bar Amisom Welcomes the Decision By the Governments of Somalia, Kenya and Ethiopia to Investigate Plane Crash Incident in Bardale By allafrica.com Published On :: Thu, 07 May 2020 09:36:10 GMT [Dalsan Radio] The African Union Mission in Somalia, AMISOM, expresses its heartfelt condolences to the families of those who perished in the plane crash of 4th May, 2020. The aircraft which left Baidoa, had six people on board and was approaching Bardale, south of Somalia and 300km northwest of the capital Mogadishu when it crashed. Full Article
bar UN human rights commissioner calls for disembarkation of migrants held on ships By www.maltatoday.com.mt Published On :: Fri,08 May 2020 17:39:07 +0200 The UN High Commissioner for Human Rights expresses ‘deep concern’ over reports of failure to assist and coordinate pushbacks of migrant boats in the central Mediterranean Full Article
bar Hamas demanding release of Barghouti and Sa’adat in prisoner swap By www.jpost.com Published On :: Thu, 07 May 2020 16:52:39 GMT Maher Obeid, member of the Hamas 'political bureau,' said that any prisoner swap must include 'all the symbols, from Marwan Barghouti to Ahmad Sa’adat.' Full Article Fatah Hamas Prisoner swap pflp
bar Danon to 'Post': UNSC must consider outcome of ending Iran arms embargo By www.jpost.com Published On :: Sat, 09 May 2020 02:14:28 GMT Israeli Ambassador to the UN Danny Danon said that the Iranian regime continues to divert its national resources in favor of its terror ambitions. Full Article Iran danny danon Security Council
bar More Than 12,000 Lawyers In Iran Reject Move To Dismantle Bar Association By www.payvand.com Published On :: Fri, 8 May 2020 09:10:08 PDT More than 12,000 Iranian lawyers have protested to a draft bill that undermines their independence and in effect replaces the Iranian Bar Association with a group of judiciary officials appointed by the government. Based on the draft the Judiciary will form a new body named the ";Supreme Council for the Coordination of Lawyers' Affairs"; that will be based at the Judiciary branch of the government ";to coordinate matters relating to attorneys."; Full Article
bar France star suffers calf knock in second Barca training session By www.nation.co.ke Published On :: 2020-05-09T14:30:11Z The 26-year-old joined Barca from Lyon in 2016. Full Article
bar Coronavirus: Hong Kong bars to reopen after weeks of Covid-19 shutdown with Lan Kwai Fong venues lining up cheap deals to attract customers By www.scmp.com Published On :: Thu, 07 May 2020 21:30:24 +0800 Bars will reopen across Hong Kong on Friday after a month-long coronavirus shutdown, as Lan Kwai Fong venues prepare to slash prices and the nightlife hub’s founder predicts takings as low as half normal levels.More than 100 frontline workers have been tested for the virus as part of the Central party zone’s relaunch, which comes as the government eases social-distancing restrictions in response to the improving Covid-19 situation in the city.Pubs and bars will only be allowed to operate half… Full Article
bar Coronavirus: Hong Kong gyms, restaurants, beauty parlours and bars reopen but owners not convinced they will fully recover By www.scmp.com Published On :: Fri, 08 May 2020 13:40:07 +0800 Hong Kong started returning to normal on Friday as the city eased the social-distancing rules brought in to help combat the spread of Covid-19.For the first time in more than a month, residents were able to go to gyms, beauty parlours, bars, cinemas, and other public venues which the government previously forced to close.With local transmission of the virus levelling off over the past two weeks, officials have allowed a partial reopening of eight types of business, but with conditions attached… Full Article
bar Coronavirus: Hong Kong bar scene back in business but it’s a slow start after social-distancing rules are eased By www.scmp.com Published On :: Fri, 08 May 2020 14:41:58 +0800 Bars and other entertainment venues were finally allowed to reopen their doors on Friday after more than a month of coronavirus measures, but Hong Kong’s famed nightlife scene was far from buzzing as people remained wary over the potential risk of infection.But along with the caution there was a sense of optimism from customers and business operators alike.A day after the city detected four imported cases in Hong Kong residents returning from Pakistan, the number of new infections dropped to… Full Article
bar Raúl and Prime Minister of Barbados hold official talks By www.granma.cu Published On :: Mon, 8 Dec 2014 09:36:33 -0800 Army General Raúl Castro Ruz, President of the Councils of State and Ministers, held official talks, on Sunday December 7, with the Honorable Freundel Stuart, Prime Minister of Barbados, who is visiting the country as the head of the Barbados delegation to the 5th CARICOM-Cuba Summit. Full Article
bar Polio case reported in Qambar Shahdadkot By feedproxy.google.com Published On :: Sat, 09 May 2020 06:00:00 +0500 SUKKUR: Another confirmed polio case was reported at Union Council Dhigano of Taluka Sajawal in Qambar Shahdadkot.Reports said the stool sample was collected from a 36-month-old girl, a suspected... [[ This is a content summary only. Visit my website for full links, other content, and more! ]] Full Article
bar Madrid and Barcelona will not move to next stage of Spain’s lockdown exit By www.dailystar.com.lb Published On :: 2020-05-09T12:52:00.0000000 Madrid and Barcelona will not progress to the next phase of Spain's exit from one of Europe’s strictest lockdowns that will allow bars, restaurants and places of worship to reopen in some areas from Monday, the government announced. Full Article World
bar Here's how we can give a boost to the SDGs in Asia and the Pacific -- by Bart Édes By blogs.adb.org Published On :: Tue, 04 Feb 2020 09:16:27 +0800 Asia and the Pacific is not where it needs to be to meet the Sustainable Development Goals but there remains a decade to make up for lost time. Full Article
bar Вот как мы можем повысить достижение ЦУР в Азиатско-Тихоокеанском регионе -- by Bart Édes By blogs.adb.org Published On :: Wed, 05 Feb 2020 14:18:15 +0800 Азия и Тихоокеанский регион находятся не там, где нужно для достижения ЦУР, но есть еще десять лет, чтобы наверстать упущенное время. Full Article
bar The world has lost a pioneer in the global effort to help the poor -- by Bart Édes By blogs.adb.org Published On :: Thu, 06 Feb 2020 11:32:04 +0800 Sir Fazle Hasan Abed dedicated his life to social development, establishing practices that will continue to help the poor for decades to come. Full Article
bar Đây là cách chúng ta có thể thúc đẩy các Mục tiêu Phát triển bền vững tại Châu Á và Thái Bình Dương -- by Bart Édes By blogs.adb.org Published On :: Tue, 11 Feb 2020 10:15:12 +0800 Châu Á và Thái Bình Dương chưa có được tiến độ cần thiết để đạt được các Mục tiêu Phát triển Bền vững nhưng vẫn còn một thập niên để bù lại thời gian đã mất. Full Article
bar 推动亚太地区实现可持续发展目标的举措 -- by Bart Édes By blogs.adb.org Published On :: Tue, 11 Feb 2020 15:56:51 +0800 亚太地区的可持续发展目标进展不及预期,但仍有十年时间来弥补落后进度。 Full Article
bar როგორ დავაჩქაროთ მდგრადი განვითარების მიზნების განხორციელება აზიასა და წყნარ ოკეანეთში -- by Bart Édes By blogs.adb.org Published On :: Tue, 25 Feb 2020 16:48:29 +0800 აზიასა და წყნარი ოკეანის რეგიონში მდგრადი განვითარების მიზნების განხორციელება ნელი ტემპით მიდის, მაგრამ დაკარგული დროის ასანაზღაურებლად წინ კიდევ ერთი ათწლეულია. Full Article
bar What’s next for supply chains scrambled by the pandemic? -- by Bart Édes By blogs.adb.org Published On :: Tue, 05 May 2020 15:47:41 +0800 The pandemic has highlighted the shortcomings of the globalized supply chain model. Full Article
bar Sindh Bar Council seeks Rs70 million for financial support for lawyers affected by lockdown By feedproxy.google.com Published On :: Sat, 09 May 2020 06:00:00 +0500 The Sindh High Court on Friday issued notices to the federal and provincial law ministries on a petition of the Sindh Bar Council seeking direction to the federal and Sindh governments for the provision of an annual grant in aid to the lawyers’ top provincial regulatory body and at least... Full Article
bar HC bars state from issuing land-use licences in NCR By www.indianrealtynews.com Published On :: Sat, 25 Jan 2014 15:23:02 +0000 CHANDIGARH: The Punjab and Haryana high court on Thursday directed the Haryana government not to issue any change of land use (CLU) licence to developers to build colonies in Gurgaon and the National Capital Region till the NCR Planning Board approves a sub-regional plan. The high court also restrained authorities from initiating any process for acquisition of land in these regions till further orders. A division bench headed by Chief Justice Sanjay Kishan Kaul passed these orders while hearing petitions alleging unregulated construction and development around Gurgaon and NCR without the mandatory sub-regional plan from the NCRPB. The petitioners had also challenged the proposed Gurgaon master plan of 2025 and […] Full Article Faridabad Gurgaon NCR
bar Work on parallel bridge at Okhla Barrage to start in February By www.indianrealtynews.com Published On :: Sat, 01 Feb 2014 12:42:24 +0000 NOIDA: The Noida Authority is set to start work on a six-lane bridge, parallel to the existing Okhla Barrage, this month bringing a sigh of relief to thousands of commuters who travel between Delhi, Noida and Faridabad. Technical bids for the project are to be finalized on February 3, while financial bids will be decided a week later. According to the officials, the construction of the Rs 150 crore bridge is expected to be ready in two years. Officials further revealed that the Central Water & Power Research Station (CWPRS), Pune, Yamuna Action Plan (YAP) and IIT-Delhi have already approved the proposed project last year and it is being fast […] Full Article Delhi Faridabad NCR Noida
bar Breaking Through the Blue-Collar Gender Barrier in the Lao People’s Democratic Republic By www.adb.org Published On :: 2019-11-25 00:00:00 The Strengthening Technical and Vocational Education and Training Project took on some of the obstacles to creating a place for women in the so-called blue-collar occupations. Full Article
bar Barriers and Solutions to Economic Integration of Caspian Sea Countries By www.adb.org Published On :: 2020-04-02 00:00:00 The Caspian region still has some alternatives that can develop it into a cohesive area. Full Article
bar JBL® Introduces Its First Soundbar with Dolby Atmos, the JBL Bar 9.1 True Wireless Surround Sound By news.harman.com Published On :: Mon, 06 Jan 2020 13:00:00 GMT CES 2020, LAS VEGAS – JANUARY 6, 2020 – Movie lovers, listen up. The latest addition to JBL’s popular Bar Series brings the audio experience of a movie theater to your living room. The JBL Bar 9.1 creates true wireless surround sound with crowd-pleasing... Full Article
bar JBL intros Boombox 2, Bar 9.1 true wireless surround sound By www.cnn.com Published On :: Tue, 21 Jan 2020 14:38:00 GMT Full Article
bar JBL verlegt de lat met een nieuwe Soundbar serie By news.harman.com Published On :: Thu, 05 Sep 2019 13:00:00 GMT Een gestroomlijnd model, krachtige bas en nog intenser geluid: JBL tilt home entertainment naar een hoger plan. Op IFA worden vandaag drie splinternieuwe producten gelanceerd: een compacte alles-in-één oplossing, een kamervullende surround-sound en een diepe bas Bar. Voor ieder wat wils in de nieuwe Soundbar serie. Full Article
bar JBL raises the bar with new Soundbar series By news.harman.com Published On :: Thu, 05 Sep 2019 13:00:00 GMT Slimmer, punchier bass and more immersive sound; JBL has taken home entertainment to the next level. With three brand new products launching today at IFA including a compact, all-in-one solution, a deep bass beauty and a surround-sound room-filler, there is something for everyone in JBL’s new soundbar range. Full Article
bar JBL raises the bar with new Soundbar series By news.harman.com Published On :: Thu, 05 Sep 2019 13:00:00 GMT Slimmer, punchier bass and more immersive sound; JBL has taken home entertainment to the next level. With three brand new products launching today at IFA including a compact, all-in-one solution, a deep bass beauty and a surround-sound room-filler, there is something for everyone in JBL’s new soundbar range. Full Article
bar 100 Millionen tragbare Lautsprecher: JBL stellt neuen Rekord auf By news.harman.com Published On :: Thu, 05 Sep 2019 13:00:00 GMT HARMAN International, eine hundertprozentige Tochtergesellschaft von Samsung Electronics Co. Ltd., die sich auf vernetzte Technologien für Automobil-, Konsum- und Unternehmensmärkte konzentriert, freut sich, dass seine Marke JBL den enormen Meilenstein von 100 Millionen weltweit ausgelieferten tragbaren Lautsprechern erreicht hat. JBL festigt damit seine Position als Marktführer für tragbare Audiogeräte und als prägende Kraft der Branche. JBL verschiebt die Grenzen des Möglichen immer weiter und erweckt Musik so zum Leben, dass sie für Zuhörer an jedem Ort fühlbar wird. Heute ist JBL nicht nur auf der ganzen Welt die treibende Kraft hinter der Leistung von Musikern und Sportlern, sondern sorgt auch für den perfekten Klang bei Veranstaltungen und in Automobilen. Außerdem ist JBL mit einem aktuellen Anteil von 34,2 Prozent auch Marktführer bei tragbaren Lautsprechern. Full Article
bar World's only known pink manta ray spotted in the Great Barrier Reef By www.newscientist.com Published On :: Wed, 04 Mar 2020 18:00:00 +0000 This pink manta ray, nicknamed Clouseau, has resurfaced off Australia’s coast. No one knows why it has a bubble-gum pink underside or if there are others out there Full Article
bar The science of pastry: Master a shortcrust and make a rhubarb tart By www.newscientist.com Published On :: Wed, 25 Mar 2020 18:00:00 +0000 Many people feel intimidated by the prospect of making pastry, says Sam Wong, but a little understanding can go a long way to successfully making this beautiful rhubarb tart Full Article
bar Cacao fever! Why people pay $6 for a chocolate bar - Felix TV By feeds.reuters.com Published On :: Tue, 27 Nov 2012 17:03:08 -0500 People craving the best ingredients and flavors are changing the economics of chocolate, making it possible for chocolate makers such as Madecasse and Cacao Prieto to produce expensive chocolates, support farmers in the developing world and turn the simple candy bar into an artisanal experience. (November 27, 2012) Full Article
bar UPDATE 1-Republicans urge Trump to bar banks from shunning fossil fuel loans By feeds.reuters.com Published On :: Fri, 08 May 2020 20:01:59 -0400 A group of Republican lawmakers from energy-producing states on Friday called on President Donald Trump to prevent banks from halting loans and investments with companies that produce oil and other fossil fuels while they have access to federal assistance programs during the COVID-19 pandemic. Full Article companyNews
bar It's about time-TTPM's Silver on Mattel's new Barbies By feeds.reuters.com Published On :: Thu, 28 Jan 2016 13:52:00 -0500 Toy industry expert Jim Silver, CEO of TTPM talks about Mattel's new Barbies which will come in petite, tall and curvy and how they will impact falling barbie sales. Bobbi Rebell reports. Full Article
bar How Dangerous Is Bariatric Surgery? By www.medicinenet.com Published On :: Wed, 18 Mar 2020 00:00:00 PDT Title: How Dangerous Is Bariatric Surgery?Category: Procedures and TestsCreated: 3/18/2020 12:00:00 AMLast Editorial Review: 3/18/2020 12:00:00 AM Full Article
bar Doctors Say Head Lice Should Not Bar Kids From School By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Doctors Say Head Lice Should Not Bar Kids From SchoolCategory: Health NewsCreated: 4/27/2015 12:00:00 AMLast Editorial Review: 4/27/2015 12:00:00 AM Full Article
bar Lumbar Puncture (LP or Spinal Tap) By www.medicinenet.com Published On :: Fri, 13 Dec 2019 00:00:00 PDT Title: Lumbar Puncture (LP or Spinal Tap)Category: Procedures and TestsCreated: 10/13/1998 12:00:00 AMLast Editorial Review: 12/13/2019 12:00:00 AM Full Article
bar How Long Does a Retrobulbar Block Last? By www.medicinenet.com Published On :: Fri, 24 Apr 2020 00:00:00 PDT Title: How Long Does a Retrobulbar Block Last?Category: Procedures and TestsCreated: 4/24/2020 12:00:00 AMLast Editorial Review: 4/24/2020 12:00:00 AM Full Article
bar Gay Blood Donors: Eager to Help, but Face Barriers By www.webmd.com Published On :: Wed, 06 May 2020 15:36:11 EST The FDA is launching a pilot study to determine if a risk-based questionnaire could take the place of the deferral periods. Full Article
bar PMC Now Offers a “Preview” Table of Contents for Embargoed Issues By www.ncbi.nlm.nih.gov Published On :: Wed, 28 Oct 2009 08:00:00 EST For any journal issue that has at least one open access or early access article, PMC is now displaying the table of contents (TOC) in advance of the whole issue becoming available. Not to worry, though—only those articles specified for early release are immediately viewable in PMC. As consistent with the terms of access in the journal agreement, the other articles will only become available on their specified release date, as shown in the TOC below. The journal's accessiblity, as indicated on the PMC Journal list also has not changed; for example, Plant Physiology's embargo period is still 12 months. What has changed is that the issues with “preview” TOCs now additionally appear on the journal's archive page. Publishers and others can rest assured, however, that no access terms for any journal have been changed with the unveiling of this new format. Full Article
bar Barrier-to-Autointegration Factor 1 Protects against a Basal cGAS-STING Response By mbio.asm.org Published On :: 2020-03-10T01:30:41-07:00 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. Full Article
bar Epstein-Barr Virus Epitope-Major Histocompatibility Complex Interaction Combined with Convergent Recombination Drives Selection of Diverse T Cell Receptor {alpha} and {beta} Repertoires By mbio.asm.org Published On :: 2020-03-17T01:30:14-07:00 ABSTRACT Recognition modes of individual T cell receptors (TCRs) are well studied, but factors driving the selection of TCR repertoires from primary through persistent human virus infections are less well understood. Using deep sequencing, we demonstrate a high degree of diversity of Epstein-Barr virus (EBV)-specific clonotypes in acute infectious mononucleosis (AIM). Only 9% of unique clonotypes detected in AIM persisted into convalescence; the majority (91%) of unique clonotypes detected in AIM were not detected in convalescence and were seeming replaced by equally diverse "de novo" clonotypes. The persistent clonotypes had a greater probability of being generated than nonpersistent clonotypes due to convergence recombination of multiple nucleotide sequences to encode the same amino acid sequence, as well as the use of shorter complementarity-determining regions 3 (CDR3s) with fewer nucleotide additions (i.e., sequences closer to germ line). Moreover, the two most immunodominant HLA-A2-restricted EBV epitopes, BRLF1109 and BMLF1280, show highly distinct antigen-specific public (i.e., shared between individuals) features. In fact, TCRα CDR3 motifs played a dominant role, while TCRβ played a minimal role, in the selection of TCR repertoire to an immunodominant EBV epitope, BRLF1. This contrasts with the majority of previously reported repertoires, which appear to be selected either on TCRβ CDR3 interactions with peptide/major histocompatibility complex (MHC) or in combination with TCRα CDR3. Understanding of how TCR-peptide-MHC complex interactions drive repertoire selection can be used to develop optimal strategies for vaccine design or generation of appropriate adoptive immunotherapies for viral infections in transplant settings or for cancer. IMPORTANCE Several lines of evidence suggest that TCRα and TCRβ repertoires play a role in disease outcomes and treatment strategies during viral infections in transplant patients and in cancer and autoimmune disease therapy. Our data suggest that it is essential that we understand the basic principles of how to drive optimum repertoires for both TCR chains, α and β. We address this important issue by characterizing the CD8 TCR repertoire to a common persistent human viral infection (EBV), which is controlled by appropriate CD8 T cell responses. The ultimate goal would be to determine if the individuals who are infected asymptomatically develop a different TCR repertoire than those that develop the immunopathology of AIM. Here, we begin by doing an in-depth characterization of both CD8 T cell TCRα and TCRβ repertoires to two immunodominant EBV epitopes over the course of AIM, identifying potential factors that may be driving their selection. Full Article
bar Long-acting, Injectable Buprenorphine: Great Promise, but Significant Barriers to Use By www.ncmedicaljournal.com Published On :: 2020-05-04T06:50:30-07:00 To the Editor—A 30-day injectable form of buprenorphine branded as SublocadeTM (Buprenorphine XR SQ) was approved by the FDA in 2017. This medication is administered by a health care professional subcutaneously in the abdomen to treat opioid use disorder. This long-acting delivery system holds great promise for many patients who have barriers to taking daily transmucosal buprenorphine-containing medications such as those with poor adherence to a daily medication. It is beneficial for those who have difficulty safely storing their medications, including patients who have children in the home, unstable housing, or live with others who have a use disorder. This product is also an option for patients who prefer mono-product buprenorphine. As Buprenorphine XR SQ is administered directly by a health care professional, it does not contain the abuse-deterrent naloxone that some patients feel causes side effects. There are two ways to acquire Buprenorphine XR SQ: 1) order product from the distributor (buy and bill); or 2) dispensed from a specialty pharmacy for a specific patient (specialty pharmacy) [1]. For the buy and bill option, the health care setting must be certified through the Risk Evaluation and Mitigation Strategy (REMS) program and adhere to dispensing regulations [2]. We found this challenging to implement in the outpatient setting, thus we pursued the specialty pharmacy option. It ultimately took us nearly one year to complete the process. The following are the barriers we faced with our first attempt. As a controlled substance, the medication must be stored in a refrigerated lockbox. Before... Full Article
bar Shellhaas RA, Burns JW, Barks JDE, Fauziya Hassan F, Chervin RD. Maternal Voice and Infant Sleep in the Neonatal Intensive Care Unit. Pediatrics. 2019;144(3):e30190288 By pediatrics.aappublications.org Published On :: 2020-05-01T01:00:46-07:00 Full Article
bar GABARAPL2 Is Critical for Growth Restriction of Toxoplasma gondii in HeLa Cells Treated with Gamma Interferon [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions] By iai.asm.org Published On :: 2020-04-20T08:00:38-07:00 Gamma interferon (IFN-)-induced innate immune responses play important roles in the inhibition of Toxoplasma gondii infection. It has been reported that IFN- stimulates non-acidification-dependent growth restriction of T. gondii in HeLa cells, but the mechanism remains unclear. Here, we found that -aminobutyric acid (GABA) receptor-associated protein-like 2 (GABARAPL2) plays a critical role in parasite restriction in IFN--treated HeLa cells. GABARAPL2 is recruited to membrane structures surrounding parasitophorous vacuoles (PV). Autophagy adaptors are required for the proper localization and function of GABARAPL2 in the IFN- -induced immune response. These findings provide further understanding of a noncanonical autophagy pathway responsible for IFN--dependent inhibition of T. gondii growth in human HeLa cells and demonstrate the critical role of GABARAPL2 in this response. Full Article
bar Putative {beta}-Barrel Outer Membrane Proteins of the Bovine Digital Dermatitis-Associated Treponemes: Identification, Functional Characterization, and Immunogenicity [Microbial Immunity and Vaccines] By iai.asm.org Published On :: 2020-04-20T08:00:38-07:00 Bovine digital dermatitis (BDD), an infectious disease of the bovine foot with a predominant treponemal etiology, is a leading cause of lameness in dairy and beef herds worldwide. BDD is poorly responsive to antimicrobial therapy and exhibits a relapsing clinical course; an effective vaccine is therefore urgently sought. Using a reverse vaccinology approach, the present study surveyed the genomes of the three BDD-associated Treponema phylogroups for putative β-barrel outer membrane proteins and considered their potential as vaccine candidates. Selection criteria included the presence of a signal peptidase I cleavage site, a predicted β-barrel fold, and cross-phylogroup homology. Four candidate genes were overexpressed in Escherichia coli BL21(DE3), refolded, and purified. Consistent with their classification as β-barrel OMPs, circular-dichroism spectroscopy revealed the adoption of a predominantly β-sheet secondary structure. These recombinant proteins, when screened for their ability to adhere to immobilized extracellular matrix (ECM) components, exhibited a diverse range of ligand specificities. All four proteins specifically and dose dependently adhered to bovine fibrinogen. One recombinant protein was identified as a candidate diagnostic antigen (disease specificity, 75%). Finally, when adjuvanted with aluminum hydroxide and administered to BDD-naive calves using a prime-boost vaccination protocol, these proteins were immunogenic, eliciting specific IgG antibodies. In summary, we present the description of four putative treponemal β-barrel OMPs that exhibit the characteristics of multispecific adhesins. The observed interactions with fibrinogen may be critical to host colonization and it is hypothesized that vaccination-induced antibody blockade of these interactions will impede treponemal virulence and thus be of therapeutic value. Full Article
bar An EBNA3A-Mutated Epstein-Barr Virus Retains the Capacity for Lymphomagenesis in a Cord Blood-Humanized Mouse Model [Transformation and Oncogenesis] By jvi.asm.org Published On :: 2020-05-04T08:00:47-07:00 Epstein-Barr virus (EBV) causes B cell lymphomas and transforms B cells in vitro. The EBV protein EBNA3A collaborates with EBNA3C to repress p16 expression and is required for efficient transformation in vitro. An EBNA3A deletion mutant EBV strain was recently reported to establish latency in humanized mice but not cause tumors. Here, we compare the phenotypes of an EBNA3A mutant EBV (3A) and wild-type (WT) EBV in a cord blood-humanized (CBH) mouse model. The hypomorphic 3A mutant, in which a stop codon is inserted downstream from the first ATG and the open reading frame is disrupted by a 1-bp insertion, expresses very small amounts of EBNA3A using an alternative ATG at residue 15. 3A caused B cell lymphomas at rates similar to their induction by WT EBV but with delayed onset. 3A and WT tumors expressed equivalent levels of EBNA2 and p16, but 3A tumors in some cases had reduced LMP1. Like the WT EBV tumors, 3A lymphomas were oligoclonal/monoclonal, with typically one dominant IGHV gene being expressed. Transcriptome sequencing (RNA-seq) analysis revealed small but consistent gene expression differences involving multiple cellular genes in the WT EBV- versus 3A-infected tumors and increased expression of genes associated with T cells, suggesting increased T cell infiltration of tumors. Consistent with an impact of EBNA3A on immune function, we found that the expression of CLEC2D, a receptor that has previously been shown to influence responses of T and NK cells, was markedly diminished in cells infected with EBNA3A mutant virus. Together, these studies suggest that EBNA3A contributes to efficient EBV-induced lymphomagenesis in CBH mice. IMPORTANCE The EBV protein EBNA3A is expressed in latently infected B cells and is important for efficient EBV-induced transformation of B cells in vitro. In this study, we used a cord blood-humanized mouse model to compare the phenotypes of an EBNA3A hypomorph mutant virus (3A) and wild-type EBV. The 3A virus caused lymphomas with delayed onset compared to the onset of those caused by WT EBV, although the tumors occurred at a similar rate. The WT EBV and EBNA3A mutant tumors expressed similar levels of the EBV protein EBNA2 and cellular protein p16, but in some cases, 3A tumors had less LMP1. Our analysis suggested that 3A-infected tumors have elevated T cell infiltrates and decreased expression of the CLEC2D receptor, which may point to potential novel roles of EBNA3A in T cell and NK cell responses to EBV-infected tumors. Full Article
bar Identification and Cloning of a New Western Epstein-Barr Virus Strain That Efficiently Replicates in Primary B Cells [Genome Replication and Regulation of Viral Gene Expression] By jvi.asm.org Published On :: 2020-05-04T08:00:47-07:00 The Epstein-Barr virus (EBV) causes human cancers, and epidemiological studies have shown that lytic replication is a risk factor for some of these tumors. This fits with the observation that EBV M81, which was isolated from a Chinese patient with nasopharyngeal carcinoma, induces potent virus production and increases the risk of genetic instability in infected B cells. To find out whether this property extends to viruses found in other parts of the world, we investigated 22 viruses isolated from Western patients. While one-third of the viruses hardly replicated, the remaining viruses showed variable levels of replication, with three isolates replicating at levels close to that of M81 in B cells. We cloned one strongly replicating virus into a bacterial artificial chromosome (BAC); the resulting recombinant virus (MSHJ) retained the properties of its nonrecombinant counterpart and showed similarities to M81, undergoing lytic replication in vitro and in vivo after 3 weeks of latency. In contrast, B cells infected with the nonreplicating Western B95-8 virus showed early but abortive replication accompanied by cytoplasmic BZLF1 expression. Sequencing confirmed that rMSHJ is a Western virus, being genetically much closer to B95-8 than to M81. Spontaneous replication in rM81- and rMSHJ-infected B cells was dependent on phosphorylated Btk and was inhibited by exposure to ibrutinib, opening the way to clinical intervention in patients with abnormal EBV replication. As rMSHJ contains the complete EBV genome and induces lytic replication in infected B cells, it is ideal to perform genetic analyses of all viral functions in Western strains and their associated diseases. IMPORTANCE The Epstein-Barr virus (EBV) infects the majority of the world population but causes different diseases in different countries. Evidence that lytic replication, the process that leads to new virus progeny, is linked to cancer development is accumulating. Indeed, viruses such as M81 that were isolated from Far Eastern nasopharyngeal carcinomas replicate strongly in B cells. We show here that some viruses isolated from Western patients, including the MSHJ strain, share this property. Moreover, replication of both M81 and of MSHJ was sensitive to ibrutinib, a commonly used drug, thereby opening an opportunity for therapeutic intervention. Sequencing of MSHJ showed that this virus is quite distant from M81 and is much closer to nonreplicating Western viruses. We conclude that Western EBV strains are heterogeneous, with some viruses being able to replicate more strongly and therefore being potentially more pathogenic than others, and that the virus sequence information alone cannot predict this property. Full Article