Sort by
Showing 21 to 30 of 2,331 entries
Show entries

Andreas Müller, Martin Neukam, Anna Ivanova, Anke Sönmez, Carla Münster, Susanne Kretschmar, Yannis Kalaidzidis, Thomas Kurth, Jean-Marc Verbavatz, Michele Solimena
A Global Approach for Quantitative Super Resolution and Electron Microscopy on Cryo and Epoxy Sections Using Self-labeling Protein Tags.
Sci Rep, 7 Art. No. 23 (2017)
  PubMed   

Correlative light and electron microscopy (CLEM) is a powerful approach to investigate the molecular ultrastructure of labeled cell compartments. However, quantitative CLEM studies are rare, mainly due to small sample sizes and the sensitivity of fluorescent proteins to strong fixatives and contrasting reagents for EM. Here, we show that fusion of a self-labeling protein to insulin allows for the quantification of age-distinct insulin granule pools in pancreatic beta cells by a combination of super resolution and transmission electron microscopy on Tokuyasu cryosections. In contrast to fluorescent proteins like GFP organic dyes covalently bound to self-labeling proteins retain their fluorescence also in epoxy resin following high pressure freezing and freeze substitution, or remarkably even after strong chemical fixation. This enables for the assessment of age-defined granule morphology and degradation. Finally, we demonstrate that this CLEM protocol is highly versatile, being suitable for single and dual fluorescent labeling and detection of different proteins with optimal ultrastructure preservation and contrast.
@article{Müller6796,
author={Andreas Müller, Martin Neukam, Anna Ivanova, Anke Sönmez, Carla Münster, Susanne Kretschmar, Yannis Kalaidzidis, Thomas Kurth, Jean-Marc Verbavatz, Michele Solimena},
title={A Global Approach for Quantitative Super Resolution and Electron Microscopy on Cryo and Epoxy Sections Using Self-labeling Protein Tags.},
journal={Scientific reports},
volume={7},
pages={null--null},
year=2017
}

Sven Karol, Tobias Nett, Pietro Incardona, Nesrine Khouzami, Jeronimo Castrillon, Ivo F. Sbalzarini
A Language and Development Environment for Parallel Particle Methods
In: V. International Conference on Particle-based Methods - Fundamentals and Applications (2017)(Eds.) Peter Wriggers, Barcelona, International Center for Numerical Methods in Engineering (CIMNE) (2017), 1-10
   

@proceedings{Karol6891,
title = {A Language and Development Environment for Parallel Particle Methods},
year = 2017,
editor = {Sven Karol, Tobias Nett, Pietro Incardona, Nesrine Khouzami, Jeronimo Castrillon, Ivo F. Sbalzarini},
volume = {V. International Conference on Particle-based Methods - Fundamentals and Applications},
series = {},
publisher = {International Center for Numerical Methods in Engineering (CIMNE)}
}

Kai Schuhmann, Henrik Thomas, Jacobo Miranda Ackerman, Konstantin O Nagornov, Yury O Tsybin, Andrej Shevchenko
Intensity-Independent Noise Filtering in FT MS and FT MS/MS Spectra for Shotgun Lipidomics.
Anal Chem, 89(13) 7046-7052 (2017)
PubMed   

Shotgun lipidomics relies on the direct infusion of total lipid extracts into a high resolution tandem mass spectrometer. A single shotgun analysis produces several hundred of densely populated FT MS and FT MS/MS spectra, each of which might comprise thousands of peaks although a very small percentage of those belong to lipids. Eliminating noise by adjusting a minimal peak intensity threshold is biased and inefficient since lipid species and classes vary in their natural abundance and ionization capacity. We developed a method of peak intensity-independent noise filtering in shotgun FT MS and FT MS/MS spectra that capitalizes on a stable composition of the infused analyte leading to consistent time-independent detection of its bona fide components. Repetition rate filtering relies on a single quantitative measure of peaks detection reproducibility irrespectively of their absolute intensities, masses, or assumed elemental compositions. In comparative experiments, it removed more than 95% of signals detectable in shotgun spectra without compromising the accuracy and scope of lipid identification and quantification. It also accelerated spectra processing by 15-fold and increased the number of simultaneously processed spectra by ∼500-fold hence eliminating the major bottleneck in high-throughput bottom-up shotgun lipidomics.
@article{Schuhmann6896,
author={Kai Schuhmann, Henrik Thomas, Jacobo Miranda Ackerman, Konstantin O Nagornov, Yury O Tsybin, Andrej Shevchenko},
title={Intensity-Independent Noise Filtering in FT MS and FT MS/MS Spectra for Shotgun Lipidomics.},
journal={Analytical chemistry},
volume={89},
issue ={13},
pages={7046--7052},
year=2017
}

Valentina Botti, François McNicoll, Michaela Steiner, Florian M Richter, Anfisa Solovyeva, Marius Wegener, Oliver D Schwich, Ina Poser, Kathi Zarnack, Ilka Wittig, Karla M. Neugebauer, Michaela Müller-McNicoll
Cellular differentiation state modulates the mRNA export activity of SR proteins.
J Cell Biol, 216(7) 1993-2009 (2017)
PubMed   

SR proteins function in nuclear pre-mRNA processing, mRNA export, and translation. To investigate their cellular dynamics, we developed a quantitative assay, which detects differences in nucleocytoplasmic shuttling among seven canonical SR protein family members. As expected, SRSF2 and SRSF5 shuttle poorly in HeLa cells but surprisingly display considerable shuttling in pluripotent murine P19 cells. Combining individual-resolution cross-linking and immunoprecipitation (iCLIP) and mass spectrometry, we show that elevated arginine methylation of SRSF5 and lower phosphorylation levels of cobound SRSF2 enhance shuttling of SRSF5 in P19 cells by modulating protein-protein and protein-RNA interactions. Moreover, SRSF5 is bound to pluripotency-specific transcripts such as Lin28a and Pou5f1/Oct4 in the cytoplasm. SRSF5 depletion reduces and overexpression increases their cytoplasmic mRNA levels, suggesting that enhanced mRNA export by SRSF5 is required for the expression of pluripotency factors. Remarkably, neural differentiation of P19 cells leads to dramatically reduced SRSF5 shuttling. Our findings indicate that posttranslational modification of SR proteins underlies the regulation of their mRNA export activities and distinguishes pluripotent from differentiated cells.
@article{Botti6900,
author={Valentina Botti, François McNicoll, Michaela Steiner, Florian M Richter, Anfisa Solovyeva, Marius Wegener, Oliver D Schwich, Ina Poser, Kathi Zarnack, Ilka Wittig, Karla M. Neugebauer, Michaela Müller-McNicoll},
title={Cellular differentiation state modulates the mRNA export activity of SR proteins.},
journal={The Journal of cell biology},
volume={216},
issue ={7},
pages={1993--2009},
year=2017
}

Serena Carra, Simon Alberti, Patrick A Arrigo, Justin L Benesch, Ivor J Benjamin, Wilbert Boelens, Britta Bartelt-Kirbach, Bianca J J M Brundel, Johannes Buchner, Bernd Bukau, John A Carver, Heath Ecroyd, Cecilia Emanuelsson, Stephanie Finet, Nikola Golenhofen, Pierre Goloubinoff, Nikolai Gusev, Martin Haslbeck, Lawrence E Hightower, Harm H Kampinga, Rachel E Klevit, Krzysztof Liberek, Hassane S Mchaourab, Kathryn A McMenimen, Angelo Poletti, Roy Quinlan, Sergei V Strelkov, Melinda E Toth, Elizabeth Vierling, Robert M Tanguay
The growing world of small heat shock proteins: from structure to functions.
Cell Stress Chaperones, 22(4) 601-611 (2017)
PubMed   

Small heat shock proteins (sHSPs) are present in all kingdoms of life and play fundamental roles in cell biology. sHSPs are key components of the cellular protein quality control system, acting as the first line of defense against conditions that affect protein homeostasis and proteome stability, from bacteria to plants to humans. sHSPs have the ability to bind to a large subset of substrates and to maintain them in a state competent for refolding or clearance with the assistance of the HSP70 machinery. sHSPs participate in a number of biological processes, from the cell cycle, to cell differentiation, from adaptation to stressful conditions, to apoptosis, and, even, to the transformation of a cell into a malignant state. As a consequence, sHSP malfunction has been implicated in abnormal placental development and preterm deliveries, in the prognosis of several types of cancer, and in the development of neurological diseases. Moreover, mutations in the genes encoding several mammalian sHSPs result in neurological, muscular, or cardiac age-related diseases in humans. Loss of protein homeostasis due to protein aggregation is typical of many age-related neurodegenerative and neuromuscular diseases. In light of the role of sHSPs in the clearance of un/misfolded aggregation-prone substrates, pharmacological modulation of sHSP expression or function and rescue of defective sHSPs represent possible routes to alleviate or cure protein conformation diseases. Here, we report the latest news and views on sHSPs discussed by many of the world's experts in the sHSP field during a dedicated workshop organized in Italy (Bertinoro, CEUB, October 12-15, 2016).
@article{Carra6808,
author={Serena Carra, Simon Alberti, Patrick A Arrigo, Justin L Benesch, Ivor J Benjamin, Wilbert Boelens, Britta Bartelt-Kirbach, Bianca J J M Brundel, Johannes Buchner, Bernd Bukau, John A Carver, Heath Ecroyd, Cecilia Emanuelsson, Stephanie Finet, Nikola Golenhofen, Pierre Goloubinoff, Nikolai Gusev, Martin Haslbeck, Lawrence E Hightower, Harm H Kampinga, Rachel E Klevit, Krzysztof Liberek, Hassane S Mchaourab, Kathryn A McMenimen, Angelo Poletti, Roy Quinlan, Sergei V Strelkov, Melinda E Toth, Elizabeth Vierling, Robert M Tanguay},
title={The growing world of small heat shock proteins: from structure to functions.},
journal={Cell stress & chaperones},
volume={22},
issue ={4},
pages={601--611},
year=2017
}

Frank Jülicher, Suzanne Eaton
Emergence of tissue shape changes from collective cell behaviours.
Semin Cell Dev Biol, 67 103-112 (2017)
PubMed   

Anyone watching a movie of embryonic development immediately appreciates the importance of morphogenetic movements and cell flows that reshape tissue. Dynamic tissue shape changes are genetically choreographed, but their execution is essentially a mechanical event. How the interplay between genetics and tissue mechanics controls tissue shape is a fundamental question. Key insights into this problem have emerged from studies in different model organisms as well as in cultured epithelia. These studies have revealed how gene expression patterns can generate patterns of planar cell polarity that orient cellular force generation and give rise to anisotropic mechanical properties of cells and tissues. These can autonomously bias the rate and orientation of cellular events such as cell divisions, extrusions, neighbor exchanges and shape changes that drive morphogenesis. However recent studies also highlight how autonomously controlled cell dynamics lead to tissue-wide stress patterns framed by mechanical constraints such as cellular connections to extracellular matrices. These stress patterns themselves can orient the cell behaviours underlying morphogenesis. As a result of this interplay, tissue shape emerges in a mechanical process that tightly couples mechanics and genetics.
@article{Jülicher6844,
author={Frank Jülicher, Suzanne Eaton},
title={Emergence of tissue shape changes from collective cell behaviours.},
journal={Seminars in cell & developmental biology},
volume={67},
pages={103--112},
year=2017
}

P Philippe Laissue, Rana A Alghamdi, Pavel Tomancak, Emmanuel G. Reynaud, Hari Shroff
Assessing phototoxicity in live fluorescence imaging.
Nat Methods, 14(7) 657-661 (2017)
  PubMed   

Are the answers to biological questions obtained via live fluorescence microscopy substantially affected by phototoxicity? Although a single set of standards for assessing phototoxicity cannot exist owing to the breadth of samples and experimental questions associated with biological imaging, we need quantitative, practical assessments and reporting standards to ensure that imaging has a minimal impact on observed biological processes and sample health. Here we discuss the problem of phototoxicity in biology and suggest guidelines to improve its reporting and assessment.
@article{Laissue6887,
author={P Philippe Laissue, Rana A Alghamdi, Pavel Tomancak, Emmanuel G. Reynaud, Hari Shroff},
title={Assessing phototoxicity in live fluorescence imaging.},
journal={Nature methods},
volume={14},
issue ={7},
pages={657--661},
year=2017
}

Koichiro Uriu, Bhavna Rajasekaran, Andrew C. Oates, Luis G Morelli
A framework for quantification and physical modeling of cell mixing applied to oscillator synchronization in vertebrate somitogenesis.
Biol Open, Art. No. bio.025148, doi: 10.1242/bio.025148 (2017)
PubMed   

In development and disease, cells move as they exchange signals. One example is found in vertebrate development, where the timing of segment formation is set by a "segmentation clock" in which oscillating gene expression is synchronized across a population of cells by Delta-Notch signaling. Delta-Notch signaling requires local cell-cell contact, but in the zebrafish embryonic tailbud oscillating cells move rapidly, exchanging neighbors. Previous theoretical studies proposed that this relative movement or cell mixing might alter signaling and thereby enhance synchronization. However, it remains unclear whether the mixing timescale in the tissue is in the right range for this effect, because a framework to reliably measure the mixing timescale and compare it with signaling timescale is lacking. Here, we develop such a framework using a quantitative description of cell mixing without the need for an external reference frame, and constructing a physical model of cell movement based on the data. Numerical simulations show that mixing with experimentally observed statistics enhances synchronization of coupled phase oscillators, suggesting that mixing in the tailbud is fast enough to affect the coherence of rhythmic gene expression. Our approach will find general application to analyzing the relative movements of communicating cells during development and disease.
@article{Uriu6895,
author={Koichiro Uriu, Bhavna Rajasekaran, Andrew C. Oates, Luis G Morelli},
title={A framework for quantification and physical modeling of cell mixing applied to oscillator synchronization in vertebrate somitogenesis.},
journal={Biology open},
volume={},
pages={null--null},
year=2017
}

J Gray Camp, Keisuke Sekine, Tobias Gerber, Henry Loeffler-Wirth, Hans Binder, Malgorzata Gac, Sabina Kanton, Jorge Kageyama, Georg Damm, Daniel Seehofer, Lenka Belicova, Marc Bickle, Rico Barsacchi, Ryo Okuda, Emi Yoshizawa, Masashi Kimura, Hiroaki Ayabe, Hideki Taniguchi, Takanori Takebe, Barbara Treutlein
Multilineage communication regulates human liver bud development from pluripotency.
Nature, 546(7659) 533-538 (2017)
PubMed   

Conventional two-dimensional differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. Three-dimensional organoids generate complex organ-like tissues; however, it is unclear how heterotypic interactions affect lineage identity. Here we use single-cell RNA sequencing to reconstruct hepatocyte-like lineage progression from pluripotency in two-dimensional culture. We then derive three-dimensional liver bud organoids by reconstituting hepatic, stromal, and endothelial interactions, and deconstruct heterogeneity during liver bud development. We find that liver bud hepatoblasts diverge from the two-dimensional lineage, and express epithelial migration signatures characteristic of organ budding. We benchmark three-dimensional liver buds against fetal and adult human liver single-cell RNA sequencing data, and find a striking correspondence between the three-dimensional liver bud and fetal liver cells. We use a receptor-ligand pairing analysis and a high-throughput inhibitor assay to interrogate signalling in liver buds, and show that vascular endothelial growth factor (VEGF) crosstalk potentiates endothelial network formation and hepatoblast differentiation. Our molecular dissection reveals interlineage communication regulating organoid development, and illuminates previously inaccessible aspects of human liver development.
@article{Camp6893,
author={J Gray Camp, Keisuke Sekine, Tobias Gerber, Henry Loeffler-Wirth, Hans Binder, Malgorzata Gac, Sabina Kanton, Jorge Kageyama, Georg Damm, Daniel Seehofer, Lenka Belicova, Marc Bickle, Rico Barsacchi, Ryo Okuda, Emi Yoshizawa, Masashi Kimura, Hiroaki Ayabe, Hideki Taniguchi, Takanori Takebe, Barbara Treutlein},
title={Multilineage communication regulates human liver bud development from pluripotency.},
journal={Nature},
volume={546},
issue ={7659},
pages={533--538},
year=2017
}

Richard Grunzke, Florian Jug, Bernd Schuller, René Jäkel, Gene Myers, Wolfgang E Nagel
Seamless HPC Integration of Data-Intensive KNIME Workflows via UNICORE
In: Euro-Par 2016: Parallel Processing Workshops : Euro-Par 2016 International Workshops, Grenoble, France, August 24-26, 2016, Revised Selected Papers (2017)(Eds.) Frédéric Desprez (Lecture Notes in Computer Science ; 10104), Cham, Springer International Publishing (2017), 480-491
 

@proceedings{Grunzke6886,
title = {Seamless HPC Integration of Data-Intensive KNIME Workflows via UNICORE},
year = 2017,
editor = {Richard Grunzke, Florian Jug, Bernd Schuller, René Jäkel, Gene Myers, Wolfgang E Nagel},
volume = {Euro-Par 2016: Parallel Processing Workshops : Euro-Par 2016 International Workshops, Grenoble, France, August 24-26, 2016, Revised Selected Papers },
series = {(Lecture Notes in Computer Science ; 10104)},
publisher = {Springer International Publishing}
}