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In recent years, the continued detection of complex organic molecules of prebiotic interest has refueled the interest in a panspermic origin of life. The prebiotic molecule glyceraldehyde is proposed to be formed from (Z)-1,2-ethenediol, a molecule recently detected toward the G+0.693-0.027 molecular cloud at the galactic center. In this work, we computationally simulate the formation of (Z)-1,2-ethenediol from vinyl alcohol on the surface of amorphous solid water in a two-step synthesis involving an OH addition and an H abstraction reaction. In total, we considered all reaction possibilities of the 1,1- and 1,2-OH addition to vinyl alcohol followed by H abstraction or H addition reactions on the resulting radicals. The combination of these reactions is capable of explaining the formation of (Z)-1,2-ethenediol provided a suprathermal diffusion of OH. We also conclude that our proposed formation pathway is not selective and also yields other abstraction and addition products. Key in our findings is the connection between the adsorption modes of the reactants and intermediates and the stereoselectivity of the reactions.

The Tousled-like kinase (TLKs) family belongs to a distinct branch of Ser/Thr kinases that exhibit the highest levels of activity during DNA replication. Here the authors present the crystal structure of the kinase domain from human TLK2 and propose an activation model for TLK2 based on biochemical and phosphoproteomics experiments.

Here we perform a large-scale study of the structural properties and the expression of proteins that constitute the human Centrosome. Centrosomal proteins tend to be larger than generic human proteins (control set), since their genes contain in average more exons (20.3 versus 14.6). They are rich in predicted disordered regions, which cover 57% of their length, compared to 39% in the general human proteome. They also contain several regions that are dually predicted to be disordered and coiled-coil at the same time: 55 proteins (15%) contain disordered and coiled-coil fragments that cover more than 20% of their length. Helices prevail over strands in regions homologous to known structures (47% predicted helical residues against 17% predicted as strands), and even more in the whole centrosomal proteome (52% against 7%), while for control human proteins 34.5% of the residues are predicted as helical and 12.8% are predicted as strands. This difference is mainly due to residues predicted as disordered and helical (30% in centrosomal and 9.4% in control proteins), which may correspond to alpha-helix forming molecular recognition features (α-MoRFs). We performed expression assays for 120 full-length centrosomal proteins and 72 domain constructs that we have predicted to be globular. These full-length proteins are often insoluble: Only 39 out of 120 expressed proteins (32%) and 19 out of 72 domains (26%) were soluble. We built or retrieved structural models for 277 out of 361 human proteins whose centrosomal localization has been experimentally verified. We could not find any suitable structural template with more than 20% sequence identity for 84 centrosomal proteins (23%), for which around 74% of the residues are predicted to be disordered or coiled-coils. The three-dimensional models that we built are available at http://ub.cbm.uam.es/centrosome/models/index.php.

The objective of this study is to compare two EGFR testing methodologies (a commercial real-time PCR kit and a specific EGFR mutant immunohistochemistry), with direct sequencing and to investigate the limit of detection (LOD) of both PCR-based methods. We identified EGFR mutations in 21 (16%) of the 136 tumours analyzed by direct sequencing. Interestingly, the Therascreen EGFR Mutation Test kit was able to characterize as wild-type one tumour that could not be analyzed by direct sequencing of the PCR product. We then compared the LOD of the kit and that of direct sequencing using the available mutant tumours. The kit was able to detect the presence of a mutation in a 1% dilution of the total DNA in nine of the 18 tumours (50%), which tested positive with the real-time quantitative PCR method. In all cases, EGFR mutation was identified at a dilution of 5%. Where the mutant DNA represented 30% of the total DNA, sequencing was able to detect mutations in 12 out of 19 cases (63%). Additional experiments with genetically defined standards (EGFR ΔE746-A750/+ and EGFR L858R/+) yielded similar results. Immunohistochemistry (IHC) staining with exon 19-specific antibody was seen in eight out of nine cases with E746-A750del detected by direct sequencing. Neither of the two tumours with complex deletions were positive. Of the five L858R-mutated tumours detected by the PCR methods, only two were positive for the exon 21-specific antibody. The specificity was 100% for both antibodies. The LOD of the real-time PCR method was lower than that of direct sequencing. The mutation specific IHC produced excellent specificity.

INTRODUCTION: While some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. Our goals in this study were (1) to further confirm our microarray data, (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to investigate the potential of P63 IHC to minimize the proportion of "carcinoma NOS (not otherwise specified)" in a prospective series of small tumor samples. METHODS: With these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma NOS, that were further classified by the result of P63 and TTF-1 IHC. RESULTS: The results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p

El objetivo de este artículo es analizar los argumentos mediante los cuales la Corte Constitucional de Colombia ha fallado en contra de integrantes de la Iglesia Testigos de Jehová, quienes se niegan a realizar «actos cívicos» por considerarlos como «adoración». Para la Corte, dicha interpretación es inadmisible, por lo cual señala la necesidad de distinguir lo religioso y lo cívico, al mismo tiempo que reafirma la importancia de participar en actos «de amor y veneración a la patria». Mediante una metodología cualitativa, los argumentos esgrimidos por el alto tribunal son analizados a la luz de recientes teorías de las ciencias sociales sobre la religión y la secularización. Se concluye que los fallos de la Corte, basados en una cuestión semántica aparentemente anodina, reflejan concepciones obsoletas y muy debatibles sobre la religión y la secularidad, al igual que evidencian inesperadas limitaciones a la libertad religiosa y demuestran la imposición de una cosmovisión estatal. Todo ello permite cuestionar el carácter secular y pluralista del Estado colombiano.

Objective/Context: This paper examines the arguments of the Constitutional Court of Colombia in a sentence declaring that Pentecostalism represents a threat to indigenous cultures and to the country’s cultural diversity. The sentence was issued in 1998, a few years after the political Constitution (1991) declared that Colombia is a pluralist nation that protects the cultural diversity of the country and the right to religious freedom. Methodology: A qualitative and hermeneutical study of the sentence was implemented to understand the arguments presented by the Court. Subsequently, a critical analysis of those arguments was carried out, questioning the pluralist presuppositions related to key categories such as “indigenous cultures,” “religion,” and “diversity.” Conclusions: The pluralist institution has been unable to recognize the dynamic and manifold realities of lived religion, as well as the problems related to the double marginalization of a religious minority within an ethnic minority. Furthermore, the pluralist imperative to protect cultural diversity places limits upon alterity and promotes new forms of exclusion. Originality: The jurisprudence under scrutiny is not studied in its legal or ethical dimensions—as it has been done in the past—but as the implementation of a pluralist ideology grounded in a certain worldview. Thus, pluralism is critically examined in its ontological, axiological, epistemological, and praxeological principles.

Este artículo examina el fallo de la Corte Constitucional de Colombia en el cual se avalan las sanciones impuestas por las autoridades tradicionales de la etnia arhuaca a los indígenas evangélicos que desean practicar libremente su religión dentro de su resguardo. Se analizan detenidamente los argumentos de dicha Corte, la cual, mediante su fallo, pretende proteger la diversidad étnica y cultural y permite el extrañamiento de los arhuacos evangélicos. Los conceptos manejados por la Corte se contrastan con recientes teorías antropológicas y sociológicas sobre temas como la identidad, las fronteras culturales, las rela ciones interétnicas y la religión. Se concluye que, si bien el ideal de proteger la diversidad étnica y cultural no es cuestionable, el ente estatal se ha basado en nociones que deben ser revaluadas.

Este artículo estudia el requisito de edad como condición para acceder a ciertos cargos y corporaciones públicas de elección popular en Colombia. Se plantea un recorrido por las normas constitucionales, las leyes y algunas jurisprudencias que se han producido sobre este tema. En particular, se investiga si el legislador está facultado para determinar la edad que deben ostentar los diputados del país, señalando, por ejemplo, la persistencia de interpretaciones erradas sobre las normas relativas al tema. Se evidencia, además, que en la práctica, algunas instituciones oficiales afirman públicamente que la edad mínima para acceder a la Asamblea Departamental es de 25 años, edad superior a la estipulada en la Constitución Política. El caso de los diputados es comparado con algunas controversias generadas a propósito de la edad en los concejales, lo cual permite problematizar la diversidad de perspectivas y la relatividad cultural de estos conceptos. Se concluye así que existen confusiones e irregularidades al nivel institucional sobre el requisito de edad, lo cual tiene graves consecuencias, ya que se están vulnerando los derechos políticos de los ciudadanos colombianos.