cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1292444
title: Chromosome segregation and organization are targets of 5′-Fluorouracil in eukaryotic cells

description: The antimetabolite 5′-Fluorouracil (5FU) is an analog of uracil commonly employed as a chemotherapeutic agent in the treatment of a range of cancers including colorectal tumors. To assess the cellular effects of 5FU, we performed a genome-wide screening of the haploid deletion library of the eukaryotic model <i>Schizosaccharomyces pombe</i>. Our analysis validated previously characterized drug targets including RNA metabolism, but it also revealed unexpected mechanisms of action associated with chromosome segregation and organization (post-translational histone modification, histone exchange, heterochromatin). Further analysis showed that 5FU affects the heterochromatin structure (decreased levels of histone H3 lysine 9 methylation) and silencing (down-regulation of heterochromatic <i>dg/dh</i> transcripts). To our knowledge, this is the first time that defects in heterochromatin have been correlated with increased cytotoxicity to an anticancer drug. Moreover, the segregation of chromosomes, a process that requires an intact heterochromatin at centromeres, was impaired after drug exposure. These defects could be related to the induction of genes involved in chromatid cohesion and kinetochore assembly. Interestingly, we also observed that thiabendazole, a microtubule-destabilizing agent, synergistically enhanced the cytotoxic effects of 5FU. These findings point to new targets and drug combinations that could potentiate the effectiveness of 5FU-based treatments.
DOI: 10.6084/m9.figshare.1292445.v2
title: Long ncRNA expression associates with tissue-specific enhancers

description: Long non-coding RNAs (ncRNA) have recently been demonstrated to be expressed from a subset of enhancers and to be required for the distant regulation of gene expression. Several approaches to predict enhancers have been developed based on various chromatin marks and occupancy of enhancer-binding proteins. Despite the rapid advances in the field, no consensus how to define tissue specific enhancers yet exists. Here, we identify 2,695 long ncRNAs annotated by ENCODE (corresponding to 28% of all ENCODE annotated long ncRNAs) that overlap tissue-specific enhancers. We use a recently developed algorithm to predict tissue-specific enhancers, PreSTIGE, that is based on the H3K4me1 mark and tissue specific expression of mRNAs. The expression of the long ncRNAs overlapping enhancers is significantly higher when the enhancer is predicted as active in a specific cell line, suggesting a general interdependency of active enhancers and expression of long ncRNAs. This dependency is not identified using previous enhancer prediction algorithms that do not account for expression of their downstream targets. The predicted enhancers that overlap annotated long ncRNAs generally have a lower ratio of H3K4me1 to H3K4me3, suggesting that enhancers expressing long ncRNAs might be associated with specific epigenetic marks. In conclusion, we demonstrate the tissue-specific predictive power of PreSTIGE and provide evidence for thousands of long ncRNAs that are expressed from active tissue-specific enhancers, suggesting a particularly important functional relationship between long ncRNAs and enhancer activity in determining tissue-specific gene expression.
DOI: 10.6084/m9.figshare.1292444.v2
title: Chromosome segregation and organization are targets of 5′-Fluorouracil in eukaryotic cells

description: The antimetabolite 5′-Fluorouracil (5FU) is an analog of uracil commonly employed as a chemotherapeutic agent in the treatment of a range of cancers including colorectal tumors. To assess the cellular effects of 5FU, we performed a genome-wide screening of the haploid deletion library of the eukaryotic model <i>Schizosaccharomyces pombe</i>. Our analysis validated previously characterized drug targets including RNA metabolism, but it also revealed unexpected mechanisms of action associated with chromosome segregation and organization (post-translational histone modification, histone exchange, heterochromatin). Further analysis showed that 5FU affects the heterochromatin structure (decreased levels of histone H3 lysine 9 methylation) and silencing (down-regulation of heterochromatic <i>dg/dh</i> transcripts). To our knowledge, this is the first time that defects in heterochromatin have been correlated with increased cytotoxicity to an anticancer drug. Moreover, the segregation of chromosomes, a process that requires an intact heterochromatin at centromeres, was impaired after drug exposure. These defects could be related to the induction of genes involved in chromatid cohesion and kinetochore assembly. Interestingly, we also observed that thiabendazole, a microtubule-destabilizing agent, synergistically enhanced the cytotoxic effects of 5FU. These findings point to new targets and drug combinations that could potentiate the effectiveness of 5FU-based treatments.
DOI: 10.6084/m9.figshare.1292445.v1
title: Long ncRNA expression associates with tissue-specific enhancers

description: Long non-coding RNAs (ncRNA) have recently been demonstrated to be expressed from a subset of enhancers and to be required for the distant regulation of gene expression. Several approaches to predict enhancers have been developed based on various chromatin marks and occupancy of enhancer-binding proteins. Despite the rapid advances in the field, no consensus how to define tissue specific enhancers yet exists. Here, we identify 2,695 long ncRNAs annotated by ENCODE (corresponding to 28% of all ENCODE annotated long ncRNAs) that overlap tissue-specific enhancers. We use a recently developed algorithm to predict tissue-specific enhancers, PreSTIGE, that is based on the H3K4me1 mark and tissue specific expression of mRNAs. The expression of the long ncRNAs overlapping enhancers is significantly higher when the enhancer is predicted as active in a specific cell line, suggesting a general interdependency of active enhancers and expression of long ncRNAs. This dependency is not identified using previous enhancer prediction algorithms that do not account for expression of their downstream targets. The predicted enhancers that overlap annotated long ncRNAs generally have a lower ratio of H3K4me1 to H3K4me3, suggesting that enhancers expressing long ncRNAs might be associated with specific epigenetic marks. In conclusion, we demonstrate the tissue-specific predictive power of PreSTIGE and provide evidence for thousands of long ncRNAs that are expressed from active tissue-specific enhancers, suggesting a particularly important functional relationship between long ncRNAs and enhancer activity in determining tissue-specific gene expression.
DOI: 10.6084/m9.figshare.1292444.v1
title: Chromosome segregation and organization are targets of 5′-Fluorouracil in eukaryotic cells

description: The antimetabolite 5′-Fluorouracil (5FU) is an analog of uracil commonly employed as a chemotherapeutic agent in the treatment of a range of cancers including colorectal tumors. To assess the cellular effects of 5FU, we performed a genome-wide screening of the haploid deletion library of the eukaryotic model <i>Schizosaccharomyces pombe</i>. Our analysis validated previously characterized drug targets including RNA metabolism, but it also revealed unexpected mechanisms of action associated with chromosome segregation and organization (post-translational histone modification, histone exchange, heterochromatin). Further analysis showed that 5FU affects the heterochromatin structure (decreased levels of histone H3 lysine 9 methylation) and silencing (down-regulation of heterochromatic <i>dg/dh</i> transcripts). To our knowledge, this is the first time that defects in heterochromatin have been correlated with increased cytotoxicity to an anticancer drug. Moreover, the segregation of chromosomes, a process that requires an intact heterochromatin at centromeres, was impaired after drug exposure. These defects could be related to the induction of genes involved in chromatid cohesion and kinetochore assembly. Interestingly, we also observed that thiabendazole, a microtubule-destabilizing agent, synergistically enhanced the cytotoxic effects of 5FU. These findings point to new targets and drug combinations that could potentiate the effectiveness of 5FU-based treatments.
DOI: 10.6084/m9.figshare.1292440
title: Screening of cell cycle fusion proteins to identify kinase signaling networks

description: Kinase signaling networks are well-established mediators of cell cycle transitions. However, how kinases interact with the ubiquitin proteasome system (UPS) to elicit protein turnover is not fully understood. We sought a means of identifying kinase-substrate interactions to better understand signaling pathways controlling protein degradation. Our prior studies used a luciferase fusion protein to uncover kinase networks controlling protein turnover. In this study, we utilized a similar approach to identify pathways controlling the cell cycle protein p27<sup>Kip1</sup>. We generated a p27<sup>Kip1</sup>-luciferase fusion and expressed it in cells incubated with compounds from a library of pharmacologically active compounds. We then compared the relative effects of the compounds on p27<sup>Kip1</sup>-luciferase fusion stabilization. This was combined with <i>in silico</i> kinome profiling to identify potential kinases inhibited by each compound. This approach effectively uncovered known kinases regulating p27<sup>Kip1</sup> turnover. Collectively, our studies suggest that this parallel screening approach is robust and can be applied to fully understand kinase-ubiquitin pathway interactions.
DOI: 10.6084/m9.figshare.1292440.v1
title: Screening of Cell Cycle Fusion Proteins to Identify Kinase Signaling Networks

description: ABSTRACTKinase signaling networks are well-established mediators of cell cycle transitions. However, how kinases interact with the ubiquitin proteasome system (UPS) to elicit protein turnover is not fully understood. We sought a means of identifying kinase-substrate interactions to better understand signaling pathways controlling protein degradation. Our prior studies used a luciferase fusion protein to uncover kinase networks controlling protein turnover. In this study, we utilized a similar approach to identify pathways controlling the cell cycle protein p27<sup>Kip1</sup>. We generated a p27<sup>Kip1</sup>-luciferase fusion and expressed it in cells incubated with compounds from a library of pharmacologically active compounds. We then compared the relative effects of the compounds on p27<sup>Kip1</sup>-luciferase fusion stabilization. This was combined with <i>in silico</i> kinome profiling to identify potential kinases inhibited by each compound. This approach effectively uncovered known kinases regulating p27<sup>Kip1</sup> turnover. Collectively, our studies suggest that this parallel screening approach is robust and can be applied to fully understand kinase-ubiquitin pathway interactions.
DOI: 10.6084/m9.figshare.1292440.v2
title: Screening of cell cycle fusion proteins to identify kinase signaling networks

description: Kinase signaling networks are well-established mediators of cell cycle transitions. However, how kinases interact with the ubiquitin proteasome system (UPS) to elicit protein turnover is not fully understood. We sought a means of identifying kinase-substrate interactions to better understand signaling pathways controlling protein degradation. Our prior studies used a luciferase fusion protein to uncover kinase networks controlling protein turnover. In this study, we utilized a similar approach to identify pathways controlling the cell cycle protein p27<sup>Kip1</sup>. We generated a p27<sup>Kip1</sup>-luciferase fusion and expressed it in cells incubated with compounds from a library of pharmacologically active compounds. We then compared the relative effects of the compounds on p27<sup>Kip1</sup>-luciferase fusion stabilization. This was combined with <i>in silico</i> kinome profiling to identify potential kinases inhibited by each compound. This approach effectively uncovered known kinases regulating p27<sup>Kip1</sup> turnover. Collectively, our studies suggest that this parallel screening approach is robust and can be applied to fully understand kinase-ubiquitin pathway interactions.
DOI: 10.6084/m9.figshare.1292069
title: Edición y comunicación científica: evolución y tendencias actuales [Scholarly communication and publishing: Evolution and current trends]

description: Slides for my Master Thesis presentation (July 2013. University Carlos III of Madrid).
DOI: 10.6084/m9.figshare.1292424
title: SGR J1550-5418 magnetron data

description: data set for the magnetron project: light curves from SGR J1550-5418 and posterior samples from using DNest3 and RJObject to fit a model with a variable number of simple shapes to the light curves.
DOI: 10.6084/m9.figshare.1292440.v3
title: Screening of cell cycle fusion proteins to identify kinase signaling networks

description: Kinase signaling networks are well-established mediators of cell cycle transitions. However, how kinases interact with the ubiquitin proteasome system (UPS) to elicit protein turnover is not fully understood. We sought a means of identifying kinase-substrate interactions to better understand signaling pathways controlling protein degradation. Our prior studies used a luciferase fusion protein to uncover kinase networks controlling protein turnover. In this study, we utilized a similar approach to identify pathways controlling the cell cycle protein p27<sup>Kip1</sup>. We generated a p27<sup>Kip1</sup>-luciferase fusion and expressed it in cells incubated with compounds from a library of pharmacologically active compounds. We then compared the relative effects of the compounds on p27<sup>Kip1</sup>-luciferase fusion stabilization. This was combined with <i>in silico</i> kinome profiling to identify potential kinases inhibited by each compound. This approach effectively uncovered known kinases regulating p27<sup>Kip1</sup> turnover. Collectively, our studies suggest that this parallel screening approach is robust and can be applied to fully understand kinase-ubiquitin pathway interactions.
DOI: 10.6084/m9.figshare.1292424.v1
title: SGR J1550-5418 magnetron data

description: data set for the magnetron project: light curves from SGR J1550-5418 and posterior samples from using DNest3 and RJObject to fit a model with a variable number of simple shapes to the light curves.
DOI: 10.6084/m9.figshare.1292440.v4
title: Screening of cell cycle fusion proteins to identify kinase signaling networks

description: Kinase signaling networks are well-established mediators of cell cycle transitions. However, how kinases interact with the ubiquitin proteasome system (UPS) to elicit protein turnover is not fully understood. We sought a means of identifying kinase-substrate interactions to better understand signaling pathways controlling protein degradation. Our prior studies used a luciferase fusion protein to uncover kinase networks controlling protein turnover. In this study, we utilized a similar approach to identify pathways controlling the cell cycle protein p27<sup>Kip1</sup>. We generated a p27<sup>Kip1</sup>-luciferase fusion and expressed it in cells incubated with compounds from a library of pharmacologically active compounds. We then compared the relative effects of the compounds on p27<sup>Kip1</sup>-luciferase fusion stabilization. This was combined with <i>in silico</i> kinome profiling to identify potential kinases inhibited by each compound. This approach effectively uncovered known kinases regulating p27<sup>Kip1</sup> turnover. Collectively, our studies suggest that this parallel screening approach is robust and can be applied to fully understand kinase-ubiquitin pathway interactions.
DOI: 10.6084/m9.figshare.1292440.v6
title: Screening of cell cycle fusion proteins to identify kinase signaling networks

description: Kinase signaling networks are well-established mediators of cell cycle transitions. However, how kinases interact with the ubiquitin proteasome system (UPS) to elicit protein turnover is not fully understood. We sought a means of identifying kinase-substrate interactions to better understand signaling pathways controlling protein degradation. Our prior studies used a luciferase fusion protein to uncover kinase networks controlling protein turnover. In this study, we utilized a similar approach to identify pathways controlling the cell cycle protein p27<sup>Kip1</sup>. We generated a p27<sup>Kip1</sup>-luciferase fusion and expressed it in cells incubated with compounds from a library of pharmacologically active compounds. We then compared the relative effects of the compounds on p27<sup>Kip1</sup>-luciferase fusion stabilization. This was combined with <i>in silico</i> kinome profiling to identify potential kinases inhibited by each compound. This approach effectively uncovered known kinases regulating p27<sup>Kip1</sup> turnover. Collectively, our studies suggest that this parallel screening approach is robust and can be applied to fully understand kinase-ubiquitin pathway interactions.
DOI: 10.6084/m9.figshare.1292069.v1
title: Evolution of and current trends in publishing and scholarly communication

description: Slides for my Master Thesis presentation (July 2013. University Carlos III of Madrid).
DOI: 10.6084/m9.figshare.1292440.v5
title: Screening of cell cycle fusion proteins to identify kinase signaling networks

description: Kinase signaling networks are well-established mediators of cell cycle transitions. However, how kinases interact with the ubiquitin proteasome system (UPS) to elicit protein turnover is not fully understood. We sought a means of identifying kinase-substrate interactions to better understand signaling pathways controlling protein degradation. Our prior studies used a luciferase fusion protein to uncover kinase networks controlling protein turnover. In this study, we utilized a similar approach to identify pathways controlling the cell cycle protein p27<sup>Kip1</sup>. We generated a p27<sup>Kip1</sup>-luciferase fusion and expressed it in cells incubated with compounds from a library of pharmacologically active compounds. We then compared the relative effects of the compounds on p27<sup>Kip1</sup>-luciferase fusion stabilization. This was combined with <i>in silico</i> kinome profiling to identify potential kinases inhibited by each compound. This approach effectively uncovered known kinases regulating p27<sup>Kip1</sup> turnover. Collectively, our studies suggest that this parallel screening approach is robust and can be applied to fully understand kinase-ubiquitin pathway interactions.
DOI: 10.6084/m9.figshare.1292069.v2
title: Edición y comunicación científica: evolución y tendencias actuales [Evolution of and current trends in publishing and scholarly communication]

description: Slides for my Master Thesis presentation (July 2013. University Carlos III of Madrid).
DOI: 10.6084/m9.figshare.1292069.v4
title: Edición y comunicación científica: evolución y tendencias actuales [Scholarly communication and publishing: Evolution and current trends]

description: Slides for my Master Thesis presentation (July 2013. University Carlos III of Madrid).
DOI: 10.6084/m9.figshare.1292069.v3
title: Edición y comunicación científica: evolución y tendencias actuales [Evolution of and current trends in scholarly communication and publishing]

description: Slides for my Master Thesis presentation (July 2013. University Carlos III of Madrid).
DOI: 10.6084/m9.figshare.1291719
title: Gaussian Job Archive for C13H18LiN3O5

description: Archive of work produced using the resources of the Imperial College High Performance Computing Service.
DOI: 10.6084/m9.figshare.1291717
title: Gaussian Job Archive for C13H17N3O3Si

description: Archive of work produced using the resources of the Imperial College High Performance Computing Service.
DOI: 10.6084/m9.figshare.1291718
title: Gaussian Job Archive for C13H16BN3O3

description: Archive of work produced using the resources of the Imperial College High Performance Computing Service.
DOI: 10.6084/m9.figshare.1291719.v1
title: Gaussian Job Archive for C13H18LiN3O5

description: Archive of work produced using the resources of the Imperial College High Performance Computing Service.
DOI: 10.6084/m9.figshare.1291717.v1
title: Gaussian Job Archive for C13H17N3O3Si

description: Archive of work produced using the resources of the Imperial College High Performance Computing Service.
DOI: 10.6084/m9.figshare.1291718.v1
title: Gaussian Job Archive for C13H16BN3O3

description: Archive of work produced using the resources of the Imperial College High Performance Computing Service.
DOI: 10.6084/m9.figshare.1291629
title: The Effects of Cathode Parameters on the Performance of Poly(2,5-Benzimidazole)-Based Polymer ElectrolyteMembrane Fuel Cell

description: The effects of electrode parameters on membrane<br>electrode assembly performance including Pt loading, hydrophobicity<br>during heat treatment, catalyst layer thickness and<br>the amount of polytetrafluoroethylene (PTFE) in the cathode<br>are investigated. The fuel cell performance is maximized via<br>catalyst utilization by optimizing the phosphoric acid content<br>in the electrodes. Heat treatment of gas diffusion electrode<br>results in an increase in hydrophobicity and a decrease in<br>phosphoric acid content in the catalyst layer, which drastically<br>affects the fuel cell performance. In our conditions, a maximum<br>fuel cell performance of 270 mW cm−2 was achieved at<br>160 °C with air using 1 mg Pt cm−2 total catalyst loading<br>(20 % PTFE). The fuel cell performance and the poisoning<br>effect of carbon monoxide in poly(2,5-benzimidazole)<br>(ABPBI)-membrane-based high-temperature membrane electrode<br>assemblies were investigated with respect to carbon<br>monoxide concentrations. Fuel cell performance of Pt alloys<br>(Pt-Cu/C, Pt-Fe/C, Pt-Ni/C) is compared with that of Pt/C at<br>temperatures between 140 and 180 °C. It was observed that<br>Pt-Cu/C alloy catalysts exhibit higher performance with lower<br>catalyst loadings (0.4 mg Pt cm−2) than Pt/C catalyst. The<br>performance of alloy catalysts follows the order of Pt-Cu/C&gt;<br>Pt-Fe/C&gt;Pt-Ni/C&gt;Pt/C.
DOI: 10.6084/m9.figshare.1291630
title: Nitrogen doped graphene nanosheet supported platinum nanoparticles as high performance electrochemical homocysteine biosensors

description: Functional carbon nanomaterials are significantly important for the development of high performance<br>sensitive and selective electrochemical biosensors. In this study, graphene supported platinum<br>nanoparticles (GN–PtNPs) and nitrogen doped graphene supported platinum nanoparticles (N-GN–<br>PtNPs) were synthesized by a simple chemical reduction method and explored as high performance<br>nanocatalyst supports, as well as doped nanocatalyst supports, toward electrochemical oxidation of<br>homocysteine (HCY) for the first the time. Our studies demonstrate that N-doped graphene supported<br>PtNPs show higher electrocatalytic activity for HCY with an experimental detection limit of 200 pM.<br>Moreover, N-doped graphene supported Pt was demonstrated to have excellent selectivity in the<br>electrochemical oxidation of HCY i.e., the detection of HCY is successful in the presence of a 20-fold<br>excess of ascorbic acid (AA). The practical application of N-doped graphene supported PtNP materials is<br>effectively shown for the determination of HCY in both human blood serum and urine samples, by<br>differential pulse voltammetry under optimized conditions. Our findings conclude that N-doped<br>graphene supported PtNPs can be developed as a high performance and versatile nano-electrocatalyst<br>for electrochemical biosensor applications.
DOI: 10.6084/m9.figshare.1291646
title: CGN tomato passport data

description: The passport data from CGN for their genebank (germline/seed) collections of Tomato
DOI: 10.6084/m9.figshare.1291648
title: Gaussian Job Archive for C13H16LiN3O4

description: Archive of work produced using the resources of the Imperial College High Performance Computing Service.