227 research outputs found
Voces significativas del pensamiento latinoamericano contemporáneo
Si en el ámbito artístico América Latina ha podido mostrar siempre una producción original importante, y también reflejar su problemática y debates históricos en el ensayo, con respecto a la filosofía predominó la actitud de seguimiento vernáculo de las corrientes y enfoques europeos, con rasgos de mayor o menor originalidad, ligado sobre todo a la institucionalización y profesionalización de la misma. En los años '60 se inició sin duda alguna una etapa diferente, en el contexto de los movimientos de liberación característicos de la época, que comenzó por plantear desde el registro de la situación de dependencia una 'filosofía de la liberación', con conciencia de la propia identidad americana y la voluntad de partir de la misma y desplegar las posibilidades abiertas de su propio acerbo histórico. Ello implicó un trabajo de autoconocimiento y valoración, desde el que debían surgir las propias sendas, que signó la década siguiente, en la que se habló de 'un nuevo punto de partida', de otro horizonte de inteligibilidad con su respectiva articulación racional, a pesar del cierre creciente que significaba la extensión de regímenes militares dictatoriales por los diversos países
Targeted online liquid chromatography electron capture dissociation mass spectrometry for the localization of sites of in vivo phosphorylation in human Sprouty2
We demonstrate a strategy employing collision-induced dissociation for phosphopeptide discovery, followed by targeted electron capture dissociation (ECD) for site localization. The high mass accuracy and low background noise of the ECD mass spectra allow facile sequencing of coeluting isobaric phosphopeptides, with up to two isobaric phosphopeptides sequenced from a single mass spectrum. In contrast to the previously described neutral loss of dependent ECD method, targeted ECD allows analysis of both phosphotyrosine peptides and lower abundance phosphopeptides. The approach was applied to phosphorylation analysis of human Sprouty2, a regulator of receptor tyrosine kinase signaling. Fifteen sites of phosphorylation were identified, 11 of which are novel
Minería de datos para el descubrimiento de patrones en enfermedades respiratorias en Bogotá, Colombia
Trabajo de InvestigaciónEl presente proyecto se basa en la aplicación de minería de datos mediante el algoritmo de clustering K- means que permita la generación de un modelo descriptivo con el análisis de los datos y con el objetivo de identificar posibles comportamientos en enfermedades respiratorias en la ciudad de Bogotá.
El conjunto de clústeres generados por la herramienta RapidMiner es la
recopilación de datos de un periodo de cinco años de 2012 a 2016, en donde se contemplan el número de casos asociados a 184 diagnósticos de enfermedades respiratorias y la edad de los pacientes corresponde de 0 a 5 años.Trabajo de Investigación1. GENERALIDADES
2. OBJETIVOS
3. JUSTIFICACIÓN
4. DELIMITACIÓN
5. MARCO REFERENCIAL
6. METODOLOGÍA
7. FUENTES DE EXTRACCIÓN Y SUS VARIABLES
8. DISEÑO
9. SELECCIÓN DE ALGORITMOS DE CLUSTERING
10. RECONOCER PATRONES A PARTIR DE LA INFORMACIÓN RECOPILADA
11. CONCLUSIONES
12. TRABAJOS FUTUROS 13. REFERENCIAS BIBLIOGRÁFICAS
14. ANEXOSPregradoIngeniero de Sistema
Direct Ubiquitin Independent Recognition and Degradation of a Folded Protein by the Eukaryotic Proteasomes-Origin of Intrinsic Degradation Signals
Eukaryotic 26S proteasomes are structurally organized to recognize, unfold and degrade globular proteins. However, all existing model substrates of the 26S proteasome in addition to ubiquitin or adaptor proteins require unstructured regions in the form of fusion tags for efficient degradation. We report for the first time that purified 26S proteasome can directly recognize and degrade apomyoglobin, a globular protein, in the absence of ubiquitin, extrinsic degradation tags or adaptor proteins. Despite a high affinity interaction, absence of a ligand and presence of only helices/loops that follow the degradation signal, apomyoglobin is degraded slowly by the proteasome. A short floppy F-helix exposed upon ligand removal and in conformational equilibrium with a disordered structure is mandatory for recognition and initiation of degradation. Holomyoglobin, in which the helix is buried, is neither recognized nor degraded. Exposure of the floppy F-helix seems to sensitize the proteasome and primes the substrate for degradation. Using peptide panning and competition experiments we speculate that initial encounters through the floppy helix and additional strong interactions with N-terminal helices anchors apomyoglobin to the proteasome. Stabilizing helical structure in the floppy F-helix slows down degradation. Destabilization of adjacent helices accelerates degradation. Unfolding seems to follow the mechanism of helix unraveling rather than global unfolding. Our findings while confirming the requirement for unstructured regions in degradation offers the following new insights: a) origin and identification of an intrinsic degradation signal in the substrate, b) identification of sequences in the native substrate that are likely to be responsible for direct interactions with the proteasome, and c) identification of critical rate limiting steps like exposure of the intrinsic degron and destabilization of an unfolding intermediate that are presumably catalyzed by the ATPases. Apomyoglobin emerges as a new model substrate to further explore the role of ATPases and protein structure in proteasomal degradatio
Genetic Variation Shapes Protein Networks Mainly through Non-transcriptional Mechanisms
Variation in the levels of co-regulated proteins that function within networks in an outbred yeast population is not driven by variation in the corresponding transcripts
Unfolding Simulations of Holomyoglobin from Four Mammals: Identification of Intermediates and β-Sheet Formation from Partially Unfolded States
Myoglobin (Mb) is a centrally important, widely studied mammalian protein. While much work has investigated multi-step unfolding of apoMb using acid or denaturant, holomyoglobin unfolding is poorly understood despite its biological relevance. We present here the first systematic unfolding simulations of holoMb and the first comparative study of unfolding of protein orthologs from different species (sperm whale, pig, horse, and harbor seal). We also provide new interpretations of experimental mean molecular ellipticities of myoglobin intermediates, notably correcting for random coil and number of helices in intermediates. The simulated holoproteins at 310 K displayed structures and dynamics in agreement with crystal structures (R g ~1.48-1.51 nm, helicity ~75%). At 400 K, heme was not lost, but some helix loss was observed in pig and horse, suggesting that these helices are less stable in terrestrial species. At 500 K, heme was lost within 1.0-3.7 ns. All four proteins displayed exponentially decaying helix structure within 20 ns. The C- and F-helices were lost quickly in all cases. Heme delayed helix loss, and sperm whale myoglobin exhibited highest retention of heme and D/E helices. Persistence of conformation (RMSD), secondary structure, and ellipticity between 2-11 ns was interpreted as intermediates of holoMb unfolding in all four species. The intermediates resemble those of apoMb notably in A and H helices, but differ substantially in the D-, E- and F-helices, which interact with heme. The identified mechanisms cast light on the role of metal/cofactor in poorly understood holoMb unfolding. We also observed β-sheet formation of several myoglobins at 500 K as seen experimentally, occurring after disruption of helices to a partially unfolded, globally disordered state; heme reduced this tendency and sperm-whale did not display any sheet propensity during the simulations
Mapping differential interactomes by affinity purification coupled with data independent mass spectrometry acquisition
Characterizing changes in protein-protein interactions associated with sequence variants (e.g. disease-associated mutations or splice forms) or following exposure to drugs, growth factors or hormones is critical to understanding how protein complexes are built, localized and regulated. Affinity purification (AP) coupled with mass spectrometry permits the analysis of protein interactions under near-physiological conditions, yet monitoring interaction changes requires the development of a robust and sensitive quantitative approach, especially for large-scale studies where cost and time are major considerations. To this end, we have coupled AP to data-independent mass spectrometric acquisition (SWATH), and implemented an automated data extraction and statistical analysis pipeline to score modulated interactions. Here, we use AP-SWATH to characterize changes in protein-protein interactions imparted by the HSP90 inhibitor NVP-AUY922 or melanoma-associated mutations in the human kinase CDK4. We show that AP-SWATH is a robust label-free approach to characterize such changes, and propose a scalable pipeline for systems biology studies
- …