A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner

Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey)

Background Transthyretin amyloidosis (ATTR) is a heterogeneous disorder with multiorgan involvement and a genetic or nongenetic basis. Objectives The goal of this study was to describe ATTR in the United States by using data from the THAOS (Transthyretin Amyloidosis Outcomes Survey) registry. Methods Demographic, clinical, and genetic features of patients enrolled in the THAOS registry in the United States (n = 390) were compared with data from patients from other regions of the world (ROW) (n = 2,140). The focus was on the phenotypic expression and survival in the majority of U.S. subjects with valine-to-isoleucine substitution at position 122 (Val122Ile) (n = 91) and wild-type ATTR (n = 189). Results U.S. subjects are older (70 vs. 46 years), more often male (85.4% vs. 50.6%), and more often of African descent (25.4% vs. 0.5%) than the ROW. A significantly higher percentage of U.S. patients with ATTR amyloid seen at cardiology sites had wild-type disease than the ROW (50.5% vs. 26.2%). In the United States, 34 different mutations (n = 201) have been reported, with the most common being Val122Ile (n = 91; 45.3%) and Thr60Ala (n = 41; 20.4%). Overall, 91 (85%) of 107 patients with Val122Ile were from the United States, where Val122Ile subjects were younger and more often female and black than patients with wild-type disease, and had similar cardiac phenotype but a greater burden of neurologic symptoms (pain, numbness, tingling, and walking disability) and worse quality of life. Advancing age and lower mean arterial pressure, but not the presence of a transthyretin mutation, were independently associated with higher mortality from a multivariate analysis of survival. Conclusions In the THAOS registry, ATTR in the United States is overwhelmingly a disorder of older adult male subjects with a cardiac-predominant phenotype. Val122Ile is the most common transthyretin mutation, and neurologic phenotypic expression differs between wild-type disease and Val122Ile, but survival from enrollment in THAOS does not. (Transthyretin-Associated Amyloidoses Outcome Survey [THAOS]; NCT00628745

Tigers Need Cover: Multi-Scale Occupancy Study of the Big Cat in Sumatran Forest and Plantation Landscapes

The critically endangered Sumatran tiger (Panthera tigris sumatrae Pocock, 1929) is generally known as a forest-dependent animal. With large-scale conversion of forests into plantations, however, it is crucial for restoration efforts to understand to what extent tigers use modified habitats. We investigated tiger-habitat relationships at 2 spatial scales: occupancy across the landscape and habitat use within the home range. Across major landcover types in central Sumatra, we conducted systematic detection, non-detection sign surveys in 47, 17×17 km grid cells. Within each cell, we surveyed 40, 1-km transects and recorded tiger detections and habitat variables in 100 m segments totaling 1,857 km surveyed. We found that tigers strongly preferred forest and used plantations of acacia and oilpalm, far less than their availability. Tiger probability of occupancy covaried positively and strongly with altitude, positively with forest area, and negatively with distance-to-forest centroids. At the fine scale, probability of habitat use by tigers across landcover types covaried positively and strongly with understory cover and altitude, and negatively and strongly with human settlement. Within forest areas, tigers strongly preferred sites that are farther from water bodies, higher in altitude, farther from edge, and closer to centroid of large forest block; and strongly preferred sites with thicker understory cover, lower level of disturbance, higher altitude, and steeper slope. These results indicate that to thrive, tigers depend on the existence of large contiguous forest blocks, and that with adjustments in plantation management, tigers could use mosaics of plantations (as additional roaming zones), riparian forests (as corridors) and smaller forest patches (as stepping stones), potentially maintaining a metapopulation structure in fragmented landscapes. This study highlights the importance of a multi-spatial scale analysis and provides crucial information relevant to restoring tigers and other wildlife in forest and plantation landscapes through improvement in habitat extent, quality, and connectivity

Plagiarism meets paraphrasing: insights for the next generation in automatic plagiarism detection

[EN] Although paraphrasing is the linguistic mechanism underlying many plagiarism cases, little attention has been paid to its analysis in the framework of automatic plagiarism detection. Therefore, state-of-the-art plagiarism detectors find it difficult to detect cases of paraphrase plagiarism. In this article, we analyze the relationship between paraphrasing and plagiarism, paying special attention to which paraphrase phenomena underlie acts of plagiarism and which of them are detected by plagiarism detection systems. With this aim in mind, we created the P4P corpus, a new resource that uses a paraphrase typology to annotate a subset of the PAN-PC-10 corpus for automatic plagiarism detection. The results of the Second International Competition on Plagiarism Detection were analyzed in the light of this annotation.The presented experiments show that (i) more complex paraphrase phenomena and a high density of paraphrase mechanisms make plagiarism detection more difficult, (ii) lexical substitutions are the paraphrase mechanisms used the most when plagiarizing, and (iii) paraphrase mechanisms tend to shorten the plagiarized text. For the first time, the paraphrase mechanisms behind plagiarism have been analyzed, providing critical insights for the improvement of automatic plagiarism detection systems.We would like to thank the people who participated in the annotation of the P4P corpus, Horacio Rodriguez for his helpful advice as experienced researcher, and the reviewers of this contribution for their valuable comments to improve this article. This research work was partially carried out during the tenure of an ERCIM "Alain Bensoussan" Fellowship Programme. The research leading to these results received funding from the EU FP7 Programme 2007-2013 (grant no. 246016), the MICINN projects TEXT-ENTERPRISE 2.0 and TEXT-KNOWLEDGE 2.0 (TIN2009-13391), the EC WIQ-EI IRSES project (grant no. 269180), and the FP7 Marie Curie People Programme. The research work of A. Barron-Cedeno and M. Vila was financed by the CONACyT-Mexico 192021 grant and the MECD-Spain FPU AP2008-02185 grant, respectively. The research work of A. Barron-Cedeno was partially done in the framework of his Ph.D. at the Universitat Politecnica de Valencia.Barrón Cedeño, LA.; Vila, M.; Martí, MA.; Rosso, P. (2013). Plagiarism meets paraphrasing: insights for the next generation in automatic plagiarism detection. Computational Linguistics. 39(4):917-947. https://doi.org/10.1162/COLI_a_00153S917947394Barzilay, Regina. 2003. Information Fusion for Multidocument Summarization: Paraphrasing and Generation. Ph.D. thesis, Columbia University, New York.Barzilay, R., & Lee, L. (2003). Learning to paraphrase. Proceedings of the 2003 Conference of the North American Chapter of the Association for Computational Linguistics on Human Language Technology - NAACL ’03. doi:10.3115/1073445.1073448Barzilay, Regina and Kathleen R. McKeown. 2001. Extracting paraphrases from a parallel corpus. In Proceedings of the 39th Annual Meeting of the Association for Computational Linguistics (ACL 2001), pages 50–57, Toulouse.Barzilay, R., McKeown, K. R., & Elhadad, M. (1999). Information fusion in the context of multi-document summarization. Proceedings of the 37th annual meeting of the Association for Computational Linguistics on Computational Linguistics -. doi:10.3115/1034678.1034760Bhagat, Rahul. 2009. Learning Paraphrases from Text. Ph.D. thesis, University of Southern California, Los Angeles.Cheung, Mei Ling Lisa. 2009. Merging Corpus Linguistics and Collaborative Knowledge Construction. Ph.D. thesis, University of Birmingham, Birmingham.Cohn, T., Callison-Burch, C., & Lapata, M. (2008). Constructing Corpora for the Development and Evaluation of Paraphrase Systems. Computational Linguistics, 34(4), 597-614. doi:10.1162/coli.08-003-r1-07-044Dras, Mark. 1999. Tree Adjoining Grammar and the Reluctant Paraphrasing of Text. Ph.D. thesis, Macquarie University, Sydney.Faigley, L., & Witte, S. (1981). Analyzing Revision. College Composition and Communication, 32(4), 400. doi:10.2307/356602Fujita, Atsushi. 2005. Automatic Generation of Syntactically Well-formed and Semantically Appropriate Paraphrases. Ph.D. thesis, Nara Institute of Science and Technology, Nara.Grozea, C., & Popescu, M. (2010). Who’s the Thief? Automatic Detection of the Direction of Plagiarism. Lecture Notes in Computer Science, 700-710. doi:10.1007/978-3-642-12116-6_59GÜLICH, E. (2003). Conversational Techniques Used in Transferring Knowledge between Medical Experts and Non-experts. Discourse Studies, 5(2), 235-263. doi:10.1177/1461445603005002005Harris, Z. S. (1957). Co-Occurrence and Transformation in Linguistic Structure. Language, 33(3), 283. doi:10.2307/411155KETCHEN Jr., D. J., & SHOOK, C. L. (1996). THE APPLICATION OF CLUSTER ANALYSIS IN STRATEGIC MANAGEMENT RESEARCH: AN ANALYSIS AND CRITIQUE. Strategic Management Journal, 17(6), 441-458. doi:10.1002/(sici)1097-0266(199606)17:63.0.co;2-gMcCarthy, D., & Navigli, R. (2009). The English lexical substitution task. Language Resources and Evaluation, 43(2), 139-159. doi:10.1007/s10579-009-9084-1Recasens, M., & Vila, M. (2010). On Paraphrase and Coreference. Computational Linguistics, 36(4), 639-647. doi:10.1162/coli_a_00014Shimohata, Mitsuo. 2004. Acquiring Paraphrases from Corpora and Its Application to Machine Translation. Ph.D. thesis, Nara Institute of Science and Technology, Nara.Stein, B., Potthast, M., Rosso, P., Barrón-Cedeño, A., Stamatatos, E., & Koppel, M. (2011). Fourth international workshop on uncovering plagiarism, authorship, and social software misuse. ACM SIGIR Forum, 45(1), 45. doi:10.1145/1988852.198886

Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk.

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer