Diana at her Bath, Antoine Watteau (1715 – 1716)

Annotazione 2019-12-07 182503.jpg

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Diana at her Bath
Antoine Watteau
Date: 1715 – 1716
Style: Rococo
Genre: mythological painting
Tag: female-nude, Greek-and-Roman-Mythology, Artemis/Diana
Dimensions: 80 x 101 cm

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Permissions: Public Domain.

Source: WikiArt, full page: https://www.wikiart.org/en/antoine-watteau/diana-at-her-bath-1716

 

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Combinatorial #screening of a panel of #FDA-approved #drugs identifies several candidates with anti- #Ebola activities (Biochem Biophys Res Commun., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Biochem Biophys Res Commun. 2019 Dec 2. pii: S0006-291X(19)32185-0. doi: 10.1016/j.bbrc.2019.11.065. [Epub ahead of print]

Combinatorial screening of a panel of FDA-approved drugs identifies several candidates with anti-Ebola activities.

Du X1, Zuo X1, Meng F1, Wu F1, Zhao X1, Li C1, Cheng G2, Qin FX3.

Author information: 1 Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, 215123, China. 2 Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, 215123, China; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA. 3 Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, 215123, China. Electronic address: fqin1@foxmail.com.

 

Abstract

Ebola virus (EBOV), pathogen of Ebola hemorrhagic fever (EHF), is an enveloped filamental RNA virus. Recently, the EHF crisis occurred in the Democratic Republic of the Congo again highlights the urgency for its clinical treatments. However, no Food and Drug Administration (FDA)-approved therapeutics are currently available. Drug repurposing screening is a time- and cost-effective approach for identifying anti-EBOV therapeutics. Here, by combinatorial screening using pseudovirion and minigenome replicon systems we have identified several FDA-approved drugs with significant anti-EBOV activities. These potential candidates include azithromycin, clomiphene, chloroquine, digitoxin, epigallocatechin-gallate, fluvastatin, tetrandrine and tamoxifen. Mechanistic studies revealed that fluvastatin inhibited EBOV pseudovirion entry by blocking the pathway of mevalonate biosynthesis, while the inhibitory effect of azithromycin on EBOV maybe due to its intrinsic cationic amphiphilic structure altering the homeostasis of later endosomal vesicle similar as tamoxifen. Moreover, based on structure and pathway analyses, the anti-EBOV activity has been extended to other family members of statins, such as simvastatin, and multiple other cardiac glycoside drugs, some of which exhibited even stronger activities. More importantly, in searching for drug interaction, we found various synergy between several anti-EBOV drug combinations, showing substantial and powerful synergistic against EBOV infection. In conclusion, our work illustrates a successful and productive approach to identify new mechanisms and targets for treating EBOV infection by combinatorial screening of FDA-approved drugs.

Copyright © 2019. Published by Elsevier Inc.

KEYWORDS: Azithromycin; Cardiac glycoside; Drug repurposing; EBOV; FDA-Approved drugs; Statin

PMID: 31806372 DOI: 10.1016/j.bbrc.2019.11.065

Keywords: Antivirals; Ebola.

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Long-lasting protective immunity against #H7N9 #infection is induced by intramuscular or CpG-adjuvanted intranasal immunization with the split H7N9 #vaccine (Int Immunopharmacol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Int Immunopharmacol. 2019 Dec 2:106013. doi: 10.1016/j.intimp.2019.106013. [Epub ahead of print]

Long-lasting protective immunity against H7N9 infection is induced by intramuscular or CpG-adjuvanted intranasal immunization with the split H7N9 vaccine.

Zhou Y1, Li S2, Bi S3, Li N3, Bi Y3, Liu W3, Wang B4.

Author information: 1 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China. 2 China National Vaccine and Serum Institute, Beijing, China. 3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China. 4 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China. Electronic address: wangbn@im.ac.cn.

 

Abstract

There is an urgent need for efficient vaccines against the highly pathogenic avian influenza A viral strain H7N9. The duration and intensity of the immune response to H7N9 critically impacts the epidemiology of influenza viral infection at the population level. However, the insufficient immunogenicity of H7N9 raises concerns about vaccine efficacy. In this study, we evaluated the impact of immunization routes and the adjuvant CpG on the immune response to a split H7N9 vaccine in mice. Determination of humoral and cellular responses to the vaccine revealed that after four vaccine doses, high titers of H7N9-specific serum IgG, determined by the influenza hemagglutination inhibition (HI) assay, were induced through the intramuscular (i.m.) route and lasted for at least 40 weeks. CpG-adjuvanted immunization increased the levels of long-lived IFN-γ+ T cells and raised the Th1-biased IgG2a/IgG1 response ratio. In addition, aside from mucosal IgA, CpG-adjuvanted intranasal (i.n.) immunization elicited serum IgG and cellular responses of a similar duration and intensity to CpG-adjuvanted i.m. immunization. Mouse challenge assays demonstrated that 24 weeks following i.m. immunization without CpG or CpG-adjuvanted immunization through the i.m. or i.n. routes, both offered a high level of protection against H7N9 infection. These results indicate that efficient long-term protection against H7N9 can be achieved via the optimization of vaccination strategies, such as immunization doses, routes, and adjuvants.

Copyright © 2019 Elsevier B.V. All rights reserved.

KEYWORDS: Ab-secreting cells; CpG; H7N9; Influenza vaccine; Mucosal immunization; NALT

PMID: 31806571 DOI: 10.1016/j.intimp.2019.106013

Keywords: Avian Influenza; H7N9; Vaccines; Animal models.

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Spontaneous #pneumomediastinum in #H1N1 #infection: uncommon complication of a common infection (J R Coll Physicians Edinb., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J R Coll Physicians Edinb. 2019 Dec;49(4):298-300. doi: 10.4997/JRCPE.2019.409.

Spontaneous pneumomediastinum in H1N1 infection: uncommon complication of a common infection.

Chekkoth SM1, Supreeth RN2, Valsala N1, Kumar P1, Raja RS1.

Author information: 1 Baby Memorial Hospital, Calicut, India. 2 C/o M.N Ramesh, 30-276/14/21&22, Dwarakamayee Colony, Old Safilguda, Secunderabad – 500056, Telangana state, India, supreeth22@gmail.com.

 

Abstract

H1N1 viral infection leads to complications, such as pneumonia, respiratory failure, myocarditis and encephalitis. Spontaneous pneumomediastinum (SPM) is an extremely rare consequence of H1N1 infection and such cases have been sparsely reported. SPM is identified only by a careful clinical examination and obtaining a timely roentgenogram. We report a case of a young male admitted with H1N1 infection complicated by pneumomediastinum. He was treated successfully with oseltamivir, high-flow oxygen and prompt care in the intensive care unit.

KEYWORDS: H1N1 influenza; acute severe asthma; respiratory infections; spontaneous pneumomediastinum; subcutaneous emphysema

PMID: 31808456 DOI: 10.4997/JRCPE.2019.409

Keywords: Seasonal Influenza; H1N1pdm09; Pneumonia.

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Multiscale #analysis for #patterns of #Zika virus #genotype emergence, #spread, and consequence (PLOS One, abstract)

[Source: PLOS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Multiscale analysis for patterns of Zika virus genotype emergence, spread, and consequence

Monica K. Borucki , Nicole M. Collette, Lark L. Coffey, Koen K. A. Van Rompay, Mona H. Hwang, James B. Thissen, Jonathan E. Allen, Adam T. Zemla

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Published: December 6, 2019 / DOI: https://doi.org/10.1371/journal.pone.0225699

 

Abstract

The question of how Zika virus (ZIKV) changed from a seemingly mild virus to a human pathogen capable of microcephaly and sexual transmission remains unanswered. The unexpected emergence of ZIKV’s pathogenicity and capacity for sexual transmission may be due to genetic changes, and future changes in phenotype may continue to occur as the virus expands its geographic range. Alternatively, the sheer size of the 2015–16 epidemic may have brought attention to a pre-existing virulent ZIKV phenotype in a highly susceptible population. Thus, it is important to identify patterns of genetic change that may yield a better understanding of ZIKV emergence and evolution. However, because ZIKV has an RNA genome and a polymerase incapable of proofreading, it undergoes rapid mutation which makes it difficult to identify combinations of mutations associated with viral emergence. As next generation sequencing technology has allowed whole genome consensus and variant sequence data to be generated for numerous virus samples, the task of analyzing these genomes for patterns of mutation has become more complex. However, understanding which combinations of mutations spread widely and become established in new geographic regions versus those that disappear relatively quickly is essential for defining the trajectory of an ongoing epidemic. In this study, multiscale analysis of the wealth of genomic data generated over the course of the epidemic combined with in vivo laboratory data allowed trends in mutations and outbreak trajectory to be assessed. Mutations were detected throughout the genome via deep sequencing, and many variants appeared in multiple samples and in some cases become consensus. Similarly, amino acids that were previously consensus in pre-outbreak samples were detected as low frequency variants in epidemic strains. Protein structural models indicate that most of the mutations associated with the epidemic transmission occur on the exposed surface of viral proteins. At the macroscale level, consensus data was organized into large and interactive databases to allow the spread of individual mutations and combinations of mutations to be visualized and assessed for temporal and geographical patterns. Thus, the use of multiscale modeling for identifying mutations or combinations of mutations that impact epidemic transmission and phenotypic impact can aid the formation of hypotheses which can then be tested using reverse genetics.

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Citation: Borucki MK, Collette NM, Coffey LL, Van Rompay KKA, Hwang MH, Thissen JB, et al. (2019) Multiscale analysis for patterns of Zika virus genotype emergence, spread, and consequence. PLoS ONE 14(12): e0225699. https://doi.org/10.1371/journal.pone.0225699

Editor: Yury E. Khudyakov, Centers for Disease Control and Prevention, UNITED STATES

Received: February 20, 2019; Accepted: November 11, 2019; Published: December 6, 2019

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Data Availability: Fastq files of the Illumina data generated for the mouse and macaque samples have been submitted to Genbank SRA as part of a BioProject.

Funding: This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. Funding was provided through LLNL LDRD-ER 17-ER-019 to MKB. The macaque work performed was supported by a CNPRC pilot research grant to LC and KVR, start-up funds from the Pathology, Microbiology and Immunology Department (University of California, Davis) to LC, NIAID 1R21AI129479-01 to KVR, and the Office of Research Infrastructure Programs/OD (P51OD011107) to the California National Primate Research Center. This work was also supported by U.S. Food and Drug Administration HHSF223201610542P to LC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Competing interests: The authors have declared that no competing interests exist.

Keywords: Zika Virus.

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#Thermotolerant #Campylobacter spp. in #chicken and #bovine #meat in #Italy: Prevalence, level of contamination and molecular characterization of isolates (PLOS One, abstract)

[Source: PLOS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Thermotolerant Campylobacter spp. in chicken and bovine meat in Italy: Prevalence, level of contamination and molecular characterization of isolates

Elisabetta Di Giannatale, Paolo Calistri, Guido Di Donato , Lucia Decastelli, Elisa Goffredo, Daniela Adriano, Maria Emanuela Mancini, Annamaria Galleggiante, Diana Neri, Salvatore Antoci, Cristina Marfoglia, Francesca Marotta, Roberta Nuvoloni, Giacomo Migliorati

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Published: December 6, 2019 / DOI: https://doi.org/10.1371/journal.pone.0225957

 

Abstract

Campylobacter species are common foodborne pathogens associated with cases of human gastroenteritis worldwide. A detailed understanding of the prevalence, contamination levels and molecular characteristics of Campylobacter spp. in cattle and chicken, which are likely the most important sources of human contamination, is imperative. A collection of 1243 poultry meat samples (665 chicken breasts and 578 chicken thighs) and 1203 bovine meat samples (689 hamburgers and 514 knife-cut meat preparations) were collected at retail outlets, in randomly selected supermarkets located in different Italian regions during one year. Of these samples, 17.38% of the poultry meat and 0.58% of the bovine meat samples tested positive for Campylobacter, of which 131 were Campylobacter jejuni (57.96%) and 95 were Campylobacter coli (42.03%). Campylobacter isolates were genotyped with the aim of assessing the genetic diversity, population structure, source distribution and Campylobacter transmission route to humans. All isolates were molecularly characterized by pulse field gel electrophoresis (PFGE), and further genotyped using multilocus sequence typing (MLST) and fla-SVR sequencing to gain better insight into the population structure. Antibiotic resistance was also investigate. The highest levels of resistance among chicken strains were observed for ciprofloxacin (88.25%), nalidixic acid (81.45%) and tetracycline (75.6%). PFGE analysis revealed 73 pulsotypes for C. jejuni and 54 pulsotypes for C. coli, demonstrating the existance of different and specific clones circulating in Italy. MLST of C.jejuni isolates mainly clustered in the CC353, CC354, CC21, CC206 and CC443; while C.coli isolates clustered only in CC828. The most common flaA alleles were 287 for C. jejuni and 66 for C. coli. Our study confirms that poultry meat is the main source of Campylobacteriosis, whereas red meat had a low level of contamination suggesting a minor role in transmission. The high presence of Campylobacter in retail chicken meat, paired with its increased resistance to antimicrobials with several multidrug resistance profiles detected, is alarming and represents a persistent threat to public health.

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Citation: Di Giannatale E, Calistri P, Di Donato G, Decastelli L, Goffredo E, Adriano D, et al. (2019) Thermotolerant Campylobacter spp. in chicken and bovine meat in Italy: Prevalence, level of contamination and molecular characterization of isolates. PLoS ONE 14(12): e0225957. https://doi.org/10.1371/journal.pone.0225957

Editor: Anderson de Souza Sant’Ana, University of Campinas, BRAZIL

Received: July 26, 2019; Accepted: November 16, 2019; Published: December 6, 2019

Copyright: © 2019 Di Giannatale et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This work was supported by the Italian Ministry of Health [grant numbers: MSRCTE0115]. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Antibiotics; Drugs Resistance; Campylobacter spp.; Food Safety; Poultry; Cattle; Italy.

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The Irwin Lighthouse, Storm Raging, John Wilson Carmichael (1851)

Annotazione 2019-12-06 182644

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The Irwin Lighthouse, Storm Raging
John Wilson Carmichael
Date: 1851
Style: Romanticism
Genre: marina

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Permissions: Public Domain.

Source: WikiArt, full page: https://www.wikiart.org/en/john-wilson-carmichael/the-irwin-lighthouse-storm-raging-1851

 

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