racier images on Instagram in recent weeks, including a shot last month that showed her lounging in the bathtub.

As The Inquisitr reported at the time, Miley posed in the nude but used her arm to cover her chest so she remained within Instagram's strict rules against overt nudity. This picture was also a viral hit, racking up many likes and comments.

From Publisher: The Inquisitr



Not to change the topic exactly:

Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis | Nature

a , Schematic of SARS-CoV-2 challenge, created with BioRender. b – f , Male and female mice were challenged with 10 3 PFU of wild-type (black) or ΔPRRA (blue) SARS-CoV-2, and evaluated for weight loss ( n = 12 for both groups) ( b ), and viral RNA from the lung ( c ), nasal turbinate ( d ), nasal wash ( e ) and brain ( f ). At 2 days post-infection (dpi), n = 9 mice infected with wild type, 11 mice infected with ΔPRRA; at 7 dpi, n = 11 mice for both. N gene copies in the brain were measured at 7 dpi only. LOD, limit of detection. g , h , Lung function evaluated at 7 dpi using Flexivent mechanical ventilator to assess inspiratory capacity ( g ) and pressure–volume loop ( h ). n = 10 mice infected with wild type; n = 9 mice infected with ΔPRRA. i – k , Lung histopathology at 7 dpi from mock- ( i ), wild-type- ( j ) and ΔPRRA- ( j ) infected mice. Images are representative of lung sections from three mice in all cases. Scale bar, 250 μm. l , Chemokine analysis of mouse lung homogenates at 7 dpi, from mock-infected mice (white), or mice infected with wild-type (black) or ΔPRRA (blue) SARS-CoV-2. n = 8 for all groups. Data are mean ± s.e.m. P values from two-tailed Student's t -test with unequal variance ( b ), Kruskal–Wallis Test for multiple comparisons ( c – e , g , h ), χ 2 test ( f ) or a two-tailed Mann–Whitney test between wild-type and ΔPRRA ( l ).

a , Schematic for ΔPRRA SARS-CoV-2 reporter virus expressing mNeonGreen gene in place of ORF7 . b , PRNT 50 values measured by mNeonGreen expression, with wild-type SARS-CoV-2 on the x axis and ΔPRRA SARS-CoV-2 on the y axis. c – e , Representative curves from low ( c ), intermediate ( d ) and high ( e ) neutralizing sera from patients with COVID-19. n = 3. f – h , Neutralization curves from three monoclonal antibodies (mAb 1 ( f ), mAb 2 ( g ) and mAb 3 ( h )). n = 3. i , Particle:PFU ratio determined from 40 fields, dividing into individual particles (left) and clusters (right) to determine ratios. j , Percentage of particles as individual virions (1), doubles (2) or larger clusters (>3). Data are mean ± s.e.m.

A number of approaches can prevent the emergence of the ΔPRRA mutation in SARS-CoV-2 stocks. In our studies, we found no evidence for PRRA deletion in infectious clone-derived wild-type SARS-CoV-2 through passage 2. By using low-passage stocks, the incorporation of this mutation was limited. One alternative is the use of Vero E6 cells expressing TMPRSS2, which removes the fitness advantage of the ΔPRRA mutant and will allow virus propagation without altering the full-length-to-S1/S2 processing ratio of the S protein. However, continued passage risks this or other tissue culture adaptations, and careful monitoring of stock composition is needed. Using plaque purification techniques, wild-type SARS-CoV-2 can be selected for by its smaller plaque morphology.

No statistical methods were used to predetermine sample size. The experiments were not randomized, and investigators were not blinded to allocation during experiments and outcome assessment.

For detection of viral RNA, the nasal washes and oral swabs of hamsters infected with wild-type SARS-CoV-2 or ΔPRRA SARS-CoV-2, RNA extraction, cDNA synthesis and RT–qPCR were performed as described in the preceding paragraph. For RT–qPCR, primer 1 and primer 3 were used for all hamster samples.

Supernatants of SARS-CoV-2 infected cells were centrifuged for 10 min at 3,000 g to remove large cellular debris. Nickel grids were incubated with clarified supernatants for 10 min followed by glutaraldehyde fixation and 2% uranyl acetate staining. Micrographs were taken using a JEM 14000 (JEOL USA). Several randomly selected fields were imaged to obtain unbiased particle counts.

Lung homogenates were incubated with Triton-X-100 (1% final concentration) for 1 h at room temperature to inactivate SARS-CoV-2. Homogenates then were analysed for cytokines and chemokines by Eve Technologies, using their Mouse Cytokine Array and Chemokine Array 31-Plex (MD31) platform.

Upon euthanasia, the lung was inflated with about 1.2 ml of 10% neutral buffered formalin using a 3-ml syringe and catheter inserted into the trachea. The airway, lungs and heart were removed en bloc and transferred to a conical flask containing 40 ml 10% neutral buffered formalin, in which the tissues were allowed to fix for suspension of neutral buffered formalin for ≥7 days. Tissues were embedded in paraffin, and sections were stained with haematoxylin and eosin by the Washington University Lung Morphology Core. Images were captured using the Nanozoomer (Hamamatsu) at the Alafi Neuroimaging Core at Washington University.

The recombinant wild-type and mutant SARS-CoV-2 described in this Article are available through the WRCEVA at UTMB through a material transfer agreement.

From Publisher: Nature



Susanna Reid, 50, defends showing a 'tiny bit of cleavage' on Good Morning Britain

Her outfits have become as much of a talking point on Good Morning Britain as her opinionated co-host Piers Morgan.

But Susanna Reid has defended showing a "tiny bit of cleavage" on the ITV breakfast show, after accusations her trademark colourful dresses have become too revealing, insisting the looks she opts for are "presentable and appealing".

Reid explained that the programme's stylist chooses what she wears, but that "if it's too low, I'll say".

Reid alluded to one particular dress that drew criticism for being too revealing after she wore it on the show last month.

Of her reaction to the news coverage sparked by the v-neck satin frock from brand Nobody's Child, she said: "I just thought, 'Blimey.' I think, 'Look, women have got boobs; let's not act shocked that they have.'"

She said: "We 50-year-olds want to be on television for as long as we possibly can. It's really important that we look presentable and appealing."

The picture garnered more than 23,000 'likes' with over 1,000 comments agreeing with her that there had been an overreaction.

A third shared: "I loved your green dress and didn't see the issue. Clearly lockdown is causing people's boredom to run rampant."

The controversial presenter said: "We're a team. It would be like splitting up '[Thierry] Henry and [Dennis] Bergkamp at Arsenal. Never going to work. You couldn't have one without the other. Yin and yang.




Caspase-8–dependent gasdermin D cleavage promotes antimicrobial defense but confers

In this study, we report that caspase-8 dimerization, autoprocessing, and activity are required for caspase-8–dependent GSDMD cleavage. We observed the strongest caspase-8 activation on TNF Complex IIb, which correlates with robust direct GSDMD cleavage. In contrast, caspase-8 is only weakly activated under other conditions of extrinsic apoptosis and, likewise, is a weak activator of GSDMD. We further demonstrate that GSDMD activation promotes anti- Yersinia defense in vivo and provide compelling evidence that caspase-8–dependent GSDMD activation promotes TNF-induced lethality independent of inflammasome activation. While GSDMD cleavage and inactivation at position D88 do not suppress pyroptosis downstream of canonical or noncanonical inflammasome activation, they are required for optimal anti- Yersinia defense in vivo and are essential to suppress TNF-induced lethality.

( A to F ) BMDMs were primed with LPS (100 ng/ml) for 4 hours and stimulated with nigericin (5 μM), ATP (2.5 mM), log-phase S. Typhimurium [multiplicity of infection (MOI) of 10], or poly(dA:dT) (1 μg/ml). Where indicated, BMDMs were treated with TNF (100 ng/ml)/TAK1i (125 nM) for 4 hours. (A and B) LDH and (C and D) IL-1β release was measured at the indicated time points. (E and F) Mixed supernatant and cell extract from (E) two C57BL/6 and two Gsdmd D88A/D88A mice were examined by immunoblotting 1 hour after stimulation or (F) at the indicated time points. FL, full-length; long exp., long exposure. ( G and H ) Bone marrow neutrophils were primed with LPS (100 ng/ml) for 4 hours and infected with log-phase S. Typhimurium (MOI of 25). (G) LDH and (H) IL-1β release was measured 3 hours after infection. ( I and J ) Mice were challenged with 1 × 10 5 colony-forming units (CFU) of log-phase S. Typhimurium by intraperitoneal injection, and bacterial burden was quantified 48 hours later. (A) Data are represented as means + SEM of cell stimulation from three mice or (B to D, G, and H) means + SD of triplicate cell stimulation from three independent experiments. (I and J) Data are geometric means and pooled from two independent experiments. Immunoblots are representative of three independent experiments.

( A ) BMDMs were costimulated with TNF (100 ng/ml)/TAK1i (125 nM), TNF (100 ng/ml)/CHX (10 μg/ml), LPS (100 ng/ml)/TAK1i (125 nM), or LPS (100 ng/ml)/CHX (10 μg/ml) for 6 hours, and mixed supernatant and cell extracts were analyzed by immunoblot. ( B ) BMDMs were primed with TNF (100 ng/ml) or LPS (100 ng/ml) for 3 hours before stimulation with TAK1i (125 nM) or CHX (10 μg/ml) for 6 hours, and mixed supernatant and cell extracts were analyzed by immunoblot. ( C ) BMDMs were costimulated with TNF (100 ng/ml)/TAK1i (125 nM) or TNF (100 ng/ml)/CHX (10 μg/ml) or primed with LPS (100 ng/ml) for 16 hours and treated with FasL (100 ng/ml) for 6 hours, and mixed supernatant and cell extracts were analyzed by immunoblot. (C) Blots are cropped from the same film. Immunoblots are representative of two to three independent experiments.

Next, we investigated whether caspase-8 activated upon plasma membrane–bound DISC, such as the Fas (CD95) complex, induces caspase-8–dependent GSDMD cleavage in BMDMs. Because Fas is weakly expressed in BMDMs, we first primed BMDMs with LPS or Pam3CSK4 to induce Fas expression ( 35 ), before stimulation with FasL. Since LPS but not Pam3CSK4 priming sensitized macrophages to FasL-induced apoptosis (fig. S2, A and B) and caspase-8 autoprocessing plateaus at 6 hours after FasL treatment (fig. S2C), we decided to examine GSDMD cleavage in LPS-primed macrophages at this time point. FasL induced weaker caspase-8 autoprocessing and GSDMD cleavage compared to TNF/CHX or TNF/TAK1i stimulation ( Fig. 2C ). Of note, FasL-induced GSDMD processing was notably reduced in Casp1 −/− BMDMs ( Fig. 2C ), indicating that similar to Complex IIa assembly ( Fig. 2, A and B ), caspase-1 is the dominant protease that processes GSDMD under conditions of DISC assembly. Together, our data indicate that in BMDMs, direct cleavage of GSDMD by caspase-8 occurs mostly upon Complex IIb formation, while caspase-8 activated on Complex IIa or the DISC can only weakly do so or indirectly via activation of caspase-1 inflammasome.

Next, we performed a time course analysis to investigate whether the difference in caspase-8 activity on various complexes might account for the enhance ability of Complex IIb to directly process GSDMD. TNF and TAK1i costimulation triggered robust caspase-8 autoprocessing and disappearance of the caspase-8 substrate RIPK1 ( 36 ) as early as 2 hours after stimulation, which correlated with GSDMD processing in both WT and Casp1 −/− BMDMs ( Fig. 3, A and B ). In contrast, caspase-8 autoprocessing into its p18 fragment and RIPK1 cleavage was significantly weaker in TNF/CHX- and LPS/FasL-stimulated cells compared to TNF/TAK1i-treated BMDMs, even after 24 hours of stimulation ( Fig. 3, A and B ). These data suggest, at least in part, that the caspase activity generated by different complexes determines the ability of caspase-8 to directly cleave GSDMD during extrinsic apoptosis.

( A to D ) BMDMs were treated with were costimulated with TNF (100 ng/ml)/TAK1i (125 nM) or TNF (100 ng/ml)/CHX (10 μg/ml) or primed with LPS (100 ng/ml) for 16 hours and treated with FasL (100 ng/ml) for the indicated time points, and mixed supernatant and cell extracts were analyzed by immunoblot or ( E to G ) LDH release into the cell culture supernatant was quantified. (A to D) Immunoblots are representative of two to three independent experiments. (E to G) Data are means + SEM of pooled data from (E and F) six or (G) five independent experiments. Data were normally distributed and analyzed using a parametric t test. * P < 0.05 or ** P < 0.01. UT, untreated.

Since cleavage of GSDMD at position D88 by apoptotic caspase-3/7 suppresses the prolytic properties of GSDMD upon Complex IIb formation ( 9 ), we wondered whether this cleavage event likewise suppresses pyroptosis upon TNF Complex IIa or DISC assembly. To examine this possibility, we compared cell lysis in WT, Gsdmd −/− , and caspase-3/7 cleavage-resistant Gsdmd D88A/D88A BMDMs upon Complex IIa, Complex IIb, and DISC assembly. TNF/CHX and LPS/FasL stimulation triggered cleavage of full-length GSDMD into the active p30 and inactive p20 fragments in WT macrophages. As anticipated, there was an accumulation of the active GSDMD p30 fragment and a complete loss of inactive p20 fragment in Gsdmd D88A/D88A cells ( Fig. 3, C and D ). However, accumulation of active GSDMD p30 in LPS/FasL- and TNF/CHX-stimulated macrophages had minimal impact on cellular lysis but significantly enhanced pyroptosis under conditions of TNF Complex IIb assembly ( Fig. 3, E to G ). Together, our data indicate that the enhanced activation of caspase-8 on Complex IIb but not Complex IIa or the DISC licenses direct GSDMD cleavage and pyroptosis and that caspase-3/7–dependent GSDMD inactivation mainly suppresses cell lysis under conditions of TNF Complex IIb assembly.

( A ) HEK 293T cells were transfected with GSDMD together with WT caspase-8 (Casp8 WT ), caspase-8 catalytic mutant (Casp8 cat. mut. ), or uncleavable caspase-8 (Casp8 uncl. ). Vector control was transfected such that each set of constructs received equivalent amounts of DNA. Twenty-four hours after transfection, transfected cells were treated with AP20187 (dimerizer) for a further 6 hours. Cell extracts (XT) and precipitated supernatants (S/N) were analyzed by immunoblotting for GSDMD and caspase-8. ( B to G ) WT or caspase-8 uncleavable (D387A) Casp8 D387A/D387A BMDMs were stimulated with TNF (100 ng/ml)/TAK1i (125 nM) or TNF (100 ng/ml)/CHX (10 μg/ml) or primed with LPS (100 ng/ml) for 16 hours and treated with FasL (100 ng/ml). Where indicated, cells were treated with GSK'872 (1 μM) 20 to 30 min before stimulation. LDH release was measured at (B and C) 4 hours or (D) 6 hours after stimulation. (E to G) Mixed supernatant (S/N) and cell extracts were examined by immunoblotting. (G) Blots are cropped from the same film. (E to G) Immunoblots are representative of three independent experiments. (B to D) Data are means + SEM of pooled data from four independent experiments. Data were normally distributed and analyzed using a parametric t test. * P < 0.05 or ** P < 0.01.

( A to K ) Mice were challenged intravenously with TNF (500 μg/kg). (A) Body temperature and (B) survival were monitored over time. (C) Plasma LDH was quantified at 4 hours after TNF challenge. A 490 , absorbance at 490 nm. (D to K) Plasma cytokines were measured 3 hours after TNF challenge. CCL2, C-C motif chemokine ligand 2; KC, keratinocyte-derived chemokine; PBS, phosphate-buffered saline; ns, not significant; G-CSF, granulocyte colony-stimulating factor. ( L ) Mice were challenged intravenously with Fc-FAS (50 μg/kg) and monitored for lethality. The number of mice ( n ) used in each experiment are indicated. (A and B) Data are means + SEM pooled from three independent experiments, and (A) statistical analysis was performed using a two-way analysis of variance (ANOVA). (B) Survival curves were compared using log-rank Mantel-Cox test. (C to K) Data are geometric means from four to five mice per genotype and analyzed using a parametric t test. * P < 0.05; ** P < 0.01.

From Publisher: Science Advances



News anchor responds to viewer who complained about cleavage

"One woman called me just to say it looked like I'd gained 50 pounds," the journalist for Canada's CHEK News told TODAY Style . "I'm constantly getting messages about my body."

Attached to the note was a photo of Sidaway delivering the news on Sunday, and a picture of a random woman in a similar shirt but with a dramatic plunge neckline.

"TOO MUCH CLEAVAGE CAN BREAK YOUR NEWS STORY. Don't let it happen to you," the troll wrote. "Episode: Sunday Sept. 6. 5-7 PM. Attached are 2 photos. What you think we see and what we actually see. Dress appropriately, it was hard work to get there."

Sidaway immediately received support from on-air personalities all over the world — and many shared similar stories.

Tamara Stanners, a former news anchor, noted that in the '90s, she "was told to always wear long sleeves" because her bare arms were too provocative.

Sidaway hopes women in her field will continue to speak out rather than internalizing the harassment.

"This problem is so widespread," she explained. "I keep thinking about the next generation. I don't want them to go through this. It's not OK."

From Publisher: TODAY.com



No comments:

Post a Comment

Popular Posts