On the Theory of Evolution Versus the Concept of Evolution: Three Observations

Here we address three misconceptions stated by Rice et al. in their observations of our article Paz-y-Miño and Espinosa (Evo Edu Outreach 2:655–675, 2009), published in this journal. The five authors titled their note “The Theory of Evolution is Not an Explanation for the Origin of Life.” First, we argue that it is fallacious to believe that because the formulation of the theory of evolution, as conceived in the 1800s, did not include an explanation for the origin of life, nor of the universe, the concept of evolution would not allow us to hypothesize the possible beginnings of life and its connections to the cosmos. Not only Stanley Miller’s experiments of 1953 led scientists to envision a continuum from the inorganic world to the origin and diversification of life, but also Darwin’s own writings of 1871. Second, to dismiss the notion of Rice et al. that evolution does not provide explanations concerning the universe or the cosmos, we identify compelling scientific discussions on the topics: Zaikowski et al. (Evo Edu Outreach 1:65–73, 2008), Krauss (Evo Edu Outreach 3:193–197, 2010), Peretó et al. (Orig Life Evol Biosph 39:395–406, 2009) and Follmann and Brownson (Naturwissenschaften 96:1265–1292, 2009). Third, although we acknowledge that the term Darwinism may not be inclusive of all new discoveries in evolution, and also that creationists and Intelligent Designers hijack the term to portray evolution as ideology, we demonstrate that there is no statistical evidence suggesting that the word Darwinism interferes with public acceptance of evolution, nor does the inclusion of the origin of life or the universe within the concept of evolution. We examine the epistemological and empirical distinction between the theory of evolution and the concept of evolution and conclude that, although the distinction is important, it should not compromise scientific logic

Relationship of an hRAD54 gene polymorphism (2290 C/T) in an Ecuadorian population with chronic myelogenous leukemia

The hRAD54 gene is a key member of the RAD52 epistasis group involved in repair of double-strand breaks (DSB) by homologous recombination (HR). Thus, alterations of the normal function of these genes could generate genetic instability, shifting the normal process of the cell cycle, leading the cells to develop into cancer. In this work we analyzed exon 18 of the hRAD54 gene, which has been previously reported by our group to carry a silent polymorphism, 2290 C/T (Ala730Ala), associated to meningiomas. We performed a PCR-SSCP method to detect the polymorphism in 239 samples including leukemia and normal control population. The results revealed that the 2290 C/T polymorphism has frequencies of 0.1 for the leukemia and 0.1 for the control group. These frequencies show no statistical differences. Additionally, we dissected the leukemia group in chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) to evaluate the polymorphism. The frequencies found in these subgroups were 0.14 for CML and 0.05 for ALL. We found statistically significant differences between CML patients and the control group (p < 0.05) but we did not find significant differences between ALL and the control group (p > 0.05). These results suggest a possible link between the 2290 C/T polymorphism of the hRAD54 gene and CML

Multiclasificadores basados en aprendizaje automático como herramienta para la evaluación del perfil neurotóxico de líquidos iónicos

Los líquidos iónicos poseen un perfil fisicoquímico único, el cual los provee de un amplio rango de aplicaciones. Su variabilidad estructural casi ilimitada permite su diseño para tareas específicas. Sin embargo, su sustentabilidad, específicamente su seguridad desde el punto de vista toxicológico, ha sido frecuentemente cuestionada. Este último aspecto limita significativamente el cumplimiento de las regulaciones establecidas por la Unión Europea para el registro, evaluación, autorización y restricción de compuestosquímicos (REACH), así como su aplicación final. Debido a que la mayoría de los líquidos iónicos no han sido sintetizados, se hace evidente la importancia del desarrollo de herramientas quimioinformáticas que, de forma eficiente, permitan evaluar el potencial toxicológico de estos compuestos. En este sentido, el uso combinado de múltiples clasificadores ha demostrado superar las limitaciones de desempeño asociadas al uso de clasificadores individuales. En el presente trabajo fueron evaluadas varias estrategias alternativas de multiclasificadores basados en técnicas de aprendizaje automático supervisado, como herramientas para la evaluación del perfil neurotóxico de líquidos iónicos basado en la inhibición de la enzima acetilcolinesterasa, como indicador de neurotoxicidad. Se obtuvieron dos multiclasificadores con una alta capacidad predictiva sobre un conjunto de validación externa (no utilizado en el proceso de aprendizaje de los modelos). De acuerdo a los resultados obtenidos el 96% de un conjunto de nuevos líquidos iónicos podrá ser correctamente clasificado con la utilizaciónde estos multiclasificadores, los cuales constituyen herramientas de toma de decisión útiles en el campo del diseño y desarrollo de nuevos líquidos iónicos sustentables

Gene Prioritization through Consensus Strategy, Enrichment Methodologies Analysis, and Networking for Osteosarcoma Pathogenesis

[Abstract] Osteosarcoma is the most common subtype of primary bone cancer, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma; however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein–protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events, such as MMP2 and MMP9, and genes associated with DNA repair complexes, like ATM, ATR, CHEK1, and RAD51. In this study, we have identified well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.Instituto Carlos III; PI17/01826Xunta de Galicia; ED431C 2018/49Xunta de Galicia; ED431G/0

Prediction of Breast Cancer Proteins Involved in Immunotherapy, Metastasis, and RNA-Binding Using Molecular Descriptors and Artifcial Neural Networks

[Abstract] Breast cancer (BC) is a heterogeneous disease where genomic alterations, protein expression deregulation, signaling pathway alterations, hormone disruption, ethnicity and environmental determinants are involved. Due to the complexity of BC, the prediction of proteins involved in this disease is a trending topic in drug design. This work is proposing accurate prediction classifer for BC proteins using six sets of protein sequence descriptors and 13 machine-learning methods. After using a univariate feature selection for the mix of fve descriptor families, the best classifer was obtained using multilayer perceptron method (artifcial neural network) and 300 features. The performance of the model is demonstrated by the area under the receiver operating characteristics (AUROC) of 0.980±0.0037, and accuracy of 0.936±0.0056 (3-fold cross-validation). Regarding the prediction of 4,504 cancer-associated proteins using this model, the best ranked cancer immunotherapy proteins related to BC were RPS27, SUPT4H1, CLPSL2, POLR2K, RPL38, AKT3, CDK3, RPS20, RASL11A and UBTD1; the best ranked metastasis driver proteins related to BC were S100A9, DDA1, TXN, PRNP, RPS27, S100A14, S100A7, MAPK1, AGR3 and NDUFA13; and the best ranked RNA-binding proteins related to BC were S100A9, TXN, RPS27L, RPS27, RPS27A, RPL38, MRPL54, PPAN, RPS20 and CSRP1. This powerful model predicts several BC-related proteins that should be deeply studied to fnd new biomarkers and better therapeutic targets. Scripts can be downloaded at https://github.com/muntisa/ neural-networks-for-breast-cancer-proteins.This work was supported by a) Universidad UTE (Ecuador), b) the Collaborative Project in Genomic Data Integration (CICLOGEN) PI17/01826 funded by the Carlos III Health Institute from the Spanish National plan for Scientific and Technical Research and Innovation 2013-2016 and the European Regional Development Funds (FEDER) - “A way to build Europe”; c) the General Directorate of Culture, Education and University Management of Xunta de Galicia ED431D 2017/16 and “Drug Discovery Galician Network” Ref. ED431G/01 and the “Galician Network for Colorectal Cancer Research” (Ref. ED431D 2017/23); d) the Spanish Ministry of Economy and Competitiveness for its support through the funding of the unique installation BIOCAI (UNLC08-1E-002, UNLC13-13-3503) and the European Regional Development Funds (FEDER) by the European Union; e) the Consolidation and Structuring of Competitive Research Units - Competitive Reference Groups (ED431C 2018/49), funded by the Ministry of Education, University and Vocational Training of the Xunta de Galicia endowed with EU FEDER funds; f) research grants from Ministry of Economy and Competitiveness, MINECO, Spain (FEDER CTQ2016-74881-P), Basque government (IT1045-16), and kind support of Ikerbasque, Basque Foundation for Science; and, g) Sociedad Latinoamericana de Farmacogenómica y Medicina Personalizada (SOLFAGEM)Xunta de Galicia; ED431D 2017/16Xunta de Galicia; ED431G/01Xunta de Galicia; ED431D 2017/23Xunta de Galicia; ED431C 2018/49Gobierno Vasco; IT1045-1

OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine

[Abstract] Breast cancer (BC) is the leading cause of cancer-related death among women and the most commonly diagnosed cancer worldwide. Although in recent years large-scale efforts have focused on identifying new therapeutic targets, a better understanding of BC molecular processes is required. Here we focused on elucidating the molecular hallmarks of BC heterogeneity and the oncogenic mutations involved in precision medicine that remains poorly defined. To fill this gap, we established an OncoOmics strategy that consists of analyzing genomic alterations, signaling pathways, protein-protein interactome network, protein expression, dependency maps in cell lines and patient-derived xenografts in 230 previously prioritized genes to reveal essential genes in breast cancer. As results, the OncoOmics BC essential genes were rationally filtered to 140. mRNA up-regulation was the most prevalent genomic alteration. The most altered signaling pathways were associated with basal-like and Her2-enriched molecular subtypes. RAC1, AKT1, CCND1, PIK3CA, ERBB2, CDH1, MAPK14, TP53, MAPK1, SRC, RAC3, BCL2, CTNNB1, EGFR, CDK2, GRB2, MED1 and GATA3 were essential genes in at least three OncoOmics approaches. Drugs with the highest amount of clinical trials in phases 3 and 4 were paclitaxel, docetaxel, trastuzumab, tamoxifen and doxorubicin. Lastly, we collected ~3,500 somatic and germline oncogenic variants associated with 50 essential genes, which in turn had therapeutic connectivity with 73 drugs. In conclusion, the OncoOmics strategy reveals essential genes capable of accelerating the development of targeted therapies for precision oncology.Instituto de Salud Carlos III; PI17/0182

Implications of a RAD54L polymorphism (2290C/T) in human meningiomas as a risk factor and/or a genetic marker

BACKGROUND: RAD54L (OMIM 603615, Locus Link 8438) has been proposed as a candidate oncosupressor in tumours bearing a non-random deletion of 1p32, such as breast or colon carcinomas, lymphomas and meningiomas. In a search for RAD54L mutations in 29 menigiomas with allelic deletions in 1p, the only genetic change observed was a silent C/T transition at nucleotide 2290 in exon 18. In this communication the possible association of the 2290C/T polymorphism with the risk of meningiomas was examined. In addition, the usefulness of this polymorphism as a genetic marker within the meningioma consensus deletion region in 1p32 was also verified. The present study comprises 287 blood control samples and 70 meningiomas from Spain and Ecuador. Matched blood samples were only available from Spanish patients. RESULTS: The frequency of the rare allele-T and heterozygotes for the 2290C/T polymorphism in the blood of Spanish meningioma patients and in the Ecuadorian meningioma tumours was higher than in the control population (P < 0.05). Four other rare variants (2290C/G, 2299C/G, 2313G/A, 2344A/G) were found within 50 bp at the 3' end of RAD54L. Frequent loss of heterozygosity for the 2290C/T SNP in meningiomas allowed to further narrow the 1p32 consensus region of deletion in meningiomas to either 2.08 Mbp – within D1S2713 (44.35 Mbp) and RAD54L (46.43 Mbp) – or to 1.47 Mbp – within RAD54L and D1S2134 (47.90 Mbp) – according to recent gene mapping results. CONCLUSION: The statistical analysis of genotypes at the 2290C/T polymorphism suggest an association between the rare T allele and the development of meningeal tumours. This polymorphism can be used as a genetic marker inside the consensus deletion region at 1p32 in meningiomas

Should the teaching of biological evolution include the origin of life?

The development of mainstream research on the origin of life as an outcome of Darwinian evolution is discussed. It is argued that prebiotic evolution and the origin of life should not be excluded from the syllabus and should be part of classes on biological evolution, and that the transition from non-living to living matter is best understood when seen as part of evolutionary biology. The wide acceptance of evolutionary approaches to the study of the emergence of life in European and Latin American countries is discussed

Mirror-Mark Tests Performed on Jackdaws Reveal Potential Methodological Problems in the Use of Stickers in Avian Mark-Test Studies

Some animals are capable of recognizing themselves in a mirror, which is considered to be demonstrated by passing the mark test. Mirror self-recognition capacity has been found in just a few mammals having very large brains and only in one bird, the magpie (Pica pica). The results obtained in magpies have enormous biological and cognitive implications because the fact that magpies were able to pass the mark test meant that this species is at the same cognitive level with great apes, that mirror self-recognition has evolved independently in the magpie and great apes (which diverged 300 million years ago), and that the neocortex (which is not present in the bird's brains) is not a prerequisite for mirror self-recognition as previously believed. Here, we have replicated the experimental design used on magpies to determine whether jackdaws (Corvus monedula) are also capable of mirror self-recognition by passing the mark test. We found that our nine jackdaws showed a very high interest towards the mirror and exhibited self-contingent behavior as soon as mirrors were introduced. However, jackdaws were not able to pass the mark test: both sticker-directed actions and sticker removal were performed with a similar frequency in both the cardboard (control) and the mirror conditions. We conclude that our jackdaws' behaviour raises non-trivial questions about the methodology used in the avian mark test. Our study suggests that the use of self-adhesive stickers on sensitive throat feathers may open the way to artefactual results because birds might perceive the stickers tactilely.JMPS was funded by Ministerio de Educación and Consejería de Innovación, C 420 iencia y Empresa under International Excellence Campus Program (CEI Granada) and TPC was funded by Ministerio de Educación y Ciencia by a postdoctoral contract from the project CGL2011-25634

Dominance relationships and coalitionary aggression against conspecifics in female carrion crows

Funding: European Research Council (ERCStG-336536 FuncSpecGen to J.W.), the Swedish Research Council Vetenskapsrådet (621-2013-4510 to J.W.), Knut and Alice Wallenberg Foundation (to J.W.) and Tovetorp fieldstation through Stockholm University.Cooperation is a prevailing feature of many animal systems. Coalitionary aggression, where a group of individuals engages in coordinated behaviour to the detriment of conspecific targets, is a form of cooperation involving complex social interactions. To date, evidence has been dominated by studies in humans and other primates with a clear bias towards studies of male-male coalitions. We here characterize coalitionary aggression behaviour in a group of female carrion crows consisting of recruitment, coordinated chase, and attack. The individual of highest social rank liaised with the second most dominant individual to engage in coordinated chase and attack of a lower ranked crow on several occasions. Despite active intervention by the third most highly ranked individual opposing the offenders, the attack finally resulted in the death of the victim. All individuals were unrelated, of the same sex, and naive to the behaviour excluding kinship, reproduction, and social learning as possible drivers. Instead, the coalition may reflect a strategy of the dominant individual to secure long-term social benefits. Overall, the study provides evidence that members of the crow family engage in coordinated alliances directed against conspecifics as a possible means to manipulate their social environment.Publisher PDFPeer reviewe