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Vital Protective Mechanism Discovered: Dying Cells Protect Their Neighbors To Maintain Tissue Integrity

Artistic rendering of dying cells protecting their neighbors to maintain tissue integrity. Holes in epithelium created by uncoordinated cell death are shown in purple. Credit: © Institut Pasteur / Léo Valon et Romain Levayer

Cells undergoing cell death protect their neighbors to maintain tissue integrity.

To enable tissue renewal, human tissues constantly eliminate millions of cells, without jeopardizing tissue integrity, form, and connectivity. The mechanisms involved in maintaining this integrity remain unknown. Scientists from the Institut Pasteur and the CNRS recently revealed a new process that allows eliminated cells to temporarily protect their neighbors from cell death, thereby maintaining tissue integrity. This protective mechanism is vital, and if disrupted can lead to a temporary loss of connectivity. The scientists observed that when the mechanism is deactivated, the simultaneous elimination of several neighboring cells compromises tissue integrity. This lack of integrity could be responsible for chronic inflammation. The results of the research were published in the journal Developmental Cell on June 2, 2021.

Human epithelia are tissues found in several parts of the body (such as the epidermis and internal mucosa). They are composed of layers of contiguous cells that serve as a physical and chemical barrier. This role is constantly being put to the test by both the outside environment and their own renewal. Tissue renewal involves the formation of new cells by cell division and the elimination of dead cells. The mechanisms that regulate the ability of epithelia to maintain their integrity in contexts involving large numbers of eliminated cells remain poorly understood, despite the fact that this situation occurs regularly during embryogenesis or the maintenance of adult tissues. For example, more than ten billion cells can be eliminated every day in an adult intestine. How are these eliminations orchestrated to maintain tissue integrity and connectivity?

Scientists from the Institut Pasteur and the CNRS set out to identify the mechanisms involved in epithelial integrity and the conditions that can affect epithelial connectivity by using Drosophila (or vinegar flies), an organism studied in the laboratory with a similar epithelial architecture to humans.

Using protein-sensitive fluorescent markers, the research team revealed that when a cell dies, the EGFR-ERK pathway – a cell activation signaling pathway known for its involvement in the regulation of cell survival – is temporarily activated in the neighboring cells. The scientists observed that the activation of the EGFR-ERK pathway protected neighboring cells from cell death for approximately one hour, thereby preventing the simultaneous elimination of a group of cells. “We already knew that this pathway plays a key role in regulating cell survival in epithelial tissue, but we were surprised to observe such protective dynamics between cells,” comments Romain Levayer, Head of the Cell Death and Epithelial Homeostasis Unit at the Institut Pasteur and last author of the study.

Drosophila Pupa Epithelium

A Drosophila pupa epithelium showing cell contours (gray) and the reporter of the EGFR-ERK pathway (yellow/purple gradient). Credit: © Institut Pasteur / Romain Levayer et Léo Valon

The scientists’ research also shows that inhibiting this protective mechanism has a drastic effect on epithelial tissue: cell elimination becomes random and neighboring cells can be eliminated simultaneously, leading to repeated losses of connectivity. The elimination of groups of neighboring cells is never observed in epithelial tissue in normal conditions, when the EGFR-ERK pathway is not deliberately inhibited, even if a large number of cells are eliminated.

By using a new optogenetic tool that can control cell death in time and space and bypass the protective mechanism, the scientists confirmed that epithelial integrity was compromised when neighboring cells were eliminated simultaneously. “Surprisingly, epithelial tissue is highly sensitive to the spatial distribution of eliminated cells. Although it can withstand the elimination of a large number of cells, epithelial integrity is affected if just three neighboring cells are eliminated simultaneously,” explains Léo Valon, a scientist in the Cell Death and Epithelial Homeostasis Unit at the Institut Pasteur and first author of the study.

The scientists’ observations confirm that tissues need to develop mechanisms preventing the elimination of neighboring groups of cells. “These observations are important as they illustrate the incredible self-organizing ability of biological tissues, a property that enables them to withstand stressful conditions. So there is no need for a conductor to orchestrate where and when the cells should die; everything is based on highly local communications between neighboring cells,” adds Romain Levayer.

This process seems to have been conserved during evolution. The same protective mechanism based on local EGFR-ERK activation was discovered independently in human cell lines by the research group led by Olivier Pertz at the University of Bern in Switzerland (the results are published in the same journal2). The results of the other study suggest that the protective mechanism is conserved between species separated by hundreds of millions of years, indicating that it is a relatively universal mechanism.

Future research will reveal whether disruption to this cell death coordination mechanism and repeated loss of connectivity in epithelial tissue could be one of the roots of chronic inflammation, a phenomenon responsible for various diseases that are currently among the leading causes of death worldwide.

Distribution of cell deaths in a Drosophila epithelium:

[embedded content]

Development of the Drosophila pupa epithelium showing the location of all cell deaths (colored dots). The cell contours are shown in gray. Credit: © Institut Pasteur / Léo Valon et Romain Levayer

Activation of the EGFR-ERK pathway in neighboring cells:

[embedded content]

Activation of the EGFR-ERK pathway in the neighbors of a cell extruded from the tissue. The reporter on the left is excluded from the nucleus when the pathway is activated (the eliminated cell is circled in green). Activation can also be viewed by other pathway sensors (the FRET sensor – red for strong activation. Credit: © Institut Pasteur / Romain Levayer et Léo Valon

References:

  1. “Robustness of epithelial sealing is an emerging property of local ERK feedback driven by cell elimination” by Léo Valon, Anđela Davidović, Florence Levillayer, Alexis Villars, Mathilde Chouly, Fabiana Cerqueira-Campos and Romain Levayer, 2 June 2021, Developmental Cell.
    DOI: 10.1016/j.devcel.2021.05.006
  2. “Collective ERK/Akt activity waves orchestrate epithelial homeostasis by driving apoptosis-induced survival” by Paolo Armando Gagliardi, Maciej Dobrzyński, Marc-Antoine Jacques, Coralie Dessauges, Pascal Ender, Yannick Blum, Robert M. Hughes, Andrew R. Cohen and Olivier Pertz, 2 June 2021, Developmental Cell.
    DOI: 10.1016/j.devcel.2021.05.007

This research project was supported by the European Research Council (ERC), a Marie Skłodowska-Curie post-doctoral fellowship, the Fondation pour la Recherche Médicale (FRM) et the Cercle Fondation Schlumberger pour l’Education et la Recherche (FSER), R.Levayer 2019 laureate.

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This post originally posted here The European Times News

Spain to maintain coronavirus restrictions into holiday season – 'Covid has not gone away'

Spain to maintain coronavirus restrictions into holiday season - 'Covid has not gone away'
Spain‘s minister for tourism has said the nation is pushing to welcome back tourists in June. However, officials have said key coronavirus restrictions will remain in place, with many impacting tourists.
Though the nation is set to lift its State of Emergency on May 9, Spain’s holiday hotspots are likely to continue coronavirus safety regulations.

The Balearics, Canary Islands and the Costa del Sol have all indicated that restrictions, including strict checks at airports, mask-wearing, curfews and even partial closure of the hotel industry, might continue after this Sunday.

The Balearic government has also gone to court to ask for special permission as leaders say they would need the backing of the law which the State of Emergency currently gives but which would disappear from May 9.

The Balearics, which include Majorca, Menorca and Ibiza, want the power to continue to impose and even strengthen if necessary coronavirus restrictions to avoid new outbreaks.

READ MORE: ‘Good god why do that!’ Britons hesitant to travel in blow to tourism

The islands’ government says it might want to increase its curfew orders, currently from 11pm to 6pm, and is asking for special permission to be allowed to impose the hours of 10pm to 7am if necessary.

The courts are also being asked to approve the need for all travellers into the Balearics to prove a negative PCR coronavirus test and to be able to close borders if needed.

The Balearics want to continue to limit social groups to six if necessary and capacity restrictions at places of worship.

And Balearic president, Francina Armengol is asking for legal permission for the partial closure of the hotel industry should coronavirus cases soar again.

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The government of the Canary Islands has further indicated that some restrictions will remain once Spain lifts the State of Emergency. This will include checks at airports and ports.

The Andalusian government, which covers the Costa del Sol, intends to announce details of measures that will be continued after May 9 and is seeking the backing of the courts.

The region wants the power to maintain perimeter closures in municipalities with incidence rates above 500 cases per 100,000 inhabitants.

President, Juanma Moreno said there are still localities above 500 and 1,000 cases of coronavirus and “we must prevent them from increasing infections in the neighbouring municipalities.

“Therefore, once the state of alarm subsides on May 9, Andalusia will request judicial endorsement to maintain the perimeter closures when necessary, something that we will do in a timely manner, safeguarding the powers of the community.”

He added: “If there is an outbreak, I will use all the instruments at our disposal and I will not hesitate to take measures no matter how harsh they may be to preserve people’s health.”

However, he has ruled out reimposing any curfews and will phase in increased hours for pubs and restaurants as more people get vaccinated.

“Covid has not gone away and people continue to die every day in Spain and Andalusia, they continue to be infected and suffer,” he said today.

“Therefore, despite starting to see the light at the end of the tunnel, we must vaccinate and meet the vaccination objectives. ”

UK citizens are currently waiting to find out when they will be able to visit the nation on holiday.

Though international travel is due to resume from May 17, this will depend on the UK Government’s “green list”.

Furthermore, Fernando Valdes Verelst, Spain’s tourism minister, has said Spain is not set to welcome back tourists until June when a COVID-19 travel certificate has been established by the EU.

“June will be the start of the recovery of tourism in Spain,” he said.

“By then, we will have a digital vaccination certificate in place and we will be able to reopen our borders.”

Additional reporting by Rita Sobot.

Author:
This post originally appeared on Daily Express :: Travel Feed

Emerging COVID-19 success story: Germany’s push to maintain progress

Emerging COVID-19 success story: Germany’s push to maintain progress
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    (ii) Health Protection Authority, City of Frankfurt, Frankfurt am Main
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  • Connolly K. German doctors pose naked in protest at PPE shortages. The Guardian. April 27, 2020. https://www.theguardian.com/world/2020/apr/27/german-doctors-pose-naked-in-protest-at-ppe-shortages.[70] Accessed June 2, 2020.
  • Martin N. Coronavirus: German ICUs see 40% more patients than in April. Deutsche Welle. December 6, 2020. https://www.dw.com/en/coronavirus-german-icus-see-40-more-patients-than-in-april/a-55836491[71]. Accessed February 3, 2021.
  • Coronavirus SARS-CoV-2: Chronik der bisherigen Maßnahmen [Coronavirus SARS-CoV-2: chronology of measures taken]. German Federal Ministry of Health. https://www.bundesgesundheitsministerium.de/en/coronavirus/chronologie-coronavirus.html.[72] Accessed June 5, 2020.
  • Netherlands airlifts coronavirus patients to Germany. Los Angeles Times. October 23, 2020. https://www.latimes.com/world-nation/story/2020-10-23/dutch-hospital-airlifts-patients-to-germany-amid-virus-surge[73]. Accessed November 24, 2020.
  • Bartsch M, Dahlkamp J, Thimm K, Weber N, Weinzierl A, Winter S. German ICUs are struggling to keep up with corona. Der Spiegel. November 12, 2020. https://www.spiegel.de/international/germany/the-second-wave-hits-the-hospitals-german-icus-are-struggling-to-keep-up-with-corona-a-c096f95a-781c-4703-889b-08b523341551[74]. Accessed November 23, 2020.
  • Coronavirus SARS-CoV-2: Chronik der bisherigen Maßnahmen [Coronavirus SARS-CoV-2: chronology of measures taken]. German Federal Ministry of Health. https://www.bundesgesundheitsministerium.de/en/coronavirus/chronologie-coronavirus.html.[75] Accessed June 5, 2020.
  • Organisation for Economic Co-operation and Development (OECD). OECD Economic Outlook, Interim Report September 2020. Paris: OECD; 2020. https://doi.org/10.1787/16097408[76].
  • Roser M, Ritchie H, Ortiz-Ospina E, Hasell J. Coronavirus pandemic (COVID-19). Our World in Data. Updated daily. https://ourworldindata.org/coronavirus/country/germany?country=~DEU[77].
  • The Editorial Board. Germany’s new coronavirus thinking. Wall Street Journal. May 14, 2020. https://www.wsj.com/articles/germanys-new-coronavirus-thinking-11589498695.[78] Accessed June 2, 2020.
  • Lu G, Razum O, Jahn A, et al. COVID-19 in Germany and China: mitigation versus elimination strategy. Global Health Action. 2021;14(1):1875601. https://doi.org/10.1080/16549716.2021.1875601[79]
  • All visualizations, data, and code produced by Our World in Data are completely open access under the Creative Commons BY license[80]. You have the permission to use, distribute, and reproduce these in any medium, provided the source and authors are credited.

    The data produced by third parties and made available by Our World in Data is subject to the license terms from the original third-party authors. We will always indicate the original source of the data in our documentation, so you should always check the license of any such third-party data before use and redistribution.

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    Guest Authors

    Liverpool maintain Mohamed Salah transfer stance as Kylian Mbappe priority comes to light

    Liverpool maintain Mohamed Salah transfer stance as Kylian Mbappe priority comes to light
    Liverpool are reportedly confident Mohamed Salah will stay at the club ahead of the summer transfer window, amid speculation linking the Egyptian star with a move to Real Madrid. Meanwhile, there’s an update on Kylian Mbappe’s future, and Thomas Muller has suggested he could follow in Thiago Alcantara’s footsteps, as Express Sport brings you the latest transfer news on Jurgen Klopp’s side.

    Liverpool’s Mohamed Salah stance

    Liverpool remain convinced that Mohamed Salah won’t be leaving Anfield any time soon.

    Salah has frequently been linked with interest from Real Madrid, and transfer speculation was ramped up earlier this season when former Egypt striker Mohamed Aboutrika claimed his compatriot was not happy at the club.

    But the Premier League club are confident Salah will see out his contract, which expires in 2023 – and are optimistic he will stay longer, according to journalist Fabrizio Romano.

    “Liverpool are convinced that they can keep Mohamed Salah,” Romano wrote in his column for Benchwarmers.

    “Soon they will have to talk about his contract expiring in June 2023, but there is no problem with the club.”

    THINK YOU KNOW SPORT? Test your sporting knowledge with our tricky quiz

    Mbappe priority amid Reds transfer talk

    One player Liverpool have freuquently been linked with in recent times is PSG star Kylian Mbappe.

    The 22-year-old World Cup winner has long been expected to join Real Madrid if and when he leaves the Parc des Princes.

    But he has also spoken of his admiration for Liverpool – and the feeling is mutual, with Klopp a confirmed fan of the forward.

    However, Mbappe has not held talks with the Reds, despite rumours to the contrary.

    That’s again according to Romano, who said Mbappe’s current focus is on extending his Paris-Saint Germain contract, which is due to expire at the end of next season.

    DON’T MISS

    “Kylian Mbappe has not started any negotiations with Liverpool so far despite the rumours,” wrote Romanon in his Benchwarmers column.

    “To date, the priority is to negotiate with Paris Saint-Germain for the renewal of his contract.”

    Muller hints at following in Thiago’s footsteps

    Thomas Muller has suggested he could follow in the footsteps of Thiago Alcantara, who joined Liverpool last summer.

    Muller broke into Bayern Munich’s first team in 2008, and has become synonymous with Bundesliga giants’ success ever since.