Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Language
Year
  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 21 June 2011, Vol.108(25), pp.10202-7
    Description: What makes embryogenesis a robust and canalized process is an important question in developmental biology. A bone morphogenetic protein (BMP) morphogen gradient plays a key role in embryonic development, and we are beginning to understand how the self-regulating properties of its signaling circuitry ensure robust embryonic patterning. An unexplored question is why the BMP signaling circuit is organized as a modular synexpression group, with a prevalence of feedback inhibitors. Here, we provide evidence from direct experimentation and mathematical modeling that the synexpressed feedback inhibitors BAMBI, SMAD6, and SMAD7 (i) expand the dynamic BMP signaling range essential for proper embryonic patterning and (ii) reduce interindividual phenotypic and molecular variability in Xenopus embryos. Thereby, negative feedback linearizes signaling responses and confers robust patterning, thus promoting canalized development. The presence of negative feedback inhibitors in other growth factor synexpression groups suggests that these properties may constitute a general principle.
    Keywords: Feedback, Physiological ; Gene Expression Regulation, Developmental ; Body Patterning -- Physiology ; Bone Morphogenetic Protein 4 -- Metabolism ; Signal Transduction -- Physiology
    ISSN: 00278424
    E-ISSN: 1091-6490
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Journal of Biomechanics, 2011, Vol.44(15), pp.2642-2648
    Description: Mechanical properties of the cell nucleus play an important role in maintaining the integrity of the genome and controlling the cellular force balance. Irregularities in these properties have been related to disruption of a variety of force-dependent processes in the cell, such as migration, division, growth or differentiation. Characterizing mechanical properties of the cell nucleus and relating these parameters to cellular phenotypes remain challenging tasks, as conventional micromanipulation techniques do not allow direct probing of intracellular structures. Here, we present a framework based on light microscopic imaging and automated mechanical modeling that enables characterization of the compressibility of the nuclear interior . Based entirely on optical methods, our approach does not require application of destructive or contacting techniques and it enables measurements of a significantly larger number of cells. Compressibility, in this paper represented by Poisson's ratio , is determined by fitting a numerical model to experimentally observed time series of microscopic images of fluorescent cell nuclei in which bleached patterns are introduced. In a proof-of-principle study, this framework was applied to estimate in wild type cells and cells lacking important structural proteins of the nuclear envelope (LMNA ). Based on measurements of a large number of cells, our study revealed distinctive changes in compressibility of the nuclear interior between these two cell types. Our method allows an automated, contact-free estimation of mechanical properties of intracellular structures. Combined with knockdown and overexpression screens, it paves the way towards a high-throughput measurement of intracellular mechanical properties in functional phenotyping screens.
    Keywords: Cell Nucleus ; Mechanical Phenotyping ; Compressibility ; Nuclear Lamina ; Microscopic Imaging ; Medicine ; Engineering ; Anatomy & Physiology
    ISSN: 0021-9290
    E-ISSN: 1873-2380
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Biophysical Journal, 2011, Vol.100(3), pp.305a-305a
    Keywords: Biology
    ISSN: 0006-3495
    E-ISSN: 1542-0086
    Source: ScienceDirect Journals (Elsevier)
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Journal of Biomechanics, 22 August 2014, Vol.47(11), pp.2598-2605
    Description: Mechanical cell properties play an important role in many basic biological functions, including motility, adhesion, proliferation and differentiation. There is a growing body of evidence that the mechanical cell phenotype can be used for detection and, possibly, treatment of various diseases, including cancer. Understanding of pathological mechanisms requires investigation of the relationship between constitutive properties and major structural components of cells, i.e., the nucleus and cytoskeleton. While the contribution of actin und microtubules to cellular rheology has been extensively studied in the past, the role of intermediate filaments has been scarcely investigated up to now. Here, for the first time we compare the effects of drug-induced disruption of actin and vimentin intermediate filaments on mechanical properties of suspended NK cells using high-throughput deformability measurements and computational modeling. Although, molecular mechanisms of actin and vimentin disruption by the applied cytoskeletal drugs, Cytochalasin-D and Withaferin-A, are different, cell softening in both cases can be attributed to reduction of the effective density and stiffness of filament networks. Our experimental data suggest that actin and vimentin deficient cells exhibit, in average, 41% and 20% higher deformability in comparison to untreated control. 3D Finite Element simulation is performed to quantify the contribution of cortical actin and perinuclear vimentin to mechanical phenotype of the whole cell. Our simulation provides quantitative estimates for decreased filament stiffness in drug-treated cells and predicts more than two-fold increase of the strain magnitude in the perinuclear vimentin layer of actin deficient cells relatively to untreated control. Thus, the mechanical function of vimentin becomes particularly essential in motile and proliferating cells that have to dynamically remodel the cortical actin network. These insights add functional cues to frequently observed overexpression of vimentin in diverse types of cancer and underline the role of vimentin targeting drugs, such as Withaferin-A, as a potent cancerostatic supplement.
    Keywords: Mechanical Cell Properties ; Actin Filaments (Af) ; Vimentin Intermediate Filaments (Vif) ; Cytoskeletal Drugs ; Cytochalasin-D ; Withaferin-A ; High-Throughput Measurements ; Microfluidic Optical Stretcher (Mos) ; Finite Element Method (Fem) ; Parameter Estimation ; Cancer ; Epithelial–Mesenchymal Transition (Emt) ; Medicine ; Engineering ; Anatomy & Physiology
    ISSN: 0021-9290
    E-ISSN: 1873-2380
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: The Journal of cell biology, 12 May 2003, Vol.161(3), pp.477-81
    Description: Microscopy of cells has changed dramatically since its early days in the mid-seventeenth century. Image analysis has concurrently evolved from measurements of hand drawings and still photographs to computational methods that (semi-) automatically quantify objects, distances, concentrations, and velocities of cells and subcellular structures. Today's imaging technologies generate a wealth of data that requires visualization and multi-dimensional and quantitative image analysis as prerequisites to turning qualitative data into quantitative values. Such quantitative data provide the basis for mathematical modeling of protein kinetics and biochemical signaling networks that, in turn, open the way toward a quantitative view of cell biology. Here, we will review technologies for analyzing and reconstructing dynamic structures and processes in the living cell. We will present live-cell studies that would have been impossible without computational imaging. These applications illustrate the potential of computational imaging to enhance our knowledge of the dynamics of cellular structures and processes.
    Keywords: Computational Biology -- Methods ; Eukaryotic Cells -- Ultrastructure ; Image Processing, Computer-Assisted -- Methods ; Microscopy -- Methods
    ISSN: 0021-9525
    E-ISSN: 15408140
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Koch, Yvonne, Thomas Wolf, Peter K. Sorger, Roland Eils, and Benedikt Brors. 2013. “Decision-Tree Based Model Analysis for Efficient Identification of Parameter Relations Leading to Different Signaling States.” PLoS ONE 8 (12): e82593. doi:10.1371/journal.pone.0082593. http://dx.doi.org/10.1371/journal.pone.0082593.
    Description: In systems biology, a mathematical description of signal transduction processes is used to gain a more detailed mechanistic understanding of cellular signaling networks. Such models typically depend on a number of parameters that have different influence on the model behavior. Local sensitivity analysis is able to identify parameters that have the largest effect on signaling strength. Bifurcation analysis shows on which parameters a qualitative model response depends. Most methods for model analysis are intrinsically univariate. They typically cannot consider combinations of parameters since the search space for such analysis would be too large. This limitation is important since activation of a signaling pathway often relies on multiple rather than on single factors. Here, we present a novel method for model analysis that overcomes this limitation. As input to a model defined by a system of ordinary differential equations, we consider parameters for initial chemical species concentrations. The model is used to simulate the system response, which is then classified into pre-defined classes (e.g., active or not active). This is combined with a scan of the parameter space. Parameter sets leading to a certain system response are subjected to a decision tree algorithm, which learns conditions that lead to this response. We compare our method to two alternative multivariate approaches to model analysis: analytical solution for steady states combined with a parameter scan, and direct Lyapunov exponent (DLE) analysis. We use three previously published models including a model for EGF receptor internalization and two apoptosis models to demonstrate the power of our approach. Our method reproduces critical parameter relations previously obtained by both steady-state and DLE analysis while being more generally applicable and substantially less computationally expensive. The method can be used as a general tool to predict multivariate control strategies for pathway activation and to suggest strategies for drug intervention.
    ISSN: 1932-6203
    Source: Harvard University Library
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 24 May 2011, Vol.108(21), pp.E136-44
    Description: The role of the intranuclear movement of chromatin in gene expression is not well-understood. Herpes simplex virus forms replication compartments (RCs) in infected cell nuclei as sites of viral DNA replication and late gene transcription. These structures develop from small compartments that grow in size, move, and coalesce. Quantitative analysis of RC trajectories, derived from 4D images, shows that most RCs move by directed motion. Directed movement is impaired in the presence of actin and myosin inhibitors as well as a transcription inhibitor. In addition, RCs coalesce at and reorganize nuclear speckles. Lastly, distinct effects of actin and myosin inhibitors on viral gene expression suggest that RC movement is not required for transcription, but rather, movement results in the bridging of transcriptionally active RCs with nuclear speckles to form structures that enhance export of viral late mRNAs.
    Keywords: Active Transport, Cell Nucleus ; Transcription, Genetic ; Virus Replication ; Herpesviridae -- Physiology ; RNA, Viral -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Nucleic acids research, 01 November 2011, Vol.39(20), pp.8689-702
    Description: During development and differentiation of an organism, accurate gene regulation is central for cells to maintain and balance their differentiation processes. Transcriptional interactions between cis-acting DNA elements such as promoters and enhancers are the basis for precise and balanced transcriptional regulation. We identified modules of combinations of binding sites in proximal and distal regulatory regions upstream of all transcription start sites (TSSs) in silico and applied these modules to gene expression time-series of mouse embryonic development and differentiation of human stem cells. In addition to tissue-specific regulation controlled by combinations of transcription factors (TFs) binding at promoters, we observed that in particular the combination of TFs binding at promoters together with TFs binding at the respective enhancers regulate highly specifically temporal progression during development: whereas 40% of TFs were specific for time intervals, 79% of TF pairs and even 97% of promoter-enhancer modules showed specificity for single time intervals of the human stem cells. Predominantly SP1 and E2F contributed to temporal specificity at promoters and the forkhead (FOX) family of TFs at enhancer regions. Altogether, we characterized three classes of TFs: with binding sites being enriched at the TSS (like SP1), depleted at the TSS (like FOX), and rather uniformly distributed.
    Keywords: Enhancer Elements, Genetic ; Gene Expression Regulation, Developmental
    ISSN: 03051048
    E-ISSN: 1362-4962
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Nucleic acids research, 01 July 2015, Vol.43(W1), pp.W547-51
    Description: Understanding the molecular dynamics of viral spreading is crucial for anticipating the epidemiological implications of disease outbreaks. In the case of influenza, reassortments or point mutations affect the adaption to new hosts or resistance to anti-viral drugs and can determine whether a new strain will result in a pandemic infection or a less severe progression. To this end, tools integrating molecular information with epidemiological parameters are important to understand how molecular characteristics reflect in the infection dynamics. We present a new web tool, MapMyFlu, which allows to spatially and temporally display influenza viruses related to a query sequence on a Google Map based on BLAST results against the NCBI Influenza Database. Temporal and geographical trends appear clearly and may help in reconstructing the evolutionary history of a particular sequence. The tool is accessible through a web server, hence without the need for local installation. The website has an intuitive design and provides an easy-to-use service, and is available at http://mapmyflu.ipmb.uni-heidelberg.de.
    Keywords: Disease Outbreaks ; Sequence Alignment ; Software ; Influenza A Virus -- Genetics ; Influenza in Birds -- Epidemiology ; Influenza, Human -- Epidemiology
    ISSN: 03051048
    E-ISSN: 1362-4962
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Biotechnology Journal, February 2015, Vol.10(2), pp.229-230
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1002/biot.201500025/abstract Byline: Roland Eils(1), Julia Ritzerfeld(2), Wolfgang Wiechert(3) ***** No abstract is available for this article. ***** Author Affiliation: (1)German Cancer Research Center (DKFZ) and University of Heidelberg, Heidelberg, Germany (2)German Cancer Research Center (DKFZ), Heidelberg, Germany (3)IBG-1: Biotechnology, Forschungszentrum Julich, Julich, Germany
    Keywords: Agriculture ; Engineering;
    ISSN: 1860-6768
    E-ISSN: 1860-7314
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages