ABSTRACT

The opportunistic bacterium Pseudomonas aeruginosa produces the fucose-specific lectin LecB, which has been identified as a virulence factor. LecB has a tetrameric structure with four opposing binding sites and has been shown to act as a cross-linker. Here, we demonstrate that LecB strongly binds to the glycosylated moieties of β1-integrins on the basolateral plasma membrane of epithelial cells and causes rapid integrin endocytosis. Whereas internalized integrins were degraded via a lysosomal pathway, washout of LecB restored integrin cell surface localization, thus indicating a specific and direct action of LecB on integrins to bring about their endocytosis. Interestingly, LecB was able to trigger uptake of active and inactive β1-integrins and also of complete α3β1-integrin–laminin complexes. We provide a mechanistic explanation for this unique endocytic process by showing that LecB has the additional ability to recognize fucose-bearing glycosphingolipids and causes the formation of membrane invaginations on giant unilamellar vesicles. In cells, LecB recruited integrins to these invaginations by cross-linking integrins and glycosphingolipids. In epithelial wound healing assays, LecB specifically cleared integrins from the surface of cells located at the wound edge and blocked cell migration and wound healing in a dose-dependent manner. Moreover, the wild-type P. aeruginosa strain PAO1 was able to loosen cell-substrate adhesion in order to crawl underneath exposed cells, whereas knockout of LecB significantly reduced crawling events. Based on these results, we suggest that LecB has a role in disseminating bacteria along the cell-basement membrane interface.

IMPORTANCE Pseudomonas aeruginosa is a ubiquitous environmental bacterium that is one of the leading causes of nosocomial infections. P. aeruginosa is able to switch between planktonic, intracellular, and biofilm-based lifestyles, which allows it to evade the immune system as well as antibiotic treatment. Hence, alternatives to antibiotic treatment are urgently required to combat P. aeruginosa infections. Lectins, like the fucose-specific LecB, are promising targets, because removal of LecB resulted in decreased virulence in mouse models. Currently, several research groups are developing LecB inhibitors. However, the role of LecB in host-pathogen interactions is not well understood. The significance of our research is in identifying cellular mechanisms of how LecB facilitates P. aeruginosa infection. We introduce LecB as a new member of the list of bacterial molecules that bind integrins and show that P. aeruginosa can move forward underneath attached epithelial cells by loosening cell-basement membrane attachment in a LecB-dependent manner.

Calcineurin B-like protein (CBL) and CBL-interacting protein kinase (CIPK)-mediated calcium signaling has been widely reported to function in plant development and various stress responses, particularly in ion homeostasis. Sugars are the most important primary metabolites, and thus sugar homeostasis requires precise regulation. Here, we describe a CBL2-CIPK6-Tonoplast-Localized Sugar Transporter2 (TST2) molecular module in cotton (Gossypium hirsutum) that regulates plant sugar homeostasis, in particular Glc homeostasis. GhCIPK6 is recruited to the tonoplast by GhCBL2 and interacts with the tonoplast-localized sugar transporter GhTST2. Overexpression of either GhCBL2, GhCIPK6, or GhTST2 was sufficient to promote sugar accumulation in transgenic cotton, whereas RNAi-mediated knockdown of GhCIPK6 expression or CRISPR-Cas9-mediated knockout of GhTST2 resulted in significantly decreased Glc content. Moreover, mutation of GhCBL2 or GhTST2 in GhCIPK6-overexpressing cotton reinstated sugar contents comparable to wild-type plants. Heterologous expression of GhCIPK6 in Arabidopsis (Arabidopsis thaliana) also promoted Glc accumulation, whereas mutation of AtTST1/2 in GhCIPK6-overexpressing Arabidopsis similarly reinstated wild-type sugar contents, thus indicating conservation of CBL2-CIPK6-TST2-mediated sugar homeostasis among different plant species. Our characterization of the molecular players behind plant sugar homeostasis may be exploited to improve sugar contents and abiotic stress resistance in plants.

Căn hộ Flora Mizuki khu đô thị được phát triển bởi Tập Đoàn Nam Long & hai đối tác đến từ Nhật Bản. Ngân hàng VCB hỗ trợ vay 70% giá trị sản phẩm, thời gian lên đến 20 năm. * Khu đô thị Mizuki Park quy mô 36 hecta tọa lạc trên đại lộ Nguyễn Văn Linh thuộc khu Nam Sài Gòn. Từ ...

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Apple dropped its brand new 13-inch MacBook Pro overnight, which is exciting because the dreaded butterfly keyboard is now finally dead. For real. In its place you'll find the newer Magic Keyboard which has previously been added to the 16-inch MacBook Pro and the MacBook Air. Today is a good day. If you're keen to get your paws on the new laptop, here's how much it will set you back in Australia. More »

The case against them has been registered for forgery, cheating, criminal breach of trust and corruption.

Kal Penn and The Walking Dead's Michael Cudlitz join Lecter-less sequel show.

Not as substantial as hoped

Keyboard aside, cheaper storage and 10th-generation Intel CPUs headline this refresh.

Philippine legislators pushed on Wednesday to get the country's biggest broadcaster back on air, amid widespread shock and dismay over an order by the industry regulator for the station to cease operations after its 25-year licence expired.

Actor returns with his beloved dog for kids channel's 'Tom Hardy week'

Most of the improvements were performance-based. The new 13-inch laptop features double the storage and a speed boost, and prices start at $1,299.

It's boom time for CBD as the capital looks for ways to relax in lockdown. Phoebe Luckhurst has a bluffer's guide to mellowing out

CBeebies tapped the mental health campaigner to narrate the new game

An 81-year-old man is charged over the alleged sexual and indecent assault of two minors in northern NSW and police say there could be more victims who were drawn in over CB radio at the time.

Over the last few years, social networks have instituted slightly stiffer policies against misinformation, but those systems are being pressed to their limit by a fast-spreading new video. The ‘Plandemic’ clip “spreads debunked conspiracy theories ab...

Coming-of-age drama Normal People, based on Irish author Sally Rooney's bestselling novel and touted as one of the best book-to-series adaptations in recent years, is set to debut in Canada on CBC Gem.

Millionaire CarAdvice founder and petrolhead Alborz Fallah just wants to hit the road. Pity the Queensland Police have a different idea.

Energy Minister Angus Taylor’s long, and at times politically painful, involvement with rural sector has run its course.

As the Government begins easing social-distancing restrictions, there are doubts once-bustling workplaces in Sydney's CBD will ever return to the way they were.

Malcolm Turnbull's memoir, A Bigger Picture, is uncomplimentary about many people and organisations. But few come out of it as badly as Rupert Murdoch's media empire, News Corp.

Millionaire CarAdvice founder and petrolhead Alborz Fallah just wants to hit the road. Pity the Queensland Police have a different idea.

Energy Minister Angus Taylor’s long, and at times politically painful, involvement with rural sector has run its course.

What's on TV Thursday, May 7: 'Tommy' on CBS; coronavirus TV coverage; movies on TV; TV talk shows and more

Join Kleinfeld, Kaplan & Becker, LLP and Vicente Sederberg on Tuesday, April 7 at 2:15 p.m. ET for a live webinar on Hemp and CBD – FDA Update and the Impact of COVID-19. Since 2015, KKB and VS have worked closely together in advising clients on the ever-evolving legal landscape for hemp-derived products. During this

The post LIVE WEBINAR: Hemp & CBD: FDA Update and the Impact of COVID-19 appeared first on Kleinfeld Kaplan & Becker LLP.

RESCHEDULED: This event has been rescheduled for November 11-13, 2020. Click here to learn more.

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Informa Connect-CBI’s Patient Support Services Congress
June 16-18, 2020 | The Westin Princeton at Forrestal Village | Princeton, NJ
www.informaconnect.com/patient-support-services-congress

Informa Connect-CBI’s Patient Support Services Congress is a comprehensive meeting for insightful and engaging dialogue around navigating compliance hurdles while strengthening and innovating patient-oriented programs.

Visit www.informaconnect.com/patient-support-services-congress for more information. Drug Channels readers will save $500 off the standard registration rate when they use code BNP667*.

Download the agenda here and see in-depth coverage on industry trends and next-generation patient services, such as:

• Critical Regulatory Updates and Effective Strategies for Monitoring & Oversight
• Novel Approaches to Services, Program Architecture and Operational Management
• The pros and cons of different support service models
• Measuring the Success of Patient Support Programs
• Innovation, AI, Changing Distribution Models and Market Mergers
• Transparency with Charitable Organizations

Create Your Own Customized Learning Experience for 2020!

Choose from Two In-Depth Tracks

• Legal and Compliance
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• Summit A: Patient Adherence – Educate, Engage and Collaborate to Enhance Outcomes
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Leading Perspectives from Industry Trendsetters:

• Robert Britting, Director, Patient Services and Strategic Solutions, Teva Pharmaceuticals
• Stella Vnook, Chief Executive Officer, Diverse Biotech
• Katherine Chaurette, Vice President healthcare Law and Compliance, Blueprint Medicines
• Kimberly Goldberg, Director, U.S Data Privacy Counsel, Novartis
• Imtiaz Hussain, Senior Director, Patient Services, Bayer
• Cory Potomis, Associate Director, Ethics & Compliance Operations, Novo Nordisk, Inc.
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Visit www.informaconnect.com/patient-support-services-congress for more information. Drug Channels readers will save $500 off the standard registration rate when they use code BNP667*.

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The content of Sponsored Posts does not necessarily reflect the views of Pembroke Consulting, Inc., Drug Channels, or any of its employees.

Informa Connect-CBI’s 22nd Annual Medicaid and Government Pricing Congress
May 19-21, 2020 | Orlando, FL
www.cbinet.com/medicaidandgovernment

Exclusive Offer: Register by April 10th and save $500* (mention promo code MDCDC5).

With a volatile healthcare system combined with an election year upon us, the stakes are incredibly high for life sciences manufacturers. Staying on the pulse of industry trends, policies and regulations has never been more critical. The 22nd Annual Medicaid and Government Pricing Congress delivers critical updates and industry best practices to effectively contract, report and comply with state and federal healthcare programs. Gain timely, up-to-the-minute insights on:

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• GTN Models
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The content of Sponsored Posts does not necessarily reflect the views of Pembroke Consulting, Inc., Drug Channels, or any of its employees.

The U.S. Food and Drug Administration posted a photo:

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CBD Product – Patriot Hemp Company: www.fda.gov/inspections-compliance-enforcement-and-crimin...

More information is available at www.fda.gov/consumers/health-fraud-scams/fraudulent-coron...

Photo by FDA's Office of Regulatory Affairs, Health Fraud Branch

This photo is free of all copyright restrictions and available for use and redistribution without permission. Credit to FDA's Office of Regulatory Affairs, Health Fraud Branch is appreciated but not required.

The Department of Justice’s Environment and Natural Resources Division announced the filing of a major lawsuit today against 10 companies and two municipalities to require continued environmental cleanup work at Wisconsin’s Lower Fox River and Green Bay Site.

Benjamin Franklin Pass, 60, and P&s Environment and Natural Resources Division and the U.S. Attorney’s Office for the Eastern District of North Carolina. The defendants admitted to, among other things, the unlawful handling of a toxic substance that resulted in widespread contamination.

Attorney General Eric Holder issued the following statement today on the resignation of U.S. Attorney for the Eastern District of Virginia Neil H. MacBride:

"Why is health care enforcement so important? A major reason is the importance of the health care industry itself. From compliance officers to physicians, from corporate executives to nurses and researchers, you contribute to producing the drugs and medical devices on which we and our loved ones rely. Your efforts help to ensure that, when we are sick, the medicines we take will heal us effectively; that when we are in pain, we can obtain relief safely," said Assistant Attorney General Delery

Titanium Metals Corporation (TIMET), one of the world’s largest producers of titanium parts for jet engines, has agreed to pay a record $13.75 million civil penalty and perform an extensive investigation and cleanup of potential contamination stemming primarily from the unauthorized manufacture and disposal of PCBs (polychlorinated biphenyls) at its manufacturing facility in Henderson, Nevada.

Benjamin Franklin Pass, 61, and P&W Waste Oil Services Inc. (P&W), of Leland, North Carolina were sentenced today in federal court in Raleigh, North Carolina. Pass was sentenced to 42 months in prison and ordered to pay restitution in the amount of $21,373,143.38 for clean-up costs associated with the environmental contamination at his business and an additional $538,857 to the Internal Revenue Service (IRS) for federal income taxes he failed to pay between 2002 and 2011

Potential brain health benefits of cannabidiol (CBD) can make it an attractive ingredient for supplement brands, but federal regulations and FDA action may hinder product success in the market.

Download the latest CBSE syllabus of all subjects of Class 9. Analyse the syllabus before studyng new chapters in new academic session.

OSCB Recruitment 2020 Online Application for 786 is being filled up at rcsodisha.nic.in . Check details here.

CBSE Result 2020: Amid COVID - 19 pandemic & lockdown, Kendriya Vidyalaya Sangathan (KVS) and many state boards (like Gujarat, Haryana, Puducherry) have decided to promote school students (Classes 1st to 9th & Class 11th). After this, many students & parents are seeking clarity from the Central Board of Secondary Education (CBSE). Check updates.

The international Joint Center for Biomedical Innovation (JCBI) is comprised of two partner research nodes using nanoparticle technologies to develop solutions for cancer and neurodegenerative diseases diagnostics. Henan University has established a new research laboratory in nano-bio system innovation and theranostics, with start-up funding and new academic positions. Macquarie’s node is built upon its established excellence in neuroscience and cancer research programs. The collaborative succes…

The Congressional Budget Office's new Budget and Economic Outlook provides a useful update on the state of the economy and the budget. While the headline news is the return of trillion-dollar annual deficits, there is much more to consider. Here are four take-aways from the latest projections: 1. Interest rates have fallen and will remain…