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Nursing homes take action to protect residents

Turkish elder care homes are taking measures to protect the elderly across the country as the world grapples with the continued dangers of coronavirus.




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Coronavirus - EU restricts exports of protective equipment - Europe

  On 15 March 2020 the European Commission published Regulation 2020/402 (“Regulation”), which prohibits unlicensed export from the EU of certain personal and protective equipment. This measure is aimed at securing domestic supply o...




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Protecting confidential information in an AI-led and augmented reality

Across the banking sector, the Bank of England and the Financial Conduct Authority predict that firms’ utilisation of artificial intelligence (AI) solutions will triple in the next three years (BoE and FCA Joint Report on Machine Learning in U...




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Growing Youth Activism for Environmental Protection in Africa

The mining sector in Africa is facing radical change as youth activists take action against the environmental degradation caused by mining industries. Tensions between activists and the mining industry have raised, however, concerns over human rights abuses. Kenya’s National Coalition for Human Rights Defenders reported, for instance, cases of harassment and intimidation “against at least […]

The post Growing Youth Activism for Environmental Protection in Africa appeared first on Inter Press Service.




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The Boardwalk For Birds: Protecting Lake Victoria’s Dunga Beach Wetland

At around 11am on a Saturday, Luke Okomo arrives at Dunga Beach, on the outskirts of Kenya’s Kisumu City, and heads straight to what is known as the ‘Dunga Papyrus Boardwalk’. He pays Sh200 ($2), the daily fee for local tourists and students, and then joins a group of five visitors already taking a tour […]

The post The Boardwalk For Birds: Protecting Lake Victoria’s Dunga Beach Wetland appeared first on Inter Press Service.




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COVID-19 Stimulus Measures Must Save Lives, Protect Livelihoods, and Safeguard Nature to Reduce the Risk of Future Pandemics

IPBES Expert Guest Article by Professors Josef Settele, Sandra Díaz and Eduardo Brondizio1 and Dr. Peter Daszak2 on 27 April 2020

The post COVID-19 Stimulus Measures Must Save Lives, Protect Livelihoods, and Safeguard Nature to Reduce the Risk of Future Pandemics appeared first on Inter Press Service.




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United States Calls for Protection of Press Freedom in Somalia

[Dalsan Radio] The United States Embassy in Mogadishu calls on the Somali Government and people to allow and encourage transparent reporting on the impact of the COVID-19 pandemic to facilitate the critical efforts to protect and preserve the health and safety of the people of Somalia.




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Did Christ Promise Us Supernatural Power and Protection?

In the lead-up to the Truth Matters conference in October, we will be focusing our attention on the sufficiency, authority, and clarity of Scripture. Of our previous blog series, none better embodies that emphasis than Frequently Abused Verses. The following entry from that series originally appeared on February 10, 2016. -ed.

Next week will mark the second anniversary of Jamie Coots’s death. He was a father, pastor, and one of the stars of the National Geographic Channel’s reality series, Snake Salvation. The show followed Coots’s life and ministry as a prominent leader in a sect of Holiness Pentecostals who incorporate handling poisonous snakes into their worship in fulfilment of the promise of supernatural power and protection in Mark 16:17-18.

Coots died from a snakebite.

Snake handling—once popular throughout the Appalachian states—has dwindled to a tiny subculture of Pentecostals who believe in the practice of the extreme signs and wonders described in Mark 16:17-18. Specifically, they teach that they have the ability to cast out demons, speak in tongues, handle poisonous snakes, drink poison, and heal the sick (they also expose themselves to open flames, although that particular sign is not included in Mark’s gospel). And every couple years, the movement garners headlines because another pastor or congregant has died attempting to fulfill those supposed promises.

Virtually all other charismatics would disavow such extreme behavior, while holding just as tightly to the promises conveyed in the closing verses of Mark’s gospel—albeit more selectively.

For example, charismatic prosperity preacher Benny Hinn cites the passage in defense of his faith-healing ministry: “I knew the Lord had told me to pray for the sick as part of preaching the gospel, just as He told the disciples, in Mark 16:18: ‘They will lay hands on the sick, and they will recover.’” [1] Benny Hinn, The Anointing (Nashville: Thomas Nelson, 1997) 49.

And in his book When Heaven Invades Earth, Bill Johnson—pastor of Bethel Redding, one of the most influential charismatic churches in the country—points to the end of Mark’s gospel as a promise of God’s ongoing miraculous work.

As our ministry teams travel around the world, we have come to expect certain things. Healing, deliverance, and conversions are the fruits of our labors. While healing is seldom the subject we teach on, it is one of the most common results. As we proclaim the message of the Kingdom of God, people get well. The Father seems to say, Amen! To His own message by confirming the word with power (see Mark 16:20). [2] Bill Johnson, When Heaven Invades Earth (Shippensburg, PA: Treasure House, 2003) 89.

We could go on with examples of how charismatics of various traditions lean heavily on the closing verses of Mark’s gospel, but you get the point. For many it’s a foundational passage—one that explicitly promises all believers the power to perform signs and wonders.

But is that really the point of the passage? And more importantly, do those verses even belong in your Bible to begin with? Even a simple reading of the text raises some significant questions about its Scriptural authenticity.

Now after He had risen early on the first day of the week, He first appeared to Mary Magdalene, from whom He had cast out seven demons. She went and reported to those who had been with Him, while they were mourning and weeping. When they heard that He was alive and had been seen by her, they refused to believe it. After that, He appeared in a different form to two of them while they were walking along on their way to the country. They went away and reported it to the others, but they did not believe them either. Afterward He appeared to the eleven themselves as they were reclining at the table; and He reproached them for their unbelief and hardness of heart, because they had not believed those who had seen Him after He had risen. And He said to them, “Go into all the world and preach the gospel to all creation. He who has believed and has been baptized shall be saved; but he who has disbelieved shall be condemned. These signs will accompany those who have believed: in My name they will cast out demons, they will speak with new tongues; they will pick up serpents, and if they drink any deadly poison, it will not hurt them; they will lay hands on the sick, and they will recover.” So then, when the Lord Jesus had spoken to them, He was received up into heaven and sat down at the right hand of God. And they went out and preached everywhere, while the Lord worked with them, and confirmed the word by the signs that followed. [And they promptly reported all these instructions to Peter and his companions. And after that, Jesus Himself sent out through them from east to west the sacred and imperishable proclamation of eternal salvation.] (Mark 16:9-20)

As you can see, there are actually two endings to Mark’s gospel contained in the above quote. Verses 9-20 are referred to as the longer ending, while the portion in brackets at the end of verse 20 is called the shorter ending—on its own it would appear immediately after verse 8. Both have appeared individually in a variety of translations—the NASB includes both.

But neither ending appears in the earliest and most reliable New Testament manuscripts. No ancient book has been more carefully preserved than the Bible—we have several thousand manuscripts, with some dating all the way back to mere decades after they were first written. And through the science of textual analysis, scholars have determined that the final verses of Mark were not in the original, inspired text.    

On top of that, as John MacArthur explains in his commentary on the passage, there are also several internal indications that Mark didn’t write either ending.

First, the transition between verse 8 and verse 9 is awkward and disjointed. The conjunction now (from the Greek word de) implies continuity with the preceding narrative, but the focus of verse 9 abruptly shifts to Mary Magdalene rather than continuing a discussion of the women referred to in verse 8. Moreover, it would be strange for Mark to wait until the end of his narrative to introduce Mary Magdalene, as if for the first time . . . when she was already mentioned three times in the prior context (Mark 15:40, 47, 16:1). A similar discontinuity regards Peter, who is singled out in verse 7 yet not mentioned again in verses 9-20. The “shorter ending” . . . attempts to rectify those incongruities by highlighting both Peter and the other women. . . . But this shorter ending has even weaker manuscript evidence to support it than the longer ending.

Second, the vocabulary, style, and structure of the longer ending is not consistent with the rest of Mark’s gospel. There are eighteen words in this section that are not used elsewhere in Mark. For example, the title “Lord Jesus” is used here (v. 19) but is never used anywhere else in Mark’s account.

Third, the inclusion of apostolic signs does not fit the way the other three gospels conclude their accounts of the resurrection and ascension of Jesus Christ. Though many signs mentioned in this section parallel portions of the book of Acts (cf. Acts 2:4; 9:17; 10:46; 28:8), some are clearly without biblical support, such as being able to “pick up” venomous “serpents” (though perhaps loosely based on Paul’s experience in Acts 28:3-5) or “drink any deadly poison.” [3] John MacArthur, The MacArthur New Testament Commentary: Mark 9-16 (Chicago: Moody Publishers, 2015) 411-412.

Summing up the case against the scriptural credentials of Mark 16:9-20, John MacArthur writes,

The evidence, both external and internal, conclusively demonstrates that verses 9-20 were not originally part of Mark’s inspired record. While they generally summarize truths taught elsewhere in the New Testament, they should always be evaluated in light of the rest of Scripture. No doctrines or practices should be established solely on them. The snake-handling preachers of the Appalachians provide a prime example of the errors that can arise from accepting these verses as authoritative.

Nonetheless, knowing that Mark 16:9-20 is not original should give believers more confidence in the accuracy of the New Testament, not less. As noted above, the science of textual analysis makes it possible for biblical scholars to identify the very few passages that were not part of the original. Such places are clearly marked in modern translations, making it easy for students of Scripture to identify them. Consequently, believers can approach the rest of the text with the settled assurance that the Bible they hold in their hands accurately reflects the original. [4] The MacArthur New Testament Commentary: Mark 9-16, 412.

That conclusion then begs the question: Where did these verses come from?

Most likely, they were added in by a scribe who felt Mark’s original ending was missing something. However, it does not appear that he was so audacious as to concoct an ending from his own imagination. Instead, Mark 16:9-20 is a patchwork quilt of other biblical passages concerning the life of Christ after His resurrection, His commissioning of the apostles, and stories from their ministry in the founding of the church.

Time and space don’t permit me to break down the probable origin of each verse, but let me encourage you to listen to John MacArthur’s sermon on the passage, called “The Fitting End to Mark’s Gospel,” or consult his commentary on Mark 9-16 for more details on how this extrabiblical passage was likely assembled.

And what of Mark’s original ending? Why was it deemed so deficient in the first place? True, it is abrupt and to the point: “They went out and fled from the tomb, for trembling and astonishment had gripped them; and they said nothing to anyone, for they were afraid” (Mark 16:8). But as John MacArthur explains, that abrupt ending perfectly fits both Mark’s style and his purpose for writing at all.

Mark’s ending is abrupt but it is not incomplete. The tomb was empty; the angelic announcement explained that Jesus had risen; and multiple eyewitnesses confirmed those events. The purpose of Mark’s gospel was to demonstrate that Jesus is the Christ, the Son of God (Mark 1:1). Having amply made that point, no further proof was necessary.

Throughout his gospel, Mark consistently punctuated key events in the life of the Lord Jesus by emphasizing the wonder He evoked in the hearts and minds of others. Mark simply moves from one point of amazement about Christ to the next. So the narrative ends where it ought to end. It climaxes with amazement and bewilderment at the resurrection of the crucified Savior (cf. John 20:31). In so doing, it leaves the reader in a place of wonder, awe, and worship, centered on its glorious subject: the Lord Jesus Christ, the Son of God. [5] The MacArthur New Testament Commentary: Mark 9-16, 417-418.

So while Mark 16:9-20 may be a significant proof text for many charismatics, their interpretation is invalidated when we understand that those verses never belonged in Scripture to begin with.




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Coronavirus: Singapore moves 2,600 nursing-home employees into hotels to protect elderly

Singapore is moving 2,600 nursing-home employees into hotels to reduce their interaction with the community, with health minister Gan Kim Yong on Tuesday saying it was critical to protect older Singaporeans as they tended to be more severely affected by Covid-19. Nineteen of the country’s 20 deaths from the disease were patients above the age of 60, and four were nursing-home residents. All 9,000 of the country’s nursing-home staff have been tested, with one positive result. The 30 residents…




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Additional measures for increased protection in Prague from Covid-19 in place

Prague Daily Monitor

Starting today, the city requests that all people using Prague public transport to wear protection across their nose and mouth. Also, the Mayor of Prague Zdeněk Hřib recommended to stores that they insist that customers cover their face and nose as well.

read more




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Press Freedom Needs Protection from Pandemic too

Farhana Haque Rahman is Senior Vice President of IPS Inter Press Service; a journalist and communications expert, she is a former senior official of the United Nations Food and Agriculture Organization and the International Fund for Agricultural Development.

The post Press Freedom Needs Protection from Pandemic too appeared first on Inter Press Service.




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Protect Journalists’ Rights so We can Stop the COVID-19 Disinfodemic

Stella Paul is the recipient of the IWMF Courage in Journalism Award, a multiple winner of the Asian Environmental Journalism Awards, the Lead Ambassador for World Pulse and a senior IPS correspondent.

The post Protect Journalists’ Rights so We can Stop the COVID-19 Disinfodemic appeared first on Inter Press Service.




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Analysis: How important are face masks in protecting us from COVID-19?

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We need better social protection to safeguard the poor from COVID-19 -- by Amir Jilani

Millions of families who were already poor and vulnerable before the COVID-19 outbreak face impossible decisions about food, healthcare, and survival. We have a responsibility to act immediately and protect those most in need.




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How to protect Asia’s rapidly aging population from COVID-19 -- by Meredith Wyse

The COVID-19 pandemic highlights the need to strengthen programs and policies affecting older persons both in times of crisis and afterward.




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Amid COVID-19, the time to act is now to protect food security -- by Hans Woldring, Susann Roth

With the impacts of the pandemic on food and nutrition being felt around the region, planning is needed to avoid higher food prices, decreased nutrition and reduced food security. 




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During COVID-19, countries need to work together to ensure the supply of protective equipment -- by Susann Roth, Jesper Pedersen

As the pandemic continues, the supply chains producing vital personal protective equipment are starting to fail, causing shortages. Countries and international organizations can fill these gaps by working together.




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Protect Against Rootkit and Bootkit Malware in Systems that Boot from External SPI Flash Memory

Protect Against Rootkit and Bootkit Malware in Systems that Boot from External SPI Flash Memory




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Climate Change and Disasters: Protecting Townships in Bhutan

A major focus of the Phuentsholing Township Development Project is to provide a safer space in which the town can grow by helping develop a new urban center with raised ground levels in an area sheltered by the embankments.




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Social Protection Support Project (Second Additional Financing)

Approved project 43407-017 in Philippines.




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Global Shortage of Personal Protective Equipment amid COVID-19: Supply Chains, Bottlenecks, and Policy Implications

This brief examines the global shortage of the personal protective equipment (PPE) needed to tackle COVID-19 and suggests policy implications.




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Leveraging Private Sector Participation to Boost Environmental Protection in the People’s Republic of China

This brief presents recommendations to further encourage public-private partnerships for the environmental protection industry in the People's Republic of China, as the country seeks to address the negative impact of rapid urbanization.




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Exploring Community-Based Financing Schemes to Finance Social Protection

Social protection, especially health care systems for the poor, is essential to reduce inequality.




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Cyborg jellyfish that swim at triple speed could help protect oceans

Jellyfish have been equipped with embedded electronics that let researchers remotely control their motion, and the next version could add sensors for monitoring ocean conditions




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Genetically modified microbiome could protect honeybees from disease

Modifying bacteria found in the guts of bees could help protect the insects against lethal infections affecting hives worldwide




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Jane Goodall: We must protect chimps from being exposed to covid-19

Jane Goodall has tirelessly fought for a better world for humans and wildlife, and with covid-19 we must stay positive, she says 




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Giving nature human rights could be the best way to protect the planet

Rivers, lakes and forests around the world are being recognised as if they were legal persons. It sounds strange, but could it effectively protect the planet?




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Risky Talk review: How to protect yourself from dodgy statistics

Everything from genetic tests to immigration numbers is full of shaky statistics. David Spiegelhalter's new podcast helps separate the factual from the flaky




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I'm protecting seabirds in one of the world's most overfished areas

West Africa's waters are a hotspot for illegal fishing, says conservationist Justine Dossa. She is working to change fishing practices and tackle pollution




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How to protect your mental health in the time of coronavirus

From social isolation to working on the front line, the mental health challenges of the pandemic are wide reaching. We ask experts how to protect ourselves




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UPDATE 2-IMF's Georgieva downbeat on global economic forecast, warns against protectionism

The head of the International Monetary Fund on Friday signaled a possible downward revision of global economic forecasts, and warned the United States and China against rekindling a trade war that could weaken a recovery from the coronavirus pandemic.




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BCG vaccine being trialled as potential protection against covid-19

A long-standing hypothesis suggests the BCG vaccine also serves to generally enhance the immune system, meaning it could protect against covid-19, and trials are under way to find out




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Will Brushing and Flossing Protect You Against Stroke?

Title: Will Brushing and Flossing Protect You Against Stroke?
Category: Health News
Created: 2/13/2020 12:00:00 AM
Last Editorial Review: 2/14/2020 12:00:00 AM




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Tamoxifen Protects Certain Women at High Risk for Breast Cancer

Title: Tamoxifen Protects Certain Women at High Risk for Breast Cancer
Category: Health News
Created: 5/3/2007 2:00:00 AM
Last Editorial Review: 5/3/2007 12:00:00 AM




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Time to Remind Teens About Sun Protection

Title: Time to Remind Teens About Sun Protection
Category: Health News
Created: 4/25/2010 10:10:00 AM
Last Editorial Review: 4/26/2010 12:00:00 AM




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Drinking Green Tea May Protect Eyes

Title: Drinking Green Tea May Protect Eyes
Category: Health News
Created: 4/24/2010 10:10:00 AM
Last Editorial Review: 4/26/2010 12:00:00 AM




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Mediterranean Diet Helps Protect Aging Brain

Title: Mediterranean Diet Helps Protect Aging Brain
Category: Health News
Created: 4/27/2010 8:10:00 AM
Last Editorial Review: 4/27/2010 12:00:00 AM




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Protect Your Kids From Pollen Allergies: Expert

Title: Protect Your Kids From Pollen Allergies: Expert
Category: Health News
Created: 4/27/2013 10:35:00 AM
Last Editorial Review: 4/29/2013 12:00:00 AM




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Training Programs Protect Young Athletes From ACL Tears: Report

Title: Training Programs Protect Young Athletes From ACL Tears: Report
Category: Health News
Created: 4/28/2014 9:35:00 AM
Last Editorial Review: 4/28/2014 12:00:00 AM




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Antibody Shot Protects Monkeys From HIV-Like Infection

Title: Antibody Shot Protects Monkeys From HIV-Like Infection
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM




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Health Tip: Protect Your Eyes During Sports

Title: Health Tip: Protect Your Eyes During Sports
Category: Health News
Created: 5/1/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM




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Parents, Protect Your Kids as Measles Outbreaks Spread

Title: Parents, Protect Your Kids as Measles Outbreaks Spread
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM




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Health Tip: Protect Yourself From Sepsis

Title: Health Tip: Protect Yourself From Sepsis
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM




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Religion Helps Protect Against 'Deaths of Despair': Study

Title: Religion Helps Protect Against 'Deaths of Despair': Study
Category: Health News
Created: 5/6/2020 12:00:00 AM
Last Editorial Review: 5/7/2020 12:00:00 AM




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One Dose of HPV Vaccine May Protect Against Cervical Cancer

Title: One Dose of HPV Vaccine May Protect Against Cervical Cancer
Category: Health News
Created: 2/10/2020 12:00:00 AM
Last Editorial Review: 2/10/2020 12:00:00 AM




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A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice [Research Articles]

Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (–/–) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women.­




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Heterosubtypic Protection Induced by a Live Attenuated Influenza Virus Vaccine Expressing Galactose-{alpha}-1,3-Galactose Epitopes in Infected Cells

ABSTRACT

Anti-galactose-α-1,3-galactose (anti-α-Gal) antibody is naturally expressed at a high level in humans. It constitutes about 1% of immunoglobulins found in human blood. Here, we designed a live attenuated influenza virus vaccine that can generate α-Gal epitopes in infected cells in order to facilitate opsonization of infected cells, thereby enhancing vaccine-induced immune responses. In the presence of normal human sera, cells infected with this mutant can enhance phagocytosis of human macrophages and cytotoxicity of NK cells in vitro. Using a knockout mouse strain that allows expression of anti-α-Gal antibody in vivo, we showed that this strategy can increase vaccine immunogenicity and the breadth of protection. This vaccine can induce 100% protection against a lethal heterosubtypic group 1 (H5) or group 2 (mouse-adapted H3) influenza virus challenge in the mouse model. In contrast, its heterosubtypic protective effect in wild-type or knockout mice that do not have anti-α-Gal antibody expression is only partial, demonstrating that the enhanced vaccine-induced protection requires anti-α-Gal antibody upon vaccination. Anti-α-Gal-expressing knockout mice immunized with this vaccine produce robust humoral and cell-mediated responses upon a lethal virus challenge. This vaccine can stimulate CD11blo/– pulmonary dendritic cells, which are known to be crucial for clearance of influenza virus. Our approach provides a novel strategy for developing next-generation influenza virus vaccines.

IMPORTANCE Influenza A viruses have multiple HA subtypes that are antigenically diverse. Classical influenza virus vaccines are subtype specific, and they cannot induce satisfactory heterosubtypic immunity against multiple influenza virus subtypes. Here, we developed a live attenuated H1N1 influenza virus vaccine that allows the expression of α-Gal epitopes by infected cells. Anti-α-Gal antibody is naturally produced by humans. In the presence of this antibody, human cells infected with this experimental vaccine virus can enhance several antibody-mediated immune responses in vitro. Importantly, mice expressing anti-α-Gal antibody in vivo can be fully protected by this H1N1 vaccine against a lethal H5 or H3 virus challenge. Our work demonstrates a new strategy for using a single influenza virus strain to induce broadly cross-reactive immune responses against different influenza virus subtypes.




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The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay

ABSTRACT

The nonsense-mediated decay (NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3' untranslated regions (UTRs). The umbravirus Pea enation mosaic virus 2 (PEMV2) is a nonsegmented, positive-sense RNA virus with an unusually long 3' UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2 long-distance movement protein p26 was previously shown to both stabilize viral RNAs and bind them for transport through the plant’s vascular system. The current study demonstrated that p26 protects both viral and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclusively in the cytoplasm independently of long-distance movement. Using a transcriptome-wide approach in the model plant Nicotiana benthamiana, p26 protected a subset of cellular NMD target transcripts, particularly those containing long, structured, GC-rich 3' UTRs. Furthermore, transcriptome sequencing (RNA-seq) revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with 1,820 (48%) of NMD targets increasing in abundance. Widespread changes in the host transcriptome are common during plant RNA virus infections, and these results suggest that, in at least some instances, virus-mediated NMD inhibition may be a major contributing factor.

IMPORTANCE Nonsense-mediated decay (NMD) represents an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3' untranslated regions. NMD targets diverse families of RNA viruses, requiring that viruses counteract the NMD pathway for successful amplification in host cells. A protein required for long-distance movement of Pea enation mosaic virus 2 (PEMV2) is shown to also protect both viral and host mRNAs from NMD. RNA-seq analyses of the Nicotiana benthamiana transcriptome revealed that PEMV2 infection significantly impairs the host NMD pathway. RNA viruses routinely induce large-scale changes in host gene expression, and, like PEMV2, may use NMD inhibition to alter the host transcriptome in an effort to increase virus amplification.




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Barrier-to-Autointegration Factor 1 Protects against a Basal cGAS-STING Response

ABSTRACT

Although the pathogen recognition receptor pathways that activate cell-intrinsic antiviral responses are well delineated, less is known about how the host regulates this response to prevent sustained signaling and possible immune-mediated damage. Using a genome-wide CRISPR-Cas9 screening approach to identify host factors that modulate interferon-stimulated gene (ISG) expression, we identified the DNA binding protein Barrier-to-autointegration factor 1 (Banf1), a previously described inhibitor of retrovirus integration, as a modulator of basal cell-intrinsic immunity. Ablation of Banf1 by gene editing resulted in chromatin activation near host defense genes with associated increased expression of ISGs, including Oas2, Rsad2 (viperin), Ifit1, and ISG15. The phenotype in Banf1-deficient cells occurred through a cGAS-, STING-, and IRF3-dependent signaling axis, was associated with reduced infection of RNA and DNA viruses, and was reversed in Banf1 complemented cells. Confocal microscopy and biochemical studies revealed that a loss of Banf1 expression resulted in higher level of cytosolic double-stranded DNA at baseline. Our study identifies an undescribed role for Banf1 in regulating the levels of cytoplasmic DNA and cGAS-dependent ISG homeostasis and suggests possible therapeutic directions for promoting or inhibiting cell-intrinsic innate immune responses.

IMPORTANCE Although the interferon (IFN) signaling pathway is a key host mechanism to restrict infection of a diverse range of viral pathogens, its unrestrained activity either at baseline or in the context of an immune response can result in host cell damage and injury. Here, we used a genome-wide CRISPR-Cas9 screen and identified the DNA binding protein Barrier-to-autointegration factor 1 (Banf1) as a modulator of basal cell-intrinsic immunity. A loss of Banf1 expression resulted in higher level of cytosolic double-stranded DNA at baseline, which triggered IFN-stimulated gene expression via a cGAS-STING-IRF3 axis that did not require type I IFN or STAT1 signaling. Our experiments define a regulatory network in which Banf1 limits basal inflammation by preventing self DNA accumulation in the cytosol.




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Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies

ABSTRACT

Recent global advocacy efforts have highlighted the importance of development of a vaccine against group A Streptococcus (GAS). Combo5 is a non-M protein-based vaccine that provides protection against GAS skin infection in mice and reduces the severity of pharyngitis in nonhuman primates. However, Combo5 with the addition of aluminum hydroxide (alum) as an adjuvant failed to protect against invasive GAS infection of mice. Here, we show that formulation of Combo5 with adjuvants containing saponin QS21 significantly improves protective efficacy, even though all 7 adjuvants tested generated high antigen-specific IgG antibody titers, including alum. Detailed characterization of Combo5 formulated with SMQ adjuvant, a squalene-in-water emulsion containing a TLR4 agonist and QS21, showed significant differences from the results obtained with alum in IgG subclasses generated following immunization, with an absence of GAS opsonizing antibodies. SMQ, but not alum, generated strong interleukin-6 (IL-6), gamma interferon (IFN-), and tumor necrosis alpha (TNF-α) responses. This work highlights the importance of adjuvant selection for non-M protein-based GAS vaccines to optimize immune responses and protective efficacy.

IMPORTANCE Availability of a group A Streptococcus vaccine remains an unmet public health need. Here, we tested different adjuvant formulations to improve the protective efficacy of non-M protein vaccine Combo5 in an invasive disease model. We show that novel adjuvants can dramatically shape the type of immune response developed following immunization with Combo5 and significantly improve protection. In addition, protection afforded by Combo5 is not mediated by opsonizing antibodies, believed to be the main correlate of protection against GAS infections. Overall, this report highlights the importance of adjuvant selection in raising protective immune responses against GAS invasive infection. Adjuvants that can provide a more balanced Th1/Th2-type response may be required to optimize protection of GAS vaccines, particularly those based on non-M protein antigens.