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  • 1
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    DANSing with Caenorhabditis elegans (2009)
    National Academy of Sciences
    Details
    Publikationsdatum: 2009-05-05
    Print ISSN: 0027-8424
    Digitale ISSN: 1091-6490
    Thema: Biologie , Medizin , Allgemeine Naturwissenschaft
    Publiziert von National Academy of Sciences
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
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    N-Ethyl-N-Nitrosourea (ENU) Mutagenesis Reveals an Intronic Residue Critical for Caenorhabditis elegans 3' Splice Site Function in Vivo (2016)
    Genetics Society of America (GSA)
    Details
    Publikationsdatum: 2016-06-02
    Beschreibung: Metazoan introns contain a polypyrimidine tract immediately upstream of the AG dinucleotide that defines the 3' splice site. In the nematode Caenorhabditis elegans , 3' splice sites are characterized by a highly conserved UUUUCAG/R octamer motif. While the conservation of pyrimidines in this motif is strongly suggestive of their importance in pre-mRNA splicing, in vivo evidence in support of this is lacking. In an N -ethyl- N -nitrosourea (ENU) mutagenesis screen in Caenorhabditis elegans , we have isolated a strain containing a point mutation in the octamer motif of a 3' splice site in the daf-12 gene. This mutation, a single base T-to-G transversion at the -5 position relative to the splice site, causes a strong daf-12 loss-of-function phenotype by abrogating splicing. The resulting transcript is predicted to encode a truncated DAF-12 protein generated by translation into the retained intron, which contains an in-frame stop codon. Other than the perfectly conserved AG dinucleotide at the site of splicing, G at the –5 position of the octamer motif is the most uncommon base in C . elegans 3' splice sites, occurring at closely paired sites where the better match to the splicing consensus is a few bases downstream. Our results highlight both the biological importance of the highly conserved –5 uridine residue in the C. elegans 3' splice site octamer motif as well as the utility of using ENU as a mutagen to study the function of polypyrimidine tracts and other AU- or AT-rich motifs in vivo .
    Digitale ISSN: 2160-1836
    Thema: Biologie
    Publiziert von Genetics Society of America (GSA)
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
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    Chromoanasynthetic Genomic Rearrangement Identified in a N-Ethyl-N-Nitrosourea (ENU) Mutagenesis Screen in Caenorhabditis elegans (2016)
    Genetics Society of America (GSA)
    Details
    Publikationsdatum: 2016-02-05
    Beschreibung: Chromoanasynthesis is a recently discovered phenomenon in humans with congenital diseases that is characterized by complex genomic rearrangements (CGRs) resulting from aberrant repair of catastrophic chromosomal damage. How these CGRs are induced is not known. Here, we describe the structure and function of dpDp667 , a causative CGR that emerged from a Caenorhabditis elegans dauer suppressor screen in which animals were treated with the point mutagen N -ethyl- N -nitrosourea (ENU). dpDp667 comprises nearly 3 Mb of sequence on the right arm of the X chromosome, contains three duplications and one triplication, and is devoid of deletions. Sequences from three out of the four breakpoint junctions in dpDp667 reveal microhomologies that are hallmarks of chromoanasynthetic CGRs. Our findings suggest that environmental insults and physiological processes that cause point mutations may give rise to chromoanasynthetic rearrangements associated with congenital disease. The relatively subtle phenotype of animals harboring dpDp667 suggests that the prevalence of CGRs in the genomes of mutant and/or phenotypically unremarkable animals may be grossly underestimated.
    Digitale ISSN: 2160-1836
    Thema: Biologie
    Publiziert von Genetics Society of America (GSA)
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
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    Influence of Steroid Hormone Signaling on Life Span Control by Caenorhabditis elegans Insulin-Like Signaling (2013)
    Genetics Society of America (GSA)
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    Publikationsdatum: 2013-05-24
    Beschreibung: Sterol-sensing nuclear receptors and insulin-like growth factor signaling play evolutionarily conserved roles in the control of aging. In the nematode Caenorhabditis elegans , bile acid-like steroid hormones known as dafachronic acids (DAs) influence longevity by binding to and regulating the activity of the conserved nuclear receptor DAF-12 , and the insulin receptor (InsR) ortholog DAF-2 controls life span by inhibiting the FoxO transcription factor DAF-16 . How the DA/ DAF-12 pathway interacts with DAF-2 /InsR signaling to control life span is poorly understood. Here we specifically investigated the roles of liganded and unliganded DAF-12 in life span control in the context of reduced DAF-2 /InsR signaling. In animals with reduced daf-2 /InsR activity, mutations that either reduce DA biosynthesis or fully abrogate DAF-12 activity shorten life span, suggesting that liganded DAF-12 promotes longevity. In animals with reduced DAF-2 /InsR activity induced by daf-2 /InsR RNAi, both liganded and unliganded DAF-12 promote longevity. However, in daf-2 /InsR mutants, liganded and unliganded DAF-12 act in opposition to control life span. Thus, multiple DAF-12 activities influence life span in distinct ways in contexts of reduced DAF-2 /InsR signaling. Our findings establish new roles for a conserved steroid signaling pathway in life span control and elucidate interactions among DA biosynthetic pathways, DAF-12 , and DAF-2 /InsR signaling in aging.
    Digitale ISSN: 2160-1836
    Thema: Biologie
    Publiziert von Genetics Society of America (GSA)
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
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    Requirement for translocon-associated protein (TRAP) {alpha} in insulin biogenesis (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2019
    Beschreibung: 〈p〉The mechanistic basis for the biogenesis of peptide hormones and growth factors is poorly understood. Here, we show that the conserved endoplasmic reticulum membrane translocon-associated protein α (TRAPα), also known as signal sequence receptor 1, plays a critical role in the biosynthesis of insulin. Genetic analysis in the nematode 〈i〉Caenorhabditis elegans〈/i〉 and biochemical studies in pancreatic β cells reveal that TRAPα deletion impairs preproinsulin translocation while unexpectedly disrupting distal steps in insulin biogenesis including proinsulin processing and secretion. The association of common intronic single-nucleotide variants in the human TRAPα gene with susceptibility to type 2 diabetes and pancreatic β cell dysfunction suggests that impairment of preproinsulin translocation and proinsulin trafficking may contribute to the pathogenesis of type 2 diabetes.〈/p〉
    Digitale ISSN: 2375-2548
    Thema: Allgemeine Naturwissenschaft
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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