Lys9 for Glu9 substitution in glucagon-like peptide-1(7-36)amide confers dipeptidylpeptidase IV resistance with cellular and metabolic actions similar to those of established antagonists glucagon-like peptide-1(9-36)amide and exendin (9-39)

The incretin hormone glucagon-like peptide-1(7-36)amide (GLP-1) has been deemed of considerable importance in the regulation of blood glucose. Its effects, mediated through the regulation of insulin, glucagon, and somatostatin, are glucose-dependent and contribute to the tight control of glucose levels. Much enthusiasm has been assigned to a possible role of GLP-1 in the treatment of type 2 diabetes. GLIP-l's action unfortunately is limited through enzymatic inactivation caused by dipeptidylpeptidase IV (DPP IV). It is now well established that modifying GLP-1 at the N-terminal amino acids, His7 and Ala8, can greatly improve resistance to this enzyme. Little research has assessed what effect Glu9-substitution has on GLP-1 activity and its degradation by DPP IV. Here, we report that the replacement of Glu9 of GLP-1 with Lys dramatically increased resistance to DPP IV. This analogue (Lys9)GLP-1, exhibited a preserved GLP-1 receptor affinity, but the usual stimulatory effects of GLP-1 were completely eliminated, a trait duplicated by the other established GLP-1-antagonists, exendin (9-39) and GLP-1 (9-36)amide. We investigated the in vivo antagonistic actions of (Lys9)GLP-1 in comparison with GLP-1(9-36)amide and exendin (9-39) and revealed that this novel analogue may serve as a functional antagonist of the GLP-1 receptor.

Novel dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1(7-36)amide have preserved biological activities in vitro conferring improved glucose-lowering action in vivo

Although the incretin hormone glucagon-like peptide-1 (GLP-1) is a potent stimulator of insulin release, its rapid degradation in vivo by the enzyme dipeptidyl peptidase IV (DPP IV) greatly limits its potential for treatment of type 2 diabetes. Here, we report two novel Ala8-substituted analogues of GLP-1, (Abu8)GLP-1 and (Val8)GLP-1 which were completely resistant to inactivation by DPP IV or human plasma. (Abu8)GLP-1 and (Val8)GLP-1 exhibited moderate affinities (IC50: 4.76 and 81.1 nM, respectively) for the human GLP-1 receptor compared with native GLP-1 (IC50: 0.37 nM). (Abu8)GLP-1 and (Val8)GLP-1 dose-dependently stimulated cAMP in insulin-secreting BRIN BD11 cells with reduced potency compared with native GLP-1 (1.5- and 3.5-fold, respectively). Consistent with other mechanisms of action, the analogues showed similar, or in the case of (Val8)GLP-1 slightly impaired insulin releasing activity in BRIN BD11 cells. Using adult obese (ob/ob) mice, (Abu8 )GLP-1 had similar glucose-lowering potency to native GLP-1 whereas the action of (Val8)GLP-1 was enhanced by 37%. The in vivo insulin-releasing activities were similar. These data indicate that substitution of Ala8 in GLP-1 with Abu or Val confers resistance to DPP IV inactivation and that (Val8)GLP-1 is a particularly potent N-terminally modified GLP-1 analogue of possible use in type 2 diabetes.

Política y propaganda durante el reinado de Felipe IV

La presente exposición hace un recorrido por los fondos de la Biblioteca Histórica “Marqués de Valdecilla” de la Universidad Complutense de Madrid correspondientes al siglo XVII, dedicados a temas políticos y, más especialmente, a cuestiones de propaganda. El riquísimo material existente entre los alrededor de 100.000 volúmenes totales permite hacerse una idea bastante aproximada de la producción cultural hispánica dedicada a la exaltación del poder Habsburgo en todas sus dimensiones, tanto pretéritas como coetáneas, así como a la defenestración del adversario o la ejecución de proyectos o disposiciones administrativas, hechas por personajes notables o modestos,vinculados a la Corte, la Iglesia o la literatura, entre otros.La variedad de tipologías pertinentes para elaborar una exposición de estas características es verdaderamente extensa. Resulta bastante sencillo apuntar hacia libelos en los que se declara de manera explícita el odio a lo franc��s, se hace un canto a las excelencias de alguno de sus territorios, se responde a este o aquel manifiesto o se relata la forma en que los ejércitos aliados consiguieron someter a la tropa enemiga,pero no es menos interesante adentrarse en los entresijos de tratados de historia donde se relata la Guerra de Flandes o la propia de España desde el Diluvio Universal.

Estudo das alterações hematológicas e urinárias em cães em diferentes estágios de disfunção renal e avaliação do biomarcador cistatina C

Chapter 2 - Cystatin C is a cationic protein is not glycosylated, produced a steady state for all nucleated and present in biological fluids cells being freely filtered by the glomeruli and almost completely catabolized in the proximal tubule, it is a promising early renal dysfunction marker. This study aimed to determine and compare the serum concentration of cystatin C biomarker in 86 dogs. The animals were divided into four groups according to serum creatinine levels: G1 - up. 1.4 mg / dL (23 animals), G2 - 1.5-2.0 mg / dL (16 animals), G3 - 2.1 to 5.0 mg / dL (24 animals) and G4 - above 5.1 mg / dL (23 animals). There was the measurement of the parameters used in the clinical routine of small animals such as urea, urinary gamma glutamyl transferase, proteinuria, alkaline phosphatase, sodium, potassium, chloride, calcium, phosphorus, calcium/phosphorus ratio and cystatin C. There was no statistical difference for urea, proteinuria, phosphorus, calcium/phosphorus, potassium and cystatin C, however, the other showed no statistical difference. Based on the results we can infer that cystatin C was not a good early indicator of kidney disease in dogs. Chapter 3 - This study aimed to determine the hematological and urinalysis elements such as density, proteinuria, cylinders and pH in 86 dogs The animals were divided into four stages according to serum creatinine levels: I - up to 1.4 mg/dL (23 animals), II - 1.5-2.0 mg/dL (16 animals), III from 2.1 to 5.0 mg/dL (24 animals) and IV - above 5.1 mg/dL (23 animals). In stage III, IV there was anemia normocytic normochromic type. Stage II had a leukocytosis frame by neutrophilia with a regenerative left shift and stage III and IV detour degenerative left. The density remained within the reference values all stages. Proteinuria showed statistical significance for the classification 2+ (1.0 g/L), between stage I and II, II and IV. Only the cylinder granular statistical difference in the classification 2+ between stage II and III, and 3+ between stage I and III. The prevailing pH was acid. The haematological values compared to serum creatinine stages showed the changes in hemoglobin and packed cell volume erythrocytes become more pronounced as serum creatinine values rise , this is also the behavior of neutrophils rods and proteinuria.

Photocatalytic activities of tin(IV) oxide surface-modified titanium(IV) dioxide show a strong sensitivity to the TiO 2 crystal form

Surface modification of rutile TiO2 with extremely small SnO2 clusters gives rise to a great increase in its UV light activity for degradation of model organic water pollutants, while the effect is much smaller for anatase TiO2. This crystal form sensitivity is rationalized in terms of the difference in the electronic modification of TiO2 through the interfacial Sn−O−Ti bonds. The increase in the density of states near the conduction band minimum of rutile by hybridization with the SnO2 cluster levels intensifies the light absorption, but this is not seen with modified anatase. The electronic transition from the valence band to the conduction band causes the bulk-to-surface interfacial electron transfer to enhance charge separation. Further, electrons relaxed to the conduction minimum are smoothly transferred to O2 due to the action of the SnO2 species as an electron transfer promoter.

Loading effect in copper(II) oxide cluster-surface-modified titanium(IV) oxide on visible- and UV-light activities

Cu(acac)2 is chemisorbed on TiO2 particles [P-25 (anatase/rutile = 4/1 w/w), Degussa] via coordination by surface Ti–OH groups without elimination of the acac ligand. Post-heating of the Cu(acac)2-adsorbed TiO2 at 773 K yields molecular scale copper(II) oxide clusters on the surface (CuO/TiO2). The copper loading amount (Γ/Cu ions nm–2) is controlled in a wide range by the Cu(acac)2 concentration and the chemisorption–calcination cycle number. Valence band (VB) X-ray photoelectron and photoluminescence spectroscopy indicated that the VB maximum of TiO2 rises up with increasing Γ, while vacant midgap levels are generated. The surface modification gives rise to visible-light activity and concomitant significant increase in UV-light activity for the degradation of 2-naphthol and p-cresol. Prolonging irradiation time leads to the decomposition to CO2, which increases in proportion to irradiation time. The photocatalytic activity strongly depends on the loading, Γ, with an optimum value of Γ for the photocatalytic activity. Electrochemical measurements suggest that the surface CuO clusters promote the reduction of adsorbed O2. First principles density functional theory simulations clearly show that, at Γ < 1, unoccupied Cu 3d levels are generated in the midgap region, and at Γ > 1, the VB maximum rises and the unoccupied Cu 3d levels move to the conduction band minimum of TiO2. These results suggest that visible-light excitation of CuO/TiO2 causes the bulk-to-surface interfacial electron transfer at low coverage and the surface-to-bulk interfacial electron transfer at high coverage. We conclude that the surface CuO clusters enhance the separation of photogenerated charge carriers by the interfacial electron transfer and the subsequent reduction of adsorbed O2 to achieve the compatibility of high levels of visible and UV-light activities.

Fuentes, redes y sistemas de información en ciencias sociales y humanidades

Este trabajo se propone analizar los recursos de información en ciencias sociales y humanidades que puedan dar apoyo a la investigación en el área. Se describen las principales fuentes, redes y sistemas existentes con posibilidades de acceso a través de Bibliotecas y Centros de Documentación del país. Se incluyen tanto aquellos contenidos que están liberados en Internet como los que son arancelados. Se realiza un balance del estado de situación de estos recursos y su perspectiva de crecimiento en la cooperación, ya que resulta imperativo impulsar actividades tendientes a compartir recursos informativos y buscar medios idóneos para acceder a los documentos en que debe basarse toda investigación

Fuentes, redes y sistemas de información en ciencias sociales y humanidades

Este trabajo se propone analizar los recursos de información en ciencias sociales y humanidades que puedan dar apoyo a la investigación en el área. Se describen las principales fuentes, redes y sistemas existentes con posibilidades de acceso a través de Bibliotecas y Centros de Documentación del país. Se incluyen tanto aquellos contenidos que están liberados en Internet como los que son arancelados. Se realiza un balance del estado de situación de estos recursos y su perspectiva de crecimiento en la cooperación, ya que resulta imperativo impulsar actividades tendientes a compartir recursos informativos y buscar medios idóneos para acceder a los documentos en que debe basarse toda investigación

Fuentes, redes y sistemas de información en ciencias sociales y humanidades

Este trabajo se propone analizar los recursos de información en ciencias sociales y humanidades que puedan dar apoyo a la investigación en el área. Se describen las principales fuentes, redes y sistemas existentes con posibilidades de acceso a través de Bibliotecas y Centros de Documentación del país. Se incluyen tanto aquellos contenidos que están liberados en Internet como los que son arancelados. Se realiza un balance del estado de situación de estos recursos y su perspectiva de crecimiento en la cooperación, ya que resulta imperativo impulsar actividades tendientes a compartir recursos informativos y buscar medios idóneos para acceder a los documentos en que debe basarse toda investigación

Fadrique Álvarez de Toledo, II Duque de Alba y su inventario de libros (1531): Una biblioteca patrimonial

Fadrique Álvarez de Toledo, que nació hacia 1460 y murió en 1531, lidera en Castilla el linaje de la casa de Alba en el tránsito de la Edad Media al Renacimiento. Primo carnal de Fernando el Católico, y colaborador íntimo de los Reyes, desarrolla una amplia labor de mecenazgo artístico y literario, de la cual son ejemplos relevantes los apoyos a poetas como Juan del Encina, Juan Boscán o Garcilaso de la Vega. A pesar de esta actividad, la crítica no se ha ocupado con detalle de este personaje por haberle eclipsado un tanto su nieto, el Gran Duque de Alba. Este artículo reproduce el inventario de la biblioteca de Don Fadrique (formado por los libros que fueron catalogados a su muerte), inédito hasta ahora y que nos muestra una rica biblioteca patrimonial de ciento ochenta y seis obras. Entre los libros religiosos encontramos biblias, tratados de oración y libros de horas; se hallan también algunos títulos indispensables de las tradiciones franciscana y dominica, que nos muestran a un personaje interesado en las nuevas corrientes devocionales de finales del siglo XV, en el escolasticismo y en las mujeres santas y visionarias del Medievo.