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  • 11
    Publikationsdatum: 2015-08-25
    Print ISSN: 0265-9247
    Digitale ISSN: 1521-1878
    Thema: Biologie , Medizin
    Publiziert von Wiley
    Standort Signatur Erwartet Verfügbarkeit
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  • 12
    Publikationsdatum: 2015-08-05
    Beschreibung: It has long been thought that transmembrane cell-surface receptors, such as receptor tyrosine kinases and cytokine receptors, among others, are activated by ligand binding through ligand-induced dimerization of the receptors. However, there is growing evidence that prior to ligand binding, various transmembrane receptors have a preformed, yet inactive, dimeric structure on the cell surface. Various studies also demonstrate that during transmembrane signaling, ligand binding to the extracellular domain of receptor dimers induces a rotation of transmembrane domains, followed by rearrangement and/or activation of intracellular domains. The paper here describes transmembrane cell-surface receptors that are known or proposed to exist in dimeric form prior to ligand binding, and discusses how these preformed dimers are activated by ligand binding. “Rotation model” for a molecular mechanism underlying ligand-induced activation of preformed, cell-surface receptor dimers. Ligand binding induces conformational changes of the extracellular domains that cause rotations of the transmembrane domains. The transmembrane domain rotations dissociate and rearrange the intracellular domain dimers for activation and/or interaction with other cytoplasmic proteins.
    Print ISSN: 0265-9247
    Digitale ISSN: 1521-1878
    Thema: Biologie , Medizin
    Publiziert von Wiley
    Standort Signatur Erwartet Verfügbarkeit
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  • 13
    Publikationsdatum: 2015-08-08
    Beschreibung: The Gulf of St. Lawrence (GSL) is a feeding ground for several baleen whale species from the North Atlantic, providing them with an abundant supply of krill during their seasonal presence. Krill aggregations are found along the abrupt topography formed by the deep channels, but the dynamics of krill aggregations have not yet been characterized at the scale of the whole GSL. In this study, we combined extensive dual-frequency acoustic observations of krill and Lagrangian numerical simulations to identify the recurrent areas of krill accumulation in summer and the mesoscale circulation mechanisms responsible for their formation. Throughout the GSL, the topographic forcing of the surface circulation appeared essential in forming convergence zones where observed krill concentrations were systematically higher than average, and within which most of the densest patches were observed. This approach can help in defining the dynamics of the feeding habitat of baleen whales in the GSL, in particular blue and fin whales whose diet is dominated by krill.
    Print ISSN: 0024-3590
    Digitale ISSN: 1939-5590
    Thema: Biologie , Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 14
    Publikationsdatum: 2015-08-08
    Beschreibung: A vast network of cellular circadian clocks regulates 24-hour rhythms of behavior and physiology in mammals. Complex environments are characterized by multiple, and often conflicting time signals demanding flexible mechanisms of adaptation of endogenous rhythms to external time. Traditionally this process of circadian entrainment has been conceptualized in a hierarchical scheme with a light-reset master pacemaker residing in the hypothalamus that subsequently aligns subordinate peripheral clocks with each other and with external time. Here we review new experiments using conditional mouse genetics suggesting that resetting of the circadian system occurs in a more “federated” and tissue-specific fashion, which allows for increased noise resistance and plasticity of circadian timekeeping under natural conditions. A network of cellular circadian clocks adapts physiology to the 24-hour day cycle. Traditionally clock entrainment has been conceptualized in a hierarchical scheme with a light-reset SCN pacemaker that subsequently aligns subordinate peripheral clocks. New experiments suggest that resetting of the circadian system occurs in a more “federated” fashion allowing for increased noise resistance and plasticity of circadian timekeeping under complex natural conditions.
    Print ISSN: 0265-9247
    Digitale ISSN: 1521-1878
    Thema: Biologie , Medizin
    Publiziert von Wiley
    Standort Signatur Erwartet Verfügbarkeit
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  • 15
    Publikationsdatum: 2015-08-08
    Beschreibung: hiCLIP (RNA hybrid and individual-nucleotide resolution ultraviolet cross-linking and immunoprecipitation), is a novel technique developed by Sugimoto et al. (2015). Here, the use of different adaptors permits a controlled ligation of the two strands of a RNA duplex allowing the identification of each arm in the duplex upon sequencing. The authors chose a notoriously difficult to study double-stranded RNA-binding protein (dsRBP) termed Staufen1, a mammalian homolog of Drosophila Staufen involved in mRNA localization and translational control. Using hiCLIP, they discovered a dominance of intramolecular RNA duplexes compared to the total RNA duplexes identified. Importantly, the authors discovered two different types of intramolecular duplexes in the cell: highly translated mRNAs with long-range duplexes in their 3′-UTRs and poorly translated mRNAs with duplexes in their coding region. In conclusion, the authors establish hiCLIP as an important novel technique for the identification of RNA secondary structures that serve as in vivo binding sites for dsRBPs. The hiCLIP technique has allowed Sugimoto et al. (2015) to unravel Staufen 1 (Stau1) function in mRNA translational regulation, showing that transcript translation is dependent on the location of intramolecular double-stranded duplexes recognized by Stau1.
    Print ISSN: 0265-9247
    Digitale ISSN: 1521-1878
    Thema: Biologie , Medizin
    Publiziert von Wiley
    Standort Signatur Erwartet Verfügbarkeit
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  • 16
    Publikationsdatum: 2015-08-08
    Beschreibung: Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The “β-amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including β-amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. Recently, we recapitulated key events of Alzheimer's disease pathogenesis in a 3D human stem cells culture system. This model enhances beta-amyloid accumulation and neurofibrillary tau tangles (NFT), providing a powerful cellular model for Alzheimer's disease. In this review, we discuss the current progress of modeling neurodegenerative diseases in 3D cultures.
    Print ISSN: 0265-9247
    Digitale ISSN: 1521-1878
    Thema: Biologie , Medizin
    Publiziert von Wiley
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 17
    Publikationsdatum: 2015-06-09
    Beschreibung: RNA binding proteins (RBPs) are key factors for the regulation of gene expression by binding to cis elements, i.e. short sequence motifs in RNAs. Recent studies demonstrate that cooperative binding of multiple RBPs is important for the sequence-specific recognition of RNA and thereby enables the regulation of diverse biological activities by a limited set of RBPs. Cross-linking immuno-precipitation (CLIP) and other recently developed high-throughput methods provide comprehensive, genome-wide maps of protein-RNA interactions in the cell. Structural biology gives detailed insights into molecular mechanisms and principles of RNA recognition by RBPs, but has so far focused on single RNA binding proteins and often on single RNA binding domains. The combination of high-throughput methods and detailed structural biology studies is expected to greatly advance our understanding of the code for protein-RNA recognition in gene regulation, as we review in this article. Multi-protein-RNA networks play important roles in post-transcriptional regulation of gene expression. Deciphering the underlying protein-RNA recognition code will greatly benefit from combining large-scale quantitative methods with integrated structural biology.
    Print ISSN: 0265-9247
    Digitale ISSN: 1521-1878
    Thema: Biologie , Medizin
    Publiziert von Wiley
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 18
    Publikationsdatum: 2015-07-30
    Beschreibung: Chromosomes are not only carriers of the genetic material, but also actively regulate the assembly of complex intracellular architectures. During mitosis, chromosome-induced microtubule polymerisation ensures spindle assembly in cells without centrosomes and plays a supportive role in centrosome-containing cells. Chromosomal signals also mediate post-mitotic nuclear envelope (NE) re-formation. Recent studies using novel approaches to manipulate histones in oocytes, where functions can be analysed in the absence of transcription, have established that nucleosomes, but not DNA alone, mediate the chromosomal regulation of spindle assembly and NE formation. Both processes require the generation of RanGTP by RCC1 recruited to nucleosomes but nucleosomes also acquire cell cycle stage specific regulators, Aurora B in mitosis and ELYS, the initiator of nuclear pore complex assembly, at mitotic exit. Here, we review the mechanisms by which nucleosomes control assembly and functions of the spindle and the NE, and discuss their implications for genome maintenance. Chromosomes act as reaction platforms for spindle assembly and nuclear envelope formation. Both processes depend on nucleosomes, which induce spindles by recruiting RCC1 and Aurora B in mitosis, and nuclear envelopes by recruiting RCC1 and ELYS in interphase. Here, we review these mechanisms, and discuss their implications for genome maintenance.
    Print ISSN: 0265-9247
    Digitale ISSN: 1521-1878
    Thema: Biologie , Medizin
    Publiziert von Wiley
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 19
    Publikationsdatum: 2015-07-30
    Beschreibung: In the organelles of plants and mammals, recent evidence suggests that genomic instability stems in large part from template switching events taking place during DNA replication. Although more than one mechanism may be responsible for this, some similarities exist between the different proposed models. These can be separated into two main categories, depending on whether they involve a single-strand-switching or a reciprocal-strand-switching event. Single-strand-switching events lead to intermediates containing Y junctions, whereas reciprocal-strand-switching creates Holliday junctions. Common features in all the described models include replication stress, fork stalling and the presence of inverted repeats, but no single element appears to be required in all cases. We review the field, and examine the ideas that several mechanisms may take place in any given genome, and that the presence of palindromes or inverted repeats in certain regions may favor specific rearrangements. Short-range inversions are a major component of genomic instability in the organelles of Arabidopsis thaliana and humans. Here, we review proposed replication-based mechanisms for the formation of these rearrangements. We identify common characteristics of the mechanisms and examine their impact on organelle genomes.
    Print ISSN: 0265-9247
    Digitale ISSN: 1521-1878
    Thema: Biologie , Medizin
    Publiziert von Wiley
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 20
    Publikationsdatum: 2015-08-07
    Beschreibung: Inflammatory responses are essential for the clearance of pathogens and the repair of injured tissues; however, if these responses are not properly controlled chronic inflammation can occur. Chronic inflammation is now recognized as a contributing factor to many age-associated diseases including metabolic disorders, arthritis, neurodegeneration, and cardiovascular disease. Due to the connection between chronic inflammation and these diseases, it is essential to understand underlying mechanisms behind this process. In this review, factors that contribute to chronic inflammation are discussed. Further, we emphasize the emerging roles of microRNAs (miRNAs) and other noncoding RNAs (ncRNA) in regulating chronic inflammatory states, making them important future diagnostic markers and therapeutic targets. Copyright Line: © 2015 The Authors BioEssays Published by Wiley-VCH Verlag GmbH & Co. KGaA. Although immune responses are necessary for proper clearance of pathogens and tissue repair, these responses can become dysregulated resulting in a chronic inflammatory state. Chronic inflammation is a contributing factor to many age-associated diseases. Recently, noncoding RNAs have been shown to regulate chronic inflammation and are emerging as potential therapeutic targets.
    Print ISSN: 0265-9247
    Digitale ISSN: 1521-1878
    Thema: Biologie , Medizin
    Publiziert von Wiley
    Standort Signatur Erwartet Verfügbarkeit
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