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  1. Article ; Online: Robust cross-cohort gut microbiome associations with COVID-19 severity.

    Li, Junhui / Ghosh, Tarini Shankar / McCann, Rachel / Mallon, Patrick / Hill, Colin / Draper, Lorraine / Schult, David / Fanning, Liam J / Shannon, Robert / Sadlier, Corinna / Horgan, Mary / O'Mahony, Liam / O'Toole, Paul W

    Gut microbes

    2023  Volume 15, Issue 1, Page(s) 2242615

    Abstract: Although many recent studies have examined associations between the gut microbiome and COVID-19 disease severity in individual patient cohorts, questions remain on the robustness across international cohorts of the biomarkers they reported. Here, we ... ...

    Abstract Although many recent studies have examined associations between the gut microbiome and COVID-19 disease severity in individual patient cohorts, questions remain on the robustness across international cohorts of the biomarkers they reported. Here, we performed a meta-analysis of eight shotgun metagenomic studies of COVID-19 patients (comprising 1,023 stool samples) and 23 > 16S rRNA gene amplicon sequencing (16S) cohorts (2,415 total stool samples). We found that disease severity (as defined by the WHO clinical progression scale) was associated with taxonomic and functional microbiome differences. This alteration in gut microbiome configuration peaks at days 7-30 post diagnosis, after which the gut microbiome returns to a configuration that becomes more similar to that of healthy controls over time. Furthermore, we identified a core set of species that were consistently associated with disease severity across shotgun metagenomic and 16S cohorts, and whose abundance can accurately predict disease severity category of SARS-CoV-2 infected subjects, with
    MeSH term(s) Humans ; Gastrointestinal Microbiome ; COVID-19 ; RNA, Ribosomal, 16S/genetics ; SARS-CoV-2 ; Biomarkers
    Chemical Substances RNA, Ribosomal, 16S ; Biomarkers
    Language English
    Publishing date 2023-08-07
    Publishing country United States
    Document type Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2575755-6
    ISSN 1949-0984 ; 1949-0984
    ISSN (online) 1949-0984
    ISSN 1949-0984
    DOI 10.1080/19490976.2023.2242615
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Impact of Airway Virus in Severe Asthmatic Patients: A Pilot Study.

    Walsh, Laura J / Sullivan, Ashley / Ward, Christopher / Fanning, Liam J / O'Byrne, Paul M / MacSharry, John A / Murphy, Desmond M

    Allergy, asthma & immunology research

    2023  Volume 15, Issue 3, Page(s) 406–411

    Abstract: The lungs have their own microbiota which seems to be altered in disease processes such as asthma. Viral infection accounts for many asthma exacerbations. Little is known about the lung virome, and the role that viruses play in non-exacerbating ... ...

    Abstract The lungs have their own microbiota which seems to be altered in disease processes such as asthma. Viral infection accounts for many asthma exacerbations. Little is known about the lung virome, and the role that viruses play in non-exacerbating asthmatics. We aimed to assess if detection of virus in bronchoscopy samples of asthmatic patients in a non-exacerbating state influences their asthma control and modulates airway cytokine composition. Patients were recruited from a specialist asthma clinic and underwent bronchoscopy with standardised bronchoalveolar lavage (BAL). Viral analysis was performed; cell differential and cytokine levels were measured. Forty-six samples were obtained of which 10.8% demonstrated evidence of airway virus, and 91.3% of patients in the cohort were classed as severe asthmatics. Oral steroid use was significantly higher in severe asthmatic patients with virus detected, and the forced expiratory volume in one second tended to be lower in the virus-detected group. It was also found that BAL interleukin-13 and tumor necrosis factor-α levels were significantly higher in severe asthmatic patients with virus detected. Our results suggest that in severe asthmatics in a non-exacerbating state, the presence of virus resulted in overall poorer asthma control. The pattern of cytokine elevation seen in asthmatic patients with virus detected may provide insight to the pathophysiology involved.
    Language English
    Publishing date 2023-01-09
    Publishing country Korea (South)
    Document type Journal Article
    ZDB-ID 2545725-1
    ISSN 2092-7363 ; 2092-7355
    ISSN (online) 2092-7363
    ISSN 2092-7355
    DOI 10.4168/aair.2023.15.3.406
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Synonymous Co-Variation across the E1/E2 Gene Junction of Hepatitis C Virus Defines Virion Fitness.

    Palmer, Brendan A / Fanning, Liam J

    PloS one

    2016  Volume 11, Issue 11, Page(s) e0167089

    Abstract: Hepatitis C virus is a positive-sense single-stranded RNA virus. The gene junction partitioning the viral glycoproteins E1 and E2 displays concurrent sequence evolution with the 3'-end of E1 highly conserved and the 5'-end of E2 highly heterogeneous. ... ...

    Abstract Hepatitis C virus is a positive-sense single-stranded RNA virus. The gene junction partitioning the viral glycoproteins E1 and E2 displays concurrent sequence evolution with the 3'-end of E1 highly conserved and the 5'-end of E2 highly heterogeneous. This gene junction is also believed to contain structured RNA elements, with a growing body of evidence suggesting that such structures can act as an additional level of viral replication and transcriptional control. We have previously used ultradeep pyrosequencing to analyze an amplicon library spanning the E1/E2 gene junction from a treatment naïve patient where samples were collected over 10 years of chronic HCV infection. During this timeframe maintenance of an in-frame insertion, recombination and humoral immune targeting of discrete virus sub-populations was reported. In the current study, we present evidence of epistatic evolution across the E1/E2 gene junction and observe the development of co-varying networks of codons set against a background of a complex virome with periodic shifts in population dominance. Overtime, the number of codons actively mutating decreases for all virus groupings. We identify strong synonymous co-variation between codon sites in a group of sequences harbouring a 3 bp in-frame insertion and propose that synonymous mutation acts to stabilize the RNA structural backbone.
    MeSH term(s) Epistasis, Genetic ; Evolution, Molecular ; Hepacivirus/genetics ; Hepatitis C, Chronic/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; RNA, Viral/genetics ; Viral Envelope Proteins/genetics ; Virion/genetics
    Chemical Substances E1 protein, Hepatitis C virus ; RNA, Viral ; Viral Envelope Proteins ; glycoprotein E2, Hepatitis C virus (157184-61-7)
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0167089
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Practical consequences of hepatitis C virus quasispecies for target-specific antivirals.

    Fanning, Liam J

    The Journal of infectious diseases

    2008  Volume 198, Issue 6, Page(s) 797–799

    MeSH term(s) Antiviral Agents/classification ; Antiviral Agents/therapeutic use ; Hepacivirus/drug effects ; Hepacivirus/genetics ; Hepatitis C/drug therapy ; Humans ; Mutation ; Species Specificity
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2008-09-15
    Publishing country United States
    Document type Comment ; Editorial
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1086/591142
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  5. Article ; Online: Synonymous Co-Variation across the E1/E2 Gene Junction of Hepatitis C Virus Defines Virion Fitness.

    Brendan A Palmer / Liam J Fanning

    PLoS ONE, Vol 11, Iss 11, p e

    2016  Volume 0167089

    Abstract: Hepatitis C virus is a positive-sense single-stranded RNA virus. The gene junction partitioning the viral glycoproteins E1 and E2 displays concurrent sequence evolution with the 3'-end of E1 highly conserved and the 5'-end of E2 highly heterogeneous. ... ...

    Abstract Hepatitis C virus is a positive-sense single-stranded RNA virus. The gene junction partitioning the viral glycoproteins E1 and E2 displays concurrent sequence evolution with the 3'-end of E1 highly conserved and the 5'-end of E2 highly heterogeneous. This gene junction is also believed to contain structured RNA elements, with a growing body of evidence suggesting that such structures can act as an additional level of viral replication and transcriptional control. We have previously used ultradeep pyrosequencing to analyze an amplicon library spanning the E1/E2 gene junction from a treatment naïve patient where samples were collected over 10 years of chronic HCV infection. During this timeframe maintenance of an in-frame insertion, recombination and humoral immune targeting of discrete virus sub-populations was reported. In the current study, we present evidence of epistatic evolution across the E1/E2 gene junction and observe the development of co-varying networks of codons set against a background of a complex virome with periodic shifts in population dominance. Overtime, the number of codons actively mutating decreases for all virus groupings. We identify strong synonymous co-variation between codon sites in a group of sequences harbouring a 3 bp in-frame insertion and propose that synonymous mutation acts to stabilize the RNA structural backbone.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Synonymous Co-Variation across the E1/E2 Gene Junction of Hepatitis C Virus Defines Virion Fitness.

    Brendan A Palmer / Liam J Fanning

    PLoS ONE, Vol 11, Iss 11, p e

    2016  Volume 0167089

    Abstract: Hepatitis C virus is a positive-sense single-stranded RNA virus. The gene junction partitioning the viral glycoproteins E1 and E2 displays concurrent sequence evolution with the 3'-end of E1 highly conserved and the 5'-end of E2 highly heterogeneous. ... ...

    Abstract Hepatitis C virus is a positive-sense single-stranded RNA virus. The gene junction partitioning the viral glycoproteins E1 and E2 displays concurrent sequence evolution with the 3'-end of E1 highly conserved and the 5'-end of E2 highly heterogeneous. This gene junction is also believed to contain structured RNA elements, with a growing body of evidence suggesting that such structures can act as an additional level of viral replication and transcriptional control. We have previously used ultradeep pyrosequencing to analyze an amplicon library spanning the E1/E2 gene junction from a treatment naïve patient where samples were collected over 10 years of chronic HCV infection. During this timeframe maintenance of an in-frame insertion, recombination and humoral immune targeting of discrete virus sub-populations was reported. In the current study, we present evidence of epistatic evolution across the E1/E2 gene junction and observe the development of co-varying networks of codons set against a background of a complex virome with periodic shifts in population dominance. Overtime, the number of codons actively mutating decreases for all virus groupings. We identify strong synonymous co-variation between codon sites in a group of sequences harbouring a 3 bp in-frame insertion and propose that synonymous mutation acts to stabilize the RNA structural backbone.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Hypermethylation of MAPK13 Promoter in Oesophageal Squamous Cell Carcinoma Is Associated with Loss of p38δ MAPK Expression.

    O' Callaghan, Carol / Fanning, Liam J / Barry, Orla P

    Cancers

    2015  Volume 7, Issue 4, Page(s) 2124–2133

    Abstract: The loss of tumour suppressor gene function is a hallmark of malignant transformation and can occur by a variety of genetic and/or epigenetic alterations. We have previously characterised p38δ mitogen-activated protein kinase (MAPK) as a tumour ... ...

    Abstract The loss of tumour suppressor gene function is a hallmark of malignant transformation and can occur by a variety of genetic and/or epigenetic alterations. We have previously characterised p38δ mitogen-activated protein kinase (MAPK) as a tumour suppressor in oesophageal squamous cell carcinoma (OESCC) and outlined how loss of p38δ MAPK expression promotes increased proliferation and migration, as well as reduced chemosensitivity. Our aim was to investigate the underlying molecular causes of loss of p38δ MAPK expression in OESCC. Sequence analysis of DNA from p38δ MAPK positive and p38δ MAPK negative OESCC cell lines was used to investigate potential loss of function causing mutations. Epigenetic control of p38δ expression in OESCC was examined using methylation-specific PCR and sequencing of bisulfite-converted DNA. We did not identify any mutations in the MAPK13 sequence in OESCC cell lines which lack p38δ MAPK expression. However, we identified a differential pattern of methylation between p38δ MAPK positive and p38δ MAPK negative cell lines. We outline here for the first time differential MAPK13 promoter methylation in OESCC. Our results suggest that epigenetic alterations are responsible, in part, for the suppression of p38δ MAPK expression and promotion of tumourigenesis in OESCC.
    Language English
    Publishing date 2015-10-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers7040881
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Detection and quantification of the hepatitis C viral genome.

    Fanning, Liam J

    Methods in molecular biology (Clifton, N.J.)

    2002  Volume 193, Page(s) 151–160

    MeSH term(s) Genome, Viral ; Hepacivirus/genetics ; Reverse Transcriptase Polymerase Chain Reaction/methods
    Language English
    Publishing date 2002
    Publishing country United States
    Document type Journal Article
    ISSN 1064-3745
    ISSN 1064-3745
    DOI 10.1385/1-59259-283-X:151
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  9. Article ; Online: Ultradeep Pyrosequencing of Hepatitis C Virus to Define Evolutionary Phenotypes.

    Palmer, Brendan A / Dimitrova, Zoya / Skums, Pavel / Crosbie, Orla / Kenny-Walsh, Elizabeth / Fanning, Liam J

    Bio-protocol

    2017  Volume 7, Issue 10, Page(s) e2284

    Abstract: Analysis of hypervariable regions (HVR) using pyrosequencing techniques is hampered by the ability of error correction algorithms to account for the heterogeneity of the variants present. Analysis of between-sample fluctuations to virome sub-populations, ...

    Abstract Analysis of hypervariable regions (HVR) using pyrosequencing techniques is hampered by the ability of error correction algorithms to account for the heterogeneity of the variants present. Analysis of between-sample fluctuations to virome sub-populations, and detection of low frequency variants, are unreliable through the application of arbitrary frequency cut offs. Cumulatively this leads to an underestimation of genetic diversity. In the following technique we describe the analysis of Hepatitis C virus (HCV) HVR1 which includes the E1/E2 glycoprotein gene junction. This procedure describes the evolution of HCV in a treatment naïve environment, from 10 samples collected over 10 years, using ultradeep pyrosequencing (UDPS) performed on the Roche GS FLX titanium platform ( Palmer
    Language English
    Publishing date 2017-05-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325 ; 2331-8325
    ISSN (online) 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.2284
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  10. Article: p38δ MAPK: Emerging Roles of a Neglected Isoform.

    O'Callaghan, Carol / Fanning, Liam J / Barry, Orla P

    International journal of cell biology

    2014  Volume 2014, Page(s) 272689

    Abstract: p38δ mitogen activated protein kinase (MAPK) is a unique stress responsive protein kinase. While the p38 MAPK family as a whole has been implicated in a wide variety of biological processes, a specific role for p38δ MAPK in cellular signalling and its ... ...

    Abstract p38δ mitogen activated protein kinase (MAPK) is a unique stress responsive protein kinase. While the p38 MAPK family as a whole has been implicated in a wide variety of biological processes, a specific role for p38δ MAPK in cellular signalling and its contribution to both physiological and pathological conditions are presently lacking. Recent emerging evidence, however, provides some insights into specific p38δ MAPK signalling. Importantly, these studies have helped to highlight functional similarities as well as differences between p38δ MAPK and the other members of the p38 MAPK family of kinases. In this review we discuss the current understanding of the molecular mechanisms underlying p38δ MAPK activity. We outline a role for p38δ MAPK in important cellular processes such as differentiation and apoptosis as well as pathological conditions such as neurodegenerative disorders, diabetes, and inflammatory disease. Interestingly, disparate roles for p38δ MAPK in tumour development have also recently been reported. Thus, we consider evidence which characterises p38δ MAPK as both a tumour promoter and a tumour suppressor. In summary, while our knowledge of p38δ MAPK has progressed somewhat since its identification in 1997, our understanding of this particular isoform in many cellular processes still strikingly lags behind that of its counterparts.
    Language English
    Publishing date 2014-09-17
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2536742-0
    ISSN 1687-8884 ; 1687-8876
    ISSN (online) 1687-8884
    ISSN 1687-8876
    DOI 10.1155/2014/272689
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