Bayesian variable selection and survival modeling: assessing the Most important comorbidities that impact lung and colorectal cancer survival in Spain

ancer survival represents one of the main indicators of interest in cancer epidemiology. However, the survival of cancer patients can be affected by several factors, such as comorbidities, that may interact with the cancer biology. Moreover, it is interesting to understand how different cancer sites and tumour stages are affected by different comorbidities. Identifying the comorbidities that affect cancer survival is thus of interest as it can be used to identify factors driving the survival of cancer patients. This information can also be used to identify vulnerable groups of patients with comorbidities that may lead to worst prognosis of cancer. We address these questions and propose a principled selection and evaluation of the effect of comorbidities on the overall survival of cancer patients. In the first step, we apply a Bayesian variable selection method that can be used to identify the comorbidities that predict overall survival. In the second step, we build a general Bayesian survival model that accounts for time-varying effects. In the third step, we derive several posterior predictive measures to quantify the effect of individual comorbidities on the population overall survival. We present applications to data on lung and colorectal cancers from two Spanish population-based cancer registries. The proposed methodology is implemented with a combination of the R-packages mombf and rstan. We provide the code for reproducibility at https://github.com/migariane/BayesVarImpComorbiCancer

Estudio de la botica de la Alhambra en el siglo XVI

Stock inventories are a very useful source of information in the study of the history of pharmaceutical science. Thisarticle reports on two accounts from the XVI century related to this subject, which on analysis provide interestingand relevant information on the functioning of a pharmacy in the citadel of the Alhambra Palace in Granada,during the early modern age.Los inventarios que recogen las existencias de las boticas son documentos de gran interés para la Historia de laFarmacia. Se informa en este artículo del hallazgo de dos relaciones de este tipo, fechadas en el siglo XVI, cuyoanálisis ofrece interesantes datos sobre la botica de la Alhambra de Granada en la Edad Moderna

Response of Quercus ilex seedlings to Phytophthora spp. root infection in a soil infestation test

[EN] Phytophthora species are the main agents associated with oak (Quercus spp.) decline, together with the changing environmental conditions and the intensive land use. The aim of this study was to evaluate the susceptibility of Quercus ilex to the inoculation with eight Phytophthora species. Seven to eight month old Q. ilex seedlings grown from acorns, obtained from two Spanish origins, were inoculated with P. cinnamomi, P. cryptogea, P. gonapodyides, P. megasperma, P. nicotianae, P. plurivora, P. psychrophila and P. quercina. All Phytophthora inoculated seedlings showed decline and symptoms including small dark necrotic root lesions, root cankers, and loss of fine roots and tap root. The most aggressive species were P. cinnamomi, P. cryptogea, P. gonapodyides, P. plurivora and P. psychrophila followed by P. megasperma., while Phytophthora quercina and P. nicotianae were the less aggressive species. Results obtained confirm that these Phytophthora species could constituted a threat to Q. ilex ecosystems and the implications are further discussed.The authors are grateful to A. Solla and his team from the Centro Universitario de Plasencia-Universidad de Extremadura (Spain) for helping in the acorns collection and to the CIEF (Centro para la Investigación y Experimentación Forestal, Generalitat Valenciana, Valencia, Spain) for providing the acorns. This research was supported by funding from the project AGL2011- 30438-C02-01 (Ministerio de Economía y Competitividad, Spain).Mora-Sala, B.; Abad Campos, P.; Berbegal Martinez, M. (2018). Response of Quercus ilex seedlings to Phytophthora spp. root infection in a soil infestation test. European Journal of Plant Pathology. https://doi.org/10.1007/s10658-018-01650-6SÁlvarez, L. A., Pérez-Sierra, A., Armengol, J., & García-Jiménez, J. (2007). 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Análisis y Prospectiva - Serie Agrinfo/Medioambiente n° 8. Ed. Ministerio de Agricultura, Alimentación y Medio Ambiente. In NIPO: 280-14-081-9.Martín-García, J., Solla, A., Corcobado, T., Siasou, E., & Woodward, S. (2015). Influence of temperature on germination of Quercus ilex in Phytophthora cinnamomi, P. gonapodyides, P. quercina and P. psychrophila infested soils. Forest Pathology, 45, 215–223.Maurel, M., Robin, C., Capron, G., & Desprez-Loustau, M. L. (2001). Effects of root damage associated with Phytophthora cinnamomi on water elations, biomass accumulation, mineral nutrition and vulnerability to water deficit of five oak and chestnut species. Forest Pathology, 31, 353–369.McKinney, H. H. (1923). Influence of soil temperature and moisture on infection of wheat seedlings by Helminthosporium sativum. Journal of Agricultural Research, 26, 195–217.Moralejo, E., Pérez-Sierra, A., Álvarez, L. A., Belbahri, L., Lefort, F., & Descals, E. (2009). Multiple alien Phytophthora taxa discovered on diseased ornamental plants in Spain. Plant Pathology, 58, 100–110.Mora-Sala, B., Berbegal, M., & Abad-Campos, P. (2018). The use of qPCR reveals a high frequency of Phytophthora quercina in two Spanish holm oak areas. Forests, 9(11):697. https://doi.org/10.3390/f9110697 .Moreira, A. C., & Martins, J. M. S. (2005). Influence of site factors on the impact of Phytophthora cinnamomi in cork oak stands in Portugal. Forest Pathology, 35, 145–162.Mrázková, M., Černý, K., Tomosovsky, M., Strnadová, V., Gregorová, B., Holub, V., Panek, M., Havrdová, L., & Hejná, M. (2013). Occurrence of Phytophthora multivora and Phytophthora plurivora in the Czech Republic. Plant Protection Science, 49, 155–164.Navarro, R. M., Gallo, L., Sánchez, M. E., Fernández, P., & Trapero, A. (2004). Efecto de distintas fertilizaciones de fósforo en la resistencia de brinzales de encina y alcornoque a Phytophthora cinnamomi Rands. Investigación Agraria. 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Estudio de la botica de la Alhambra en el siglo XVI Study of the Alhambra pharmacy in the XVI century

Los inventarios que recogen las existencias de las boticas son documentos de gran interés para la Historia de la Farmacia. Se informa en este artículo del hallazgo de dos relaciones de este tipo, fechadas en el siglo XVI, cuyo análisis ofrece interesantes datos sobre la botica de la Alhambra de Granada en la Edad Modern

Vitamin C activates young LINE-1 elements in mouse embryonic stem cells via H3K9me3 demethylation.

BACKGROUND: Vitamin C (vitC) enhances the activity of 2-oxoglutarate-dependent dioxygenases, including TET enzymes, which catalyse DNA demethylation, and Jumonji-domain histone demethylases. The epigenetic remodelling promoted by vitC improves the efficiency of induced pluripotent stem cell derivation, and is required to attain a ground-state of pluripotency in embryonic stem cells (ESCs) that closely mimics the inner cell mass of the early blastocyst. However, genome-wide DNA and histone demethylation can lead to upregulation of transposable elements (TEs), and it is not known how vitC addition in culture media affects TE expression in pluripotent stem cells. RESULTS: Here we show that vitC increases the expression of several TE families, including evolutionarily young LINE-1 (L1) elements, in mouse ESCs. We find that TET activity is dispensable for L1 upregulation, and that instead it occurs largely as a result of H3K9me3 loss mediated by KDM4A/C histone demethylases. Despite increased L1 levels, we did not detect increased somatic insertion rates in vitC-treated cells. Notably, treatment of human ESCs with vitC also increases L1 protein levels, albeit through a distinct, post-transcriptional mechanism. CONCLUSION: VitC directly modulates the expression of mouse L1s and other TEs through epigenetic mechanisms, with potential for downstream effects related to the multiple emerging roles of L1s in cellular function

Proliferating Cell Nuclear Antigen (PCNA) Interactions in Solution Studied by NMR

PCNA is an essential factor for DNA replication and repair. It forms a ring shaped structure of 86 kDa by the symmetric association of three identical protomers. The ring encircles the DNA and acts as a docking platform for other proteins, most of them containing the PCNA Interaction Protein sequence (PIP-box). We have used NMR to characterize the interactions of PCNA with several other proteins and fragments in solution. The binding of the PIP-box peptide of the cell cycle inhibitor p21 to PCNA is consistent with the crystal structure of the complex. A shorter p21 peptide binds with reduced affinity but retains most of the molecular recognition determinants. However the binding of the corresponding peptide of the tumor suppressor ING1 is extremely weak, indicating that slight deviations from the consensus PIP-box sequence dramatically reduce the affinity for PCNA, in contrast with a proposed less stringent PIP-box sequence requirement. We could not detect any binding between PCNA and the MCL-1 or the CDK2 protein, reported to interact with PCNA in biochemical assays. This suggests that they do not bind directly to PCNA, or they do but very weakly, with additional unidentified factors stabilizing the interactions in the cell. Backbone dynamics measurements show three PCNA regions with high relative flexibility, including the interdomain connector loop (IDCL) and the C-terminus, both of them involved in the interaction with the PIP-box. Our work provides the basis for high resolution studies of direct ligand binding to PCNA in solution.This work was supported by the Spanish Ministry of Economic Affairs and Competitiveness (www.mineco.gob.es)grants CTQ2011-28680 to FJB and BIO2009-13265-CO2-01 to IL, and by the grant BIPEDD-CM (P-BIO-0214-2006) from Comunidad Autónoma de Madrid (www.madrid.org) to RCO. ADB was supported by a Juan de la Cierva contract from the Spanish Ministry of Economic Affairs and Competitiveness

Co-transcriptional Analysis of Self-Cleaving Ribozymes and Their Ligand Dependence.

Self-cleaving ribozymes are RNA molecules that catalyze a site-specific self-scission reaction. Analysis of self-cleavage is a crucial aspect of the biochemical study and understanding of these molecules. Here we describe a co-transcriptional assay that allows the analysis of self-cleaving ribozymes in different reaction conditions and in the presence of desired ligands and/or cofactors. Utilizing a standard T7 RNA polymerase in vitro transcription system under limiting Mg2+ concentration, followed by a 25-fold dilution of the reaction in desired conditions of self-cleavage (buffer, ions, ligands, pH, temperature, etc.) to halt the synthesis of new RNA molecules, allows the study of self-scission of these molecules without the need for purification or additional preparation steps, such as refolding procedures. Furthermore, because the transcripts are not denatured, this assay likely yields RNAs in conformations relevant to co-transcriptionally folded species in vivo