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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Photochemistry and Photobiology A: Chemistry 76 (1993), S. 217-224 
    ISSN: 1010-6030
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2011-09-28
    Description: The identification of factors that define adipocyte precursor potential has important implications for obesity. Preadipocytes are fibroblastoid cells committed to becoming round lipid-laden adipocytes. In vitro, this differentiation process is facilitated by confluency, followed by adipogenic stimuli. During adipogenesis, a large number of cytostructural genes are repressed before adipocyte gene induction. Here we report that the transcriptional repressor transcription factor 7-like 1 (TCF7L1) binds and directly regulates the expression of cell structure genes. Depletion of TCF7L1 inhibits differentiation, because TCF7L1 indirectly induces the adipogenic transcription factor peroxisome proliferator-activated receptor γ in a manner that can be replaced by inhibition of myosin II activity. TCF7L1 is induced by cell contact in adipogenic cell lines, and ectopic expression of TCF7L1 alleviates the confluency requirement for adipocytic differentiation of precursor cells. In contrast, TCF7L1 is not induced during confluency of non-adipogenic fibroblasts, and, remarkably, forced expression of TCF7L1 is sufficient to commit non-adipogenic fibroblasts to an adipogenic fate. These results establish TCF7L1 as a transcriptional hub coordinating cell–cell contact with the transcriptional repression required for adipogenic competency.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 3
    Publication Date: 2018-03-16
    Description: Mammalian physiology exhibits 24-hour cyclicity due to circadian rhythms of gene expression controlled by transcription factors that constitute molecular clocks. Core clock transcription factors bind to the genome at enhancer sequences to regulate circadian gene expression, but not all binding sites are equally functional. We found that in mice, circadian gene expression in the liver is controlled by rhythmic chromatin interactions between enhancers and promoters. Rev-erbα, a core repressive transcription factor of the clock, opposes functional loop formation between Rev-erbα–regulated enhancers and circadian target gene promoters by recruitment of the NCoR-HDAC3 co-repressor complex, histone deacetylation, and eviction of the elongation factor BRD4 and the looping factor MED1. Thus, a repressive arm of the molecular clock operates by rhythmically modulating chromatin loops to control circadian gene transcription.
    Keywords: Molecular Biology, Physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2016-05-14
    Description: FGF21 is an atypical member of the FGF family that functions as a hormone to regulate carbohydrate and lipid metabolism. Here we demonstrate that the actions of FGF21 in mouse adipose tissue, but not in liver, are modulated by the nuclear receptor Rev-erbα, a potent transcriptional repressor. Interrogation of genes induced in the absence of Rev-erbα for Rev-erbα-binding sites identified βKlotho, an essential coreceptor for FGF21, as a direct target gene of Rev-erbα in white adipose tissue but not liver. Rev-erbα ablation led to the robust elevated expression of βKlotho. Consequently, the effects of FGF21 were markedly enhanced in the white adipose tissue of mice lacking Rev-erbα. A major Rev-erbα-controlled enhancer at the Klb locus was also bound by the adipocytic transcription factor peroxisome proliferator-activated receptor (PPAR) γ, which regulates its activity in the opposite direction. These findings establish Rev-erbα as a specific modulator of FGF21 signaling in adipose tissue.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 5
    Publication Date: 2014-05-02
    Description: Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for peroxisome proliferator-activated receptor (PPAR), the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to the NR on DNA, explains positive regulation of gene expression, but ligand-dependent repression is not well understood. We addressed this issue by studying the direct effects of rosi on gene transcription using global run-on sequencing (GRO-seq). Rosi-induced changes in gene body transcription were pronounced after 10 min and correlated with steady-state mRNA levels as well as with transcription at nearby enhancers (enhancer RNAs [eRNAs]). Up-regulated eRNAs occurred almost exclusively at PPAR-binding sites, to which rosi treatment recruited coactivators, including MED1, p300, and CBP. In contrast, transcriptional repression by rosi involved a loss of coactivators from eRNA sites devoid of PPAR and enriched for other transcription factors, including AP-1 factors and C/EBPs. Thus, rosi activates and represses transcription by fundamentally different mechanisms that could inform the future development of anti-diabetic drugs.
    Print ISSN: 0890-9369
    Topics: Biology
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  • 6
    Publication Date: 2015-02-03
    Description: PR (PRD1–BF1–RIZ1 homologous) domain-containing 16 (PRDM16) drives a brown fat differentiation program, but the mechanisms by which PRDM16 activates brown fat-selective genes have been unclear. Through chromatin immunoprecipitation (ChIP) followed by deep sequencing (ChIP-seq) analyses in brown adipose tissue (BAT), we reveal that PRDM16 binding is highly enriched at a broad set of brown fat-selective genes. Importantly, we found that PRDM16 physically binds to MED1, a component of the Mediator complex, and recruits it to superenhancers at brown fat-selective genes. PRDM16 deficiency in BAT reduces MED1 binding at PRDM16 target sites and causes a fundamental change in chromatin architecture at key brown fat-selective genes. Together, these data indicate that PRDM16 controls chromatin architecture and superenhancer activity in BAT.
    Print ISSN: 0890-9369
    Topics: Biology
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  • 7
    Publication Date: 2015-06-02
    Description: Glucocorticoids (GCs) are commonly prescribed drugs, but their anti-inflammatory benefits are mitigated by metabolic side effects. Their transcriptional effects, including tissue-specific gene activation and repression, are mediated by the glucocorticoid receptor (GR), which is known to bind as a homodimer to a palindromic DNA sequence. Using ChIP-exo in mouse liver under endogenous corticosterone exposure, we report here that monomeric GR interaction with a half-site motif is more prevalent than homodimer binding. Monomers colocalize with lineage-determining transcription factors in both liver and primary macrophages, and the GR half-site motif drives transcription, suggesting that monomeric binding is fundamental to GR's tissue-specific functions. In response to exogenous GC in vivo, GR dimers assemble on chromatin near ligand-activated genes, concomitant with monomer evacuation of sites near repressed genes. Thus, pharmacological GCs mediate gene expression by favoring GR homodimer occupancy at classic palindromic sites at the expense of monomeric binding. The findings have important implications for improving therapies that target GR.
    Electronic ISSN: 1549-5469
    Topics: Biology , Medicine
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  • 8
    Publication Date: 2023-01-25
    Description: Ecological research, just as all Earth System Sciences, is becoming increasingly data-rich. Tools for processing of “big data” are continuously developed to meet corresponding technical and logistical challenges. However, even at smaller scales, data sets may be challenging when best practices in data exploration, quality control and reproducibility are to be met. This can occur when conventional methods, such as generating and assessing diagnostic visualizations or tables, become unfeasible due to time and practicality constraints. Interactive processing can alleviate this issue, and is increasingly utilized to ensure that large data sets are diligently handled. However, recent interactive tools rarely enable data manipulation, may not generate reproducible outputs, or are typically data/domain-specific. We developed datacleanr, an interactive tool that facilitates best practices in data exploration, quality control (e.g., outlier assessment) and flexible processing for multiple tabular data types, including time series and georeferenced data. The package is open-source, and based on the R programming language. A key functionality of datacleanr is the “reproducible recipe”—a translation of all interactive actions into R code, which can be integrated into existing analyses pipelines. This enables researchers experienced with script-based workflows to utilize the strengths of interactive processing without sacrificing their usual work style or functionalities from other (R) packages. We demonstrate the package’s utility by addressing two common issues during data analyses, namely 1) identifying problematic structures and artefacts in hierarchically nested data, and 2) preventing excessive loss of data from ‘coarse,’ code-based filtering of time series. Ultimately, with datacleanr we aim to improve researchers’ workflows and increase confidence in and reproducibility of their results.
    Type: info:eu-repo/semantics/article
    Format: application/pdf
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  • 9
    Publication Date: 2024-03-20
    Description: The response of evapotranspiration to anthropogenic warming is of critical importance for the water and carbon cycle. Contradictory conclusions about evapotranspiration changes are caused primarily by their brevity in time and sparsity in space, as well as the strong influence of internal variability. Here, we present the first gridded reconstruction of the summer (June, July, and August) vapor pressure deficit (VPD) for the past 4 centuries at the European level. This gridded reconstruction is based on 26 European tree ring oxygen isotope records and is obtained using a random forest approach. According to validation scores obtained with the Nash–Sutcliffe model efficiency, our reconstruction is robust over large parts of Europe since 1600, in particular for the westernmost and northernmost regions, where most tree ring records are located. Based on our reconstruction, we show that from the mid-1700s a trend towards higher summer VPD occurred in central Europe and the Mediterranean region that is related to a simultaneous increase in temperature and decrease in precipitation. This increasing summer VPD trend continues throughout the observational period and in recent times. Moreover, our summer VPD reconstruction helps to visualize the local and regional impacts of the current climate change, as well as to minimize statistical uncertainties of historical VPD variability. This paper provides also new insights into the relationship between summer VPD and large-scale atmospheric circulation, and we show that summer VPD has two preferred modes of variability, namely a NW–SE dipole-like mode and a N–S dipole-like mode. Furthermore, the interdisciplinary use of the data should be emphasized, as summer VPD is a crucial parameter for many climatological feedback processes in the Earth's surface system. The reconstructed summer VPD gridded data over the last 400 years are available at the following link: https://doi.org/10.5281/zenodo.5958836 (Balting et al., 2022).
    Type: info:eu-repo/semantics/article
    Format: application/pdf
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  • 10
    Publication Date: 2024-02-12
    Description: Tree-specific canopy conductance (Gc) and its adjustment play a critical role in mitigating excess water loss in changing environmental conditions. However, the change of Gc sensitivity to environmental conditions due to drought remains unclear for European tree species. Here we quantified the environmental operational space of Gc, i.e., the water supply (soil moisture, tree water deficit) and demand conditions (vapor pressure deficit) under which Gc ≥ 50% is possible (Gc50OS), at two sites with different soil water availability for three common European tree species. We collected sap flow and dendrometer measurements for co-occurring Pinus sylvestris, Fagus sylvatica and Quercus petraea growing under different soil hydrological conditions (drier/wetter). These measurements were combined with meteorological variables and soil moisture conditions in five depths. Dendrometer measurements were used to confirm soil water availability patterns. For all analyses, the contrasting soil hydrology between sites was the main driver of Gc response. At the drier sites, F. sylvatica and P. sylvestris reduced their water consumption in response to decreasing soil water supply earlier in the growing season than Q. petraea. However, our analysis on the Gc50OS revealed that at the drier sites, F. sylvatica and Q. petraea reduced the extent of their Gc50OS to a higher degree than P. sylvestris. This indicates a higher level of Gc50OS adjustment to the drier site conditions for the two broadleaved species. These differences were more pronounced when using the dendrometer-derived tree internal water status as proxy for tree water supply. Our results provide preliminary evidence for diverging short-term Gc responses when temperate trees are exposed to prolonged reduction in water availability. These findings suggest that Gc50OS can help to constrain species-specific predictions of water use by mature trees, especially when combined with high-resolution water potential measurements.
    Type: info:eu-repo/semantics/article
    Format: application/pdf
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