Probing the interaction of brain fatty acid binding protein (B-FABP) with model membranes

Brain fatty acid-binding protein (B-FABP) interacts with biological membranes and delivers polyunsaturated fatty acids (FAs) via a collisional mechanism. The binding of FAs in the protein and the interaction with membranes involve a motif called "portal region", formed by two small α-helices, A1 and A2, connected by a loop. We used a combination of site-directed mutagenesis and electron spin resonance to probe the changes in the protein and in the membrane model induced by their interaction. Spin labeled B-FABP mutants and lipidic spin probes incorporated into a membrane model confirmed that BFABP interacts with micelles through the portal region and led to structural changes in the protein as well in the micelles. These changes were greater in the presence of LPG when compared to the LPC models. ESR spectra of B-FABP labeled mutants showed the presence of two groups of residues that responded to the presence of micelles in opposite ways. In the presence of lysophospholipids, group I of residues, whose side chains point outwards from the contact region between the helices, had their mobility decreased in an environment of lower polarity when compared to the same residues in solution. The second group, composed by residues with side chains situated at the interface between the α-helices, experienced an increase in mobility in the presence of the model membranes. These modifications in the ESR spectra of B-FABP mutants are compatible with a less ordered structure of the portal region inner residues (group II) that is likely to facilitate the delivery of FAs to target membranes. On the other hand, residues in group I and micelle components have their mobilities decreased probably as a result of the formation of a collisional complex. Our results bring new insights for the understanding of the gating and delivery mechanisms of FABPs.

Aplicación Web para Ayuntamiento de Las Palmas de Gran Canaria : [Parte B]

[ES] Este Trabajo de Fin de Grado es un servicio basado en tecnologías web. El objetivo principal es ofrecer un servicio de creación y gestión de actas para el Ayuntamiento de Las Palmas de Gran Canaria. Para ello, consta de dos módulos principales, uno para “crear actas” y otro para “editar actas”. También se ha desarrollado otro módulo llamado plantillas donde se genera un PDF a partir de una plantilla preestablecida. Esta aplicación ha sido dividida en diferentes partes. La primera parte consistió en generar todas las configuraciones de base de datos necesarias para el funcionamiento de la aplicación. Después generamos todos los ficheros HTML y las interconexiones entre ellos. Finalmente, dotamos  a esos HTML estáticos de un estilo mucho más claro y organizado, dando a la aplicación una apariencia mucho más bonita. Una vez finalizada la parte frontal de la aplicación, empezamos a implementar la lógica detrás de la aplicación. Los módulos de “crear” y “editar” se hicieron utilizando formularios HTML y combinando la información obtenida de esos formularios con unas plantillas HTML generadas por nosotros. Toda esa información obtenida de los formularios se guarda en unos ficheros .txt para poder ser utilizados por el módulo editar. El módulo de plantillas nos muestra un editor HTML rellenado con una plantilla que ha sido previamente seleccionada por el usuario. Los ficheros pdf de este módulo no pueden editados con posterioridad  por lo que no se generan ficheros .txt. Por último, hay dos módulos que nos permiten ver todas las actas generadas por la aplicación. El primero de los dos módulos es el módulo de b��squeda, que nos permite buscar una palabra clave dentro de todos los ficheros pdf. El otro módulo nos muestra todas las actas que han sido marcadas como “cerradas”. Esta aplicación ha sido diseñada de forma modular, de manera que podemos añadir o quitar módulos de manera sencilla.

Evaluación anatomoclínica mediante tomografía computerizada en 100 perros presentados en EVAC (Estudios Veterinarios de Alta Complejidad), Facultad de Veterinaria de la U.B.A. (2000-2001)

Programa de doctorado: Clínica e investigación terapéutica

Adenosine Kinase of T. b. Rhodesiense identified as the putative target of 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine using chemical proteomics

BACKGROUND: Human African trypanosomiasis (HAT), a major parasitic disease spread in Africa, urgently needs novel targets and new efficacious chemotherapeutic agents. Recently, we discovered that 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine (compound 1) exhibits specific antitrypanosomal activity with an IC(50) of 1.0 microM on Trypanosoma brucei rhodesiense (T. b. rhodesiense), the causative agent of the acute form of HAT. METHODOLOGY/PRINCIPAL FINDINGS: In this work we show adenosine kinase of T. b. rhodesiense (TbrAK), a key enzyme of the parasite purine salvage pathway which is vital for parasite survival, to be the putative intracellular target of compound 1 using a chemical proteomics approach. This finding was confirmed by RNA interference experiments showing that down-regulation of adenosine kinase counteracts compound 1 activity. Further chemical validation demonstrated that compound 1 interacts specifically and tightly with TbrAK with nanomolar affinity, and in vitro activity measurements showed that compound 1 is an enhancer of TbrAK activity. The subsequent kinetic analysis provided strong evidence that the observed hyperactivation of TbrAK is due to the abolishment of the intrinsic substrate-inhibition. CONCLUSIONS/SIGNIFICANCE: The results suggest that TbrAK is the putative target of this compound, and that hyperactivation of TbrAK may represent a novel therapeutic strategy for the development of trypanocides.

Les Juifs dans le moyen âge : essai historique sur leur état civil, commercial et littéraire ...

par G. B. Depping

La controverse religieuse entre les crétiens et les juifs au moyen âge en France et en Espagne

par Isidore Loeb

Sēfer derek hay-yāšār le-ʿôlām hab-b�� : dizś sefer iz fer gmaini laaiṭn oich fr waibr un meidn ... ali dinim pif ṭaiṭš gišṭelṭ ...

... ham-meḥaber ... Jeḥiel Michel B.... Avraham Segel ... Epšṭain

Ms. Ff. Mus. 1503 - Am 2ten Christ=Feyertage : Wie theuer ist deine Güte, Gott, daß pp. ; C. A. T. B., 2 Clarinetti, 2 Flauti traversi, 2 Hautbois se piace, 2 Violini, 1 Viola, Violoncello et Organo

von Telemann

Ms. Ff. Mus. 1339 - Am 2. Advent : Seyd wacker allezeit, und bethet, daß ihr p. ; C. A. T. B., 2 oboe, 2 violini, 1 viola, violoncello et organo

von Teleman[n]. [Textverf.: Gottfried Simonis]

Retention in care of HIV-infected pregnant and lactating women starting art under Option B+ in rural Mozambique.

OBJECTIVE In 2013, Mozambique adopted Option B+, universal lifelong antiretroviral therapy (ART) for all pregnant and lactating women, as national strategy for prevention of mother-to-child transmission of HIV. We analyzed retention in care of pregnant and lactating women starting Option B+ in rural northern Mozambique. METHODS We compared ART outcomes in pregnant ("B+pregnant"), lactating ("B+lactating") and non-pregnant-non-lactating women of childbearing age starting ART after clinical and/or immunological criteria ("own health") between July 2013 and June 2014. Lost to follow-up was defined as no contact >180 days after the last visit. Multivariable competing risk models were adjusted for type of facility (type 1 vs. peripheral type 2 health center), age, WHO stage and time from HIV diagnosis to ART. RESULTS Over 333 person-years of follow-up (of 243 "B+pregnant", 65″B+lactating" and 317 "own health" women), 3.7% of women died and 48.5% were lost to follow-up. "B+pregnant" and "B+lactating" women were more likely to be lost in the first year (57% vs. 56.9% vs. 31.6%; p<0.001) and to have no follow-up after the first visit (42.4% vs. 29.2% vs. 16.4%; p<0.001) than "own health" women. In adjusted analyses, risk of being lost to follow-up was higher in "B+pregnant" (adjusted subhazard ratio [asHR]: 2.77; 95% CI: 2.18-3.50; p<0.001) and "B+lactating" (asHR: 1.94; 95% CI: 1.37-2.74; p<0.001). Type 2 health center was the only additional significant risk factor for loss to follow-up. CONCLUSIONS Retaining pregnant and lactating women in option B+ ART was poor; losses to follow-up were mainly early. The success of Option B+ for prevention of mother-to-child transmission of HIV in rural settings with weak health systems will depend on specific improvements in counseling and retention measures, especially at the beginning of treatment. This article is protected by copyright. All rights reserved.

Libellus Sodalitatis : Hoc Est Christianarum Institutionum Libri quinque, in gratiam Sodalitatis B. Virginis Mariae

Auctore Francisco Costero

Ms. Ff. Mus. 1135 - Am 1. Advent : Hosianna dem Sohne David! ; gelobet sey p. ; C. C. A. T. B., 2 oboe et flauti, 2 violini, 1 viola, violoncello et organo

von Telemann. [Textdichter: Gottfried Simonis]

Ms. Ff. Mus. 755 - Am Sonnt. nach Christ-Tag : Alle, die gottseelig leben wollen in Christo pp. ; C. A. T. B., 2 oboe, 2 violini, 1 viola, violoncello obl. et organo

von Telemann. [Text: Gottfried Simonis]