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Article: Profile of David L. Denlinger.

Mossman, Kaspar

Proceedings of the National Academy of Sciences of the United States of America

2007 Volume 104, Issue 27, Page(s) 11127–11129

MeSH term(s)	Animals ; Antarctic Regions ; Diptera/physiology ; Entomology/history ; History, 20th Century ; History, 21st Century ; Kenya ; Pennsylvania
Language	English
Publishing date	2007-07-03
Publishing country	United States
Document type	Biography ; Historical Article ; Journal Article ; Portraits
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.0705358104
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Article: Profile of David L. Denlinger

Mossman, Kaspar

Proceedings of the National Academy of Sciences of the United States of America. 2007 July 3, v. 104, no. 27

2007

Language	English
Dates of publication	2007-0703
Size	p. 11127-11129.
Publishing place	National Academy of Sciences
Document type	Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Detecting single cell interferon-beta production using a fluorescent reporter telomerase-immortalized human fibroblast cell line.

Hare, David N / Subapanditha, Minomi K / Mossman, Karen L

STAR protocols

2021 Volume 2, Issue 2, Page(s) 100436

Abstract: Recent data suggest that cells respond to infection by upregulating the antiviral cytokine interferon-beta (IFN-ß) in a fraction of infected cells. Approaches are thus needed to study these responses on a single-cell level rather than bulk population. ... ...

Abstract	Recent data suggest that cells respond to infection by upregulating the antiviral cytokine interferon-beta (IFN-ß) in a fraction of infected cells. Approaches are thus needed to study these responses on a single-cell level rather than bulk population. Here, we describe a protocol to analyze the IFN-ß response of individual cells using flow cytometry and immunofluorescence microscopy. We show the heterogeneous IFN-ß response to inactivated Sendai virus and human cytomegalovirus, but this protocol can be adapted to other viruses. For complete details on the use and execution of this protocol, please refer to Hare et al. (2020).
MeSH term(s)	Cell Line ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Fluorescent Dyes/analysis ; Fluorescent Dyes/metabolism ; Humans ; Interferon-beta/analysis ; Interferon-beta/metabolism ; Single Molecule Imaging/methods ; Single-Cell Analysis/methods ; Telomerase/genetics ; Telomerase/metabolism
Chemical Substances	Fluorescent Dyes ; Interferon-beta (77238-31-4) ; Telomerase (EC 2.7.7.49)
Language	English
Publishing date	2021-04-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2021.100436
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Article ; Online: Mitonuclear conflict and cooperation govern the integration of genotypes, phenotypes and environments.

Rand, David M / Mossman, Jim A

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

2019 Volume 375, Issue 1790, Page(s) 20190188

Abstract: The mitonuclear genome is the most successful co-evolved mutualism in the history of life on Earth. The cross-talk between the mitochondrial and nuclear genomes has been shaped by conflict and cooperation for more than 1.5 billion years, yet this system ... ...

Abstract	The mitonuclear genome is the most successful co-evolved mutualism in the history of life on Earth. The cross-talk between the mitochondrial and nuclear genomes has been shaped by conflict and cooperation for more than 1.5 billion years, yet this system has adapted to countless genomic reorganizations by each partner, and done so under changing environments that have placed dramatic biochemical and physiological pressures on evolving lineages. From putative anaerobic origins, mitochondria emerged as the defining aerobic organelle. During this transition, the two genomes resolved rules for sex determination and transmission that made uniparental inheritance the dominant, but not a universal pattern. Mitochondria are much more than energy-producing organelles and play crucial roles in nutrient and stress signalling that can alter how nuclear genes are expressed as phenotypes. All of these interactions are examples of genotype-by-environment (GxE) interactions, gene-by-gene (GxG) interactions (epistasis) or more generally context-dependent effects on the link between genotype and phenotype. We provide evidence from our own studies in
MeSH term(s)	Animals ; Cell Nucleus/genetics ; Drosophila melanogaster/genetics ; Environment ; Epistasis, Genetic ; Gene-Environment Interaction ; Genotype ; Mitochondria/genetics ; Phenotype
Language	English
Publishing date	2019-12-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	208382-6
ISSN	1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
ISSN (online)	1471-2970
ISSN	0080-4622 ; 0264-3839 ; 0962-8436
DOI	10.1098/rstb.2019.0188
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Article ; Online: Mitochondria as environments for the nuclear genome in Drosophila: mitonuclear G×G×E.

Rand, David M / Mossman, James A / Spierer, Adam N / Santiago, John A

The Journal of heredity

2021 Volume 113, Issue 1, Page(s) 37–47

Abstract: Mitochondria evolved from a union of microbial cells belonging to distinct lineages that were likely anaerobic. The evolution of eukaryotes required a massive reorganization of the 2 genomes and eventual adaptation to aerobic environments. The nutrients ... ...

Abstract	Mitochondria evolved from a union of microbial cells belonging to distinct lineages that were likely anaerobic. The evolution of eukaryotes required a massive reorganization of the 2 genomes and eventual adaptation to aerobic environments. The nutrients and oxygen that sustain eukaryotic metabolism today are processed in mitochondria through coordinated expression of 37 mitochondrial genes and over 1000 nuclear genes. This puts mitochondria at the nexus of gene-by-gene (G×G) and gene-by-environment (G×E) interactions that sustain life. Here we use a Drosophila model of mitonuclear genetic interactions to explore the notion that mitochondria are environments for the nuclear genome, and vice versa. We construct factorial combinations of mtDNA and nuclear chromosomes to test for epistatic interactions (G×G), and expose these mitonuclear genotypes to altered dietary environments to examine G×E interactions. We use development time and genome-wide RNAseq analyses to assess the relative contributions of mtDNA, nuclear chromosomes, and environmental effects on these traits (mitonuclear G×G×E). We show that the nuclear transcriptional response to alternative mitochondrial "environments" (G×G) has significant overlap with the transcriptional response of mitonuclear genotypes to altered dietary environments. These analyses point to specific transcription factors (e.g., giant) that mediated these interactions, and identified coexpressed modules of genes that may account for the overlap in differentially expressed genes. Roughly 20% of the transcriptome includes G×G genes that are concordant with G×E genes, suggesting that mitonuclear interactions are part of an organism's environment.
MeSH term(s)	Animals ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Drosophila/genetics ; Epistasis, Genetic ; Genome, Mitochondrial ; Mitochondria/genetics
Chemical Substances	DNA, Mitochondrial
Language	English
Publishing date	2021-12-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3044-2
ISSN	1465-7333 ; 0022-1503
ISSN (online)	1465-7333
ISSN	0022-1503
DOI	10.1093/jhered/esab066
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Article ; Online: Strain-dependent lung transcriptomic differences in cigarette smoke and LPS models of lung injury in mice.

Siamwala, Jamila H / Mossman, Jim A / Schorl, Christoph / Borgas, Diana / Sakhatskyy, Pavlo / Rand, David M / Lu, Qing / Rounds, Sharon

Physiological genomics

2023 Volume 55, Issue 6, Page(s) 259–274

Abstract: Cigarette smoking increases the risk of acute respiratory distress syndrome (ARDS; Calfee CS, Matthay MA, Eisner MD, Benowitz N, Call M, Pittet J-F, Cohen MJ. ...

Abstract	Cigarette smoking increases the risk of acute respiratory distress syndrome (ARDS; Calfee CS, Matthay MA, Eisner MD, Benowitz N, Call M, Pittet J-F, Cohen MJ.
MeSH term(s)	Humans ; Male ; Mice ; Animals ; Lipopolysaccharides/pharmacology ; Transcriptome ; Mice, Inbred AKR ; Cigarette Smoking ; Mice, Inbred C57BL ; Lung/pathology ; Acute Lung Injury/pathology ; Respiratory Distress Syndrome/genetics ; Emphysema/metabolism ; Emphysema/pathology ; Disease Models, Animal
Chemical Substances	Lipopolysaccharides
Language	English
Publishing date	2023-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2038823-8
ISSN	1531-2267 ; 1094-8341
ISSN (online)	1531-2267
ISSN	1094-8341
DOI	10.1152/physiolgenomics.00152.2022
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Article ; Online: Differential Cellular Sensing of Fusion from within and Fusion from without during Virus Infection.

Hare, David N / Murdza, Tetyana / Collins, Susan / Schulz, Katharina / Mukherjee, Subhendu / de Antueno, Roberto / Janssen, Luke / Duncan, Roy / Mossman, Karen L

Viruses

2023 Volume 15, Issue 2

Abstract: The physical entry of virus particles into cells triggers an innate immune response that is dependent on both calcium and nucleic acid sensors, with particles containing RNA or DNA genomes detected by RNA or DNA sensors, respectively. While membrane ... ...

Abstract	The physical entry of virus particles into cells triggers an innate immune response that is dependent on both calcium and nucleic acid sensors, with particles containing RNA or DNA genomes detected by RNA or DNA sensors, respectively. While membrane fusion in the absence of viral nucleic acid causes an innate immune response that is dependent on calcium, the involvement of nucleic acid sensors is poorly understood. Here, we used lipoplexes containing purified reovirus p14 fusion protein as a model of exogenous or fusion from without and a cell line expressing inducible p14 protein as a model of endogenous or fusion from within to examine cellular membrane fusion sensing events. We show that the cellular response to membrane fusion in both models is dependent on calcium, IRF3 and IFN. The method of sensing fusion, however, differs between fusion from without and fusion from within. Exogenous p14 lipoplexes are detected by RIG-I-like RNA sensors, whereas fusion by endogenous p14 requires both RIG-I and STING to trigger an IFN response. The source of nucleic acid that is sensed appears to be cellular in origin. Future studies will investigate the source of endogenous nucleic acids recognized following membrane fusion events.
MeSH term(s)	Humans ; Calcium ; Nucleic Acids ; Virus Diseases ; RNA ; Antibodies, Viral
Chemical Substances	Calcium (SY7Q814VUP) ; Nucleic Acids ; RNA (63231-63-0) ; Antibodies, Viral
Language	English
Publishing date	2023-01-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15020301
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Article ; Online: Virus-Intrinsic Differences and Heterogeneous IRF3 Activation Influence IFN-Independent Antiviral Protection.

Hare, David N / Baid, Kaushal / Dvorkin-Gheva, Anna / Mossman, Karen L

iScience

2020 Volume 23, Issue 12, Page(s) 101864

Abstract: Type 1 interferon (IFN) plays a critical role in early antiviral defense and priming of adaptive immunity by signaling upregulation of host antiviral IFN-stimulated genes (ISGs). Certain stimuli trigger strong activation of IFN regulatory factor 3 (IRF3) ...

Abstract	Type 1 interferon (IFN) plays a critical role in early antiviral defense and priming of adaptive immunity by signaling upregulation of host antiviral IFN-stimulated genes (ISGs). Certain stimuli trigger strong activation of IFN regulatory factor 3 (IRF3) and direct upregulation of ISGs in addition to IFN. It remains unclear why some stimuli are stronger activators of IRF3 and how this leads to IFN-independent antiviral protection. We found that UV-inactivated human cytomegalovirus (HCMV) particles triggered an IFN-independent ISG signature that was absent in cells infected with UV-inactivated Sendai virus particles. HCMV particles triggered mostly uniform activation of IRF3 and low-level IFN-
Language	English
Publishing date	2020-11-27
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2020.101864
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Article ; Online: Mitochondrial genomic variation drives differential nuclear gene expression in discrete regions of Drosophila gene and protein interaction networks.

Mossman, Jim A / Biancani, Leann M / Rand, David M

BMC genomics

2019 Volume 20, Issue 1, Page(s) 691

Abstract: Background: Mitochondria perform many key roles in their eukaryotic hosts, from integrating signaling pathways through to modulating whole organism phenotypes. The > 1 billion years of nuclear and mitochondrial gene co-evolution has necessitated ... ...

Abstract	Background: Mitochondria perform many key roles in their eukaryotic hosts, from integrating signaling pathways through to modulating whole organism phenotypes. The > 1 billion years of nuclear and mitochondrial gene co-evolution has necessitated coordinated expression of gene products from both genomes that maintain mitochondrial, and more generally, eukaryotic cellular function. How mitochondrial DNA (mtDNA) variation modifies host fitness has proved a challenging question but has profound implications for evolutionary and medical genetics. In Drosophila, we have previously shown that recently diverged mtDNA haplotypes within-species can have more impact on organismal phenotypes than older, deeply diverged haplotypes from different species. Here, we tested the effects of mtDNA haplotype variation on gene expression in Drosophila under standardized conditions. Using the Drosophila Genetic Reference Panel (DGRP), we constructed a panel of mitonuclear genotypes that consists of factorial variation in nuclear and mtDNA genomes, with mtDNAs originating in D. melanogaster (2x haplotypes) and D. simulans (2x haplotypes). Results: We show that mtDNA haplotype variation unequivocally alters nuclear gene expression in both females and males, and mitonuclear interactions are pervasive modifying factors for gene expression. There was appreciable overlap between the sexes for mtDNA-sensitive genes, and considerable transcriptional variation attributed to particular mtDNA contrasts. These genes are generally found in low-connectivity gene co-expression networks, occur in gene clusters along chromosomes, are often flanked by non-coding RNA, and are under-represented among housekeeping genes. Finally, we identify the giant (gt) transcription factor motif as a putative regulatory sequence associated with mtDNA-sensitive genes. Conclusions: There are predictive conditions for nuclear genes that are influenced by mtDNA variation.
MeSH term(s)	Amino Acid Motifs/genetics ; Animals ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; Drosophila/genetics ; Drosophila/growth & development ; Female ; Gene Expression Regulation ; Gene Regulatory Networks/genetics ; Gene Regulatory Networks/physiology ; Genes, Essential/genetics ; Genes, Essential/physiology ; Genetic Variation ; Genome, Mitochondrial/genetics ; Genotype ; Haplotypes ; Male ; Multigene Family ; Phenotype ; Protein Interaction Maps/genetics ; Protein Interaction Maps/physiology ; RNA, Untranslated/genetics ; RNA, Untranslated/metabolism ; RNA-Seq ; Transcriptome
Chemical Substances	RNA, Untranslated
Language	English
Publishing date	2019-09-02
Publishing country	England
Document type	Journal Article
ISSN	1471-2164
ISSN (online)	1471-2164
DOI	10.1186/s12864-019-6061-y
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Article: Ethnic Diversity of DPD Activity and the

White, Cassandra / Scott, Rodney J / Paul, Christine / Ziolkowski, Andrew / Mossman, David / Ackland, Stephen

Pharmacogenomics and personalized medicine

2021 Volume 14, Page(s) 1603–1617

Abstract: Pharmacogenomic screening can identify patients with gene variants that predispose them to the development of severe toxicity from fluoropyrimidine (FP) chemotherapy. Deficiency of the critical metabolic enzyme dihydropyrimidine dehydrogenase (DPD) leads ...

Abstract	Pharmacogenomic screening can identify patients with gene variants that predispose them to the development of severe toxicity from fluoropyrimidine (FP) chemotherapy. Deficiency of the critical metabolic enzyme dihydropyrimidine dehydrogenase (DPD) leads to excessive toxicity on exposure to fluoropyrimidine chemotherapy. This can result in hospitalisation, intensive care admissions and even death. Upfront screening of the gene that encodes for DPD (
Language	English
Publishing date	2021-12-09
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2508173-1
ISSN	1178-7066
ISSN	1178-7066
DOI	10.2147/PGPM.S337147
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