Discrete Particle Swarm Optimization for the minimum labelling Steiner tree problem

Particle Swarm Optimization is an evolutionary method inspired by the social behaviour of individuals inside swarms in nature. Solutions of the problem are modelled as members of the swarm which fly in the solution space. The evolution is obtained from the continuous movement of the particles that constitute the swarm submitted to the effect of the inertia and the attraction of the members who lead the swarm. This work focuses on a recent Discrete Particle Swarm Optimization for combinatorial optimization, called Jumping Particle Swarm Optimization. Its effectiveness is illustrated on the minimum labelling Steiner tree problem: given an undirected labelled connected graph, the aim is to find a spanning tree covering a given subset of nodes, whose edges have the smallest number of distinct labels

Direct visualization of the native structure of viroid RNAs at single-molecule resolution by atomic force microscopy

[EN] Viroids are small infectious, non-protein-coding circular RNAs that replicate independently and, in some cases, incite diseases in plants. They are classified into two families: Pospiviroidae, composed of species that have a central conserved region (CCR) and replicate in the cell nucleus, and Avsunviroidae, containing species that lack a CCR and whose multimeric replicative intermediates of either polarity generated in plastids self-cleave through hammerhead ribozymes. The compact, rod-like or branched, secondary structures of viroid RNAs have been predicted by RNA folding algorithms and further examined using different in vitro and in vivo experimental techniques. However, direct data about their native tertiary structure remain scarce. Here we have applied atomic force microscopy (AFM) to image at single-molecule resolution different variant RNAs of three representative viroids: potato spindle tuber viroid (PSTVd, family Pospiviroidae), peach latent mosaic viroid and eggplant latent viroid (PLMVd and ELVd, family Avsunviroidae). Our results provide a direct visualization of their native, three-dimensional conformations at 0 and 4 mM Mg2+ and highlight the role that some elements of tertiary structure play in their stabilization. The AFM images show that addition of 4 mM Mg2+ to the folding buffer results in a size contraction in PSTVd and ELVd, as well as in PLMVd when the kissing-loop interaction that stabilizes its 3D structure is preserved.This work was supported by the Spanish Ministerio de Economia y Competitividad (MINECO) grants BIO2016-79618-R (funded by EU under the FEDER programme) to C.B. and BFU2104-56812-P to R.F., as well as by the Comunidad de Madrid grant S2018/NMT-4349 to L.V. CIBERehd is funded by the Instituto de Salud Carlos III (ISCIII).Moreno, M.; Vázquez, L.; López Carrasco, A.; Martín-Gago, JA.; Flores Pedauye, R.; Briones, C. (2019). Direct visualization of the native structure of viroid RNAs at single-molecule resolution by atomic force microscopy. RNA Biology. 16(3):295-308. https://doi.org/10.1080/15476286.2019.1572436S295308163Diener, T. O. (2003). Discovering viroids — a personal perspective. Nature Reviews Microbiology, 1(1), 75-80. doi:10.1038/nrmicro736Flores, R., Hernández, C., Alba, A. E. M. de, Daròs, J.-A., & Serio, F. D. (2005). Viroids and Viroid-Host Interactions. Annual Review of Phytopathology, 43(1), 117-139. doi:10.1146/annurev.phyto.43.040204.140243Ding, B. (2009). The Biology of Viroid-Host Interactions. Annual Review of Phytopathology, 47(1), 105-131. doi:10.1146/annurev-phyto-080508-081927Zhang, Z., Qi, S., Tang, N., Zhang, X., Chen, S., Zhu, P., … Wu, Q. (2014). Discovery of Replicating Circular RNAs by RNA-Seq and Computational Algorithms. PLoS Pathogens, 10(12), e1004553. doi:10.1371/journal.ppat.1004553Serra, P., Messmer, A., Sanderson, D., James, D., & Flores, R. (2018). Apple hammerhead viroid-like RNA is a bona fide viroid: Autonomous replication and structural features support its inclusion as a new member in the genus Pelamoviroid. Virus Research, 249, 8-15. doi:10.1016/j.virusres.2018.03.001Hadidi, A., Barba, M., Hong, N., & Hallan, V. (2017). Apple Scar Skin Viroid. Viroids and Satellites, 217-228. doi:10.1016/b978-0-12-801498-1.00021-8Flores, R., Minoia, S., Carbonell, A., Gisel, A., Delgado, S., López-Carrasco, A., … Di Serio, F. (2015). Viroids, the simplest RNA replicons: How they manipulate their hosts for being propagated and how their hosts react for containing the infection. Virus Research, 209, 136-145. doi:10.1016/j.virusres.2015.02.027Hammann, C., & Steger, G. (2012). Viroid-specific small RNA in plant disease. RNA Biology, 9(6), 809-819. doi:10.4161/rna.19810Kovalskaya, N., & Hammond, R. W. (2014). Molecular biology of viroid–host interactions and disease control strategies. Plant Science, 228, 48-60. doi:10.1016/j.plantsci.2014.05.006Tsagris, E. M., Martínez de Alba, Á. E., Gozmanova, M., & Kalantidis, K. (2008). Viroids. Cellular Microbiology, 10(11), 2168-2179. doi:10.1111/j.1462-5822.2008.01231.xGrill, L. K., & Semancik, J. S. (1978). RNA sequences complementary to citrus exocortis viroid in nucleic acid preparations from infected Gynura aurantiaca. Proceedings of the National Academy of Sciences, 75(2), 896-900. doi:10.1073/pnas.75.2.896Branch, A. D., Benenfeld, B. J., & Robertson, H. D. (1988). Evidence for a single rolling circle in the replication of potato spindle tuber viroid. Proceedings of the National Academy of Sciences, 85(23), 9128-9132. doi:10.1073/pnas.85.23.9128Branch, A. D., & Robertson, H. D. (1984). A Replication Cycle for Viroids and Other Small Infectious RNA’s. Science, 223(4635), 450-455. doi:10.1126/science.6197756Daros, J. A., Marcos, J. F., Hernandez, C., & Flores, R. (1994). Replication of avocado sunblotch viroid: evidence for a symmetric pathway with two rolling circles and hammerhead ribozyme processing. Proceedings of the National Academy of Sciences, 91(26), 12813-12817. doi:10.1073/pnas.91.26.12813Feldstein, P. A., Hu, Y., & Owens, R. A. (1998). Precisely full length, circularizable, complementary RNA: An infectious form of potato spindle tuber viroid. Proceedings of the National Academy of Sciences, 95(11), 6560-6565. doi:10.1073/pnas.95.11.6560Daros, J.-A., & Flores, R. (2004). Arabidopsis thaliana has the enzymatic machinery for replicating representative viroid species of the family Pospiviroidae. Proceedings of the National Academy of Sciences, 101(17), 6792-6797. doi:10.1073/pnas.0401090101Flores, R., Gago-Zachert, S., Serra, P., Sanjuán, R., & Elena, S. F. (2014). Viroids: Survivors from the RNA World? Annual Review of Microbiology, 68(1), 395-414. doi:10.1146/annurev-micro-091313-103416Diener, T. O. (1989). Circular RNAs: relics of precellular evolution? Proceedings of the National Academy of Sciences, 86(23), 9370-9374. doi:10.1073/pnas.86.23.9370Ruiz-Mirazo, K., Briones, C., & de la Escosura, A. (2013). Prebiotic Systems Chemistry: New Perspectives for the Origins of Life. Chemical Reviews, 114(1), 285-366. doi:10.1021/cr2004844Flores, R., Serra, P., Minoia, S., Di Serio, F., & Navarro, B. (2012). Viroids: From Genotype to Phenotype Just Relying on RNA Sequence and Structural Motifs. Frontiers in Microbiology, 3. doi:10.3389/fmicb.2012.00217Steger, G., & Perreault, J.-P. (2016). Structure and Associated Biological Functions of Viroids. Advances in Virus Research, 141-172. doi:10.1016/bs.aivir.2015.11.002Diener, T. O. (1972). Potato spindle tuber viroid. Virology, 50(2), 606-609. doi:10.1016/0042-6822(72)90412-6Gross, H. J., Domdey, H., Lossow, C., Jank, P., Raba, M., Alberty, H., & Sänger, H. L. (1978). Nucleotide sequence and secondary structure of potato spindle tuber viroid. Nature, 273(5659), 203-208. doi:10.1038/273203a0Gast, F.-U., Kempe, D., Spieker, R. L., & Sänger, H. L. (1996). Secondary Structure Probing of Potato Spindle Tuber Viroid (PSTVd) and Sequence Comparison with Other Small Pathogenic RNA Replicons Provides Evidence for Central Non-canonical Base-pairs, Large A-rich Loops, and a Terminal Branch. Journal of Molecular Biology, 262(5), 652-670. doi:10.1006/jmbi.1996.0543Giguère, T., Raj Adkar-Purushothama, C., & Perreault, J.-P. (2014). Comprehensive Secondary Structure Elucidation of Four Genera of the Family Pospiviroidae. PLoS ONE, 9(6), e98655. doi:10.1371/journal.pone.0098655López-Carrasco, A., & Flores, R. (2016). Dissecting the secondary structure of the circular RNA of a nuclear viroid in vivo: A «naked» rod-like conformation similar but not identical to that observed in vitro. RNA Biology, 14(8), 1046-1054. doi:10.1080/15476286.2016.1223005Wang, Y., Zirbel, C. L., Leontis, N. B., & Ding, B. (2018). RNA 3-dimensional structural motifs as a critical constraint of viroid RNA evolution. PLOS Pathogens, 14(2), e1006801. doi:10.1371/journal.ppat.1006801Zhong, X., Leontis, N., Qian, S., Itaya, A., Qi, Y., Boris-Lawrie, K., & Ding, B. (2006). Tertiary Structural and Functional Analyses of a Viroid RNA Motif by Isostericity Matrix and Mutagenesis Reveal Its Essential Role in Replication. Journal of Virology, 80(17), 8566-8581. doi:10.1128/jvi.00837-06Zhong, X., Tao, X., Stombaugh, J., Leontis, N., & Ding, B. (2007). Tertiary structure and function of an RNA motif required for plant vascular entry to initiate systemic trafficking. The EMBO Journal, 26(16), 3836-3846. doi:10.1038/sj.emboj.7601812Zhong, X., Archual, A. J., Amin, A. A., & Ding, B. (2008). A Genomic Map of Viroid RNA Motifs Critical for Replication and Systemic Trafficking. The Plant Cell, 20(1), 35-47. doi:10.1105/tpc.107.056606Hernandez, C., & Flores, R. (1992). Plus and minus RNAs of peach latent mosaic viroid self-cleave in vitro via hammerhead structures. Proceedings of the National Academy of Sciences, 89(9), 3711-3715. doi:10.1073/pnas.89.9.3711Fadda, Z., Daròs, J. A., Fagoaga, C., Flores, R., & Duran-Vila, N. (2003). Eggplant Latent Viroid , the Candidate Type Species for a New Genus within the Family Avsunviroidae (Hammerhead Viroids). Journal of Virology, 77(11), 6528-6532. doi:10.1128/jvi.77.11.6528-6532.2003Navarro, B., & Flores, R. (1997). Chrysanthemum chlorotic mottle viroid: Unusual structural properties of a subgroup of self-cleaving viroids with hammerhead ribozymes. Proceedings of the National Academy of Sciences, 94(21), 11262-11267. doi:10.1073/pnas.94.21.11262Bussière, F., Ouellet, J., Côté, F., Lévesque, D., & Perreault, J. P. (2000). Mapping in Solution Shows the Peach Latent Mosaic Viroid To Possess a New Pseudoknot in a Complex, Branched Secondary Structure. Journal of Virology, 74(6), 2647-2654. doi:10.1128/jvi.74.6.2647-2654.2000GAGO, S. (2005). A kissing-loop interaction in a hammerhead viroid RNA critical for its in vitro folding and in vivo viability. RNA, 11(7), 1073-1083. doi:10.1261/rna.2230605Dube, A., Baumstark, T., Bisaillon, M., & Perreault, J.-P. (2010). The RNA strands of the plus and minus polarities of peach latent mosaic viroid fold into different structures. RNA, 16(3), 463-473. doi:10.1261/rna.1826710Sogo, J. M., Koller, T., & Diener, T. O. (1973). Potato spindle tuber viroid. Virology, 55(1), 70-80. doi:10.1016/s0042-6822(73)81009-8Goodman, T. C., Nagel, L., Rappold, W., Klotz, G., & Riesner, D. (1984). Viroid replication: equilibrium association constant and comparative activity measurements for the viroid-polymerase interaction. Nucleic Acids Research, 12(15), 6231-6246. doi:10.1093/nar/12.15.6231Sanger, H. L., Klotz, G., Riesner, D., Gross, H. J., & Kleinschmidt, A. K. (1976). Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proceedings of the National Academy of Sciences, 73(11), 3852-3856. doi:10.1073/pnas.73.11.3852McClements, W. L., & Kaesberg, P. (1977). Size and secondary structure of potato spindle tuber viroid. Virology, 76(2), 477-484. doi:10.1016/0042-6822(77)90230-6Bustamante, C., & Keller, D. (1995). Scanning Force Microscopy in Biology. Physics Today, 48(12), 32-38. doi:10.1063/1.881478Hansma, H. G., Kasuya, K., & Oroudjev, E. (2004). Atomic force microscopy imaging and pulling of nucleic acids. Current Opinion in Structural Biology, 14(3), 380-385. doi:10.1016/j.sbi.2004.05.005Kuznetsov, Y. G., Daijogo, S., Zhou, J., Semler, B. L., & McPherson, A. (2005). Atomic Force Microscopy Analysis of Icosahedral Virus RNA. Journal of Molecular Biology, 347(1), 41-52. doi:10.1016/j.jmb.2005.01.006Alvarez, D. E., Lodeiro, M. F., Ludueña, S. J., Pietrasanta, L. I., & Gamarnik, A. V. (2005). Long-Range RNA-RNA Interactions Circularize the Dengue Virus Genome. Journal of Virology, 79(11), 6631-6643. doi:10.1128/jvi.79.11.6631-6643.200

Epigenetic and post-transcriptional regulation of somatostatin receptor subtype 5 (SST5 ) in pituitary and pancreatic neuroendocrine tumors.

Somatostatin receptor subtype 5 (SST5 ) is an emerging biomarker and actionable target in pituitary (PitNETs) and pancreatic (PanNETs) neuroendocrine tumors. Transcriptional and epigenetic regulation of SSTR5 gene expression and mRNA biogenesis is poorly understood. Recently, an overlapping natural antisense transcript, SSTR5-AS1, potentially regulating SSTR5 expression, was identified. We aimed to elucidate whether epigenetic processes contribute to the regulation of SSTR5 expression in PitNETs (somatotropinomas) and PanNETs. We analyzed the SSTR5/SSTR5-AS1 human locus in silico to identify CpG islands. SSTR5 and SSTR5-AS1 expression was assessed by quantitative real-time PCR (qPCR) in 27 somatotropinomas, 11 normal pituitaries (NPs), and 15 PanNETs/paired adjacent (control) samples. We evaluated methylation grade in four CpG islands in the SSTR5/SSTR5-AS1 genes. Results revealed that SSTR5 and SSTR5-AS1 were directly correlated in NP, somatotropinoma and PanNET samples. Interestingly, selected CpG islands were differentially methylated in somatotropinomas compared with NPs. In PanNETs cell lines, SSTR5-AS1 silencing downregulated SSTR5 expression, altered aggressiveness features, and influenced pasireotide response. These results provide evidence that SSTR5 expression in PitNETs and PanNETs can be epigenetically regulated by the SSTR5-AS1 antisense transcript and, indirectly, by DNA methylation, which may thereby impact tumor behavior and treatment response

The impact of predation by marine mammals on Patagonian toothfish longline fisheries

Predatory interaction of marine mammals with longline fisheries is observed globally, leading to partial or complete loss of the catch and in some parts of the world to considerable financial loss. Depredation can also create additional unrecorded fishing mortality of a stock and has the potential to introduce bias to stock assessments. Here we aim to characterise depredation in the Patagonian toothfish (Dissostichus eleginoides) fishery around South Georgia focusing on the spatio-temporal component of these interactions. Antarctic fur seals (Arctocephalus gazella), sperm whales (Physeter macrocephalus), and orcas (Orcinus orca) frequently feed on fish hooked on longlines around South Georgia. A third of longlines encounter sperm whales, but loss of catch due to sperm whales is insignificant when compared to that due to orcas, which interact with only 5% of longlines but can take more than half of the catch in some cases. Orca depredation around South Georgia is spatially limited and focused in areas of putative migration routes, and the impact is compounded as a result of the fishery also concentrating in those areas at those times. Understanding the seasonal behaviour of orcas and the spatial and temporal distribution of “depredation hot spots” can reduce marine mammal interactions, will improve assessment and management of the stock and contribute to increased operational efficiency of the fishery. Such information is valuable in the effort to resolve the human-mammal conflict for resources

Exploring the effectiveness of the output-based aid voucher program to increase uptake of gender-based violence recovery services in Kenya: a qualitative evaluation

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Few studies in Africa have explored in detail the ability of output-based aid (OBA) voucher programs to increase access to gender-based violence recovery (GBVR) services. Methods: A qualitative study was conducted in 2010 and involved: (i) in-depth interviews (IDIs) with health managers, service providers, voucher management agency (VMA) managers and (ii) focus group discussions (FGDs) with voucher users, voucher non-users, voucher distributors and opinion leaders drawn from five program sites in Kenya. Results: The findings showed promising prospects for the uptake of OBA GBVR services among target population. However, a number of factors affect the uptake of the services. These include lack of general awareness of the GBVR services vouchers, lack of understanding of the benefit package, immediate financial needs of survivors, as well as stigma and cultural beliefs that undermine reporting of cases or seeking essential medical services. Moreover, accreditation of only hospitals to offer GBVR services undermines access to the services in rural areas. Poor responsiveness from law enforcement agencies and fear of reprisal from perpetrators also undermine treatment options and access to medical services. Low provider knowledge on GBVR services and lack of supplies also affect effective provision and management of GBVR services. Conclusions: The above findings suggest that there is a need to build the capacity of health care providers and police officers, strengthen the community strategy component of the OBA program to promote the GBVR services voucher, and conduct widespread community education programs aimed at prevention, ensuring survivors know how and where to access services and addressing stigma and cultural barriers.The Bill and Melinda Gates Foundatio

Tensor voting for robust color edge detection

The final publication is available at Springer via http://dx.doi.org/10.1007/978-94-007-7584-8_9This chapter proposes two robust color edge detection methods based on tensor voting. The first method is a direct adaptation of the classical tensor voting to color images where tensors are initialized with either the gradient or the local color structure tensor. The second method is based on an extension of tensor voting in which the encoding and voting processes are specifically tailored to robust edge detection in color images. In this case, three tensors are used to encode local CIELAB color channels and edginess, while the voting process propagates both color and edginess by applying perception-based rules. Unlike the classical tensor voting, the second method considers the context in the voting process. Recall, discriminability, precision, false alarm rejection and robustness measurements with respect to three different ground-truths have been used to compare the proposed methods with the state-of-the-art. Experimental results show that the proposed methods are competitive, especially in robustness. Moreover, these experiments evidence the difficulty of proposing an edge detector with a perfect performance with respect to all features and fields of application.This research has been supported by the Swedish Research Council under the project VR 2012-3512

The atypical iron-coordination geometry of cytochrome f remains unchanged upon binding to plastocyanin, as inferred by XAS

The transient complex between cytochrome f and plastocyanin from the cyanobacterium Nostoc sp. PCC 7119 has been analysed by X-ray Absorption Spectroscopy in solution, using both proteins in their oxidized and reduced states. Fe K-edge data mainly shows that the atypical metal coordination geometry of cytochrome f, in which the N-terminal amino acid acts as an axial ligand of the heme group, remains unaltered upon binding to its redox partner, plastocyanin. This fact suggests that cytochrome f provides a stable binding site for plastocyanin and minimizes the reorganization energy required in the transient complex formation, which could facilitate the electron transfer between the two redox partners

Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values and small sample sizes.

The data set supporting the results of this article is available in the Dryad repository, http://dx.doi.org/10.5061/dryad.6f4qs. Moustakas, A. and Evans, M. R. (2015) Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values.Plant survival is a key factor in forest dynamics and survival probabilities often vary across life stages. Studies specifically aimed at assessing tree survival are unusual and so data initially designed for other purposes often need to be used; such data are more likely to contain errors than data collected for this specific purpose

Evaluating the Quality of Research into a Single Prognostic Biomarker: A Systematic Review and Meta-analysis of 83 Studies of C-Reactive Protein in Stable Coronary Artery Disease

Background Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease. Methods and Findings We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78–2.17), with substantial heterogeneity (I2 = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39–1.96), I2 = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13–1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57–0.66). Conclusion Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research