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  • Articles  (19)
  • Nature Publishing Group (NPG)  (14)
  • Wiley-Blackwell  (5)
  • 2010-2014  (19)
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  • Articles  (19)
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  • 1
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    Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-10-04
    Description: Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling The EMBO Journal 31, 3795 (2012). doi:10.1038/emboj.2012.207 Authors: Irina Vetter, Filip Touska, Andreas Hess, Rachel Hinsbey, Simon Sattler, Angelika Lampert, Marina Sergejeva, Anastasia Sharov, Lindon S Collins, Mirjam Eberhardt, Matthias Engel, Peter J Cabot, John N Wood, Viktorie Vlachová, Peter W Reeh, Richard J Lewis & Katharina Zimmermann Ciguatoxins are sodium channel activator toxins that cause ciguatera, the most common form of ichthyosarcotoxism, which presents with peripheral sensory disturbances, including the pathognomonic symptom of cold allodynia which is characterized by intense stabbing and burning pain in response to mild cooling. We show that
    Keywords: ciguatoxincold allodyniaNavnociceptorTRPA1
    Print ISSN: 0261-4189
    Electronic ISSN: 1460-2075
    Topics: Biology , Medicine
    Published by Nature Publishing Group (NPG) on behalf of The European Molecular Biology Organization (EMBO).
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  • 2
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    Genome-wide RNA interference analysis of renal carcinoma survival regulators identifies MCT4 as a Warburg effect metabolic target (2012)
    Wiley-Blackwell
    Details
    Publication Date: 2012-04-17
    Description: Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of kidney cancer. Here, we integrated an unbiased genome-wide RNA interference screen for ccRCC survival regulators with an analysis of recurrently over-expressed genes in ccRCC to identify new therapeutic targets in this disease. One of the most potent survival regulators, the monocarboxylate transporter MCT4 (SLC16A3), impaired ccRCC viability in all 8 ccRCC lines tested and was the 7th most over-expressed gene in a meta-analysis of 5 ccRCC expression datasets. MCT4-silencing impaired secretion of lactate generated through glycolysis and induced cell cycle arrest and apoptosis. Silencing MCT4 resulted in intracellular acidosis, and reduction in intracellular ATP production together with partial reversion of the Warburg effect in ccRCC cell lines. Intratumoral heterogeneity in the intensity of MCT4 protein expression was observed in primary ccRCCs. MCT4 protein expression analysis based on the highest intensity of expression in primary ccRCCs was associated with poorer relapse free survival, whereas modal intensity correlated with Fuhrman nuclear grade. Consistent with the potential selection of subclones enriched for MCT4 expression during disease progression, MCT4 expression was greater at sites of metastatic disease. These data suggest that MCT4 may serve as a novel metabolic target to reverse the Warburg effect and limit disease progression in ccRCC. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Print ISSN: 0022-3417
    Electronic ISSN: 1096-9896
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 3
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    The interplay between RPGR, PDEδ and Arl2/3 regulate the ciliary targeting of farnesylated cargo (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-05-03
    Description: EMBO Reports 14, 465 (2013). doi:10.1038/embor.2013.37 Authors: Denise Wätzlich, Ingrid Vetter, Katja Gotthardt, Mandy Miertzschke, Yong-Xiang Chen, Alfred Wittinghofer & Shehab Ismail Defects in primary cilia result in human diseases known as ciliopathies. The retinitis pigmentosa GTPase regulator (RPGR), mutated in the most severe form of the eye disease, is located at the transition zone of the ciliary organelle. The RPGR-interacting partner PDEδ is involved in trafficking
    Keywords: ciliary traffickingretinitis pigmentosaRPGRArl2/Arl3PDEδ
    Print ISSN: 1469-221X
    Electronic ISSN: 1469-3178
    Topics: Biology , Medicine
    Published by Nature Publishing Group (NPG) on behalf of The European Molecular Biology Organization (EMBO).
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  • 4
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    LA-ICP-MS depth profiling perspective on cleaning protocols for elemental analyses in planktic foraminifers (2013)
    Wiley-Blackwell
    Details
    Publication Date: 2013-05-09
    Description: Measurements of trace metal ratios in foraminiferal calcite are routinely used to reconstruct paleoceanographic conditions. Analyses using solution-based inductively coupled plasma mass spectrometry (ICP-MS) require dissolution of the entire foraminifer shell. The potential exists for contamination from adherent clays, mineralized coatings, and other diagenetic components that confound the biogenic trace metal signal. We present results from a cleaning experiment on fossil specimens of the planktic foraminifer Orbulina universa that were cracked into several shell fragments and subjected to different cleaning protocols. We use LA-ICP-MS depth profiling to evaluate the effects of reductive, oxidative, and chelating (DTPA) cleaning protocols on shell Mg/Ca and Ba/Ca ratios. Using the natural pattern of intrashell Mg/Ca heterogeneity exhibited by O. universa , we demonstrate that reductive and oxidative cleaning can dissolve shell calcite from available surfaces, although intrashell Mg/Ca minima and maxima are unaffected. High-resolution depth profiles can be used to identify areas of heterogeneous intrashell Ba/Ca, which can be excluded from computations of whole-shell Ba/Ca. The size and density of shell pores plays a major role in the degree of contamination from sedimentary material. We demonstrate an approach for computing whole-shell Me/Ca ratios from LA-ICP-MS depth profiles that accounts for potential contamination and diagenetic overprinting.
    Electronic ISSN: 1525-2027
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Published by Wiley-Blackwell on behalf of American Geophysical Union (AGU).
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  • 5
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    Genome-wide association study of Arabidopsis thaliana leaf microbial community (2014)
    Nature Publishing Group (NPG)
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    Publication Date: 2014-11-12
    Description: Article The effect of a host's genetic variation on the structure of its microbial community is poorly understood. Here, Horton et al. reveal associations between genetic variants in the plant model species Arabidopsis thaliana and the composition of the leaves' microbial communities. Nature Communications doi: 10.1038/ncomms6320 Authors: Matthew W. Horton, Natacha Bodenhausen, Kathleen Beilsmith, Dazhe Meng, Brian D. Muegge, Sathish Subramanian, M. Madlen Vetter, Bjarni J. Vilhjálmsson, Magnus Nordborg, Jeffrey I. Gordon, Joy Bergelson
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 6
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    GSK3β phosphorylation of the KLF6 tumor suppressor promotes its transactivation of p21 (2013)
    Nature Publishing Group (NPG)
    In: Oncogene
    Details
    Publication Date: 2013-09-20
    Description: GSK3β phosphorylation of the KLF6 tumor suppressor promotes its transactivation of p21 Oncogene 32, 4557 (19 September 2013). doi:10.1038/onc.2012.457 Authors: U E Lang, P Kocabayoglu, G Z Cheng, Z Ghiassi-Nejad, U Muñoz, D Vetter, D A Eckstein, R A Hannivoort, M J Walsh & S L Friedman
    Keywords: KLF6GSK3βp21phosphorylation
    Print ISSN: 0950-9232
    Topics: Medicine
    Published by Nature Publishing Group (NPG)
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  • 7
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    Regulation of epithelial plasticity by miR-424 and miR-200 in a new prostate cancer metastasis model (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-11-07
    Description: Using an in vivo cycling strategy, we selected metastatic cancer cells from the lymph nodes (LN) of mice bearing orthotopic DU145 human prostate tumors. Repeated rounds of metastatic selection (LN1–LN4) progressively increased the epithelial phenotype, resulting in a new model of tumor cell mesenchymal-epithelial transition (MET). DU145-LN4 showed increased cell-cell adhesions, higher expression of multiple epithelial markers, such as E-cadherin, EpCAM and cytokeratin 18, and reduced expression of mesenchymal markers such as vimentin. The MET in DU145-LN4 cells was accompanied by increased expression of the miR-200 family, and antimiRs to miR-200c and miR-141 induced an EMT. MET also correlated with the loss of miR-424. Ectopic transient and stable miR-424 expression induced EMT, with reduced epithelial marker expression and increased cell scattering. Our model provides evidence for spontaneous MET in vivo. We show that this cellular plasticity can be mediated through the combined action of miR-424 and the miR-200 family. Scientific Reports 3 doi: 10.1038/srep03151
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Nature Publishing Group (NPG)
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  • 8
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    Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-03-26
    Description: Article Marine cone snails use venom for defence and predation. Here, Dutertre et al. show that cone snails produce structurally and functionally distinct venoms for each purpose and that defence toxins are potent on fish and mammalian targets, suggesting that they have evolved specifically for protection. Nature Communications doi: 10.1038/ncomms4521 Authors: Sébastien Dutertre, Ai-Hua Jin, Irina Vetter, Brett Hamilton, Kartik Sunagar, Vincent Lavergne, Valentin Dutertre, Bryan G. Fry, Agostinho Antunes, Deon J. Venter, Paul F. Alewood, Richard J. Lewis
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 9
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    Mechanism of Tc toxin action revealed in molecular detail (2014)
    Nature Publishing Group (NPG)
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    Publication Date: 2014-02-28
    Description: Tripartite Tc toxin complexes of bacterial pathogens perforate the host membrane and translocate toxic enzymes into the host cell, including in humans. The underlying mechanism is complex but poorly understood. Here we report the first, to our knowledge, high-resolution structures of a TcA subunit in its prepore and pore state and of a complete 1.7 megadalton Tc complex. The structures reveal that, in addition to a translocation channel, TcA forms four receptor-binding sites and a neuraminidase-like region, which are important for its host specificity. pH-induced opening of the shell releases an entropic spring that drives the injection of the TcA channel into the membrane. Binding of TcB/TcC to TcA opens a gate formed by a six-bladed beta-propeller and results in a continuous protein translocation channel, whose architecture and properties suggest a novel mode of protein unfolding and translocation. Our results allow us to understand key steps of infections involving Tc toxins at the molecular level.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meusch, Dominic -- Gatsogiannis, Christos -- Efremov, Rouslan G -- Lang, Alexander E -- Hofnagel, Oliver -- Vetter, Ingrid R -- Aktories, Klaus -- Raunser, Stefan -- England -- Nature. 2014 Apr 3;508(7494):61-5. doi: 10.1038/nature13015. Epub 2014 Feb 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany [2]. ; Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universitat Freiburg, 79104 Freiburg, Germany. ; Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany. ; Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany. ; 1] Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universitat Freiburg, 79104 Freiburg, Germany [2] BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universitat Freiburg, 79104 Freiburg, Germany. ; 1] Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany [2] Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Thielallee 63, 14195 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572368" target="_blank"〉PubMed〈/a〉
    Keywords: ADP Ribose Transferases/metabolism ; Bacterial Toxins/*chemistry/*metabolism ; Binding Sites ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Host Specificity ; Hydrogen-Ion Concentration ; Models, Molecular ; Neuraminidase/chemistry ; Photorhabdus/*chemistry ; Porosity ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Protein Transport ; Protein Unfolding ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 10
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    Riffle-pool morphometry and stage-dependant morphodynamics of a large floodplain river (Vereinigte Mulde, Sachsen-Anhalt, Germany) (2011)
    Wiley-Blackwell
    Details
    Publication Date: 2011-05-21
    Description: ABSTRACT Riffle-pool sequences are a common feature of gravel-bed rivers. However, mechanisms of their generation and maintenance are still not fully understood. In this study a monitoring approach similar to the one of Andrews (1979 and 1982) is employed. It focuses on analysing cross-sectional and longitudinal channel geometry of a large floodplain river (Vereinigte Mulde, Sachsen-Anhalt, Germany) with a high temporal and spatial resolution, in order to conclude from stage-dependant morphometric changes to riffle and pool maintaining processes. In accordance with Richards (1976a), Andrews (1979 and 1982) among others, pool cross sections of the Mulde River are narrow and riffle cross sections are wide suggesting that they should rather be addressed as two general types of channel cross-sections than solely as bedforms. At high flows, riffles and pools in the study reaches changed in length and height but not in position. Pools were scoured and riffles aggraded, a development which was reversed during receding flows below the threshold of 0.4·Q bf (40% bankfull discharge). An index for the longitudinal amplitude of riffle-pool sequences, the bed undulation intensity or bedform amplitude, is introduced and proved to be highly significant as a form parameter, its first derivative as a process parameter. The process of pool scour and riffle fill is addressed as bedform maintenance or bedform accentuation. It is indicated by increasing longitudinal bed amplitudes. According to the observed dynamics of bed amplitudes, maintenance of riffle-pool sequences lags behind discharge peaks. Maximum bed amplitudes may be reached with a delay of several days after peak discharges. Increasing bed undulation intensity is interpreted to indicate bed mobility. Post-flood decrease of the bed undulation intensity indicates a retrograde phase when transport from pools to riffles has ceased and bed mobility is restricted to riffle tails and heads of pools. This type of transport behaviour is referred to as disconnected mobility. The comparison of two river reaches, one with undisturbed sediment supply, the other with sediment deficit, suggests that high bed undulation intensity values at low flows indicate sediment deficit and potentially channel degrading conditions. It is more generally hypothesised that channel bed undulations constitute a major component of form roughness and that increased bed amplitudes are an important feature of channel bed adjustment to sediment deficit be it temporally during late floods or permanently due to a supply limitation of bedload. Copyright © 2011 John Wiley & Sons, Ltd.
    Print ISSN: 0197-9337
    Electronic ISSN: 1096-9837
    Topics: Geography , Geosciences
    Published by Wiley-Blackwell
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