Maturing the Old: Sophie's Journey towards Self-Recognition in Howl's Moving Castle by Diana Wynne Jones

The proliferation of the Children’s Literature novels by Diana Wynne Jones has converted her into a prominent figure in the fantastic genre. Although several scholars have researched diverse aspects of Jones’s narratives, there may still be approaches to adopt. Thus, the aim of this dissertation is to analyse the book Howl’s Moving Castle (1986) by the abovementioned author and examine the protagonist Sophie’s transition from having a self-imposed personality to finding her true identity. To that end, we will firstly examine the biography of the author. Secondly, we will briefly explain the categorisation of Fantasy, followed by a contextualisation of this literary genre in the second half of the 20th century in comparison with Jones’s own standpoint as an avant-garde writer. Thirdly, we will focus on the aforesaid novel in relation to the importance of names, the opposition of fate and free will, and finally, Sophie’s search of her original identity. Lastly, we will provide a summary of the main conclusions we have previously come to regarding the entire journey

Maturing the Old: Sophie's Journey towards Self-Recognition in Howl's Moving Castle by Diana Wynne Jones

The proliferation of the Children’s Literature novels by Diana Wynne Jones has converted her into a prominent figure in the fantastic genre. Although several scholars have researched diverse aspects of Jones’s narratives, there may still be approaches to adopt. Thus, the aim of this dissertation is to analyse the book Howl’s Moving Castle (1986) by the abovementioned author and examine the protagonist Sophie’s transition from having a self-imposed personality to finding her true identity. To that end, we will firstly examine the biography of the author. Secondly, we will briefly explain the categorisation of Fantasy, followed by a contextualisation of this literary genre in the second half of the 20th century in comparison with Jones’s own standpoint as an avant-garde writer. Thirdly, we will focus on the aforesaid novel in relation to the importance of names, the opposition of fate and free will, and finally, Sophie’s search of her original identity. Lastly, we will provide a summary of the main conclusions we have previously come to regarding the entire journey

Semantic Characterization of Context of Use and Contents for User-Centric Media Retrieval

When users access online media, they need and desire to get an experience tailored to their specific, personal context and situation. This is becoming more and more relevant with the ever-increasing amount of available contents users may choose from. In order to provide user-centric functionalities (such as relevant searches, content adaptation, customization and recommendation), both the annotation of contents with semantically rich metadata and an accurate model of the individual users and their respective contexts of use are needed. In this context, we propose a solution to automatically characterize both the context of use and the contents. It provides dynamic, adaptive user models, with explicit and implicit information; as well as content descriptors that may be later used to match the most suitable contents for each user. Users always keep a pivotal role throughout the whole process: providing new contents, contributing to moderated folks onomies, overseeing their own user model, etc

Modelado Semántico y Centrado en el Usuario de Servicios Adaptados al Contexto de Uso

Cuando los usuarios acceden a servicios telemáticos, esperan obtener experiencias cada vez más adaptadas a su contexto específico, en especial, ante la gran cantidad de contenidos en línea a su alcance a través de dichos servicios. Para que estos servicios proporcionen funcionalidades centradas en el usuario –por ejemplo, búsquedas relevantes, adaptación de contenidos, personalización y recomendación– es necesario que los contenidos estén anotados semánticamente y disponer de un modelo preciso que represente al usuario y su contexto de uso. En este escenario, presentamos un marco genérico de servicios centrados en el usuario basado en la caracterización semántica de los usuarios y su mapeo con los contenidos. En concreto, aplicamos dicho marco a un buscador semántico que caracteriza automáticamente tanto los contenidos a los que los usuarios pueden acceder como el contexto de uso desde el que se accede. La solución propuesta incluye modelos de usuario dinámicos y adaptativos, con información explícita e implícita; así como descriptores de los contenidos que pueden utilizarse para determinar cuáles son más adecuados para cada usuari

Servicios Centrados en el Usuario Basados en la Caracterización Semántica de los Contenidos y del Contexto de Uso.

Cuando los usuarios acceden a servicios telemáticos, esperan obtener experiencias cada vez más adaptadas a su contexto y situación específicos. Esto adquiere especial relevancia al aumentar la cantidad de contenidos en línea al alcance de los usuarios a través de dichos servicios. Con el fin de que los servicios telemáticos proporcionen funcionalidades centradas en el usuario –como, por ejemplo, búsquedas relevantes, adaptación de contenidos, personalización y recomendación– es necesario que los contenidos estén correctamente anotados (enriquecidos con metadatos semánticos) y disponer de un modelo preciso que represente al usuario junto con su respectivo contexto de uso. En este escenario, presentamos un marco genérico de servicios centrados en el usuario a partir de su caracterización semántica y del mapeo a los contenidos. En concreto, aplicamos dicho marco a un buscador semántico que caracteriza automáticamente tanto los contenidos a los que los usuarios pueden acceder como el contexto de uso desde el que acceden. La solución propuesta incluye, pues, modelos de usuario dinámicos y adaptativos, con información explícita e implícita; así como descriptores de los contenidos que pueden utilizarse para determinar cuáles son más adecuados para cada usuario. Durante todo este proceso, los usuarios mantienen un rol fundamental: proveyendo nuevos contenidos, contribuyendo a folksonomías moderadas, supervisando su propio modelo de usuario, etc

Complex anatomy difficulting left atrial appendage closure.

Left atrial appendage closure is a useful technique for patients at high thromboembolic risk and contraindications for oral anticoagulation therapy. However, it can be challenging when anatomical difficulties are encountered. We present a unique case of atypical appendage uptake and how we completed the procedure.peer-reviewed409 K

Virus variants with differences in the P1 protein coexist in a Plum pox virus population and display particular host-dependent pathogenicity features

[EN] Subisolates segregated from an M-type Plum pox virus (PPV) isolate, PPV-PS, differ widely in pathogenicity despite their high degree of sequence similarity. A single amino acid substitution, K109E, in the helper component proteinase (HCPro) protein of PPV caused a significant enhancement of symptom severity in herbaceous hosts, and notably modified virus infectivity in peach seedlings. The presence of this substitution in certain subisolates that induced mild symptoms in herbaceous hosts and did not infect peach seedlings suggested the existence of uncharacterized attenuating factors in these subisolates. In this study, we show that two amino acid changes in the P1 protein are specifically associated with the mild pathogenicity exhibited by some PS subisolates. Site-directed mutagenesis studies demonstrated that both substitutions, W29R and V139E, but especially W29R, resulted in lower levels of virus accumulation and symptom severity in a woody host, Prunus persica. Furthermore, when W29R and V139E mutations were expressed concomitantly, PPV infectivity was completely abolished in this host. In contrast, the V139E substitution, but not W29R, was found to be responsible for symptom attenuation in herbaceous hosts. Deep sequencing analysis demonstrated that the W29R and V139E heterogeneities already existed in the original PPV-PS isolate before its segregation in different subisolates by local lesion cloning. These results highlight the potential complexity of potyviral populations and the relevance of the P1 protein of potyviruses in pathogenesis and viral adaptation to the host.We wish to thank Elvira Dominguez for technical assistance. This work was supported by grants BIO2010-18541 from the Spanish Ministerio de Educacion y Ciencia (MEC), SAL/0185/2006 from Comunidad de Madrid and KBBE-204429 from the European Union. B. S. was a recipient of a Formacion de Personal Investigador fellowship from MEC.Maliogka, VI.; Salvador, B.; Carbonell, A.; Saenz, P.; San Leon, D.; Oliveros, JC.; Delgadillo, MO.... (2012). Virus variants with differences in the P1 protein coexist in a Plum pox virus population and display particular host-dependent pathogenicity features. Molecular Plant Pathology. 13(8):877-886. https://doi.org/10.1111/j.1364-3703.2012.00796.xS877886138Adams, M. J., Antoniw, J. F., & Fauquet, C. M. (2004). Molecular criteria for genus and species discrimination within the family Potyviridae. Archives of Virology, 150(3), 459-479. doi:10.1007/s00705-004-0440-6Ayme, V., Petit-Pierre, J., Souche, S., Palloix, A., & Moury, B. (2007). Molecular dissection of the potato virus Y VPg virulence factor reveals complex adaptations to the pvr2 resistance allelic series in pepper. Journal of General Virology, 88(5), 1594-1601. doi:10.1099/vir.0.82702-0Biebricher, C. K., & Eigen, M. (s. f.). What Is a Quasispecies? Quasispecies: Concept and Implications for Virology, 1-31. doi:10.1007/3-540-26397-7_1Brantley, J. D., & Hunt, A. G. (1993). The N-terminal protein of the polyprotein encoded by the potyvirus tobacco vein mottling virus is an RNA-binding protein. Journal of General Virology, 74(6), 1157-1162. doi:10.1099/0022-1317-74-6-1157Charron, C., Nicolaï, M., Gallois, J.-L., Robaglia, C., Moury, B., Palloix, A., & Caranta, C. (2008). Natural variation and functional analyses provide evidence for co-evolution between plant eIF4E and potyviral VPg. The Plant Journal, 54(1), 56-68. doi:10.1111/j.1365-313x.2008.03407.xChiang, C.-H., Lee, C.-Y., Wang, C.-H., Jan, F.-J., Lin, S.-S., Chen, T.-C., … Yeh, S.-D. (2007). Genetic analysis of an attenuated Papaya ringspot virus strain applied for cross-protection. European Journal of Plant Pathology, 118(4), 333-348. doi:10.1007/s10658-007-9130-zChung, B. Y.-W., Miller, W. A., Atkins, J. F., & Firth, A. E. (2008). An overlapping essential gene in the Potyviridae. Proceedings of the National Academy of Sciences, 105(15), 5897-5902. doi:10.1073/pnas.0800468105Domingo, E., & Holland, J. J. (1997). RNA VIRUS MUTATIONS AND FITNESS FOR SURVIVAL. Annual Review of Microbiology, 51(1), 151-178. doi:10.1146/annurev.micro.51.1.151EIGEN, M. (1996). On the nature of virus quasispecies. Trends in Microbiology, 4(6), 216-218. doi:10.1016/0966-842x(96)20011-3Hajimorad, M. R., Wen, R.-H., Eggenberger, A. L., Hill, J. H., & Maroof, M. A. S. (2011). Experimental Adaptation of an RNA Virus Mimics Natural Evolution. Journal of Virology, 85(6), 2557-2564. doi:10.1128/jvi.01935-10Holmes, E. C., & Moya, A. (2002). Is the Quasispecies Concept Relevant to RNA Viruses? Journal of Virology, 76(1), 460-462. doi:10.1128/jvi.76.1.460-462.2002Jenkins, G. M., Worobey, M., Woelk, C. H., & Holmes, E. C. (2001). Evidence for the Non-quasispecies Evolution of RNA Viruses. Molecular Biology and Evolution, 18(6), 987-994. doi:10.1093/oxfordjournals.molbev.a003900Jridi, C., Martin, J.-F., Marie-Jeanne, V., Labonne, G., & Blanc, S. (2006). Distinct Viral Populations Differentiate and Evolve Independently in a Single Perennial Host Plant. Journal of Virology, 80(5), 2349-2357. doi:10.1128/jvi.80.5.2349-2357.2006Li, H., & Durbin, R. (2010). Fast and accurate long-read alignment with Burrows–Wheeler transform. Bioinformatics, 26(5), 589-595. doi:10.1093/bioinformatics/btp698López-Moya, J. J., & Garcı́a, J. A. (2000). Construction of a stable and highly infectious intron-containing cDNA clone of plum pox potyvirus and its use to infect plants by particle bombardment. Virus Research, 68(2), 99-107. doi:10.1016/s0168-1702(00)00161-1Moxon, S., Schwach, F., Dalmay, T., MacLean, D., Studholme, D. J., & Moulton, V. (2008). A toolkit for analysing large-scale plant small RNA datasets. Bioinformatics, 24(19), 2252-2253. doi:10.1093/bioinformatics/btn428Nakahara, K. S., Shimada, R., Choi, S.-H., Yamamoto, H., Shao, J., & Uyeda, I. (2010). Involvement of the P1 Cistron in Overcoming eIF4E-Mediated Recessive Resistance Against Clover yellow vein virus in Pea. Molecular Plant-Microbe Interactions®, 23(11), 1460-1469. doi:10.1094/mpmi-11-09-0277Ohshima, K., Akaishi, S., Kajiyama, H., Koga, R., & Gibbs, A. J. (2009). Evolutionary trajectory of turnip mosaic virus populations adapting to a new host. Journal of General Virology, 91(3), 788-801. doi:10.1099/vir.0.016055-0Pruss, G., Ge, X., Shi, X. M., Carrington, J. C., & Bowman Vance, V. (1997). Plant viral synergism: the potyviral genome encodes a broad-range pathogenicity enhancer that transactivates replication of heterologous viruses. The Plant Cell, 9(6), 859-868. doi:10.1105/tpc.9.6.859Rajamäki, M.-L., Kelloniemi, J., Alminaite, A., Kekarainen, T., Rabenstein, F., & Valkonen, J. P. T. (2005). 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Small RNA profiling reveals regulation of Arabidopsis miR168 and heterochromatic siRNA415 in response to fungal elicitors

[Background] Small RNAs (sRNAs), including small interfering RNAs (siRNAs) and microRNAs (miRNAs), have emerged as important regulators of eukaryotic gene expression. In plants, miRNAs play critical roles in development, nutrient homeostasis and abiotic stress responses. Accumulating evidence also reveals that sRNAs are involved in plant immunity. Most studies on pathogen-regulated sRNAs have been conducted in Arabidopsis plants infected with the bacterial pathogen Pseudomonas syringae, or treated with the flagelin-derived elicitor peptide flg22 from P. syringae. This work investigates sRNAs that are regulated by elicitors from the fungus Fusarium oxysporum in Arabidopsis.[Results] Microarray analysis revealed alterations on the accumulation of a set of sRNAs in response to elicitor treatment, including miRNAs and small RNA sequences derived from massively parallel signature sequencing. Among the elicitor-regulated miRNAs was miR168 which regulates ARGONAUTE1, the core component of the RNA-induced silencing complex involved in miRNA functioning. Promoter analysis in transgenic Arabidopsis plants revealed transcriptional activation of MIR168 by fungal elicitors. Furthermore, transgenic plants expressing a GFP-miR168 sensor gene confirmed that the elicitor-induced miR168 is active. MiR823, targeting Chromomethylase3 (CMT3) involved in RNA-directed DNA methylation (RdDM) was also found to be regulated by fungal elicitors. In addition to known miRNAs, microarray analysis allowed the identification of an elicitor-inducible small RNA that was incorrectly annotated as a miRNA. Studies on Arabidopsis mutants impaired in small RNA biogenesis demonstrated that this sRNA, is a heterochromatic-siRNA (hc-siRNA) named as siRNA415. Hc-siRNAs are known to be involved in RNA-directed DNA methylation (RdDM). SiRNA415 is detected in several plant species.[Conclusion] Results here presented support a transcriptional regulatory mechanism underlying MIR168 expression. This finding highlights the importance of miRNA functioning in adaptive processes of Arabidopsis plants to fungal infection. The results of this study also lay a foundation for the involvement of RdDM processes through the activity of siRNA415 and miR823 in mediating regulation of immune responses in Arabidopsis plants.P. Baldrich is a recipient of a Ph.D grant from the “Ministerio de Ciencia e Innovación, Formación de Personal Investigador-FPI, ref. BES-2010-032879). This work was supported by grants BIO2009-08719 and BIO2012-32838 to BSS, AGL2010-14949 to JJLM, and BFU2008-04251 to JLR, from the Spanish Ministry of Economy and Competitiveness (MINECO), and grant 2010–0520193 to JLR from the National Science Foundation (NSF). We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer Reviewe

DNA damage triggers squamous metaplasia in human lung and mammary cells via mitotic checkpoints

Epithelial transdifferentiation is frequent in tissue hyperplasia and contributes to disease in various degrees. Squamous metaplasia (SQM) precedes epidermoid lung cancer, an aggressive and frequent malignancy, but it is rare in the epithelium of the mammary gland. The mechanisms leading to SQM in the lung have been very poorly investigated. We have studied this issue on human freshly isolated cells and organoids. Here we show that human lung or mammary cells strikingly undergo SQM with polyploidisation when they are exposed to genotoxic or mitotic drugs, such as Doxorubicin or the cigarette carcinogen DMBA, Nocodazole, Taxol or inhibitors of Aurora-B kinase or Polo-like kinase. To note, the epidermoid response was attenuated when DNA repair was enhanced by Enoxacin or when mitotic checkpoints where abrogated by inhibition of Chk1 and Chk2. The results show that DNA damage has the potential to drive SQM via mitotic checkpoints, thus providing novel molecular candidate targets to tackle lung SCC. Our findings might also explain why SCC is frequent in the lung, but not in the mammary gland and why chemotherapy often causes complicating skin toxicity