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  1. Article: Different gametogenesis states uniquely impact longevity in

    Chaturbedi, Amaresh / Lee, Siu Sylvia

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Curtailed reproduction affects lifespan and fat metabolism in diverse organisms, suggesting a regulatory axis between these processes. ... ...

    Abstract Curtailed reproduction affects lifespan and fat metabolism in diverse organisms, suggesting a regulatory axis between these processes. In
    Language English
    Publishing date 2023-06-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.06.13.544885
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Evolutionarily related host and microbial pathways regulate fat desaturation in C. elegans.

    Fox, Bennett W / Helf, Maximilian J / Burkhardt, Russell N / Artyukhin, Alexander B / Curtis, Brian J / Palomino, Diana Fajardo / Schroeder, Allen F / Chaturbedi, Amaresh / Tauffenberger, Arnaud / Wrobel, Chester J J / Zhang, Ying K / Lee, Siu Sylvia / Schroeder, Frank C

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1520

    Abstract: Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression, but the ... ...

    Abstract Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression, but the underlying mechanisms have remained unclear. Here, we show that endogenous and microbiota-dependent small molecule signals promote lipid desaturation via the nuclear receptor NHR-49/PPARα in C. elegans. Untargeted metabolomics of a β-oxidation mutant, acdh-11, in which expression of the stearoyl-CoA desaturase FAT-7/SCD1 is constitutively increased, revealed accumulation of a β-cyclopropyl fatty acid, becyp#1, that potently activates fat-7 expression via NHR-49. Biosynthesis of becyp#1 is strictly dependent on expression of cyclopropane synthase by associated bacteria, e.g., E. coli. Screening for structurally related endogenous metabolites revealed a β-methyl fatty acid, bemeth#1, which mimics the activity of microbiota-dependent becyp#1 but is derived from a methyltransferase, fcmt-1, that is conserved across Nematoda and likely originates from bacterial cyclopropane synthase via ancient horizontal gene transfer. Activation of fat-7 expression by these structurally similar metabolites is controlled by distinct mechanisms, as microbiota-dependent becyp#1 is metabolized by a dedicated β-oxidation pathway, while the endogenous bemeth#1 is metabolized via α-oxidation. Collectively, we demonstrate that evolutionarily related biosynthetic pathways in metazoan host and associated microbiota converge on NHR-49/PPARα to regulate fat desaturation.
    MeSH term(s) Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/metabolism ; PPAR alpha/metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Fatty Acids/metabolism ; Cyclopropanes/metabolism
    Chemical Substances Caenorhabditis elegans Proteins ; PPAR alpha ; Fatty Acids ; Cyclopropanes
    Language English
    Publishing date 2024-02-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45782-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Region-specific H3K9me3 gain in aged somatic tissues in Caenorhabditis elegans.

    Li, Cheng-Lin / Pu, Mintie / Wang, Wenke / Chaturbedi, Amaresh / Emerson, Felicity J / Lee, Siu Sylvia

    PLoS genetics

    2021  Volume 17, Issue 9, Page(s) e1009432

    Abstract: Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulation of the epigenome has been associated with increased susceptibility to age-related disorders. In ... ...

    Abstract Epigenetic alterations occur as organisms age, and lead to chromatin deterioration, loss of transcriptional silencing and genomic instability. Dysregulation of the epigenome has been associated with increased susceptibility to age-related disorders. In this study, we aimed to characterize the age-dependent changes of the epigenome and, in turn, to understand epigenetic processes that drive aging phenotypes. We focused on the aging-associated changes in the repressive histone marks H3K9me3 and H3K27me3 in C. elegans. We observed region-specific gain and loss of both histone marks, but the changes are more evident for H3K9me3. We further found alteration of heterochromatic boundaries in aged somatic tissues. Interestingly, we discovered that the most statistically significant changes reflected H3K9me3-marked regions that are formed during aging, and are absent in developing worms, which we termed "aging-specific repressive regions" (ASRRs). These ASRRs preferentially occur in genic regions that are marked by high levels of H3K9me2 and H3K36me2 in larval stages. Maintenance of high H3K9me2 levels in these regions have been shown to correlate with a longer lifespan. Next, we examined whether the changes in repressive histone marks lead to de-silencing of repetitive DNA elements, as reported for several other organisms. We observed increased expression of active repetitive DNA elements but not global re-activation of silent repeats in old worms, likely due to the distributed nature of repetitive elements in the C. elegans genome. Intriguingly, CELE45, a putative short interspersed nuclear element (SINE), was greatly overexpressed at old age and upon heat stress. SINEs have been suggested to regulate transcription in response to various cellular stresses in mammals. It is likely that CELE45 RNAs also play roles in stress response and aging in C. elegans. Taken together, our study revealed significant and specific age-dependent changes in repressive histone modifications and repetitive elements, providing important insights into aging biology.
    MeSH term(s) Aging/genetics ; Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/genetics ; Histones/genetics ; Mutation ; RNA/genetics ; RNA/metabolism ; Receptors, Notch/genetics ; Retroelements ; Stress, Physiological/genetics
    Chemical Substances Caenorhabditis elegans Proteins ; Glp-1 protein, C elegans ; Histones ; Receptors, Notch ; Retroelements ; RNA (63231-63-0)
    Language English
    Publishing date 2021-09-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1009432
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  4. Article: Evolutionarily related host and microbial pathways regulate fat desaturation.

    Fox, Bennett W / Helf, Maximilian J / Burkhardt, Russell N / Artyukhin, Alexander B / Curtis, Brian J / Palomino, Diana Fajardo / Chaturbedi, Amaresh / Tauffenberger, Arnaud / Wrobel, Chester J J / Zhang, Ying K / Lee, Siu Sylvia / Schroeder, Frank C

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase ... ...

    Abstract Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression
    Language English
    Publishing date 2023-08-31
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.31.555782
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Sex-specificity of the C. elegans metabolome.

    Burkhardt, Russell N / Artyukhin, Alexander B / Aprison, Erin Z / Curtis, Brian J / Fox, Bennett W / Ludewig, Andreas H / Palomino, Diana Fajardo / Luo, Jintao / Chaturbedi, Amaresh / Panda, Oishika / Wrobel, Chester J J / Baumann, Victor / Portman, Douglas S / Lee, Siu Sylvia / Ruvinsky, Ilya / Schroeder, Frank C

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 320

    Abstract: Recent studies of animal metabolism have revealed large numbers of novel metabolites that are involved in all aspects of organismal biology, but it is unclear to what extent metabolomes differ between sexes. Here, using untargeted comparative ... ...

    Abstract Recent studies of animal metabolism have revealed large numbers of novel metabolites that are involved in all aspects of organismal biology, but it is unclear to what extent metabolomes differ between sexes. Here, using untargeted comparative metabolomics for the analysis of wildtype animals and sex determination mutants, we show that C. elegans hermaphrodites and males exhibit pervasive metabolomic differences. Several hundred small molecules are produced exclusively or in much larger amounts in one sex, including a host of previously unreported metabolites that incorporate building blocks from nucleoside, carbohydrate, lipid, and amino acid metabolism. A subset of male-enriched metabolites is specifically associated with the presence of a male germline, whereas enrichment of other compounds requires a male soma. Further, we show that one of the male germline-dependent metabolites, an unusual dipeptide incorporating N,N-dimethyltryptophan, increases food consumption, reduces lifespan, and accelerates the last stage of larval development in hermaphrodites. Our results serve as a foundation for mechanistic studies of how the genetic sex of soma and germline shape the C. elegans metabolome and provide a blueprint for the discovery of sex-dependent metabolites in other animals.
    MeSH term(s) Animals ; Male ; Caenorhabditis elegans/metabolism ; Metabolome ; Caenorhabditis elegans Proteins/metabolism ; Metabolomics/methods ; Longevity
    Chemical Substances Caenorhabditis elegans Proteins
    Language English
    Publishing date 2023-01-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-36040-y
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  6. Article ; Online: SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity.

    Wang, Wenke / Chaturbedi, Amaresh / Wang, Minghui / An, Serim / Santhi Velayudhan, Satheeja / Lee, Siu Sylvia

    eLife

    2018  Volume 7

    Abstract: ... C. ... ...

    Abstract C. elegans
    MeSH term(s) Animals ; Caenorhabditis elegans/growth & development ; Caenorhabditis elegans/physiology ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Germ Cells/cytology ; Germ Cells/metabolism ; Heat-Shock Response ; Histones/genetics ; Histones/metabolism ; Longevity
    Chemical Substances Caenorhabditis elegans Proteins ; Histones ; histone H3 trimethyl Lys4
    Language English
    Publishing date 2018-05-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.34970
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  7. Article ; Online: Transcription factors CEP-1/p53 and CEH-23 collaborate with AAK-2/AMPK to modulate longevity in Caenorhabditis elegans.

    Chang, Hsin-Wen / Pisano, Steve / Chaturbedi, Amaresh / Chen, Jennifer / Gordon, Sarah / Baruah, Aiswarya / Lee, Siu Sylvia

    Aging cell

    2017  Volume 16, Issue 4, Page(s) 814–824

    Abstract: A decline in mitochondrial electron transport chain (ETC) function has long been implicated in aging and various diseases. Recently, moderate mitochondrial ETC dysfunction has been found to prolong lifespan in diverse organisms, suggesting a conserved ... ...

    Abstract A decline in mitochondrial electron transport chain (ETC) function has long been implicated in aging and various diseases. Recently, moderate mitochondrial ETC dysfunction has been found to prolong lifespan in diverse organisms, suggesting a conserved and complex role of mitochondria in longevity determination. Several nuclear transcription factors have been demonstrated to mediate the lifespan extension effect associated with partial impairment of the ETC, suggesting that compensatory transcriptional response to be crucial. In this study, we showed that the transcription factors CEP-1/p53 and CEH-23 act through a similar mechanism to modulate longevity in response to defective ETC in Caenorhabditis elegans. Genomewide gene expression profiling comparison revealed a new link between these two transcription factors and AAK-2/AMP kinase (AMPK) signaling. Further functional analyses suggested that CEP-1/p53 and CEH-23 act downstream of AAK-2/AMPK signaling and CRTC-1 transcriptional coactivator to promote stress resistance and lifespan. As AAK-2, CEP-1, and CEH-23 are all highly conserved, our findings likely provide important insights for understanding the organismal adaptive response to mitochondrial dysfunction in diverse organisms and will be relevant to aging and pathologies with a mitochondrial etiology in human.
    MeSH term(s) Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Electron Transport Chain Complex Proteins/genetics ; Electron Transport Chain Complex Proteins/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Longevity/genetics ; Mitochondria/genetics ; Mitochondria/metabolism ; Protein Binding ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Signal Transduction ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Transcription, Genetic ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances CEH-23 protein, C elegans ; CEP-1 protein, C elegans ; CRTC-1 protein, C elegans ; Caenorhabditis elegans Proteins ; Electron Transport Chain Complex Proteins ; Homeodomain Proteins ; Trans-Activators ; Tumor Suppressor Protein p53 ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; AAK-2 protein, C elegans (EC 2.7.11.31)
    Language English
    Publishing date 2017-05-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2113083-8
    ISSN 1474-9726 ; 1474-9718
    ISSN (online) 1474-9726
    ISSN 1474-9718
    DOI 10.1111/acel.12619
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    Zs.A 6581: Show issues Location:
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  8. Article ; Online: PUF-8 negatively regulates RAS/MAPK signalling to promote differentiation of C. elegans germ cells.

    Vaid, Samir / Ariz, Mohd / Chaturbedi, Amaresh / Kumar, Ganga Anil / Subramaniam, Kuppuswamy

    Development (Cambridge, England)

    2013  Volume 140, Issue 8, Page(s) 1645–1654

    Abstract: Signals that promote germ cell self-renewal by preventing premature meiotic entry are well understood. However, signals that control mitotic proliferation to promote meiotic differentiation have not been well characterized. In Caenorhabditis elegans, GLP- ...

    Abstract Signals that promote germ cell self-renewal by preventing premature meiotic entry are well understood. However, signals that control mitotic proliferation to promote meiotic differentiation have not been well characterized. In Caenorhabditis elegans, GLP-1 Notch signalling promotes the proliferative fate by preventing premature meiotic entry. The germline niche cell, which is the source of the ligand for GLP-1, spatially restricts GLP-1 signalling and thus enables the germ cells that have moved away from the niche to enter meiosis. Here, we show that the suppression of RAS/MAP kinase signalling in the mitotic and meiotic-entry regions is essential for the regulation of the mitosis-meiosis switch by niche signalling. We provide evidence that the conserved PUF family RNA-binding protein PUF-8 and the RAS GAP protein GAP-3 function redundantly to suppress the LET-60 RAS in the mitotic and meiotic entry regions. Germ cells missing both PUF-8 and GAP-3 proliferate in an uncontrolled fashion and fail to undergo meiotic development. MPK-1, the MAP kinase downstream of the LET-60 RAS, is prematurely activated in these cells; downregulation of MPK-1 activation eliminates tumours and restores differentiation. Our results further reveal that PUF-8 negatively regulates LET-60 expression at a post-transcriptional step. LET-60 is misexpressed in the puf-8(-) mutant germlines and PUF-8 physically interacts with the let-60 3' UTR. Furthermore, PUF-8 suppresses let-60 3' UTR-mediated expression in the germ cells that are transitioning from the mitotic to meiotic fate. These results reveal that PUF-8-mediated inhibition of the RAS/MAPK pathway is essential for mitotic-to-meiotic fate transition.
    MeSH term(s) Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/embryology ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Cell Differentiation/physiology ; Electrophoretic Mobility Shift Assay ; Germ Cells/physiology ; Immunoprecipitation ; Microscopy, Fluorescence ; Mitogen-Activated Protein Kinase 1/metabolism ; Mutagenesis ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/physiology ; ras Proteins/metabolism
    Chemical Substances Caenorhabditis elegans Proteins ; PUF-8 protein, C elegans ; RNA-Binding Proteins ; let-60 protein, C elegans (133135-08-7) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24) ; mpk-1 protein, C elegans (EC 2.7.11.24) ; ras Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2013-03-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.088013
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    In stock of ZB MED Cologne/Königswinter

    Ub I Zs.183: Show issues Location:
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    Zs.MG 91: Show issues

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