Desde la transdisciplinariedad hacia el auto-conocimiento y el diálogo comunitario de saberes: simplicidad ante la crisis

Partiendo de mi experiencia de vida, enmarcada en la crisis, no sólo de la modernidad, sino de la contradicción entre el alma latinoamericana y la imposición desde la globalización de una mecánica social eficientista, abordo cómo se construyen las costumbres del pensamiento en los intelectuales y académicos latinoamericanos. En este contexto reflexiono sobre la crisis civilizatoria-planetaria, identificando al positivismo-racionalismo como una de sus piedras nodales. La transdisciplinariedad y el pensamiento complejo, son abordados como una respuesta valiosa y fértil a la crisis del sistema académico-moderno del conocimiento, proponiendo al mismo tiempo, la necesidad de no detenerse en estos sistemas del pensar como tablas de salvación de la modernidad. Con base en esto, me pregunto si estamos siendo incapaces de percatarnos de las dimensiones de la inviabilidad de una racionalidad que ignora la naturaleza orgánica-holística de nuestro pensamiento. Evidencio también nuestra incapacidad de emprender afectiva y efectivamente formas participativas del conocimiento, así como del diálogo de saberes, proponiendo algunos de los elementos clave para la reconstrucción hacia una praxis académica sustentable.From my life experience, contextualized by the crisis, not only of modernity, but of the contradiction between the Latin American soul and the imposition from globalization of a social mechanic efficiency, I aboard how customs in intellectual thought are created by Latin American scholars. In this context I analyze on civilizing-planetary crisis, identifying positivism-rationalism as one of its nodal stones. Transdisciplinarity and complex thought are addressed as a valuable and fertile response to the crisis of the modern-academic knowledge system, proposing at the same time, the need to not dwell on these systems of thought as a life guard of modernity. Based on this, I ask myself if we are still unable to realize the dimensions of the inviability of a rationality that ignores the organic-holistic nature of our thinking. I also make evident our inability to effectively and affectively engage in participatory forms of knowledge, as well as on a dialogue on knowledges, and propose some key principles to re-build a sustainable academic practice.Com base na minha experiência de vida, emoldurada na crise, não só a modernidade, mas a contradição entre a alma latino-americana e a imposição desde a globalização de uma mecânica social eficientista, abordo como são construídos os hábitos de pensamento em intelectuais e acadêmicos latino-americanos. Neste contexto, reflexiono sobre a crise civilização planetária, identificando ao racionalismo-positivismo como uma das suas pedras nodais. A transdisciplinaridade e o pensamento complexo são abordados como uma resposta valiosa e profícua para a crise do sistema de conhecimento acadêmico moderno, propondo ao mesmo tempo, a necessidade de não deter-se sobre estes sistemas de pensamento como tabelas salvação da modernidade. Com base nisso, eu me pergunto se estamos sendo incapazes de perceber as dimensões da impossibilidade de uma racionalidade que ignora a natureza orgânico-holística do nosso pensamento. Evidencio também a nossa incapacidade para realizar efetivamente as formas afetivas e participativas de conhecimento, bem como o diálogo de saberes, oferecendo alguns dos principais elementos para a reconstrução de uma praxis académica sustentável

Disjoint combinations profiling (DCP): a new method for the prediction of antibody CDR conformation from sequence

The accurate prediction of the conformation of Complementarity-Determining Regions (CDRs) is important in modelling antibodies for protein engineering applications. Specifically, the Canonical paradigm has proved successful in predicting the CDR conformation in antibody variable regions. It relies on canonical templates which detail allowed residues at key positions in the variable region framework or in the CDR itself for 5 of the 6 CDRs. While no templates have as yet been defined for the hypervariable CDR-H3, instead, reliable sequence rules have been devised for predicting the base of the CDR-H3 loop. Here a new method termed Disjoint Combinations Profiling (DCP) is presented, which contributes a considerable advance in the prediction of CDR conformations. This novel method is explained and compared with canonical templates and sequence rules in a 3-way blind prediction. DCP achieved 93 accuracy over 951 blind predictions and showed an improvement in cumulative accuracy compared to predictions with canonical templates or sequence rules. In addition to its overall improvement in prediction accuracy, it is suggested that DCP is open to better implementations in the future and that it can improve as more antibody structures are deposited in the databank. In contrast, it is argued that canonical templates and sequence rules may have reached their peak

Estrategia sistémica para conformar colectivos colaborativos inter-transdisciplinarios: conocimiento al servicio de la sociedad

This text proposes a methodology for re-learning and incubating Inter-Transdisciplinary Collaborative Collectives in higher education institutions that allows addressing the urgent needs in the face of the complex socio-environmental problems of the 21st century. Through the transdisciplinary participatory action-research methodology, the research results of more than six years of collective academic work are reported. As institutions that generate knowledge, the universities are increasingly obliged to influence the restoration of our chaotic humanity and nature in general. Everyday realities present situations (problems and paradoxes) that are more difficult to address with reductionist, linear approaches and individual and disciplinary practices. It becomes relevant and urgent to build actions based on new paradigms, with logics of thought and action capable of generating empathy scenarios based on inter-transdisciplinary approaches. In this sense, what is presented here is an experience of knowledge generation within the university educational field. It arises from the collaborative work that has been generated by the academic group that writes this article from different areas of knowledge of the University of Veracruz, from the construction of synergies from inter and transdisciplinary dialogue. This proposal aims to be an instrument that, step-by-step, guides the formation of groups of academics and/or students and can move towards collaborative inter-transdisciplinary research. In this way, situations can be approached with a more comprehensive approach, and responses can be given considering the interwoven, complex, transversal, and sustainably human wholes. Keywords: Human Sustainability; Complexity; University Transformation; Planetary Crisis; Alternatives.El presente texto plantea una metodología de re-aprendizaje e incubación de Colectivos Colaborativos Inter-Transdisciplinarios en las instituciones de educación superior, que permita atender las urgentes necesidades frente a las complejas problemáticas socioambientales del siglo XXI. Mediante la metodología de investigación-acción participativa transdisciplinaria, se reportan los resultados de investigación de más de seis años de trabajo colectivo académico. Las universidades, como instituciones generadoras de conocimiento, se encuentran cada día más obligadas a incidir en la restauración de nuestra caótica humanidad y de la naturaleza en lo general. Cada día las realidades presentan situaciones (problemáticas y paradojas) más difíciles de abordar con enfoques reduccionistas, lineales y con prácticas individuales y unidisciplinarias. Se torna relevante y urgente, constituir acciones basadas en nuevos paradigmas, con lógicas de pensamiento y acción que sean capaces de generar escenarios de empatía, basados en enfoques inter-transdisciplinarios. En este sentido, lo que aquí presentado es una experiencia de generación del conocimiento dentro del ámbito educativo universitario. Surge del trabajo colaborativo que ha venido generando el colectivo académico que escribe este artículo de diferentes áreas del conocimiento de la Universidad Veracruzana, a partir de la construcción de sinergias desde el diálogo inter y transdisciplinario. La presente propuesta pretende ser un instrumento que paso a paso guíe la conformación de grupos de académicos y/o estudiantes y puedan transitar hacia la investigación colaborativa inter-transdisciplinaria. De esta manera se podrán abordar situaciones con un enfoque más integral, y dar respuestas considerando las totalidades entramadas, complejas, transversales y sustentablemente humanas. Palabras clave: Sustentabilidad Humana; Complejidad; Transformación Universitaria; Crisis Planetaria; Alternativas

PseudoGeneQuest – Service for identification of different pseudogene types in the human genome

<p>Abstract</p> <p>Background</p> <p>Pseudogenes, nonfunctional copies of genes, evolve fast due the lack of evolutionary pressures and thus appear in several different forms. PseudoGeneQuest is an online tool to search the human genome for a given query sequence and to identify different types of pseudogenes as well as novel genes and gene fragments.</p> <p>Description</p> <p>The service can detect pseudogenes, that have arisen either by retrotransposition or segmental genome duplication, many of which are not listed in the public pseudogene databases. The service has a user-friendly web interface and uses a powerful computer cluster in order to perform parallel searches and provide relatively fast runtimes despite exhaustive database searches and analyses.</p> <p>Conclusion</p> <p>PseudoGeneQuest is a versatile tool for detecting novel pseudogene candidates from the human genome. The service searches human genome sequences for five types of pseudogenes and provides an output that allows easy further analysis of observations. In addition to the result file the system provides visualization of the results linked to Ensembl Genome Browser. PseudoGeneQuest service is freely available.</p

Pairwise maximum entropy models for studying large biological systems: when they can and when they can't work

One of the most critical problems we face in the study of biological systems is building accurate statistical descriptions of them. This problem has been particularly challenging because biological systems typically contain large numbers of interacting elements, which precludes the use of standard brute force approaches. Recently, though, several groups have reported that there may be an alternate strategy. The reports show that reliable statistical models can be built without knowledge of all the interactions in a system; instead, pairwise interactions can suffice. These findings, however, are based on the analysis of small subsystems. Here we ask whether the observations will generalize to systems of realistic size, that is, whether pairwise models will provide reliable descriptions of true biological systems. Our results show that, in most cases, they will not. The reason is that there is a crossover in the predictive power of pairwise models: If the size of the subsystem is below the crossover point, then the results have no predictive power for large systems. If the size is above the crossover point, the results do have predictive power. This work thus provides a general framework for determining the extent to which pairwise models can be used to predict the behavior of whole biological systems. Applied to neural data, the size of most systems studied so far is below the crossover point

SnugDock: Paratope Structural Optimization during Antibody-Antigen Docking Compensates for Errors in Antibody Homology Models

High resolution structures of antibody-antigen complexes are useful for analyzing the binding interface and to make rational choices for antibody engineering. When a crystallographic structure of a complex is unavailable, the structure must be predicted using computational tools. In this work, we illustrate a novel approach, named SnugDock, to predict high-resolution antibody-antigen complex structures by simultaneously structurally optimizing the antibody-antigen rigid-body positions, the relative orientation of the antibody light and heavy chains, and the conformations of the six complementarity determining region loops. This approach is especially useful when the crystal structure of the antibody is not available, requiring allowances for inaccuracies in an antibody homology model which would otherwise frustrate rigid-backbone docking predictions. Local docking using SnugDock with the lowest-energy RosettaAntibody homology model produced more accurate predictions than standard rigid-body docking. SnugDock can be combined with ensemble docking to mimic conformer selection and induced fit resulting in increased sampling of diverse antibody conformations. The combined algorithm produced four medium (Critical Assessment of PRediction of Interactions-CAPRI rating) and seven acceptable lowest-interface-energy predictions in a test set of fifteen complexes. Structural analysis shows that diverse paratope conformations are sampled, but docked paratope backbones are not necessarily closer to the crystal structure conformations than the starting homology models. The accuracy of SnugDock predictions suggests a new genre of general docking algorithms with flexible binding interfaces targeted towards making homology models useful for further high-resolution predictions

Novel structural parameters of Ig -Ag complexes yield a quantitative description of interaction specificity and binding affinity

Antibody-antigen complexes challenge our understanding, as analyses to datefailed to unveil the key determinants of binding affinity and interaction specificity. We par-tially fill this gap based on novel quantitative analyses using two standardized databases, theIMGT/3Dstructure-DB and the structure affinity benchmark.First, we introduce a statistical analysis of interfaces which enables the classification of ligand types(protein, peptide, chemical; cross-validated classification error of 9.6%), and yield binding affinitypredictions of unprecedented accuracy (median absolute error of 0.878 kcal/mol). Second, weexploit the contributions made by CDRs in terms of position at the interface and atomic packingproperties to show that in general, VH CDR3 and VL CDR3 make dominant contributions tothe binding affinity, a fact also shown to be consistent with the enthalpy - entropy compensationassociated with pre-configuration of CDR3.Our work suggests that the affinity prediction problem could be solved from databases of highresolution crystal structures of complexes with known affinity

A Preliminary Analysis of the Immunoglobulin Genes in the African Elephant (Loxodonta africana)

The genomic organization of the IgH (Immunoglobulin heavy chain), Igκ (Immunoglobulin kappa chain), and Igλ (Immunoglobulin lambda chain) loci in the African elephant (Loxodonta africana) was annotated using available genome data. The elephant IgH locus on scaffold 57 spans over 2,974 kb, and consists of at least 112 VH gene segments, 87 DH gene segments (the largest number in mammals examined so far), six JH gene segments, a single μ, a δ remnant, and eight γ genes (α and ε genes are missing, most likely due to sequence gaps). The Igκ locus, found on three scaffolds (202, 50 and 86), contains a total of 153 Vκ gene segments, three Jκ segments, and a single Cκ gene. Two different transcriptional orientations were determined for these Vκ gene segments. In contrast, the Igλ locus on scaffold 68 includes 15 Vλ gene segments, all with the same transcriptional polarity as the downstream Jλ-Cλ cluster. These data suggest that the elephant immunoglobulin gene repertoire is highly diverse and complex. Our results provide insights into the immunoglobulin genes in a placental mammal that is evolutionarily distant from humans, mice, and domestic animals

Immunoglobulin Genomics in the Guinea Pig (Cavia porcellus)

In science, the guinea pig is known as one of the gold standards for modeling human disease. It is especially important as a molecular and cellular biology model for studying the human immune system, as its immunological genes are more similar to human genes than are those of mice. The utility of the guinea pig as a model organism can be further enhanced by further characterization of the genes encoding components of the immune system. Here, we report the genomic organization of the guinea pig immunoglobulin (Ig) heavy and light chain genes. The guinea pig IgH locus is located in genomic scaffolds 54 and 75, and spans approximately 6,480 kb. 507 VH segments (94 potentially functional genes and 413 pseudogenes), 41 DH segments, six JH segments, four constant region genes (μ, γ, ε, and α), and one reverse δ remnant fragment were identified within the two scaffolds. Many VH pseudogenes were found within the guinea pig, and likely constituted a potential donor pool for gene conversion during evolution. The Igκ locus mapped to a 4,029 kb region of scaffold 37 and 24 is composed of 349 Vκ (111 potentially functional genes and 238 pseudogenes), three Jκ and one Cκ genes. The Igλ locus spans 1,642 kb in scaffold 4 and consists of 142 Vλ (58 potentially functional genes and 84 pseudogenes) and 11 Jλ -Cλ clusters. Phylogenetic analysis suggested the guinea pig’s large germline VH gene segments appear to form limited gene families. Therefore, this species may generate antibody diversity via a gene conversion-like mechanism associated with its pseudogene reserves

Search for invisible decays of the Higgs boson produced via vector boson fusion in proton-proton collisions at s\sqrt{s} = 13 TeV

A search for invisible decays of the Higgs boson produced via vector boson fusion (VBF) has been performed with 101  fb$^{-1}$ of proton-proton collisions delivered by the LHC at $\sqrt{s}$ =13  TeV and collected by the CMS detector in 2017 and 2018. The sensitivity to the VBF production mechanism is enhanced by constructing two analysis categories, one based on missing transverse momentum and a second based on the properties of jets. In addition to control regions with Z and W boson candidate events, a highly populated control region, based on the production of a photon in association with jets, is used to constrain the dominant irreducible background from the invisible decay of a Z boson produced in association with jets. The results of this search are combined with all previous measurements in the VBF topology, based on data collected in 2012 (at $\sqrt{s}$ =8  TeV), 2015, and 2016, corresponding to integrated luminosities of 19.7, 2.3, and 36.3  fb$^{-1}$, respectively. The observed (expected) upper limit on the invisible branching fraction of the Higgs boson is found to be 0.18 (0.10) at the 95% confidence level, assuming the standard model production cross section. The results are also interpreted in the context of Higgs-portal models