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Die vorliegende, von Studierenden der Fachhochschule für Bibliothekswesen in Frankfurt am Main erstellte Projektarbeit befaßt sich mit Fragen, Aspekten und Möglichkeiten der Flexibilisierung von Arbeitszeiten und Arbeitsformen in Bibliotheken. Im ersten Teil der Arbeit werden die wichtigsten Arbeitsteilzeitmodelle vorgestellt und deren Vorteile für Arbeitgeber und nehmer herausgearbeitet. Anschließend erfolgt eine durch Graphiken und Tabellen veranschaulichte Untersuchung von drei ausgewählte Universitätsbibliotheken (Gießen, Marburg, Mainz) in bezug auf bereits existierende Arbeitszeitflexibilisierung. Ein Ausblick geht der Frage nach, ob die dargestellten Teilzeitmodelle für Bibliotheken notwendig und ausreichend sind. Der zweite Themenkomplex befaßt sich mit der Telearbeit als einer innovativen Arbeitsform in Bibliotheken. Ausgehend von einer Begriffsbestimung werden verschiedene Formen der Telearbeit sowie deren Vor und Nachteile geschildert. Es wird erläutert, welche Bedingungen an den Telearbeiter und seinen Arbeitsplatz geknüpft sind, welche rechtlichen Voraussetzungen erfüllt werden müssen, welche finanziellen Aspekte eine Rolle spielen und welche Anwendungsmöglichkeiten für Telearbeit in Bibliotheken bestehen. An drei konkreten Beispielen wird dann geschildert, wie Telearbeit in Bibliotheken bereits verwirklicht wurde. Abschließend wird der Frage nachgegangen, welche Perspektiven der Einsatz von Telearbeit in Bibliotheken hat. Der dritte Abschnitt der Ausarbeitung stellt das bibliothekarische Call Center als neue Form einer benutzerorientierten Einrichtung vor. Zielsetzungen und Dienstleistungsformen des Call Centers werden ebenso abgehandelt wie Aspekte der Planung, Einrichtung und Arbeitsplatzergonomie sowie des Einsatzes von Telearbeit. Anhand des Beispiels der Zentral und Landesbibliothek Berlin wird schließlich dokumentiert, wie sich ein bibliothekarisches Call Center in der Praxis bereits bewährt hat.
Background: Leukocyte progenitors derived from clonal hematopoiesis of undetermined potential (CHIP) are associated with increased cardiovascular events. However, the prevalence and functional relevance of CHIP in coronary artery disease (CAD) are unclear, and cells affected by CHIP have not been detected in human atherosclerotic plaques.
Methods: CHIP mutations in blood and tissues were identified by targeted deep-DNA-sequencing (DNAseq: coverage >3,000) and whole-genome-sequencing (WGS: coverage >35). CHIP-mutated leukocytes were visualized in human atherosclerotic plaques by mutaFISHTM. Functional relevance of CHIP mutations was studied by RNAseq.
Results: DNAseq of whole blood from 540 deceased CAD patients of the Munich cardIovaScular StudIes biObaNk (MISSION) identified 253 (46.9%) CHIP mutation carriers (mean age 78.3 years). DNAseq on myocardium, atherosclerotic coronary and carotid arteries detected identical CHIP mutations in 18 out of 25 mutation carriers in tissue DNA. MutaFISHTM visualized individual macrophages carrying DNMT3A CHIP mutations in human atherosclerotic plaques. Studying monocyte-derived macrophages from Stockholm-Tartu Atherosclerosis Reverse Networks Engineering Task (STARNET; n=941) by WGS revealed CHIP mutations in 14.2% (mean age 67.1 years). RNAseq of these macrophages revealed that expression patterns in CHIP mutation carriers differed substantially from those of non-carriers. Moreover, patterns were different depending on the underlying mutations, e.g. those carrying TET2 mutations predominantly displayed upregulated inflammatory signaling whereas ASXL1 mutations showed stronger effects on metabolic pathways.
Conclusions: Deep-DNA-sequencing reveals a high prevalence of CHIP mutations in whole blood of CAD patients. CHIP-affected leukocytes invade plaques in human coronary arteries. RNAseq data obtained from macrophages of CHIP-affected patients suggest that pro-atherosclerotic signaling differs depending on the underlying mutations. Further studies are necessary to understand whether specific pathways affected by CHIP mutations may be targeted for personalized treatment.
Alzheimer’s Disease (AD) is a progressive and irreversible neurodegenerative disorder, characterized by the accumulation of abeta-amyloid aggregates, which triggers tau hyperphosphorylation and neuronal loss. While the precise mechanisms underlying neurodegeneration in AD are not entirely understood, it is known that loss of proteostasis is implicated in this process. Maintaining neuronal proteostasis requires proper transfer RNA (tRNA) modifications, which are crucial for optimal translation. However, research into tRNA epitranscriptome in AD is limited, and it is not yet clear how alterations in tRNA modifying enzymes and tRNA modifications might contribute to disease progression. Here, we report that expression of the tRNA modifying enzyme ELP3 is reduced in the brain of AD patients and amyloid AD mouse models, suggesting ELP3 is implicated in proteostasis dysregulation observed in AD. To investigate the role of ELP3 specifically in neuronal proteostasis impairments in the context of amyloid pathology, we analyzed SH-SY5Y neuronal cells carrying the amyloidogenic Swedish familial AD mutation in the APP gene (SH-SWE) or the wild-type gene (SH-WT). Similarly to the amyloid mouse models, SH-SWE exhibited reduced levels of ELP3 which was associated with tRNA hypomodifications and reduced abundance, as well as proteostasis impairments. Furthermore, the knock-down of ELP3 in SH-WT recapitulated the proteostasis impairments observed in SH-SWE cells. Importantly, the correction of tRNA deficits due to ELP3 reduction rescued and reverted proteostasis impairments of SH-SWE and SH-WT knock-down for ELP3, respectively. Additionally, SH-WT exposed to the secretome of SH-SWE or synthetic amyloid aggregates recapitulate the SH-SWE phenotype, characterized by reduced ELP3 expression, tRNA hypomodification and increased protein aggregation. Taken together, our data suggest that amyloid pathology dysregulates neuronal proteostasis through the reduction of ELP3 and tRNA modifications. This study highlights the modulation of tRNA modifications as a potential therapeutic avenue to restore neuronal proteostasis in AD and preserve neuronal function.
Nicotinamide adenine dinucleotide (NAD) serves as a cap-like structure on cellular RNAs (NAD-RNAs) in all domains of life including the bacterium Escherichia coli. NAD also acts as a key molecule in phage-host interactions, where bacterial immune systems deplete NAD to abort phage infection. Nevertheless, NAD-RNAs have not yet been identified during phage infections of bacteria and the mechanisms of their synthesis and degradation are unknown in this context. The T4 phage that specifically infects E. coli presents an important model to study phage infections, but a systematic analysis of the presence and dynamics of NAD-RNAs during T4 phage infection is lacking. Here, we investigate the presence of NAD-RNAs during T4 phage infection in a dual manner. By applying time-resolved NAD captureSeq, we identify NAD-capped host and phage transcripts and their dynamic regulation during phage infection. We provide evidence that NAD-RNAs are – as reported earlier – generated by the host RNA polymerase by initiating transcription with NAD at canonical transcription start sites. In addition, we characterize NudE.1 – a T4 phage-encoded Nudix hydrolase – as the first phage-encoded NAD-RNA decapping enzyme. T4 phages carrying inactive NudE.1 display a delayed lysis phenotype. This study investigates for the first time the dual epitranscriptome of a phage and its host, thereby introducing epitranscriptomics as an important field of phage research.
In this report, we perform structure validation of recently reported RNA phosphorothioate (PT) modifications, a new set of epitranscriptome marks found in bacteria and eukaryotes including humans. By comparing synthetic PT-containing diribonucleotides with native species in RNA hydrolysates by high-resolution mass spectrometry (MS), metabolic stable isotope labeling, and PT-specific iodine-desulfurization, we disprove the existence of PTs in RNA from E. coli, S. cerevisiae, human cell lines, and mouse brain. Furthermore, we discuss how an MS artifact led to the initial misidentification of 2′-O-methylated diribonucleotides as RNA phosphorothioates. To aid structure validation of new nucleic acid modifications, we present a detailed guideline for MS analysis of RNA hydrolysates, emphasizing how the chosen RNA hydrolysis protocol can be a decisive factor in discovering and quantifying RNA modifications in biological samples.
Different modification pathways for m1A58 incorporation in yeast elongator and initiator tRNAs
(2022)
As essential components of the cellular protein synthesis machineries, tRNAs undergo a tightly controlled biogenesis process, which include the incorporation of a large number of posttranscriptional chemical modifications. Maturation defaults resulting in lack of modifications in the tRNA core may lead to the degradation of hypomodified tRNAs by the rapid tRNA decay (RTD) and nuclear surveillance pathways. Although modifications are typically introduced in tRNAs independently of each other, several modification circuits have been identified in which one or more modifications stimulate or repress the incorporation of others. We previously identified m1A58 as a late modification introduced after more initial modifications, such as Ѱ55 and T54 in yeast elongator tRNAPhe. However, previous reports suggested that m1A58 is introduced early along the tRNA modification process, with m1A58 being introduced on initial transcripts of initiator tRNAiMet, and hence preventing its degradation by the nuclear surveillance and RTD pathways. Here, aiming to reconcile this apparent inconsistency on the temporality of m1A58 incorporation, we examined the m1A58 modification pathways in yeast elongator and initiator tRNAs. For that, we first implemented a generic approach enabling the preparation of tRNAs containing specific modifications. We then used these specifically modified tRNAs to demonstrate that the incorporation of T54 in tRNAPhe is directly stimulated by Ѱ55, and that the incorporation of m1A58 is directly and individually stimulated by Ѱ55 and T54, thereby reporting on the molecular aspects controlling the Ѱ55 → T54 → m1A58 modification circuit in yeast elongator tRNAs. We also show that m1A58 is efficiently introduced on unmodified tRNAiMet, and does not depend on prior modifications. Finally, we show that the m1A58 single modification has tremendous effects on the structural properties of yeast tRNAiMet, with the tRNA elbow structure being properly assembled only when this modification is present. This rationalizes on structural grounds the degradation of hypomodified tRNAiMet lacking m1A58 by the nuclear surveillance and RTD pathways.
Discoveries of new species often depend on one or a few specimens, leading to delays as researchers wait for additional context, sometimes for decades. There is currently little professional incentive for a single expert to publish a stand-alone species description. Additionally, while many journals accept taxonomic descriptions, even specialist journals expect insights beyond the descriptive work itself. The combination of these factors exacerbates the issue that only a small fraction of marine species are known and new discoveries are described at a slow pace, while they face increasing threats from accelerating global change. To tackle this challenge, this first compilation of Ocean Species Discoveries (OSD) presents a new collaborative framework to accelerate the description and naming of marine invertebrate taxa that can be extended across all phyla. Through a mode of publication that can be speedy, taxonomy-focused and generate higher citation rates, OSD aims to create an attractive home for single species descriptions. This Senckenberg Ocean Species Alliance (SOSA) approach emphasises thorough, but compact species descriptions and diagnoses, with supporting illustrations and with molecular data when available. Even basic species descriptions carry key data for distributions and ecological interactions (e.g., host-parasite relationships) besides universally valid species names; these are essential for downstream uses, such as conservation assessments and communicating biodiversity to the broader public.This paper presents thirteen marine invertebrate taxa, comprising one new genus, eleven new species and one re-description and reinstatement, covering wide taxonomic, geographic, bathymetric and ecological ranges. The taxa addressed herein span three phyla (Mollusca, Arthropoda, Echinodermata), five classes, eight orders and twelve families. Apart from the new genus, an updated generic diagnosis is provided for four other genera. The newly-described species of the phylum Mollusca are Placiphorella methanophila Vončina, sp. nov. (Polyplacophora, Mopaliidae), Lepetodrilus marianae Chen, Watanabe & Tsuda, sp. nov. (Gastropoda, Lepetodrilidae), Shinkailepas gigas Chen, Watanabe & Tsuda, sp. nov. (Gastropoda, Phenacolepadidae) and Lyonsiella illaesa Machado & Sigwart, sp. nov. (Bivalvia, Lyonsiellidae). The new taxa of the phylum Arthropoda are all members of the subphylum Crustacea: Lepechinella naces Lörz & Engel, sp. nov. (Amphipoda, Lepechinellidae), Cuniculomaera grata Tandberg & Jażdżewska, gen. et sp. nov. (Amphipoda, Maeridae), Pseudionella pumulaensis Williams & Landschoff, sp. nov. (Isopoda, Bopyridae), Mastigoniscus minimus Wenz, Knauber & Riehl, sp. nov. (Isopoda, Haploniscidae), Macrostylis papandreas Jonannsen, Riehl & Brandt, sp. nov. (Isopoda, Macrostylidae), Austroniscus indobathyasellus Kaiser, Kniesz & Kihara, sp. nov. (Isopoda, Nannoniscidae) and Apseudopsis daria Esquete & Tato, sp. nov. (Tanaidacea, Apseudidae). In the phylum Echinodermata, the reinstated species is Psychropotes buglossa E. Perrier, 1886 (Holothuroidea, Psychropotidae).The study areas span the North and Central Atlantic Ocean, the Indian Ocean and the North, East and West Pacific Ocean and depths from 5.2 m to 7081 m. Specimens of eleven free-living and one parasite species were collected from habitats ranging from an estuary to deep-sea trenches. The species were illustrated with photographs, line drawings, micro-computed tomography, confocal laser scanning microscopy and scanning electron microscopy images. Molecular data are included for nine species and four species include a molecular diagnosis in addition to their morphological diagnosis.The five new geographic and bathymetric distribution records comprise Lepechinella naces Lörz & Engel, sp. nov., Cuniculomaera grata Tandberg & Jażdżewska, sp. nov., Pseudionella pumulaensis Williams & Landschoff, sp. nov., Austroniscus indobathyasellus Kaiser, Kniesz & Kihara, sp. nov. and Psychropotes buglossa E. Perrier, 1886, with the novelty spanning from the species to the family level. The new parasite record is Pseudionella pumulaensis Williams & Landschoff, sp. nov., found in association with the hermit crab Pagurus fraserorum Landschoff & Komai, 2018.