Extraction of Transcript Diversity from Scientific Literature

Transcript diversity generated by alternative splicing and associated mechanisms contributes heavily to the functional complexity of biological systems. The numerous examples of the mechanisms and functional implications of these events are scattered throughout the scientific literature. Thus, it is crucial to have a tool that can automatically extract the relevant facts and collect them in a knowledge base that can aid the interpretation of data from high-throughput methods. We have developed and applied a composite text-mining method for extracting information on transcript diversity from the entire MEDLINE database in order to create a database of genes with alternative transcripts. It contains information on tissue specificity, number of isoforms, causative mechanisms, functional implications, and experimental methods used for detection. We have mined this resource to identify 959 instances of tissue-specific splicing. Our results in combination with those from EST-based methods suggest that alternative splicing is the preferred mechanism for generating transcript diversity in the nervous system. We provide new annotations for 1,860 genes with the potential for generating transcript diversity. We assign the MeSH term “alternative splicing” to 1,536 additional abstracts in the MEDLINE database and suggest new MeSH terms for other events. We have successfully extracted information about transcript diversity and semiautomatically generated a database, LSAT, that can provide a quantitative understanding of the mechanisms behind tissue-specific gene expression. LSAT (Literature Support for Alternative Transcripts) is publicly available at http://www.bork.embl.de/LSAT/

The What, Why and How of openness in science

We give a short introduction to open science followed by an overview of Creative Commons and open source licenses

STRING and STITCH: known and predicted interactions between proteins and chemicals

Information on protein-protein and protein-chemical interactions is essential for understanding cellular functions. The STRING and STITCH web resources integrate interaction evidence derived from pathways, automatic literature mining, primary experimental data, and genomic context. The resulting interaction networks cover 1.5 million proteins from 373 organisms and 68,000 chemicals

Just-in-time assembly of cell-cycle protein complexes

Our comparative analysis of eukaryotic cell-cycle complexes reveals that the identity of the periodically expressed subunits differs significantly between organisms and is often mirrored by changes in cell-cycle-dependent phosphorylation of the protein products. This indicates that many different solutions have evolved for just-in-time assembly of the same molecular machines

Current driven magnetization dynamics in helical spin density waves

A mechanism is proposed for manipulating the magnetic state of a helical spin density wave using a current. In this paper, we show that a current through a bulk system with a helical spin density wave induces a spin transfer torque, giving rise to a rotation of the order parameter.The use of spin transfer torque to manipulate the magnetization in bulk systems does not suffer from the obstacles seen for magnetization reversal using interface spin transfer torque in multilayered systems. We demonstrate the effect by a quantitative calculation of the current induced magnetization dynamics of Erbium. Finally we propose a setup for experimental verification.Comment: In the previous version of this paper was a small numerical mistake made when evaluating equation 3 and 9. The number of digits given in the calculation of the torque current tensor is reduced to better represent the accuracy of the calculation. A slightly modified paper have been published in Phys. Rev. Lett. 96, 256601 (2006) 4 pages 3 figure

Analysis of Predicted Host-Parasite Interactomes Reveals Commonalities and Specificities Related to Parasitic Lifestyle and Tissues Tropism

Submitted by Nuzia Santos ([email protected]) on 2019-10-17T14:02:06Z No. of bitstreams: 1 Analysis of Predicted Host–Parasite Interactomes.pdf: 1430961 bytes, checksum: 8cf36831373b15c9d21f8f34d419bf26 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2019-10-17T14:04:47Z (GMT) No. of bitstreams: 1 Analysis of Predicted Host–Parasite Interactomes.pdf: 1430961 bytes, checksum: 8cf36831373b15c9d21f8f34d419bf26 (MD5)Made available in DSpace on 2019-10-17T14:04:47Z (GMT). No. of bitstreams: 1 Analysis of Predicted Host–Parasite Interactomes.pdf: 1430961 bytes, checksum: 8cf36831373b15c9d21f8f34d419bf26 (MD5) Previous issue date: 2019Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Novo Nordisk Foundation Center for Protein Research. Faculty of Health and Medical Sciences. University of Copenhagen. Copenhagen, Denmark.Instituto Tecnológico Vale. Desenvolvimento Genômico. Belém, PA, Brasil.Novo Nordisk Foundation Center for Protein Research. Faculty of Health and Medical Sciences. University of Copenhagen. Copenhagen, Denmark.The study of molecular host-parasite interactions is essential to understand parasitic infection and adaptation within the host system. As well, prevention and treatment of infectious diseases require a clear understanding of the molecular crosstalk between parasites and their hosts. Yet, large-scale experimental identification of host-parasite molecular interactions remains challenging, and the use of computational predictions becomes then necessary. Here, we propose a computational integrative approach to predict host-parasite protein-protein interaction (PPI) networks resulting from the human infection by 15 different eukaryotic parasites. We used an orthology-based approach to transfer high-confidence intraspecies interactions obtained from the STRING database to the corresponding interspecies homolog protein pairs in the host-parasite system. Our approach uses either the parasites predicted secretome and membrane proteins, or only the secretome, depending on whether they are uni- or multi-cellular, respectively, to reduce the number of false predictions. Moreover, the host proteome is filtered for proteins expressed in selected cellular localizations and tissues supporting the parasite growth. We evaluated the inferred interactions by analyzing the enriched biological processes and pathways in the predicted networks and their association with known parasitic invasion and evasion mechanisms. The resulting PPI networks were compared across parasites to identify common mechanisms that may define a global pathogenic hallmark. We also provided a study case focusing on a closer examination of the human-S. mansoni predicted interactome, detecting central proteins that have relevant roles in the human-S. mansoni network, and identifying tissue-specific interactions with key roles in the life cycle of the parasite

Metabolism-Independent Sugar Sensing in Central Orexin Neurons

OBJECTIVE— Glucose sensing by specialized neurons of the hypothalamus is vital for normal energy balance. In many glucose-activated neurons, glucose metabolism is considered a critical step in glucose sensing, but whether glucose-inhibited neurons follow the same strategy is unclear. Orexin/hypocretin neurons of the lateral hypothalamus are widely projecting glucose-inhibited cells essential for normal cognitive arousal and feeding behavior. Here, we used different sugars, energy metabolites, and pharmacological tools to explore the glucose-sensing strategy of orexin cells

Proton Pump Activity of Mitochondria-rich Cells : The Interpretation of External Proton-concentration Gradients

We have hypothesized that a major role of the apical H+-pump in mitochondria-rich (MR) cells of amphibian skin is to energize active uptake of Cl− via an apical Cl−/HCO3−-exchanger. The activity of the H+ pump was studied by monitoring mucosal [H+]-profiles with a pH-sensitive microelectrode. With gluconate as mucosal anion, pH adjacent to the cornified cell layer was 0.98 ± 0.07 (mean ± SEM) pH-units below that of the lightly buffered bulk solution (pH = 7.40). The average distance at which the pH-gradient is dissipated was 382 ± 18 μm, corresponding to an estimated “unstirred layer” thickness of 329 ± 29 μm. Mucosal acidification was dependent on serosal pCO2, and abolished after depression of cellular energy metabolism, confirming that mucosal acidification results from active transport of H+. The [H+] was practically similar adjacent to all cells and independent of whether the microelectrode tip was positioned near an MR-cell or a principal cell. To evaluate [H+]-profiles created by a multitude of MR-cells, a mathematical model is proposed which assumes that the H+ distribution is governed by steady diffusion from a number of point sources defining a set of particular solutions to Laplace's equation. Model calculations predicted that with a physiological density of MR cells, the [H+] profile would be governed by so many sources that their individual contributions could not be experimentally resolved. The flux equation was integrated to provide a general mathematical expression for an external standing [H+]–gradient in the unstirred layer. This case was treated as free diffusion of protons and proton-loaded buffer molecules carrying away the protons extruded by the pump into the unstirred layer; the expression derived was used for estimating stationary proton-fluxes. The external [H+]-gradient depended on the mucosal anion such as to indicate that base (HCO3−) is excreted in exchange not only for Cl −, but also for Br− and I−, indicating that the active fluxes of these anions can be attributed to mitochondria-rich cells