| 1. |
- Ferreira, Ruben, 1982, et al.
(författare)
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Design, Synthesis and Inhibitory Activity of Photoswitchable RET Kinase Inhibitors.
- 2015
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase required for normal development and maintenance of neurons of the central and peripheral nervous systems. Deregulation of RET and hyperactivity of the RET kinase is intimately connected to several types of human cancers, most notably thyroid cancers, making it an attractive therapeutic target for small-molecule kinase inhibitors. Novel approaches, allowing external control of the activity of RET, would be key additions to the signal transduction toolbox. In this work, photoswitchable RET kinase inhibitors based on azo-functionalized pyrazolopyrimidines were developed, enabling photonic control of RET activity. The most promising compound displays excellent switching properties and stability with good inhibitory effect towards RET in cell-free as well as live-cell assays and a significant difference in inhibitory activity between its two photoisomeric forms. As the first reported photoswitchable small-molecule kinase inhibitor, we consider the herein presented effector to be a significant step forward in the development of tools for kinase signal transduction studies with spatiotemporal control over inhibitor concentration in situ.
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| 2. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Marchand, Adrien, et al.
(författare)
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Sequence and solvent effects on telomeric DNA bimolecular G-quadruplex folding kinetics
- 2013
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 117:41, s. 12391-12401
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Tidskriftsartikel (refereegranskat)abstract
- Telomeric DNA sequences are particularly polymorphic: the adopted structure is exquisitely sensitive to the sequence and to the chemical environment, for example, solvation. Dehydrating conditions are known to stabilize G-quadruplex structures, but information on how solvation influences the individual rates of folding and unfolding of G-quadruplexes remains scarce. Here, we used electrospray mass spectrometry for the first time to monitor bimolecular G-quadruplex formation from 12-mer telomeric strands, in the presence of common organic cosolvents (methanol, ethanol, isopropanol, and acetonitrile). Based on the ammonium ion distribution, the total dimer signal was decomposed into contributions from the parallel and antiparallel structures to obtain individual reaction rates, and the antiparallel G-quadruplex structure was found to form faster than the parallel one. A dimeric reaction intermediate, in rapid equilibrium with the single strands, was also identified. Organic cosolvents increase the stability of the final structures mainly by increasing the folding rates. Our quantitative analysis of reaction rate dependence on cosolvent percentage shows that organic cosolvent molecules can be captured or released upon G-quadruplex formation, highlighting that they are not inert with DNA. In contrast to the folding rates, the G-quadruplex unfolding rates are almost insensitive to solvation effects, but are instead governed by the sequence and by the final structure: parallel dimers dissociate slower than antiparallel dimers only when thymine bases are present at the 5′-end. These results contribute unraveling the folding pathways of telomeric G-quadruplexes. The solvent effects revealed here enlighten that G-quadruplex structure in dehydrated, and molecularly crowded environments are modulated by the nature of cosolvent (e.g., methanol favors antiparallel structures) due to direct interactions, and by the time scale of the reaction, with > 200-fold acceleration of bimolecular G-quadruplex formation in the presence of 60% cosolvent. © 2013 American Chemical Society.
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| 4. |
- Marquez, Juan Carlos, 1976-, et al.
(författare)
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Textile electrode straps for wrist-to-ankle bioimpedance measurements for Body Composition Analysis : Initial validation & experimental results
- 2010
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Ingår i: 2010 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC). - : IEEE Engineering in Medicine and Biology Society. - 9781424441235 ; 2010, s. 6385-8
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Konferensbidrag (refereegranskat)abstract
- Electrical Bioimpedance (EBI) is one of the non-invasive monitoring technologies that could benefit from the emerging textile based measurement systems. If reliable and reproducible EBI measurements could be done with textile electrodes, that would facilitate the utilization of EBI-based personalized healthcare monitoring applications. In this work the performance of a custom-made dry-textile electrode prototype is tested. Four-electrodes ankle-to-wrist EBI measurements have been taken on healthy subjects with the Impedimed spectrometer SFB7 in the frequency range 5 kHz to 1 MHz. The EBI spectroscopy measurements taken with dry electrodes were analyzed via the Cole and Body Composition Analysis (BCA) parameters, which were compared with EBI measurements obtained with standard electrolytic electrodes. The analysis of the obtained results indicate that even when dry textile electrodes may be used for EBI spectroscopy measurements, the measurements present remarkable differences that influence in the Cole parameter estimation process and in the final production of the BCA parameters. These initial results indicate that more research work must be done to in order to obtain a textile-based electrode that ensures reliable and reproducible EBI spectroscopy measurements.
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| 5. |
- Seoane, Fernando, 1976-, et al.
(författare)
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Adaptive frequency distribution for Electrical Bioimpedance Spectroscopy measurements
- 2012
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Ingår i: Engineering in Medicine and Biology Society (EMBC), 2012 Annual International Conference of the IEEE. - : IEEE. - 9781424441198 ; 2012, s. 562-5
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Konferensbidrag (refereegranskat)abstract
- This paper presents a novel frequency distribution scheme intended to provide more accurate estimations of Cole parameters. Nowadays a logarithmic frequency distribution is mostly used in Electrical Bioimpedance Spectroscopy (EBIS) applications. However it is not optimized following any criterion. Our hypothesis is that an EBIS signal contains more information where the variation of the measurement regarding the frequency is larger; and that there ought to be more measuring frequencies where there is more information. Results show that for EBIS data with characteristic frequencies up to 200 kHz the error obtained with both frequency distribution schemes is similar. However, for EBIS data with higher values of characteristic frequency the error produced when estimating the values from EBIS measurements using an adaptive frequency distribution is smaller. Thus it may useful for EBIS applications with high values of characteristic frequency, e.g. cerebral bioimpedance.
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| 6. |
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| 7. |
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| 8. |
- Valencia-Sanchez, M. I., et al.
(författare)
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Structural Insights into the Polyphyletic Origins of Glycyl tRNA Synthetases
- 2016
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 291:28, s. 14430-14446
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Tidskriftsartikel (refereegranskat)abstract
- Glycyl tRNA synthetase (GlyRS) provides a unique case among class II aminoacyl tRNA synthetases, with two clearly widespread types of enzymes: a dimeric ((2)) species present in some bacteria, archaea, and eukaryotes; and a heterotetrameric form ((22)) present in most bacteria. Although the differences between both types of GlyRS at the anticodon binding domain level are evident, the extent and implications of the variations in the catalytic domain have not been described, and it is unclear whether the mechanism of amino acid recognition is also dissimilar. Here, we show that the -subunit of the (22) GlyRS from the bacterium Aquifex aeolicus is able to perform the first step of the aminoacylation reaction, which involves the activation of the amino acid with ATP. The crystal structure of the -subunit in the complex with an analog of glycyl adenylate at 2.8 angstrom resolution presents a conformational arrangement that properly positions the cognate amino acid. This work shows that glycine is recognized by a subset of different residues in the two types of GlyRS. A structural and sequence analysis of class II catalytic domains shows that bacterial GlyRS is closely related to alanyl tRNA synthetase, which led us to define a new subclassification of these ancient enzymes and to propose an evolutionary path of (22) GlyRS, convergent with (2) GlyRS and divergent from AlaRS, thus providing a possible explanation for the puzzling existence of two proteins sharing the same fold and function but not a common ancestor.
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