Protease-activated receptor 2 (PAR-2) is activated by secreted proteases from immune cells or fungi. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells. We hypothesized that epithelial remodeling during diseases characterized by cilial loss and squamous metaplasia may alter PAR-2 polarization. Here, using a fluorescent arrestin assay, we confirmed that the common fungal airway pathogen Aspergillus fumigatus activates heterologously-expressed PAR-2. Endogenous PAR-2 activation in submerged airway RPMI 2650 or NCI–H520 squamous cells increased intracellular calcium levels and granulocyte macrophage–colony-stimulating factor, tumor necrosis factor α, and interleukin (IL)-6 secretion. RPMI 2650 cells cultured at an air–liquid interface (ALI) responded to apically or basolaterally applied PAR-2 agonists. However, well-differentiated primary nasal epithelial ALIs responded only to basolateral PAR-2 stimulation, indicated by calcium elevation, increased cilia beat frequency, and increased fluid and cytokine secretion. We exposed primary cells to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency, at concentrations and times that altered epithelial morphology without causing breakdown of the epithelial barrier to model early disease states. These altered primary cultures responded to both apical and basolateral PAR-2 stimulation. Imaging nasal polyps and control middle turbinate explants, we found that nasal polyps, but not turbinates, exhibit apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyps and turbinates maintained basolateral PAR-2 polarization, suggesting that the calcium responses originated from nonciliated cells. Altered PAR-2 polarization in disease-remodeled epithelia may enhance apical responses and increase sensitivity to inhaled proteases.

Contact between inflammatory cells and endothelial cells (ECs) is a crucial step in vascular inflammation. Recently, we demonstrated that the cell-surface level of endomucin (EMCN), a heavily O-glycosylated single-transmembrane sialomucin, interferes with the interactions between inflammatory cells and ECs. We have also shown that, in response to an inflammatory stimulus, EMCN is cleared from the cell surface by an unknown mechanism. In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Release of the C-terminal fragment of EMCN by TNF-α treatment was blocked by chemical inhibition of ADAM10 alone or in combination with ADAM17. These results indicate that cell-surface EMCN undergoes constitutive cleavage and that TNF-α treatment dramatically increases this cleavage, which is mediated predominantly by ADAM10 and ADAM17. As endothelial cell-surface EMCN attenuates leukocyte–EC interactions during inflammation, we propose that EMCN is a potential therapeutic target to manage vascular inflammation.

Cavalier’s technical director, Rudolph Speid, says the recent positive ranking by CIES (International Centre for Sports Studies) Football Observatory, a research group based in Switzerland, is a reflection of the work the club is doing in trying to...

The National Water Commission (NWC) says a loss in power supply forced the shutdown of the Dinthill facility today, leaving some northern St Catherine communities without water.  The affected communities are: Linstead,...

Education officials across the Caribbean and Latin America have asserted that teachers will be in need of psycho-social support for their return to the classroom, following the COVID-19 pandemic. Approximately 91,710 teachers and seven million...

In this instalment of our series, Dear Diary: In a Time of COVID-19, Karen Pollock tells us about learning the ukulele and how it’s helping her stay connected with her father.

During a three week outreach in November, OM Italy speaks to the heart of a young man called Antonio.

OMer Michelle* and a team of women taking the gospel out in Istanbul, Turkey, are invited to a refugee's home.

The TACO team in Turkey uses creative arts like dance, music, and drama to share the good news with Muslim people groups across the region.

OM Russia leader Colin Cleaver discusses why he values the involvement of families in OM Russia’s ministry and encourages other families to consider missions.

OM Serbia, with the help of volunteers from several nations, are providing sweet tea, and friendship, to the refugees at a camp in Sid, Serbia.

OM Spain's traveling team is back at base after nearly two months on the road visiting and serving in various churches.

Some people may not think that getting somebody a cup of tea is missionary work, but for Rachel, it’s an important part of her ministry.

Community encounter teams seek to serve their local communities and bring Jesus to their neighbourhoods.

The Turning Point Community Encounter team in northwest London learns to share Christ’s love with people from a Muslim background.

An OM Lifehope Community Encounter team works to plant churches in an area of England full of beauty, but one that desperately needs Christ.

Chorley Mission is a small church of mostly elderly people; a Lifehope team brings new life to the congregation through working with children and youth.

Believers bring a positive identity message to teenage girls living in a remote village.

Workers in the OM Near East Field structure a new team around church planting principles.

The accepted unit of measurement for long books is War and Peace. Library shelves bend and buckle under the weight of bigger doorstops, but it's Tolstoy's classic that has become the shorthand for a hefty tome.

A team of 38 from El Salvador and Guatemala visited the Salvadoran city of Perquín to spread the message of the Saviour.

Source: www.sohh.com - Friday, May 08, 2020
Canadian hip-hop artist NAV isn’t letting quarantine stop him from having fun. The rap star has linked up with Young Thug for their new “No Debate” music video premiere. Watch and comment below! The post Watch: NAV Teams Up W/ Young Thug For New No Debate Music Video appeared first on .

Response to Intervention (RTI) has been proven to work with students. Why don't we use it with teachers?

A story of God's grace and the life changing transformation of Juan and his family in Santay Island, Ecuador.

"Life is incomplete without that special someone, who lights up every moment of life," wrote Salman Khan

AC Milan said that the team would continue the individual training programmes that they and other Serie A clubs had begun this week.

Tips from executives on how to inspire creativity in the workplace

"Life is incomplete without that special someone, who lights up every moment of life," wrote Salman Khan

Hyundai Motor India has restarted the production at its Chennai-based plant by ensuring 100 per cent compliance to social distancing and adhering to all the guidelines issued by the State and Central...

Both, the BMW F 900 XR and the S 1000 XR are expected to be launched by mid this year with bookings likely to open next month.

The Ducati Panigale V2 draws power from a 955cc, V-twin Superquadro engine which is now BS6/Euro5 compliant and pumps out 151 horses.

Tips from executives on how to inspire creativity in the workplace

Even now, a state like West Bengal’s data looks dodgy; others like Gujarat and UP also pose challenges

If you don't know about the role and make-up of a digital team, and how it can impact customer experience and brand success, Matt Harris of Sendwithus has the answers

While the government reportedly prepares a second economic relief package to mitigate the fallout of coronavirus, handing out direct cash to people amid the ongoing lockdown is not a desired solution.

The teams are being sent to Gujarat, Tamil Nadu, Uttar Pradesh, Delhi, Rajasthan, Madhya Pradesh, Punjab, West Bengal, Andhra Pradesh and Telangana.

Ambassador Sandhu also expressed some of the cooperation the US government has shown in the evacuation effort by the Indian government for its citizens stranded in the US post the lockdown across the world.

phpLiteAdmin version 1.1 suffers from cross site request forgery and cross site scripting vulnerabilities.

Thursday is the final working day for a British provincial reconstruction team in the Afghan province of Helmand, British Foreign Secretary William Hague said.

Fanny Amun also speaks on the debate for the extension or termination of Gernot Rohr’s contract as the Super Eagles.

The post INTERVIEW: Why Nigeria’s successful youth teams don’t succeed at senior level – Fanny Amun appeared first on Premium Times Nigeria.

The Plateau State Government on Saturday disclosed that most of the cases of COVID-19, which led to the number rising to 15 in state were all imported from outside the state, particularly from Kano and Lagos States. The State Government equally stated that out of the 15 confirmed cases of COVID-19 in the State, 7 […]

COVID-19: Most cases were imported from Kano, Lagos – Plateau Health Commissioner decries

Educators say challenges have been tough but there are benefits worth exploring in the future

On Sunday morning, the Health Ministry showed only 4,826 active cases of coronavirus in Israel, among them, 65 who were intubated. So far, 248 people have died.

Trust must be strong in your team: your trust in your team members; and their trust in you.

Like any other post-conflict nation, it deserves a new lease of life.

Miss Rizos uses African and African-American hairstyles to affirm blackness in straight-hair-obsessed country

1. Tere Bina teaser: Salman Khan romances Jacqueline Fernandez in his ‘cheapest production’. Watch  Hindustan Times
2. Tere Bina Teaser: Salman Khan And Jacqueline Fernandez Redefine Romance  NDTV
3. Salman Khan and Jacqueline Fernandez share the inspiration behind their upcoming track 'Tere Bina' in the  Times of India
4. Inside Salman Khan's Panvel farmhouse: Actor bonds with Jacqueline, Iulia Vantur, and Waluscha - entertainment  Mid-Day
5. KBC 2020 Registrations Begin, Iulia Vantur Reacts to Marriage Rumours with Salman Khan  News18
6. View Full coverage on Google News

Bhagyashree in a scene, instead of running and hugging Salman Khan, ended up bursting into tears