Correlation between local structural dynamics of proteins inferred from NMR ensembles and evolutionary dynamics of homologues of known structure

Conformational changes in proteins are extremely important for their biochemical functions. Correlation between inherent conformational variations in a protein and conformational differences in its homologues of known structure is still unclear. In this study, we have used a structural alphabet called Protein Blocks (PBs). PBs are used to perform abstraction of protein 3-D structures into a 1-D strings of 16 alphabets (a-p) based on dihedral angles of overlapping pentapeptides. We have analyzed the variations in local conformations in terms of PBs represented in the ensembles of 801 protein structures determined using NMR spectroscopy. In the analysis of concatenated data over all the residues in all the NMR ensembles, we observe that the overall nature of inherent local structural variations in NMR ensembles is similar to the nature of local structural differences in homologous proteins with a high correlation coefficient of .94. High correlation at the alignment positions corresponding to helical and beta-sheet regions is only expected. However, the correlation coefficient by considering only the loop regions is also quite high (.91). Surprisingly, segregated position-wise analysis shows that this high correlation does not hold true to loop regions at the structurally equivalent positions in NMR ensembles and their homologues of known structure. This suggests that the general nature of local structural changes is unique; however most of the local structural variations in loop regions of NMR ensembles do not correlate to their local structural differences at structurally equivalent positions in homologues.

THE KNICKKOPF DOMON DOMAIN IS ESSENTIAL FOR CUTICLE DIFFERENTIATION IN Drosophila melanogaster

The dopamine monoxygenase N-terminal (DOMON) domain is found in extracellular proteins across several eukaryotic and prokaryotic taxa. It has been proposed that this domain binds to heme or sugar moieties. Here, we have analyzed the role of four highly conserved amino acids in the DOMON domain of the Drosophila melanogaster Knickkopf protein that is inserted into the apical plasma membrane and assists extracellular chitin organization. In principal, we generated Knickkopf versions with exchanged residues tryptophan(299,) methionine(333), arginine(401), or histidine(437), and scored for the ability of the respective engineered protein to normalize the knickkopf mutant phenotype. Our results confirm the absolute necessity of tryptophan(299,) methionine(333), and histidine(437) for Knickkopf function and stability, the latter two being predicted to be critical for heme binding. In contrast, arginine(401) is required for full efficiency of Knickkopf activity. Taken together, our genetic data support the prediction of these residues to mediate the function of Knickkopf during cuticle differentiation in insects. Hence, the DOMON domain is apparently an essential factor contributing to the construction of polysaccharide-based extracellular matrices.

Use of a structural alphabet to find compatible folds for amino acid sequences

The structural annotation of proteins with no detectable homologs of known 3D structure identified using sequence-search methods is a major challenge today. We propose an original method that computes the conditional probabilities for the amino-acid sequence of a protein to fit to known protein 3D structures using a structural alphabet, known as Protein Blocks (PBs). PBs constitute a library of 16 local structural prototypes that approximate every part of protein backbone structures. It is used to encode 3D protein structures into 1D PB sequences and to capture sequence to structure relationships. Our method relies on amino acid occurrence matrices, one for each PB, to score global and local threading of query amino acid sequences to protein folds encoded into PB sequences. It does not use any information from residue contacts or sequence-search methods or explicit incorporation of hydrophobic effect. The performance of the method was assessed with independent test datasets derived from SCOP 1.75A. With a Z-score cutoff that achieved 95% specificity (i.e., less than 5% false positives), global and local threading showed sensitivity of 64.1% and 34.2%, respectively. We further tested its performance on 57 difficult CASP10 targets that had no known homologs in PDB: 38 compatible templates were identified by our approach and 66% of these hits yielded correctly predicted structures. This method scales-up well and offers promising perspectives for structural annotations at genomic level. It has been implemented in the form of a web-server that is freely available at http://www.bo-protscience.fr/forsa.

Key challenges for the creation and maintenance of specialist protein resources

As the volume of data relating to proteins increases, researchers rely more and more on the analysis of published data, thus increasing the importance of good access to these data that vary from the supplemental material of individual articles, all the way to major reference databases with professional staff and long-term funding. Specialist protein resources fill an important middle ground, providing interactive web interfaces to their databases for a focused topic or family of proteins, using specialized approaches that are not feasible in the major reference databases. Many are labors of love, run by a single lab with little or no dedicated funding and there are many challenges to building and maintaining them. This perspective arose from a meeting of several specialist protein resources and major reference databases held at the Wellcome Trust Genome Campus (Cambridge, UK) on August 11 and 12, 2014. During this meeting some common key challenges involved in creating and maintaining such resources were discussed, along with various approaches to address them. In laying out these challenges, we aim to inform users about how these issues impact our resources and illustrate ways in which our working together could enhance their accuracy, currency, and overall value. Proteins 2015; 83:1005-1013. (c) 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Creating a specialist protein resource network: a meeting report for the protein bioinformatics and community resources retreat

During 11-12 August 2014, a Protein Bioinformatics and Community Resources Retreat was held at the Wellcome Trust Genome Campus in Hinxton, UK. This meeting brought together the principal investigators of several specialized protein resources (such as CAZy, TCDB and MEROPS) as well as those from protein databases from the large Bioinformatics centres (including UniProt and RefSeq). The retreat was divided into five sessions: (1) key challenges, (2) the databases represented, (3) best practices for maintenance and curation, (4) information flow to and from large data centers and (5) communication and funding. An important outcome of this meeting was the creation of a Specialist Protein Resource Network that we believe will improve coordination of the activities of its member resources. We invite further protein database resources to join the network and continue the dialogue.

La cuestión de los fundamentos en la ética de Lonergan

Resumen: En este artículo se explica cómo a partir del método trascendental de Lonergan surge una comprensión de la ética cómo ética existencial, la cual nos invita a dejar a un lado las categorías metafísicas-abstractas y reflexionar éticamente usando categorías que surjan de los actos de nuestra conciencia. La conciencia moral se presenta distintiva en cuanto a la decisión, inclusiva en cuanto que integra los niveles del entender y del juzgar y elevada en cuanto que está abierta a la posibilidad de una integración superior, puesto que la noción trascendental de valor puede ser enriquecida intrínsecamente con la experiencia religiosa de estar enamorado de un modo irrestricto.La explicitación de los fundamentos a partir del método trascendental permite tener en cuenta la realidad del hombre como ser histórico en devenir e integra la experiencia moral y religiosa a la comprensión del actuar ético. De este modo la reflexión ética surge a partir de la historia vividaen la cual se manifiesta el hacerse a sí mismo de los sujetos y la auto-constitución de lavida moral de una comunidad o de un pueblo.

Sapientia, 1996, Vol. LI, nº 200 (número completo)

Contenido: Del acto de ser a la acción moral / Gustavo Eloy Ponferrada – La dignidad humana desde una perspectiva metafísica / Abelardo Lobato – Ser y no ser en el sofista de Platón / Raúl Echauri – Feminismo y tercer milenio / María Fernanda Balmaseda Cinquina -- ¿La filosofía como amor del saber o saber efectivo? / Bernard Schumacher – Karl Popper y su crítica al verificacionismo de Freud / Horacio M. Sánchez Parodi – Moral virtue and contemplation : a note on the unity of the moral life / David M. Gallagher – El titular de la autoridad política en Santo Tomás y Rousseau / Avelino Manuel Quintas – La dignidad del hombre y la dignidad de la persona / Eudaldo Forment – Ensayo de síntesis acerca de la distinción especulativo-práctico y su estructuración metodológica / Carlos Ignacio Massini Correas – Conocimiento del alma después de la muerte : presentación de la doctrina de Santo Tomás de Aquino expuesta en las Quaestiones disputatae de veritate Q. 19 A. 1 / Luis Rodrigo Ewart -- Sufrimiento y humildad ontológica : Kant y Schopenhauer / Francisco Torralba Roselló – Significación contemporánea de las nociones de experiencia y derecho natural según Santo Tomás de Aquino / Jorge Martínez Barrera – Contemplación filosófica y contemplación mística en San Buenaventura / Ignacio E. M. Andereggen – Sul duplice fine del matrimonio secondo la doctrina tomista / Horst Seidl – La concepción del espacio en la física de Santo Tomás de Aquino / Mario Enrique Sacchi – Notas y comentarios -- Bibliografía

Medición y realidad : reflexiones para una economía realista

Resumen: El trabajo constituye una presentación general del análisis de la circulación económica elaborado por B. Lonergan quien, desde presupuestos filosóficos diferentes de los implícitos en la teoría económica dominante, desarrolló una aproximación sistémica a la problemática económica que revela ciertas insuficiencias en las mediciones vigentes. En efecto, las variables de interés se ven modificadas cuando cambian las categorías fundamentales de análisis. En la primera sección se exponen los supuestos gnoseológicos y epistemológicos realistas desarrollados por este autor. Estos fundamentos permiten reconocer con mayor claridad las bases endebles de los abordajes actuales. Tras una breve enumeración de algunas críticas al paradigma vigente de parte de diversos autores, se exponen las líneas generales del esquema propuesto por Lonergan.

La crisis financiera y la crisis de civilización

"La crisis financiera internacional que estamos atravesando es una oportunidad para comprender con mayor profundidad cómo funciona el sistema capitalista y las bases sobre las cuales está edificado. Toda crisis opera como una falla, en el sentido geológico del término. La falla, la ruptura, como señalara Heidegger, revela la existencia de lo que antes era obvio o que formaba el fondo sobre el cual organizamos nuestras vidas. Vivimos en un mundo organizado de cuya existencia y producción no nos percatamos mientras funciona. Cuando deja de hacerlo salta a la luz su carácter no natural, construido, histórico, y por tanto, perfectible. En este trabajo sostendré la hipótesis de que la actual crisis financiera es consecuencia de una asignación disfuncional del crédito a nivel global. Por tanto, las divergentes explicaciones técnicas al respecto diferirán en la idea de y lugar que asignen al crédito en el sistema económico. Lo que pueden parecen inocentes conceptos “técnicos” o “científicos” suponen, en verdad, una concepción del mundo, una ontología; más: una teología fundamental. Por ello en lo que sigue opondré a la explicación convencional de la crisis una interpretación alternativa a partir de la explanación del sistema económico que propone Bernard Lonergan, para pasar, en un segundo momento, a un nivel más fundamental de análisis que busca dar con los valores que sostienen la teoría económica capitalista..."

Thermovibrational Instability Of Rayleigh-Marangoni-Benard Convection In Two-Layer Fluid Systems

The thermovibrational instability of Rayleigh-Marangoni-Benard convection in a two-layer system under the high-frequency vibration has been investigated by linear instability analysis in the present paper. General equations for the description of the convective flow and within this framework, the generalized Boussinesq approximation are formulated. These equations are dealt with using the averaging method. The theoretical analysis results show that the high-frequency thermovibrations can change the Marangoni-Benard convection instabilities as well as the oscillatory gaps of the Rayleigh-Marangoni-Benard convection in two-layer liquid systems. It is found that vertical high-frequency vibrations can delay convective instability of this system, and damp the convective flow down. (C) 2007 COSPAR. Published by Elsevier Ltd. All rights reserved.

¿Visionaria o mística? Hildegarda de Bingen en la encrucijada de lenguaje y experiencia del misterio cristiano

Resumen: Ante la próxima proclamación de Hildegarda de Bingen como doctora de la Iglesia, anunciada por el Papa Benedicto XVI para el 7 de octubre de 2012, el artículo realiza una reflexión sobre la relación entre experiencia y lenguaje en la mística cristiana. Tras el necesario deslinde de los marcos epistemológicos en los que ha sido tratada la cuestión –histórico, fenomenológico y teológico–, plantea una respuesta integradora de ambas tradiciones sobre la base del principio estético teológico que Hans Urs von Balthasar denominó como “visión de la figura”. La tesis se apoya sobre el análisis del texto descriptivo, interpretativo y plástico del Prólogo y Primera Visión; I Parte de Scivias y sobre el Corpus epistolar que tuvieron por destinatarios a Bernardo de Claraval y a Guibert de Gembloux.

Sapientia, 2004, Vol. LIX, nº 216 (número completo)

Contenido: Josef Pieper en el centenario de su nacimiento / Héctor J. Delbosco – Misterio filosófico y misterio teológico en Josef Pieper y en Santo Tomás de Aquino / Ignacio Andereggen – El status de la filosofía en la posciencia. Respuestas desde Josef Pieper / Miriam Dolly Arancibía de Calmels – “Miseria y esplendor de la interpretación”. En torno a los límites de la hermenéutica en Pieper y en Ortega / Roberto E. Aras – Si sí : la condicionalidad metafísica de una afirmación absoluta / Santiago Argüello – Una perspectiva del saber y de la fortaleza en el héroe unamuniano a la luz de Josef Pieper / Angélica S. Arza de Bousquet – Manía, mito y conmoción erótica / Luis Baliña ; Juan Torbidoni – Juventud, fiesta y esperanza en la obra de Josef Pieper : una respuesta a la cultura posmoderna / Santiago Bellomo – Pieper y Guardini en Rothenfels : un encuentro fecundo / Alberto Berro – La afirmación real del amor / María José Binetti – Josef Pieper al encuentro de Platón : una relectura de las relaciones entre mito y filosofía / Claudio Calabrese – Orientación y pautas de discernimiento en el ámbito poético-literario : la doctrina de la contemplación terrena enunciada por Josef Pieper e ilustrada en Albert Camus / Inés de Cassagne – La imposibilidad de una filosofía no cristiana según Josef Pieper / Agustín Ignacio Echavarría – Ética y psicoterapia según Josef Pieper / Martín Echavarría – Enseñanzas de un gran maestro : la corruptibilidad de la palabra / María del Carmen Fernández – La inspiración platónica de la filosofía de Josef Pieper / Juan Francisco Franck – Método y lenguaje en el pensamiento de Josef Pieper / Jean Lauand – Josef Pieper y Peter Wust / Juan Andrés Levermann – Aprobación creadora : un aspecto de la dimensión social del bien de la persona / Marisa Mosto – Josef Pieper y la reflexión sobre el mito y la cultura / Héctor Jorge Padrón – Josef Pieper y el tomismo medieval : la controversia sobre la creación / François-Xavier Putallaz – Algunas consideraciones sobre J. Pieper y el tema del mal en la problemática filosófica contemporánea / Juan Pablo Roldán – Josef Pieper y la acedia : la causa afectiva de ciertas deformaciones intelectuales / El hombre de ocio : parásito o transformador del mundo / Bernard N. Schumacher – La templanza en Josef Pieper y Santo Tomás / Zelmira Seligmann – El ideal del trabajo en Josef Pieper / Ludovico Antonio Videla – Valor para la realidad – Valor para la persona : reafirmación cristiana como crítica de la cultura en la obra temprana de Josef Pieper / Berthold Wald – Notas y comentarios -- Bibliografía

有关多层流体对流的研究

简述多层不相混流体系统的研究发展，尤其是在空间材料生长过程中的应用；介绍多层流体系统内流体对流及传热现象，以及利用理论分析、实验研究和数值模拟方法研究二层及三层流体内的自然对流及热毛细对流的成果，并分析探讨覆盖液体层对被覆盖液体的动力控制特性及其系统的稳定性。

Isolation of mineralizing Nestin+ Nkx6.1+ vascular muscular cells from the adult human spinal cord

Background: The adult central nervous system (CNS) contains different populations of immature cells that could possibly be used to repair brain and spinal cord lesions. The diversity and the properties of these cells in the human adult CNS remain to be fully explored. We previously isolated Nestin(+) Sox2(+) neural multipotential cells from the adult human spinal cord using the neurosphere method (i.e. non adherent conditions and defined medium). -- Results: Here we report the isolation and long term propagation of another population of Nestin(+) cells from this tissue using adherent culture conditions and serum. QPCR and immunofluorescence indicated that these cells had mesenchymal features as evidenced by the expression of Snai2 and Twist1 and lack of expression of neural markers such as Sox2, Olig2 or GFAP. Indeed, these cells expressed markers typical of smooth muscle vascular cells such as Calponin, Caldesmone and Acta2 (Smooth muscle actin). These cells could not differentiate into chondrocytes, adipocytes, neuronal and glial cells, however they readily mineralized when placed in osteogenic conditions. Further characterization allowed us to identify the Nkx6.1 transcription factor as a marker for these cells. Nkx6.1 was expressed in vivo by CNS vascular muscular cells located in the parenchyma and the meninges. -- Conclusion: Smooth muscle cells expressing Nestin and Nkx6.1 is the main cell population derived from culturing human spinal cord cells in adherent conditions with serum. Mineralization of these cells in vitro could represent a valuable model for studying calcifications of CNS vessels which are observed in pathological situations or as part of the normal aging. In addition, long term propagation of these cells will allow the study of their interaction with other CNS cells and their implication in scar formation during spinal cord injury.

PICES-GLOBEC International Program on Climate Change and Carrying Capacity

Introduction [pdf, 0.27 MB] Methods [pdf, 0.15 MB] Results and discussion [pdf, 2.1 MB] Conclusions [pdf, 0.12 MB] Appendix A: Data gathering review, results and balancing [pdf, 0.3 MB] Appendix B: Data tables [pdf, 0.35 MB] Appendix C: BASS Workshop on the "Development of a conceptual model of the subarctic Pacific Basin ecosystems" [pdf, 0.16 MB] Appendix D: BASS/MODEL Workshop on "Higher trohic level modeling" [pdf, 0.24 MB] Appendix E: BASS/MODEL Workshop to review ecosystem models for the subarctic Pacific gyres [pdf, 4.39 MB] Appendix F: BASS/MODEL Workshop on "Perturbation analysis" on subarctic Pacific gyre ecosystem models using ECOPATH/ECOSIM" [pdf, 0.37 MB] Appendix G: Proposal for a BASS Workshop on "Linkages between open and coastal systems" [pdf, 0.15 MB] References [pdf, 0.14 MB] (97 page document)